Indinavir Sulfate (Crixivan)
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Indinavir Sulfate (Crixivan)

CRIXIVAN®
(indinavir sulfate) Capsules

DRUG DESCRIPTION

CRIXIVAN (indinavir sulfate) is an inhibitor of the human immunodeficiency virus (HIV) protease. CRIXIVAN Capsules are formulated as a sulfate salt and are available for oral administration in strengths of 100, 200, and 400 mg of indinavir (corresponding to 125, 250, and 500 mg indinavir sulfate, respectively). Each capsule also contains the inactive ingredients anhydrous lactose and magnesium stearate. The capsule shell has the following inactive ingredients and dyes: gelatin and titanium dioxide.

The chemical name for indinavir sulfate is [1(1S,2R),5(S)]-2,3,5-trideoxy-N-(2,3-dihydro-2-hydroxy-1Hinden-1-yl)-5-[2-[[(1,1-dimethylethyl)amino]carbonyl]-4-(3-pyridinylmethyl)-1-piperazinyl]-2(phenylmethyl)-D-erythro-pentonamide sulfate (1:1) salt. Indinavir sulfate has the following structural formula:

CRIXIVAN® (indinavir sulfate) Structural Formula Illustration

Indinavir sulfate is a white to off-white, hygroscopic, crystalline powder with the molecular formula C36H47N5O4•H2SO4 and a molecular weight of 711.88. It is very soluble in water and in methanol.

What are the possible side effects of indinavir (Crixivan)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking indinavir and call your doctor at once if you have any of these serious side effects:

  • fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;
  • pale or yellowed skin, dark colored urine, fever, confusion or weakness;
  • increased urination or extreme thirst;
  • pain in your side or lower back, blood in your urine;
  • easy bruising or...

Read All Potential Side Effects and See Pictures of Crixivan »

What are the precautions when taking indinavir sulfate (Crixivan)?

Before taking indinavir, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood fat levels (cholesterol/triglycerides), diabetes, hemophilia, kidney problems (including kidney stones), heart problems (coronary artery disease, heart attack), liver problems.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Children may be more sensitive to the side effects of this drug,...

Read All Potential Precautions of Crixivan »

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

CRIXIVAN in combination with antiretroviral agents is indicated for the treatment of HIV infection.

This indication is based on two clinical trials of approximately 1 year duration that demonstrated: 1) a reduction in the risk of AIDS-defining illnesses or death; 2) a prolonged suppression of HIV RNA.

DOSAGE AND ADMINISTRATION

The recommended dosage of CRIXIVAN is 800 mg (usually two 400-mg capsules) orally every 8 hours.

CRIXIVAN must be taken at intervals of 8 hours. For optimal absorption, CRIXIVAN should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, CRIXIVAN may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal, e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; or corn flakes, skim milk and sugar. (See CLINICAL PHARMACOLOGY, Effect of Food on Oral Absorption.)

To ensure adequate hydration, it is recommended that adults drink at least 1.5 liters (approximately 48 ounces) of liquids during the course of 24 hours. Concomitant Therapy (See CLINICAL PHARMACOLOGY, Drug Interactions, and/or PRECAUTIONS: DRUG INTERACTIONS.)

Delavirdine

Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered when administering delavirdine 400 mg three times a day.

Didanosine

If indinavir and didanosine are administered concomitantly, they should be administered at least one hour apart on an empty stomach (consult the manufacturer's product circular for didanosine).

Itraconazole

Dose reduction of CRIXIVAN to 600 mg every 8 hours is recommended when administering itraconazole 200 mg twice daily concurrently.

Ketoconazole

Dose reduction of CRIXIVAN to 600 mg every 8 hours is recommended when administering ketoconazole concurrently.

Rifabutin

Dose reduction of rifabutin to half the standard dose (consult the manufacturer's product circular for rifabutin) and a dose increase of CRIXIVAN to 1000 mg every 8 hours are recommended when rifabutin and CRIXIVAN are coadministered.

Hepatic Insufficiency

The dosage of CRIXIVAN should be reduced to 600 mg every 8 hours in patients with mild-tomoderate hepatic insufficiency due to cirrhosis.

Nephrolithiasis/Urolithiasis

In addition to adequate hydration, medical management in patients who experience nephrolithiasis/urolithiasis may include temporary interruption (e.g., 1 to 3 days) or discontinuation of therapy.

HOW SUPPLIED

CRIXIVAN Capsules are supplied as follows:

No. 3755 — 100 mg capsules: semi-translucent white capsules coded “CRIXIVAN100 mg” in green. Available as:

NDC 0006-0570-62 unit-of-use bottles of 180 (with desiccant).

No. 3756 — 200 mg capsules: semi-translucent white capsules coded “CRIXIVAN™ 200 mg” in blue. Available as:

NDC 0006-0571-43 unit-of-use bottles of 360 (with desiccant).

No. 3758 — 400 mg capsules: semi-translucent white capsules coded “CRIXIVAN™ 400 mg” in green. Available as:

NDC 0006-0573-42 unit-dose packages of 42
NDC 0006-0573-40 unit-of-use bottles of 120 (with desiccant)
NDC
0006-0573-62 unit-of-use bottles of 180 (with desiccant)
NDC
0006-0573-54 unit-of-use bottles of 90 (with desiccant)
NDC
0006-0573-18 unit-of-use bottles of 18 (with desiccant).

Storage

Bottles: Store in a tightly-closed container at room temperature, 15-30°C (59-86°F). Protect from moisture.

CRIXIVAN Capsules are sensitive to moisture. CRIXIVAN should be dispensed and stored in the original container. The desiccant should remain in the original bottle.

Unit-Dose Packages: Store at room temperature, 15-30°C (59-86°F). Protect from moisture.

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trials in Adults

Nephrolithiasis/urolithiasis, including flank pain with or without hematuria (including microscopic hematuria), has been reported in approximately 12.4% (301/2429; range across individual trials: 4.7% to 34.4%) of patients receiving CRIXIVAN at the recommended dose in clinical trials with a median follow-up of 47 weeks (range: 1 day to 242 weeks; 2238 patient-years follow-up). The cumulative frequency of nephrolithiasis events increases with duration of exposure to CRIXIVAN; however, the risk over time remains relatively constant. Of the patients treated with CRIXIVAN who developed nephrolithiasis/urolithiasis in clinical trials during the double-blind phase, 2.8% (7/246) were reported to develop hydronephrosis and 4.5% (11/246) underwent stent placement. Following the acute episode, 4.9% (12/246) of patients discontinued therapy. (See WARNINGS and DOSAGE AND ADMINISTRATION, Nephrolithiasis/Urolithiasis.)

Asymptomatic hyperbilirubinemia (total bilirubin ≥ 2.5 mg/dL), reported predominantly as elevated indirect bilirubin, has occurred in approximately 14% of patients treated with CRIXIVAN. In < 1% this was associated with elevations in ALT or AST.

Hyperbilirubinemia and nephrolithiasis/urolithiasis occurred more frequently at doses exceeding 2.4 g/day compared to doses ≤ 2.4 g/day.

Clinical adverse experiences reported in ≥ 2% of patients treated with CRIXIVAN alone, CRIXIVAN in combination with zidovudine or zidovudine plus lamivudine, zidovudine alone, or zidovudine plus lamivudine are presented in Table 10.

Table 10 : Clinical Adverse Experiences Reported in ≥ 2% of Patients

Adverse Experience Study 02 Considered Drug-Related and of Moderate or Severe Intensity Study ACTG 320 of Unknown Drug Relationship and of Severe or Life-threatening Intensity
CRIXIVAN Percent
(n=332)
CRIXIVAN plus Zidovudine Percent
(n=332)
Zidovudine Percent
(n=332)
CRIXIVAN plus Zidovudine plus Lamivudine Percent
(n=571)
Zidovudine plus Lamivudine Percent
(n=575)
Body as a Whole
  Abdominal pain 16.6 16.0 12.0 1.9 0.7
  Asthenia/fatigue 2.1 4.2 3.6 2.4 4.5
  Fever 1.5 1.5 2.1 3.8 3.0
  Malaise 2.1 2.7 1.8 0 0
Digestive System
  Nausea 11.7 31.9 19.6 2.8 1.4
  Diarrhea 3.3 3.0 2.4 0.9 1.2
  Vomiting 8.4 17.8 9.0 1.4 1.4
  Acid regurgitation 2.7 5.4 1.8 0.4 0
  Anorexia 2.7 5.4 3.0 0.5 0.2
  Appetite increase 2.1 1.5 1.2 0 0
  Dyspepsia 1.5 2.7 0.9 0 0
  Jaundice 1.5 2.1 0.3 0 0
Hemic and Lymphatic System
  Anemia 0.6 1.2 2.1 2.4 3.5
Musculoskeletal System
  Back pain 8.4 4.5 1.5 0.9 0.7
Nervous System/Psychiatric
  Headache 5.4 9.6 6.0 2.4 2.8
  Dizziness 3.0 3.9 0.9 0.5 0.7
  Somnolence 2.4 3.3 3.3 0 0
Skin and Skin Appendage
  Pruritus 4.2 2.4 1.8 0.5 0
  Rash 1.2 0.6 2.4 1.1 0.5
Respiratory System
  Cough  1.5 0.3 0.6 1.6 1.0
  Difficulty breathing/dyspnea/shortness of breath Urogenital System 0 0.6 0.3 1.8 1.0
  Nephrolithiasis/urolithiasis* 8.7 7.8 2.1 2.6 0.3
  Dysuria 1.5 2.4 0.3 0.4 0.2
Special Senses 
  Taste perversion 2.7 8.4 1.2 0.2 0
*Including renal colic, and flank pain with and without hematuria

In Phase I and II controlled trials, the following adverse events were reported significantly more frequently by those randomized to the arms containing CRIXIVAN than by those randomized to nucleoside analogues: rash, upper respiratory infection, dry skin, pharyngitis, taste perversion.

Selected laboratory abnormalities of severe or life-threatening intensity reported in patients treated with CRIXIVAN alone, CRIXIVAN in combination with zidovudine or zidovudine plus lamivudine, zidovudine alone, or zidovudine plus lamivudine are presented in Table 11.

Table 11 : Selected Laboratory Abnormalities of Severe or Life-threatening Intensity Reported in Studies 028 and ACTG 320

  Study 028 Study ACTG 320
CRIXIVAN Percent
(n=329)
CRIXIVAN plus Zidovudine Percent
(n=320)
Zidovudine Percent
(n=330)
CRIXIVAN plus Zidovudine plus Lamivudine Percent
(n=571)
Zidovudine plus Lamivudine Percent
(n=575)
Hematology
Decreased hemoglobin < 7.0 g/dL 0.6 0.9 3.3 2.4 3.5
Decreased platelet count < 50 THS/mm³ 0.9 0.9 1.8 0.2 0.9
Decreased neutrophils < 0.75 THS/mm³ 2.4 2.2 6.7 5.1 14.6
Blood chemistry
Increased ALT > 500% ULN* 4.9 4.1 3.0 2.6 2.6
Increased AST > 500% ULN 3.7 2.8 2.7 3.3 2.8
Total serum bilirubin > 250% ULN 11.9 9.7 0.6 6.1 1.4
Increased serum amylase > 200% ULN 2.1 1.9 1.8 0.9 0.3
Increased glucose > 250 mg/dL 0.9 0.9 0.6 1.6 1.9
Increased creatinine > 300% ULN 0 0 0.6 0.2 0
*Upper limit of the normal range.

Post-Marketing Experience

Body As A Whole:redistribution/accumulation of body fat (see PRECAUTIONS, Fat Redistribution).

Cardiovascular System: cardiovascular disorders including myocardial infarction and angina pectoris; cerebrovascular disorder.

Digestive System: liver function abnormalities; hepatitis including reports of hepatic failure (see WARNINGS); pancreatitis; jaundice; abdominal distention; dyspepsia.

Hematologic: increased spontaneous bleeding in patients with hemophilia (see PRECAUTIONS); acute hemolytic anemia (see WARNINGS).

Endocrine/Metabolic: new onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, hyperglycemia (see WARNINGS).

Hypersensitivity: anaphylactoid reactions; urticaria; vasculitis.

Musculoskeletal System: arthralgia.

Nervous System/Psychiatric: oral paresthesia; depression.

Skin and Skin Appendage: rash including erythema multiforme and Stevens-Johnson syndrome; hyperpigmentation; alopecia; ingrown toenails and/or paronychia; pruritus.

Urogenital System:nephrolithiasis/urolithiasis, in some cases resulting in renal insufficiency or acute renal failure, pyelonephritis with or without bacteremia (see WARNINGS); interstitial nephritis sometimes with indinavir crystal deposits; in some patients, the interstitial nephritis did not resolve following discontinuation of CRIXIVAN; renal insufficiency; renal failure; leukocyturia (see PRECAUTIONS), crystalluria; dysuria.

Laboratory Abnormalities

Increased serum triglycerides; increased serum cholesterol.

Read the Crixivan (indinavir sulfate) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Indinavir is an inhibitor of the cytochrome P450 isoform CYP3A4. Coadministration of CRIXIVAN and drugs primarily metabolized by CYP3A4 may result in increased plasma concentrations of the other drug, which could increase or prolong its therapeutic and adverse effects (see CONTRAINDICATIONS and WARNINGS).

Indinavir is metabolized by CYP3A4. Drugs that induce CYP3A4 activity would be expected to increase the clearance of indinavir, resulting in lowered plasma concentrations of indinavir. Coadministration of CRIXIVAN and other drugs that inhibit CYP3A4 may decrease the clearance of indinavir and may result in increased plasma concentrations of indinavir.

Table 8 : Drugs That Should Not Be Coadministered with CRIXIVAN

Druq Class: Drug Name Clinical Comment
Alpha 1-adrenoreceptor antagonist: alfuzosin Potentially increased alfuzosin concentrations can result in hypotension.
Antiarrhythmics: amiodarone CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Antimycobacterial: rifampin May lead to loss of virologic response and possible resistance to CRIXIVAN or to the class of protease inhibitors or other coadministered antiretroviral agents.
Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues.
GI motility agents: cisapride CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Herbal products: St. John's wort (Hypericum perforatum) May lead to loss of virologic response and possible resistance to CRIXIVAN or to the class of protease inhibitors.
HMG-CoA Reductase inhibitors: lovastatin, simvastatin CONTRAINDICATED due to an increased risk for serious reactions such as myopathy including rhabdomyolysis.
Neuroleptic: pimozide CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
PDE5 inhibitor: Revatio1 (sildenafil) [for treatment of pulmonary arterial hypertension] A safe and effective dose has not been established when used with CRIXIVAN. There is increased potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope).
Protease inhibitor: atazanavir Both CRIXIVAN and atazanavir are associated with indirect (unconjugated) hyperbilirubinemia. Combinations of these drugs have not been studied and coadministration of CRIXIVAN and atazanavir is not recommended.
Sedative/hypnotics: Oral midazolam, triazolam, alprazolam CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.
1Registered trademark of Pfizer, Inc.

Table 9 : Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction (See also CLINICAL PHARMACOLOGY for magnitude of interaction, WARNINGS and DOSAGE AND ADMINISTRATION.)

Drug Name Effect Clinical Comment
HIV Antiviral Agents
Delavirdine ↑ indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered when taking delavirdine 400 mg three times a day.
Didanosine   Indinavir and didanosine formulations containing buffer should be administered at least one hour apart on an empty stomach.
Efavirenz ↓indinavir concentration The optimal dose of indinavir, when given in combination with efavirenz, is not known. Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to efavirenz.
Nelfinavir ↑ indinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established.
Nevirapine ↓ indinavir concentration Indinavir concentrations may be decreased in the presence of nevirapine. The appropriate doses for this combination, with respect to efficacy and safety, have not been established.
Ritonavir ↑ indinavir concentration
↑ritonavir concentration
The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Preliminary clinical data suggest that the incidence of nephrolithiasis is higher in patients receiving indinavir in combination with ritonavir than those receiving CRIXIVAN 800 mg q8h.
Saquinavir ↑ saquinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established.
Other Agents
Antiarrhythmics: bepridil, lidocaine (systemic) and quinidine ↑antiarrhythmic agents concentration Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when coadministered with CRIXIVAN.
Anticonvulsants: carbamazepine, phenobarbital, phenytoin ↓ indinavir concentration Use with caution. CRIXIVAN may not be effective due to decreased indinavir concentrations in patients taking these agents concomitantly.
Antidepressant: Trazodone ↑ trazodone concentration Concomitant use of trazodone and CRIXIVAN may increase plasma concentrations of trazodone. Adverse events of nausea, dizziness, hypotension and syncope have been observed following coadministration of trazodone and ritonavir. If trazodone is used with a CYP3A4 inhibitor such as CRIXIVAN, the combination should be used with caution and a lower dose of trazodone should be considered.
Anti-gout: Colchicine ↑ colchicine concentration Patients with renal or hepatic impairment should not be given colchicine with CRIXIVAN.
Treatment of gout flares:
Co-administration of colchicine in patients on CRIXIVAN: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days.
Prophylaxis of gout flares:
Co-administration of colchicine in patients on CRIXIVAN:
If the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.
Treatment of familial Mediterranean fever (FMF):
Co-administration of colchicine in patients on CRIXIVAN: Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Calcium Channel Blockers, Dihydropyridine: e.g., felodipine, nifedipine, nicardipine ↑dihydropyridine calcium channel blockers concentration Caution is warranted and clinical monitoring of patients is recommended.
Clarithromycin ↑ clarithromycin concentration
↑indinavir concentration
The appropriate doses for this combination, with respect to efficacy and safety, have not been established.
Endothelin receptor antagonist: ↑ bosentan concentration Co-administration of bosentan in patients on CRIXIVAN or coadministration of CRIXIVAN in patients on bosentan: Start at or
Bosentan   adjust bosentan to 62.5 mg once daily or every other day based upon individual tolerability.
HMG-CoA Reductase Inhibitors: atorvastatin, rosuvastatin ↑atorvastatin concentration
↑ rosuvastatin concentration
The atorvastatin and rosuvastatin doses should be carefully titrated; use the lowest dose necessary with careful monitoring during treatment with CRIXIVAN.
Immunosuppressants: cyclosporine, tacrolimus, sirolimus ↑immunosuppressant agents concentration Plasma concentrations may be increased by CRIXIVAN.
Inhaled beta agonist: Salmeterol ↑ salmeterol Concurrent administration of salmeterol with CRIXIVAN is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia.
Inhaled/nasal steroid: Fluticasone ↑fluticasone concentration Concomitant use of fluticasone propionate and CRIXIVAN may increase plasma concentrations of fluticasone propionate. Use with caution. Consider alternatives to fluticasone propionate, particularly for long-term use.
Fluticasone use is not recommended in situations where CRIXIVAN is coadministered with a potent CYP3A4 inhibitor such as ritonavir unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
Itraconazole ↑ indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours is recommended when administering itraconazole concurrently.
Ketoconazole ↑indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered.
Midazolam (parenteral administration) ↑ midazolam concentration Concomitant use of parenteral midazolam with CRIXIVAN may increase plasma concentrations of midazolam. Coadministration should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. Coadministration of oral midazolam with CRIXIVAN is CONTRAINDICATED (see Table 8).
Rifabutin ↓indinavir concentration
↑rifabutin concentration
Dose reduction of rifabutin to half the standard dose and a dose increase of CRIXIVAN to 1000 mg every 8 hours are recommended when rifabutin and CRIXIVAN are coadministered.
Sildenafil ↑sildenafil concentration (only the use of sildenafil at doses used for treatment of erectile dysfunction has been studied with CRIXIVAN) May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism.
Use of sildenafil for pulmonary arterial hypertension (PAH):
Use of Revatio1 (sildenafil) is contraindicated when used for the treatment of pulmonary arterial hypertension (PAH) [see CONTRAINDICATIONS].
Use of sildenafil for erectile dysfunction:
Sildenafil dose should not exceed a maximum of 25 mg in a 48-hour period in patients receiving concomitant CRIXIVAN therapy. Use with increased monitoring for adverse events.
Tadalafil ↑tadalafil concentration May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, visual disturbances, and priapism.
Use of tadalafil for pulmonary arterial hypertension (PAH):
The following dose adjustments are recommended for use of Adcirca2 (tadalafil) with CRIXIVAN:
Co-administration of Adcirca in patients on CRIXIVAN or coadministration of CRIXIVAN in patients on Adcirca:
Start at or adjust Adcirca to 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
Use of tadalafil for erectile dysfunction:
Tadalafil dose should not exceed a maximum of 10 mg in a 72-hour period in patients receiving concomitant CRIXIVAN therapy. Use with increased monitoring for adverse events.
Vardenafil ↑vardenafil concentration Vardenafil dose should not exceed a maximum of 2.5 mg in a 24-hour period in patients receiving concomitant indinavir therapy.
Venlafaxine ↓indinavir concentration In a study of 9 healthy volunteers, venlafaxine administered under steady-state conditions at 150 mg/day resulted in a 28% decrease in the AUC of a single 800 mg oral dose of indinavir and a 36% decrease in indinavir Cmax. Indinavir did not affect the pharmacokinetics of venlafaxine and ODV. The clinical significance of this finding is unknown.
1Registered trademark of Pfizer, Inc.
2Registered trademark of Eli Lilly and Company.

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

ALERT: Find out about medicines that should NOT be taken with CRIXIVAN .This statement is included on the product's bottle label.

Nephrolithiasis/Urolithiasis

Nephrolithiasis/urolithiasis has occurred with CRIXIVAN therapy. The cumulative frequency of nephrolithiasis is substantially higher in pediatric patients (29%) than in adult patients (12.4%; range across individual trials: 4.7% to 34.4%). The cumulative frequency of nephrolithiasis events increases with increasing exposure to CRIXIVAN; however, the risk over time remains relatively constant. In some cases, nephrolithiasis/urolithiasis has been associated with renal insufficiency or acute renal failure, pyelonephritis with or without bacteremia. If signs or symptoms of nephrolithiasis/urolithiasis occur, (including flank pain, with or without hematuria or microscopic hematuria), temporary interruption (e.g., 13 days) or discontinuation of therapy may be considered. Adequate hydration is recommended in all patients treated with CRIXIVAN. (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION, Nephrolithiasis/Urolithiasis.)

Hemolytic Anemia

Acute hemolytic anemia, including cases resulting in death, has been reported in patients treated with CRIXIVAN. Once a diagnosis is apparent, appropriate measures for the treatment of hemolytic anemia should be instituted, including discontinuation of CRIXIVAN.

Hepatitis

Hepatitis including cases resulting in hepatic failure and death has been reported in patients treated with CRIXIVAN. Because the majority of these patients had confounding medical conditions and/or were receiving concomitant therapy(ies), a causal relationship between CRIXIVAN and these events has not been established.

Hyperglycemia

New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycemia have been reported during post-marketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established.

Drug Interactions

Concomitant use of CRIXIVAN with lovastatin or simvastatin is contraindicated due to increased risk of myopathy including rhabdomyolysis. Caution should be exercised if CRIXIVAN is used concurrently with atorvastatin or rosuvastatin. Titrate the atorvastatin and rosuvastatin doses carefully and use the lowest necessary dose with CRIXIVAN. (See PRECAUTIONS: DRUG INTERACTIONS.)

Midazolam is extensively metabolized by CYP3A4. Co-administration with CRIXIVAN with or without ritonavir may cause a large increase in the concentration of this benzodiazepine. No drug interaction study has been performed for the co-administration of CRIXIVAN with benzodiazepines. Based on data from other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally. Therefore CRIXIVAN should not be co-administered with orally administered midazolam (see CONTRAINDICATIONS), whereas caution should be used with coadministration of CRIXIVAN and parenteral midazolam. Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels. If CRIXIVAN with or without ritonavir is co-administered with parenteral midazolam, it should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.

Particular caution should be used when prescribing sildenafil, tadalafil, or vardenafil in patients receiving indinavir. Coadministration of CRIXIVAN with these medications is expected to substantially increase plasma concentrations of sildenafil, tadalafil, and vardenafil and may result in an increase in adverse events, including hypotension, visual changes, and priapism, which have been associated with sildenafil, tadalafil, and vardenafil (see CONTRAINDICATIONS and PRECAUTIONS: DRUG INTERACTIONS and PATIENT INFORMATION , and the manufacturer's complete prescribing information for sildenafil, tadalafil, or vardenafil).

Concomitant use of CRIXIVAN and St. John's wort (Hypericum perforatum) or products containing St. John's wort is not recommended. Coadministration of CRIXIVAN and St. John's wort has been shown to substantially decrease indinavir concentrations (see CLINICAL PHARMACOLOGY, Drug Interactions) and may lead to loss of virologic response and possible resistance to CRIXIVAN or to the class of protease inhibitors.

PRECAUTIONS

General

Indirect hyperbilirubinemia has occurred frequently during treatment with CRIXIVAN and has infrequently been associated with increases in serum transaminases (see also ADVERSE REACTIONS, Clinical Trials and Post-Marketing Experience). It is not known whether CRIXIVAN will exacerbate the physiologic hyperbilirubinemia seen in neonates. (See Pregnancy.)

Tubulointerstitial Nephritis

Reports of tubulointerstitial nephritis with medullary calcification and cortical atrophy have been observed in patients with asymptomatic severe leukocyturia ( > 100 cells/ high power field). Patients with asymptomatic severe leukocyturia should be followed closely and monitored frequently with urinalyses. Further diagnostic evaluation may be warranted, and discontinuation of CRIXIVAN should be considered in all patients with severe leukocyturia.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including CRIXIVAN. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Coexisting Conditions

Patients with hemophilia: There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. In some patients, additional factor VIII was required. In many of the reported cases, treatment with protease inhibitors was continued or restarted. A causal relationship between protease inhibitor therapy and these episodes has not been established. (See ADVERSE REACTIONS, Post-Marketing Experience.)

Patients with hepatic insufficiency due to cirrhosis: In these patients, the dosage of CRIXIVAN should be lowered because of decreased metabolism of CRIXIVAN (see DOSAGE AND ADMINISTRATION).

Patients with renal insufficiency: Patients with renal insufficiency have not been studied.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Information for Patients

A statement to patients and health care providers is included on the product's bottle label. ALERT: Find out about medicines that should NOT be taken with CRIXIVAN. A Patient Package Insert (PPI) for CRIXIVAN is available for patient information.

CRIXIVAN is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a physician when using CRIXIVAN.

Patients should be advised to avoid doing things that can spread HIV-1 infection to others.

  • Do not share needles or other injection equipment.
  • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
  • Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.
  • Do not breastfeed. We do not know if CRIXIVAN can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Patients should be advised to remain under the care of a physician when using CRIXIVAN and should not modify or discontinue treatment without first consulting the physician. Therefore, if a dose is missed, patients should take the next dose at the regularly scheduled time and should not double this dose. Therapy with CRIXIVAN should be initiated and maintained at the recommended dosage.

CRIXIVAN may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John's wort.

For optimal absorption, CRIXIVAN should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, CRIXIVAN may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal, e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; or corn flakes, skim milk and sugar (see CLINICAL PHARMACOLOGY, Effect of Food on Oral Absorption and DOSAGE AND ADMINISTRATION). Ingestion of CRIXIVAN with a meal high in calories, fat, and protein reduces the absorption of indinavir.

Patients receiving a phosphodiesterase type 5 (PDE5) inhibitor (sildenafil, tadalafil, or vardenafil) should be advised that they may be at an increased risk of PDE5 inhibitor-associated adverse events including hypotension, visual changes, and priapism, and should promptly report any symptoms to their doctors (see CONTRAINDICATIONS and WARNINGS, Drug Interactions).

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

CRIXIVAN Capsules are sensitive to moisture. Patients should be informed that CRIXIVAN should be stored and used in the original container and the desiccant should remain in the bottle.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies were conducted in mice and rats. In mice, no increased incidence of any tumor type was observed. The highest dose tested in rats was 640 mg/kg/day; at this dose a statistically significant increased incidence of thyroid adenomas was seen only in male rats. At that dose, daily systemic exposure in rats was approximately 1.3 times higher than daily systemic exposure in humans. No evidence of mutagenicity or genotoxicity was observed in in vitro microbial mutagenesis (Ames) tests, in vitro alkaline elution assays for DNA breakage, in vitro and in vivo chromosomal aberration studies, and in vitro mammalian cell mutagenesis assays. No treatment-related effects on mating, fertility, or embryo survival were seen in female rats and no treatment-related effects on mating performance were seen in male rats at doses providing systemic exposure comparable to or slightly higher than that with the clinical dose. In addition, no treatment-related effects were observed in fecundity or fertility of untreated females mated to treated males.

Pregnancy

Pregnancy Category C: Developmental toxicity studies were performed in rabbits (at doses up to 240 mg/kg/day), dogs (at doses up to 80 mg/kg/day), and rats (at doses up to 640 mg/kg/day). The highest doses in these studies produced systemic exposures in these species comparable to or slightly greater than human exposure. No treatment-related external, visceral, or skeletal changes were observed in rabbits or dogs. No treatment-related external or visceral changes were observed in rats. Treatment-related increases over controls in the incidence of supernumerary ribs (at exposures at or below those in humans) and of cervical ribs (at exposures comparable to or slightly greater than those in humans) were seen in rats. In all three species, no treatment-related effects on embryonic/fetal survival or fetal weights were observed.

In rabbits, at a maternal dose of 240 mg/kg/day, no drug was detected in fetal plasma 1 hour after dosing. Fetal plasma drug levels 2 hours after dosing were approximately 3% of maternal plasma drug levels. In dogs, at a maternal dose of 80 mg/kg/day, fetal plasma drug levels were approximately 50% of maternal plasma drug levels both 1 and 2 hours after dosing. In rats, at maternal doses of 40 and 640 mg/kg/day, fetal plasma drug levels were approximately 10 to 15% and 10 to 20% of maternal plasma drug levels 1 and 2 hours after dosing, respectively.

Indinavir was administered to Rhesus monkeys during the third trimester of pregnancy (at doses up to 160 mg/kg twice daily) and to neonatal Rhesus monkeys (at doses up to 160 mg/kg twice daily). When administered to neonates, indinavir caused an exacerbation of the transient physiologic hyperbilirubinemia seen in this species after birth; serum bilirubin values were approximately fourfold above controls at 160 mg/kg twice daily. A similar exacerbation did not occur in neonates after in utero exposure to indinavir during the third trimester of pregnancy. In Rhesus monkeys, fetal plasma drug levels were approximately 1 to 2% of maternal plasma drug levels approximately 1 hour after maternal dosing at 40, 80, or 160 mg/kg twice daily.

Hyperbilirubinemia has occurred during treatment with CRIXIVAN (see PRECAUTIONS and ADVERSE REACTIONS). It is unknown whether CRIXIVAN administered to the mother in the perinatal period will exacerbate physiologic hyperbilirubinemia in neonates.

There are no adequate and well-controlled studies in pregnant patients. CRIXIVAN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

A CRIXIVAN dose of 800 mg every 8 hours (with zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day) has been studied in 16 HIV-infected pregnant patients at 14 to 28 weeks of gestation at enrollment (study PACTG 358). Given the substantially lower antepartum exposures observed and the limited data in this patient population, indinavir use is not recommended in HIV-infected pregnant patients (see CLINICAL PHARMACOLOGY, Pregnant Patients).

Antiretroviral Pregnancy Registry

To monitor maternal-fetal outcomes of pregnant patients exposed to CRIXIVAN, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1800-258-4263.

Nursing Mothers

Studies in lactating rats have demonstrated that indinavir is excreted in milk. Although it is not known whether CRIXIVAN is excreted in human milk, there exists the potential for adverse effects from indinavir in nursing infants. Mothers should be instructed to discontinue nursing if they are receiving CRIXIVAN. This is consistent with the recommendation by the U.S. Public Health Service Centers for Disease Control and Prevention that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV.

Pediatric Use

The optimal dosing regimen for use of indinavir in pediatric patients has not been established. A dose of 500 mg/m² every eight hours has been studied in uncontrolled studies of 70 children, 3 to 18 years of age. The pharmacokinetic profiles of indinavir at this dose were not comparable to profiles previously observed in adults receiving the recommended dose (see CLINICAL PHARMACOLOGY, Pediatric). Although viral suppression was observed in some of the 32 children who were followed on this regimen through 24 weeks, a substantially higher rate of nephrolithiasis was reported when compared to adult historical data (see WARNINGS, Nephrolithiasis/Urolithiasis). Physicians considering the use of indinavir in pediatric patients without other protease inhibitor options should be aware of the limited data available in this population and the increased risk of nephrolithiasis.

Geriatric Use

Clinical studies of CRIXIVAN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy.

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There have been more than 60 reports of acute or chronic human overdosage (up to 23 times the recommended total daily dose of 2400 mg) with CRIXIVAN. The most commonly reported symptoms were renal (e.g., nephrolithiasis/urolithiasis, flank pain, hematuria) and gastrointestinal (e.g., nausea, vomiting, diarrhea).

It is not known whether CRIXIVAN is dialyzable by peritoneal or hemodialysis.

CONTRAINDICATIONS

CRIXIVAN is contraindicated in patients with clinically significant hypersensitivity to any of its components.

Inhibition of CYP3A4 by CRIXIVAN can result in elevated plasma concentrations of the following drugs, potentially causing serious or life-threatening reactions:

Table 7 : Drug Interactions With Crixivan: Contraindicated Drugs

Druq Class Druqs Within Class That Are Contraindicated With CRIXIVAN
Alpha 1-adrenoreceptor antagonist alfuzosin
Antiarrhythmics amiodarone
Ergot derivatives dihydroergotamine, ergonovine, ergotamine, methylergonovine
GI motility agents cisapride
HMG-CoA Reductase Inhibitors lovastatin, simvastatin
Neuroleptics pimozide
PDE5 Inhibitors Revatio1 (sildenafil) [for treatment of pulmonary arterial hypertension]
Sedative/hypnotics oral midazolam, triazolam, alprazolam
1Registered trademark of Pfizer, Inc.

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Microbiology

Mechanism of Action

HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Indinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles.

Antiretroviral Activity In Vitro

The in vitro activity of indinavir was assessed in cell lines of lymphoblastic and monocytic origin and in peripheral blood lymphocytes. HIV-1 variants used to infect the different cell types include laboratory-adapted variants, primary clinical isolates and clinical isolates resistant to nucleoside analogue and nonnucleoside inhibitors of the HIV-1 reverse transcriptase. The IC95 (95% inhibitory concentration) of indinavir in these test systems was in the range of 25 to 100 nM. In drug combination studies with the nucleoside analogues zidovudine and didanosine, indinavir showed synergistic activity in cell culture. The relationship between in vitro susceptibility of HIV-1 to indinavir and inhibition of HIV-1 replication in humans has not been established.

Drug Resistance

Isolates of HIV-1 with reduced susceptibility to the drug have been recovered from some patients treated with indinavir. Viral resistance was correlated with the accumulation of mutations that resulted in the expression of amino acid substitutions in the viral protease. Eleven amino acid residue positions, (L10l/V/R, K20l/M/R, L24l, M46l/L, l54A/V, L63P, l64V, A71T/V, V82A/F/T, l84V, and L90M), at which substitutions are associated with resistance, have been identified. Resistance was mediated by the co-expression of multiple and variable substitutions at these positions. No single substitution was either necessary or sufficient for measurable resistance ( ≥ 4-fold increase in IC95). In general, higher levels of resistance were associated with the co-expression of greater numbers of substitutions, although their individual effects varied and were not additive. At least 3 amino acid substitutions must be present for phenotypic resistance to indinavir to reach measurable levels. In addition, mutations in the p7/ p1 and p1/ p6 gag cleavage sites were observed in some indinavir resistant HIV-1 isolates.

In vitrophenotypic susceptibilities to indinavir were determined for 38 viral isolates from 13 patients who experienced virologic rebounds during indinavir monotherapy. Pre-treatment isolates from five patients exhibited indinavir IC95 values of 50-100 nM. At or following viral RNA rebound (after 12-76 weeks of therapy), IC95 values ranged from 25 to > 3000 nM, and the viruses carried 2 to 10 mutations in the protease gene relative to baseline.

Cross-Resistance to Other Antiviral Agents: Varying degrees of HIV-1 cross-resistance have been observed between indinavir and other HIV-1 protease inhibitors. In studies with ritonavir, saquinavir, and amprenavir, the extent and spectrum of cross-resistance varied with the specific mutational patterns observed. In general, the degree of cross-resistance increased with the accumulation of resistance-associated amino acid substitutions. Within a panel of 29 viral isolates from indinavir-treated patients that exhibited measurable ( ≥ 4-fold) phenotypic resistance to indinavir, all were resistant to ritonavir. Of the indinavir resistant HIV-1 isolates, 63% showed resistance to saquinavir and 81% to amprenavir.

Pharmacokinetics

Absorption

Indinavir was rapidly absorbed in the fasted state with a time to peak plasma concentration (Tmax) of 0.8 ± 0.3 hours (mean ± S.D.) (n=11). A greater than dose-proportional increase in indinavir plasma concentrations was observed over the 200-1000 mg dose range. At a dosing regimen of 800 mg every 8 hours, steady-state area under the plasma concentration time curve (AUC) was 30,691 ± 11,407 nM•hour (n=16), peak plasma concentration (Cmax) was 12,617 ± 4037 nM (n=16), and plasma concentration eight hours post dose (trough) was 251 ± 178 nM (n=16).

Effect of Food on Oral Absorption

Administration of indinavir with a meal high in calories, fat, and protein (784 kcal, 48.6 g fat, 31.3 g protein) resulted in a 77% ± 8% reduction in AUC and an 84% ± 7% reduction in Cmax (n=10). Administration with lighter meals (e.g., a meal of dry toast with jelly, apple juice, and coffee with skim milk and sugar or a meal of corn flakes, skim milk and sugar) resulted in little or no change in AUC, Cmax or trough concentration.

Distribution

Indinavir was approximately 60% bound to human plasma proteins over a concentration range of 81 nM to 16,300 nM.

Metabolism

Following a 400-mg dose of 14C-indinavir, 83 ± 1% (n=4) and 19 ± 3% (n=6) of the total radioactivity was recovered in feces and urine, respectively; radioactivity due to parent drug in feces and urine was 19.1% and 9.4%, respectively. Seven metabolites have been identified, one glucuronide conjugate and six oxidative metabolites. In vitro studies indicate that cytochrome P-450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites.

Elimination

Less than 20% of indinavir is excreted unchanged in the urine. Mean urinary excretion of unchanged drug was 10.4 ± 4.9% (n=10) and 12.0 ± 4.9% (n=10) following a single 700-mg and 1000-mg dose, respectively. Indinavir was rapidly eliminated with a half-life of 1.8 ± 0.4 hours (n=10). Significant accumulation was not observed after multiple dosing at 800 mg every 8 hours.

Special Populations

Hepatic Insufficiency

Patients with mild to moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of indinavir resulting in approximately 60% higher mean AUC following a single 400-mg dose (n=12). The half-life of indinavir increased to 2.8 ± 0.5 hours. Indinavir pharmacokinetics have not been studied in patients with severe hepatic insufficiency (see DOSAGE AND ADMINISTRATION, Hepatic Insufficiency).

Renal Insufficiency

The pharmacokinetics of indinavir have not been studied in patients with renal insufficiency.

Gender

The effect of gender on the pharmacokinetics of indinavir was evaluated in 10 HIV seropositive women who received CRIXIVAN 800 mg every 8 hours with zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day for one week. Indinavir pharmacokinetic parameters in these women were compared to those in HIV seropositive men (pooled historical control data). Differences in indinavir exposure, peak concentrations, and trough concentrations between males and females are shown in Table 1 below:

Table 1

PK Parameter % change in PK parameter for females relative to males 90% Confidence Interval
AUC0-8h (nM•hr) ↓13% (↓32%, ↑12%)
Cmax (nM) ↓13% (↓32%, ↑10%)
C8h (nM) ↓22% (↓47%, ↑15%)
↓Indicates a decrease in the PK parameter; ↑indicates an increase in the PK parameter.

The clinical significance of these gender differences in the pharmacokinetics of indinavir is not known.

Race

Pharmacokinetics of indinavir appear to be comparable in Caucasians and Blacks based on pharmacokinetic studies including 42 Caucasians (26 HIV-positive) and 16 Blacks (4 HIV-positive).

Pediatric

The optimal dosing regimen for use of indinavir in pediatric patients has not been established. In HIV-infected pediatric patients (age 4-15 years), a dosage regimen of indinavir capsules, 500 mg/m² every 8 hours, produced AUC0-8hr of 38,742 ± 24,098 nM•hour (n=34), Cmax of 17,181 ± 9809 nM (n=34), and trough concentrations of 134 ± 91 nM (n=28). The pharmacokinetic profiles of indinavir in pediatric patients were not comparable to profiles previously observed in HIV-infected adults receiving the recommended dose of 800 mg every 8 hours. The AUC and Cmax values were slightly higher and the trough concentrations were considerably lower in pediatric patients. Approximately 50% of the pediatric patients had trough values below 100 nM; whereas, approximately 10% of adult patients had trough levels below 100 nM. The relationship between specific trough values and inhibition of HIV replication has not been established.

Pregnant Patients

The optimal dosing regimen for use of indinavir in pregnant patients has not been established. A CRIXIVAN dose of 800 mg every 8 hours (with zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day) has been studied in 16 HIV-infected pregnant patients at 14 to 28 weeks of gestation at enrollment (study PACTG 358). The mean indinavir plasma AUC0-8hr at weeks 30-32 of gestation (n=11) was 9231 nM•hr, which is 74% (95% CI: 50%, 86%) lower than that observed 6 weeks postpartum. Six of these 11 (55%) patients had mean indinavir plasma concentrations 8 hours post-dose (Cmin) below assay threshold of reliable quantification. The pharmacokinetics of indinavir in these 11 patients at 6 weeks postpartum were generally similar to those observed in non-pregnant patients in another study (see PRECAUTIONS, Pregnancy).

Drug Interactions

(also see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS: DRUG INTERACTIONS)

Indinavir is an inhibitor of the cytochrome P450 isoform CYP3A4. Coadministration of CRIXIVAN and drugs primarily metabolized by CYP3A4 may result in increased plasma concentrations of the other drug, which could increase or prolong its therapeutic and adverse effects (see CONTRAINDICATIONS and WARNINGS). Based on in vitro data in human liver microsomes, indinavir does not inhibit CYP1A2, CYP2C9, CYP2E1 and CYP2B6. However, indinavir may be a weak inhibitor of CYP2D6.

Indinavir is metabolized by CYP3A4. Drugs that induce CYP3A4 activity would be expected to increase the clearance of indinavir, resulting in lowered plasma concentrations of indinavir. Coadministration of CRIXIVAN and other drugs that inhibit CYP3A4 may decrease the clearance of indinavir and may result in increased plasma concentrations of indinavir.

Drug interaction studies were performed with CRIXIVAN and other drugs likely to be coadministered and some drugs commonly used as probes for pharmacokinetic interactions. The effects of coadministration of CRIXIVAN on the AUC, Cmax and Cmin are summarized in Table 2 (effect of other drugs on indinavir) and Table 3 (effect of indinavir on other drugs). For information regarding clinical recommendations, see Table 9 in PRECAUTIONS.

Table 2 : Drug Interactions: Pharmacokinetic Parameters for Indinavir in the Presence of the Coadministered Drug (See PRECAUTIONS, Table 9 for Recommended Alterations in Dose or Regimen)

Coadministered drug Dose of Coadministered drug (mg) Dose of CRIXIVAN (mg) n Ratio (with/without coadministered drug) of Indinavir Pharmacokinetic Parameters (90% CI); No Effect = 1.00    
Cmax AUC Cmin
Cimetidine 600 twice daily, 6 days 400 single dose 12 1.07 (0.77, 1.49) 0.98 (0.81, 1.19) 0.82 (0.69, 0.99)
Clarithromycin 500 q12h, 7 days 800 three times daily, 7 days 10 1.08 (0.85, 1.38) 1.19 (1.00, 1.42) 1.57 (1.16, 2.12)
Delavirdine 400 three times daily 400 three times daily, 7 days 28 0.641 (0.48, 0.86) No significant change1 2.181 (1.16, 4.12)
Delavirdine 400 three times daily 600 three times daily, 7 days 28 No significant change 1.531 (1.07, 2.20) 3.981 (2.04, 7.78)
Efavirenz2 600 once daily, 10 days 1000 three times daily, 10 days 20
After morning dose No significant change1 0.671 (0.61, 0.74) 0.611 (0.49, 0.76)
After afternoon dose No significant change1 0.631 (0.54, 0.74) 0.481 (0.43, 0.53)
After evening dose 0.711 (0.57, 0.89) 0.541 (0.46, 0.63) 0.431 (0.37, 0.50)
Fluconazole2 400 once daily, 8 days 1000 three times daily, 7 days 11 0.87 (0.72, 1.05) 0.76 (0.59, 0.98) 0.90 (0.72, 1.12)
Grapefruit Juice 8 oz. 400 single dose 10 0.65 (0.53, 0.79) 0.73 (0.60, 0.87) 0.90 (0.71, 1.15)
Isoniazid 300 once daily in the morning, 8 days 800 three times daily, 7 days 11 0.95 (0.88, 1.03) 0.99 (0.87, 1.13) 0.89 (0.75, 1.06)
Itraconazole 200 twice daily, 7 days 600 three times daily, 7 days 12 0.781 (0.69, 0.88) 0.991 (0.91, 1.06) 1.491 (1.28, 1.74)
Ketoconazole 400 once daily, 7 days 600 three times daily, 7 days 12 0.691 (0.61, 0.78) 0.801 (0.74, 0.87) 1.291 (1.11, 1.51)
400 once daily, 7 days 400 three times daily, 7 days 12 0.421 (0.37, 0.47) 0.441 (0.41, 0.48) 0.731 (0.62, 0.85)
Methadone 20-60 once daily in the morning, 8 days 800 three times daily, 8 days 10 See text below for discussion of interaction.
Quinidine 200 single dose 400 single dose 10 0.96 (0.79, 1.18) 1.07 (0.89, 1.28) 0.93 (0.73, 1.19)
Rifabutin 150 once daily in the morning, 10 days 800 three times daily, 10 days 14 0.80 (0.72, 0.89) 0.68 (0.60, 0.76) 0.60 (0.51, 0.72)
Rifabutin 300 once daily in the morning, 10 days 800 three times daily, 10 days 10 0.75 (0.61, 0.91) 0.66 (0.56, 0.77) 0.61 (0.50, 0.75)
Rifampin 600 once daily in the morning, 8 days 800 three times daily, 7 days 12 0.13 (0.08, 0.22) 0.08 (0.06, 0.11) Not Done
Ritonavir 100 twice daily, 14 days 800 twice daily, 14 days 10, 163 See text below for discussion of interaction.
Ritonavir 200 twice daily, 14 days 800 twice daily, 14 days 9, 163 See text below for discussion of interaction.
Sildenafil 25 single dose 800 three times daily 6 See text below for discussion of interaction.
St. John's wort (Hypericum perforatum, standardized to 0.3 % hypericin) 300 three times daily with meals, 14 days 800 three times daily 8 Not Available 0.46 (0.34, 0.58)4 0.19 (0.06, 0.33)4
Stavudine (d4T)2 40 twice daily, 7 days 800 three times daily, 7 days 11 0.95 (0.80, 1.11) 0.95 (0.80, 1.12) 1.13 (0.83, 1.53)
Trimethoprim/ Sulfamethoxazole 800 Trimethoprim/ 160 Sulfamethoxazole q12h, 7 days 400 four times daily, 7 days 12 1.12 (0.87, 1.46) 0.98 (0.81, 1.18) 0.83 (0.72, 0.95)
Zidovudine2 200 three times daily, 7 days 1000 three times daily, 7 days 12 1.06 (0.91, 1.25) 1.05 (0.86, 1.28) 1.02 (0.77, 1.35)
Zidovudine/ Lamivudine (3TC)2 200/150 three times daily, 7 days 800 three times daily, 7 days 6, 95 1.05 (0.83, 1.33) 1.04 (0.67, 1.61) 0.98 (0.56, 1.73)
All interaction studies conducted in healthy, HIV-negative adult subjects, unless otherwise indicated.
1Relative to indinavir 800 mg three times daily alone.
2Study conducted in HIV-positive subjects.
3Comparison to historical data on 16 subjects receiving indinavir alone.
495% CI.
5Parallel group design; n for indinavir + coadministered drug, n for indinavir alone.

Table 3 : Drug Interactions: Pharmacokinetic Parameters for Coadministered Drug in the Presence of Indinavir (See PRECAUTIONS, Table 9 for Recommended Alterations in Dose or Regimen)

Coadministered drug Dose of Coadministered drug (mg) Dose of CRIXIVAN (mg) n Ratio (with/without CRIXIVAN) of Coadministered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00
Cmax AUC Cmin
Clarithromycin 500 twice daily, 7 days 800 three times daily, 7 days 12 1.19 (1.02, 1.39) 1.47 (1.30, 1.65) 1.97 (1.58, 2.46)
n=11
Efavirenz 200 once daily, 14 days 800 three times daily, 14 days 20 No significant change No significant change --
Ethinyl Estradiol (ORTHO-NOVUM 1/35)1 35 mcg, 8 days 800 three times daily, 8 days 18 1.02 (0.96, 1.09) 1.22 (1.15, 1.30) 1.37 (1.24, 1.51)
Isoniazid 300 once daily in the morning, 8 days 800 three times daily, 8 days 11 1.34 (1.12, 1.60) 1.12 (1.03, 1.22) 1.00 (0.92, 1.08)
Methadone2 20-60 once daily in the morning, 8 days 800 three times daily, 8 days 12 0.93 (0.84, 1.03) 0.96 (0.86, 1.06) 1.06 (0.94, 1.19)
Norethindrone (ORTHO-NOVUM 1/35)1 1 mcg, 8 days 800 three times daily, 8 days 18 1.05 (0.95, 1.16) 1.26 (1.20, 1.31) 1.44 (1.32, 1.57)
Rifabutin *150 mg once daily in the morning, 11 days + indinavir compared to 300 mg once daily in the morning, 11 days alone 150 once daily in the morning, 10 days 800 three times daily, 10 days 14 1.29 (1.05, 1.59) 1.54 (1.33, 1.79) 1.99 (1.71, 2.31)
n=13
300 once daily in the morning, 10 days 800 three times daily, 10 days 10 2.34 (1.64, 3.35) 2.73 (1.99, 3.77) 3.44 (2.65, 4.46)
n=9
Ritonavir 100 twice daily, 14 days 800 twice daily, 14 days 10, 43 1.61 (1.13, 2.29) 1.72 (1.20, 2.48) 1.62 (0.93, 2.85)
  200 twice daily, 14 days 800 twice daily, 14 days 9, 53 1.19 (0.85, 1.66) 1.96 (1.39, 2.76) 4.71 (2.66, 8.33)
n=9, 4
Saquinavir
Hard gel formulation 600 single dose 800 three times daily, 2 days 6 4.7 (2.7, 8.1) 6.0 (4.0, 9.1) 2.9 (1.7, 4.7)4
Soft gel formulation 800 single dose 800 three times daily, 2 days 6 6.5 (4.7, 9.1) 7.2 (4.3, 11.9) 5.5 (2.2, 14.1)4
Soft gel formulation 1200 single dose 800 three times daily, 2 days 6 4.0 (2.7, 5.9) 4.6 (3.2, 6.7) 5.5 (3.7, 8.3)4
Sildenafil 25 single dose 800 three times daily 6 See text below for discussion of interaction.
Stavudine5 40 twice daily, 7 days 800 three times daily, 7 days 13 0.86 (0.73, 1.03) 1.21 (1.09, 1.33) Not Done
Theophylline 250 single dose (on Days 1 and 7) 800 three times daily, 6 days (Days 2 to 7) 12, 43 0.88 (0.76, 1.03) 1.14 (1.04, 1.24) 1.13 (0.86, 1.49)
n=7, 3
Trimethoprim/ Sulfamethoxazole
Trimethoprim 800 Trimethoprim/ 160 Sulfamethoxazole q12h, 7 days 400 q6h, 7 days 12 1.18 (1.05, 1.32) 1.18 (1.05, 1.33) 1.18 (1.00, 1.39)
Trimethoprim/ Sulfamethoxazole
Sulfamethoxazole 800 Trimethoprim/ 160 Sulfamethoxazole q12h, 7 days 400 q6h, 7 days 12 1.01 (0.95, 1.08) 1.05 (1.01, 1.09) 1.05 (0.97, 1.14)
Vardenafil 10 single dose 800 three times daily 18 See text below for discussion of interaction.
Zidovudine5 200 three times daily, 7 days 1000 three times daily, 7 days 12 0.89 (0.73, 1.09) 1.17 (1.07, 1.29) 1.51 (0.71, 3.20)
n=4
Zidovudine/Lamivudine5 Zidovudine 200/150 three times daily, 7 days 800 three times daily, 7 days 6, 73 1.23 (0.74, 2.03) 1.39 (1.02, 1.89) 1.08 (0.77, 1.50)
n=5, 5
Zidovudine/Lamivudine5 Lamivudine 200/150 three times daily, 7 days 800 three times daily, 7 days 6, 73 0.73 (0.52, 1.02) 0.91 (0.66, 1.26) 0.88 (0.59, 1.33)
All interaction studies conducted in healthy, HIV-negative adult subjects, unless otherwise indicated.
1Registered trademark of Ortho Pharmaceutical Corporation.
2 Study conducted in subjects on methadone maintenance.
3 Parallel group design; n for coadministered drug + indinavir, n for coadministered drug alone.
4 C6hr
5 Study conducted in HIV-positive subjects.

Delavirdine

Delavirdine inhibits the metabolism of indinavir such that coadministration of 400-mg or 600-mg indinavir three times daily with 400-mg delavirdine three times daily alters indinavir AUC, Cmax and Cmin (see Table 2). Indinavir had no effect on delavirdine pharmacokinetics (see DOSAGE AND ADMINISTRATION, Concomitant Therapy, Delavirdine), based on a comparison to historical delavirdine pharmacokinetic data.

Methadone

Administration of indinavir (800 mg every 8 hours) with methadone (20 mg to 60 mg daily) for one week in subjects on methadone maintenance resulted in no change in methadone AUC. Based on a comparison to historical data, there was little or no change in indinavir AUC.

Ritonavir

Compared to historical data in patients who received indinavir 800 mg every 8 hours alone, twice-daily coadministration to volunteers of indinavir 800 mg and ritonavir with food for two weeks resulted in a 2.7-fold increase of indinavir AUC24h, a 1.6-fold increase in indinavir Cmax, and an 11-fold increase in indinavir Cmin for a 100-mg ritonavir dose and a 3.6-fold increase of indinavir AUC24h, a 1.8fold increase in indinavir Cmax, and a 24-fold increase in indinavir Cmin for a 200-mg ritonavir dose. In the same study, twice-daily coadministration of indinavir (800 mg) and ritonavir (100 or 200 mg) resulted in ritonavir AUC24h increases versus the same doses of ritonavir alone (see Table 3).

Sildenafil

The results of one published study in HIV-infected men (n=6) indicated that coadministration of indinavir (800 mg every 8 hours chronically) with a single 25-mg dose of sildenafil resulted in an 11% increase in average AUC0-8hr of indinavir and a 48% increase in average indinavir peak concentration (Cmax) compared to 800 mg every 8 hours alone. Average sildenafil AUC was increased by 340% following coadministration of sildenafil and indinavir compared to historical data following administration of sildenafil alone (see CONTRAINDICATIONS, WARNINGS, Drug Interactions and PRECAUTIONS: DRUG INTERACTIONS).

Vardenafil

Indinavir (800 mg every 8 hours) coadministered with a single 10-mg dose of vardenafil resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil Cmax, and a 2-fold increase in vardenafil half-life (see WARNINGS, Drug Interactions and PRECAUTIONS: DRUG INTERACTIONS).

Description of Studies

In all clinical studies, with the exception of ACTG 320, the AMPLICOR HIV MONITOR assay was used to determine the level of circulating HIV RNA in serum. This is an experimental use of the assay. HIV RNA results should not be directly compared to results from other trials using different HIV RNA assays or using other sample sources.

Study ACTG 320 was a multicenter, randomized, double-blind clinical endpoint trial to compare the effect of CRIXIVAN in combination with zidovudine and lamivudine with that of zidovudine plus lamivudine on the progression to an AIDS-defining illness (ADI) or death. Patients were protease inhibitor and lamivudine naive and zidovudine experienced, with CD4 cell counts of ≤ 200 cells/mm³. The study enrolled 1156 HIV-infected patients (17% female, 28% Black, 18% Hispanic, mean age 39 years). The mean baseline CD4 cell count was 87 cells/mm³. The mean baseline HIV RNA was 4.95 log10 copies/mL (89,035 copies/mL). The study was terminated after a planned interim analysis, resulting in a median follow-up of 38 weeks and a maximum follow-up of 52 weeks. Results are shown in Table 4 and Figures 1 & 2.

Table 4: ACTG 320

Endpoint Number (%) of Patients with AIDS-defining Illness or Death
IDV+ZDV+L
(n=577)
ZDV+L
(n=579)
HIV Progression or Death 35 (6.1) 63 (10.9)
Death* 10 (1.7) 19 (3.3)

Figure 1 : Study ACTG 320:
Indinavir Protocol ACTG 320 Zidovudine Experienced Plasma Viral RNA - Proportions Below 400 copies/mL

Indinavir Protocol ACTG 320 Zidovudine Experienced Plasma Viral RNA - Proportions Below 400 copies/mL - Illustration

Figure 2 : Study ACTG 320: Zidovudine Experienced CD4 Cell Counts - Mean Change from Baseline

Zidovudine Experienced CD4 Cell Counts - Mean Change from Baseline -  Illustration

Study 028, a double-blind, multicenter, randomized, clinical endpoint trial conducted in Brazil, compared the effects of CRIXIVAN plus zidovudine with those of CRIXIVAN alone or zidovudine alone on the progression to an ADI or death, and on surrogate marker responses. All patients were antiretroviral naive with CD4 cell counts of 50 to 250 cells/mm³. The study enrolled 996 HIV-1 seropositive patients [28% female, 11% Black, 1% Asian/Other, median age 33 years, mean baseline CD4 cell count of 152 cells/mm³, mean serum viral RNA of 4.44 log10 copies/mL (27,824 copies/mL)]. Treatment regimens containing zidovudine were modified in a blinded manner with the optional addition of lamivudine (median time: week 40). The median length of follow-up was 56 weeks with a maximum of 97 weeks. The study was terminated after a planned interim analysis, resulting in a median follow-up of 56 weeks and a maximum follow-up of 97 weeks. Results are shown in Table 5 and Figures 3 and 4.

Table 5 : Protocol 028

Endpoint Number (%) of Patients with AIDS-defining Illness or Death
IDV+ZDV
(n=332)
IDV
(n=332)
ZDV
(n=332)
HIV Progression or Death 21 (6.3) 27 (8.1) 62 (18.7)
Death* 8 (2.4) 5 05 11 (3.3)
* The number of deaths is inadequate to assess the impact of Indinavir on survival.

Figure 3 : Study 028:
Indinavir Protocol 028 Zidovudine Naive Viral RNA - Proportions Below 500 Copies/mL in Serum

Indinavir Protocol 028 Zidovudine Naive Viral RNA - Proportions Below 500 Copies/mL in Serum  - Illustration

Figure 4 : Study 028
Indinavir Protocol 028 Zidovudine Naive CD4 Cell Counts - Mean Change from Baseline

Indinavir Protocol 028 Zidovudine Naive CD4 Cell Counts - Mean Change from Baseline  - Illustration

Study 035 was a multicenter, randomized trial in 97 HIV-1 seropositive patients who were zidovudineexperienced (median exposure 30 months), protease-inhibitor- and lamivudine-naive, with mean baseline CD4 count 175 cells/mm³ and mean baseline serum viral RNA 4.62 log10 copies/mL (41,230 copies/mL). Comparisons included CRIXIVAN plus zidovudine plus lamivudine vs. CRIXIVAN alone vs. zidovudine plus lamivudine. After at least 24 weeks of randomized, double-blind therapy, patients were switched to open-label CRIXIVAN plus lamivudine plus zidovudine. Mean changes in log10 viral RNA in serum, the proportions of patients with viral RNA below 500 copies/mL in serum, and mean changes in CD4 cell counts, during 24 weeks of randomized, double-blinded therapy are summarized in Figures 5, 6, and 7, respectively. A limited number of patients remained on randomized, double-blind treatment for longer periods; based on this extended treatment experience, it appears that a greater number of subjects randomized to CRIXIVAN plus zidovudine plus lamivudine demonstrated HIV RNA levels below 500 copies/mL during one year of therapy as compared to those in other treatment groups

Figure 5 : Study 035

Study 035 - Illustration

Figure 6 : Study 035

Study 035 - Illustration

Figure 7 : Study 035

Study 035 - Illustration

Genotypic Resistance in Clinical Studies

Study 006 (10/15/93-10/12/94) was a dose-ranging study in which patients were initially treated with CRIXIVAN at a dose of < 2.4 g/day followed by 2.4 g/day. Study 019 (6/23/94-4/10/95) was a randomized comparison of CRIXIVAN 600 mg every 6 hours, CRIXIVAN plus zidovudine, and zidovudine alone. Table 6 shows the incidence of genotypic resistance at 24 weeks in these studies.

Table 6 : Genotypic Resistance at 24 Weeks

Treatment Group Resistance to IDV
n/N*
Resistance to ZDV
n/N*
IDV
   < 2.4 g/day 31/37 (84%)
  2.4 g/day 9/21 (43%) 1/17 (6%)
IDV/ZDV 4/22 (18%) 1/22 (5%)
ZDV 1/18 (6%) 11/17 (65%)
*N - includes patients with non-amplifiable virus at 24 weeks who had amplifiable virus at week 0.

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

CRIXIVAN ®
(indinavir sulfate) Capsules

CRIXIVAN
(KRIK-sih-van) for HIV (Human Immunodeficiency Virus) Infection Generic name: indinavir (in-DIH-nuh-veer) sulfate

ALERT: Find out about medicines that should NOT be taken with CRIXIVAN . Please also read the section “MEDICINES YOU SHOULD NOT TAKE WITH CRIXIVAN”.

Please read this information before you start taking CRIXIVAN. Also, read the leaflet each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss CRIXIVAN when you start taking your medication and at regular checkups. You should remain under a doctor's care when using CRIXIVAN and should not change or stop treatment without first talking with your doctor.

What is CRIXIVAN?

CRIXIVAN is an oral capsule used for the treatment of HIV (Human Immunodeficiency Virus). HIV is the virus that causes AIDS (acquired immune deficiency syndrome). CRIXIVAN is a type of HIV drug called a protease (PRO-tee-ase) inhibitor.

How does CRIXIVAN work?

CRIXIVAN is a protease inhibitor that fights HIV. CRIXIVAN can help reduce your chances of getting illnesses associated with HIV. CRIXIVAN can also help lower the amount of HIV in your body (called “viral load”) and raise your CD4 (T) cell count. CRIXIVAN may not have these effects in all patients.

CRIXIVAN is usually prescribed with other anti-HIV drugs such as ZDV (also called AZT), 3TC, ddI, ddC, or d4T. CRIXIVAN works differently from these other anti-HIV drugs. Talk with your doctor about how you should take CRIXIVAN.

How should I take CRIXIVAN?

There are six important things you must do to help you benefit from CRIXIVAN:

  1. Take CRIXIVAN capsules every day as prescribed by your doctor. Continue taking CRIXIVAN unless your doctor tells you to stop. Take the exact amount of CRIXIVAN that your doctor tells you to take, right from the very start. To help make sure you will benefit from CRIXIVAN, you must not skip doses or take “drug holidays”. If you don't take CRIXIVAN as prescribed, the activity of CRIXIVAN may be reduced (due to resistance).
  2. Take CRIXIVAN capsules every 8 hours around the clock, every day. It may be easier to remember to take CRIXIVAN if you take it at the same time every day. If you have questions about when to take CRIXIVAN, your doctor or health care provider can help you decide what schedule works for you.
  3. If you miss a dose by more than 2 hours, wait and then take the next dose at the regularly scheduled time. However, if you miss a dose by less than 2 hours, take your missed dose immediately. Then take your next dose at the regularly scheduled time. Do not take more or less than your prescribed dose of CRIXIVAN at any one time.
  4. Take CRIXIVAN with water. You can also take CRIXIVAN with other beverages such as skim or non-fat milk, juice, coffee, or tea.
  5. Ideally, take each dose of CRIXIVAN without food but with water at least one hour before or two hours after a meal. Or you can take CRIXIVAN with a light meal. Examples of light meals include:
    dry toast with jelly, juice, and coffee (with skim or non-fat milk and sugar if you want)
    cornflakes with skim or non-fat milk and sugar Do not take CRIXIVAN at the same time as any meals that are high in calories, fat, and protein (for example — a bacon and egg breakfast). When taken at the same time as CRIXIVAN, these foods can interfere with CRIXIVAN being absorbed into your bloodstream and may lessen its effect.
  6. It is critical to drink plenty of fluids while taking CRIXIVAN. Adults should drink at least six 8ounce glasses of liquids (preferably water) throughout the day, every day. Your health care provider will give you further instructions on the amount of fluid that you should drink. CRIXIVAN can cause kidney stones. Having enough fluids in your body should help reduce the chances of forming a kidney stone. Call your doctor or other health care provider if you develop kidney pains (middle to lower stomach or back pain) or blood in the urine.

Does CRIXIVAN cure HIV or AIDS?

CRIXIVAN does not cure HIV infection or AIDS and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using CRIXIVAN.

Avoid doing things that can spread HIV-1 infection.

  • Do not share needles or other injection equipment.
  • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
  • Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

Who should not take CRIXIVAN?

Do not take CRIXIVAN if you have had a serious allergic reaction to CRIXIVAN or any of its components.

What other medical problems or conditions should I discuss with my doctor?

Talk to your doctor if:

  • You are pregnant or if you become pregnant while you are taking CRIXIVAN. We do not yet know how CRIXIVAN affects pregnant women or their developing babies.
  • You are breastfeeding. Do not breastfeed. We do not know if CRIXIVAN can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Also talk to your doctor if you have:

Tell your doctor about any medicines you are taking or plan to take, including non-prescription medicines, herbal products including St. John's wort (Hypericum perforatum), or dietary supplements.

Can CRIXIVAN be taken with other medications?

MEDICINES YOU SHOULD NOT TAKE WITH CRIXIVAN

Oral VERSED® (midazolam) HALCION® (triazolam)
ORAP® (pimozide) XANAX® (alprazolam)
PROPULSID® (cisapride) REVATIO® (sildenafil for the treatment of pulmonary arterial hypertension)
CORDARONE® (amiodarone) UROXATRAL® (alfuzosin)
HISMANAL® (astemizole) Ergot medications (e.g., Wigraine®, Cafergot®, D.H.E. 45®, Migranal®, Ergotrate®, and Methergine®) ZOCOR®* (simvastatin) MEVACOR®* (lovastatin)

Taking CRIXIVAN with the above medications could result in serious or life-threatening problems (such as irregular heartbeat or excessive sleepiness).

In addition, you should not take CRIXIVAN with the following:

Rifampin, known as RIFADIN®, RIFAMATE®, RIFATER®, or RIMACTANE®.

There is also an increased risk of drug interactions between CRIXIVAN and LIPITOR® (atorvastatin) and CRESTOR® (rosuvastatin); talk to your doctor before you take any of these cholesterol-reducing drugs with CRIXIVAN.

Taking CRIXIVAN with REYATAZ® (atazanavir) is not recommended because they can both sometimes cause increased levels of bilirubin in the blood.

Taking CRIXIVAN with St. John's wort (Hypericum perforatum), an herbal product sold as a dietary supplement, or products containing St. John's wort is not recommended. Taking St. John's wort has been shown to decrease CRIXIVAN levels and may lead to increased viral load and possible resistance to CRIXIVAN or cross resistance to other antiretroviral drugs.

Before you take VIAGRA® (sildenafil), CIALIS® (tadalafil), or LEVITRA® (vardenafil) with CRIXIVAN, talk to your doctor about possible drug interactions and side effects. If you take any of these medicines together with CRIXIVAN, you may be at increased risk of side effects such as low blood pressure, visual changes, and penile erection lasting more than 4 hours, which have been associated with sildenafil, tadalafil, and vardenafil. If an erection lasts longer than 4 hours, you should seek immediate medical assistance to avoid permanent damage to your penis. Your doctor can explain these symptoms to you.

MEDICINES YOU CAN TAKE WITH CRIXIVAN

RETROVIR® (zidovudine, ZDV also called AZT) EPIVIR™ (lamivudine, 3TC)
ZERIT® (stavudine, d4T) isoniazid (INH)
BACTRIM®/SEPTRA® (trimethoprim/sulfamethoxazole) DIFLUCAN® (fluconazole)
BIAXIN® (clarithromycin) ORTHO-NOVUM 1/35® (oral contraceptive)
TAGAMET® (cimetidine) Methadone

VIDEX® (didanosine, ddI) — If you take CRIXIVAN with VIDEX, take them at least one hour apart.

MYCOBUTIN® (rifabutin) — If you take CRIXIVAN with MYCOBUTIN, your doctor may adjust both the dose of MYCOBUTIN and the dose of CRIXIVAN. NIZORAL® (ketoconazole) — If you take CRIXIVAN with NIZORAL, your doctor may adjust the dose of CRIXIVAN.

RESCRIPTOR® (delavirdine) — If you take CRIXIVAN with RESCRIPTOR, your doctor may adjust the dose of CRIXIVAN.

SPORANOX® (itraconazole) — If you take CRIXIVAN with SPORANOX, your doctor may adjust the dose of CRIXIVAN.

SUSTIVA™ (efavirenz) — If you take CRIXIVAN with SUSTIVA, check with your doctor.

Intravenous VERSED® (midazolam) — If you take CRIXIVAN with Intravenous VERSED®, your doctor may adjust the dose of VERSED®.

Talk to your doctor about any medications you are taking.

Calcium Channel Blockers: Tell your doctor if you are taking calcium channel blockers (e.g., amlodipine, felodipine).

Antiarrhythmics: Tell your doctor if you are taking antiarrhythmics (e.g., quinidine). Anticonvulsants: Tell your doctor if you are taking anticonvulsants (e.g., phenobarbital, phenytoin, or carbamazepine).

Steroids: Tell your doctor if you are taking steroids (e.g., dexamethasone).

What are the possible side effects of CRIXIVAN?

Like all prescription drugs, CRIXIVAN can cause side effects. The following is not a complete list of side effects reported with CRIXIVAN when taken either alone or with other anti-HIV drugs. Do not rely on this leaflet alone for information about side effects. Your doctor can discuss with you a more complete list of side effects.

Some patients treated with CRIXIVAN developed kidney stones. In some of these patients this led to more severe kidney problems, including kidney failure or inflammation of the kidneys or kidney infection which sometimes spread to the blood. Drinking at least six 8-ounce glasses of liquids (preferably water) each day should help reduce the chances of forming a kidney stone ( see How should I take CRIXIVAN?). Call your doctor or other health care provider if you develop kidney pains (middle to lower stomach or back pain) or blood in the urine.

Some patients treated with CRIXIVAN have had rapid breakdown of red blood cells (hemolytic anemia) which in some cases was severe or resulted in death.

Some patients treated with CRIXIVAN have had liver problems including liver failure and death. Some patients had other illnesses or were taking other drugs. It is uncertain if CRIXIVAN caused these liver problems.

Diabetes and high blood sugar (hyperglycemia) have occurred in patients taking protease inhibitors. In some of these patients, this led to ketoacidosis, a serious condition caused by poorly controlled blood sugar. Some patients had diabetes before starting protease inhibitors, others did not. Some patients required adjustments to their diabetes medication. Others needed new diabetes medication.

In some patients with hemophilia, increased bleeding has been reported.

Severe muscle pain and weakness have occurred in patients taking protease inhibitors, including CRIXIVAN, together with some of the cholesterol-lowering medicines called “statins”. Call your doctor if you develop severe muscle pain or weakness.

Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the trunk. Loss of fat from the legs, arms and face may also happen. The cause and long term health effects of these conditions are not known at this time.

In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from opportunistic infections may occur when combination antiretroviral treatment is started.

Clinical Studies

Increases in bilirubin (one laboratory test of liver function) have been reported in approximately 14% of patients. Usually, this finding has not been associated with liver problems. However, on rare occasions, a person may develop yellowing of the skin and/or eyes.

Side effects occurring in 2% or more of patients included: abdominal pain, fatigue or weakness, low red blood cell count, flank pain, painful urination, feeling unwell, nausea, upset stomach, diarrhea, vomiting, acid regurgitation, increased or decreased appetite, back pain, headache, dizziness, taste changes, rash, itchy skin, yellowing of the skin and/or eyes, upper respiratory infection, dry skin, and sore throat.

Swollen kidneys due to blocked urine flow occurred rarely.

Marketing Experience

Other side effects reported since CRIXIVAN has been marketed include: allergic reactions; severe skin reactions; yellowing of the skin and/or eyes; heart problems including heart attack; stroke; abdominal swelling; indigestion; inflammation of the kidneys; decreased kidney function; inflammation of the pancreas; joint pain; depression; itching; hives; change in skin color; hair loss; ingrown toenails with or without infection; crystals in the urine; painful urination; numbness of the mouth and increased cholesterol.

Tell your doctor promptly about these or any other unusual symptoms. If the condition persists or worsens, seek medical attention.

How should I store CRIXIVAN capsules?

  • Keep CRIXIVAN capsules in the bottle they came in and at room temperature (59°-86°F).
  • Keep CRIXIVAN capsules dry by leaving the small desiccant in the bottle. Keep the bottle closed.

This medication was prescribed for your particular condition. Do not use it for any other condition or give it to anybody else. Keep CRIXIVAN and all medicines out of the reach of children. If you suspect that more than the prescribed dose of this medicine has been taken, contact your local poison control center or emergency room immediately.

This leaflet provides a summary of information about CRIXIVAN. If you have any questions or concerns about either CRIXIVAN or HIV, talk to your doctor.

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

CRIXIVAN ®
(indinavir sulfate) Capsules

CRIXIVAN
(KRIK-sih-van) for HIV (Human Immunodeficiency Virus) Infection Generic name: indinavir (in-DIH-nuh-veer) sulfate

ALERT: Find out about medicines that should NOT be taken with CRIXIVAN . Please also read the section “MEDICINES YOU SHOULD NOT TAKE WITH CRIXIVAN”.

Please read this information before you start taking CRIXIVAN. Also, read the leaflet each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss CRIXIVAN when you start taking your medication and at regular checkups. You should remain under a doctor's care when using CRIXIVAN and should not change or stop treatment without first talking with your doctor.

What is CRIXIVAN?

CRIXIVAN is an oral capsule used for the treatment of HIV (Human Immunodeficiency Virus). HIV is the virus that causes AIDS (acquired immune deficiency syndrome). CRIXIVAN is a type of HIV drug called a protease (PRO-tee-ase) inhibitor.

How does CRIXIVAN work?

CRIXIVAN is a protease inhibitor that fights HIV. CRIXIVAN can help reduce your chances of getting illnesses associated with HIV. CRIXIVAN can also help lower the amount of HIV in your body (called “viral load”) and raise your CD4 (T) cell count. CRIXIVAN may not have these effects in all patients.

CRIXIVAN is usually prescribed with other anti-HIV drugs such as ZDV (also called AZT), 3TC, ddI, ddC, or d4T. CRIXIVAN works differently from these other anti-HIV drugs. Talk with your doctor about how you should take CRIXIVAN.

How should I take CRIXIVAN?

There are six important things you must do to help you benefit from CRIXIVAN:

  1. Take CRIXIVAN capsules every day as prescribed by your doctor. Continue taking CRIXIVAN unless your doctor tells you to stop. Take the exact amount of CRIXIVAN that your doctor tells you to take, right from the very start. To help make sure you will benefit from CRIXIVAN, you must not skip doses or take “drug holidays”. If you don't take CRIXIVAN as prescribed, the activity of CRIXIVAN may be reduced (due to resistance).
  2. Take CRIXIVAN capsules every 8 hours around the clock, every day. It may be easier to remember to take CRIXIVAN if you take it at the same time every day. If you have questions about when to take CRIXIVAN, your doctor or health care provider can help you decide what schedule works for you.
  3. If you miss a dose by more than 2 hours, wait and then take the next dose at the regularly scheduled time. However, if you miss a dose by less than 2 hours, take your missed dose immediately. Then take your next dose at the regularly scheduled time. Do not take more or less than your prescribed dose of CRIXIVAN at any one time.
  4. Take CRIXIVAN with water. You can also take CRIXIVAN with other beverages such as skim or non-fat milk, juice, coffee, or tea.
  5. Ideally, take each dose of CRIXIVAN without food but with water at least one hour before or two hours after a meal. Or you can take CRIXIVAN with a light meal. Examples of light meals include:
    dry toast with jelly, juice, and coffee (with skim or non-fat milk and sugar if you want)
    cornflakes with skim or non-fat milk and sugar Do not take CRIXIVAN at the same time as any meals that are high in calories, fat, and protein (for example — a bacon and egg breakfast). When taken at the same time as CRIXIVAN, these foods can interfere with CRIXIVAN being absorbed into your bloodstream and may lessen its effect.
  6. It is critical to drink plenty of fluids while taking CRIXIVAN. Adults should drink at least six 8ounce glasses of liquids (preferably water) throughout the day, every day. Your health care provider will give you further instructions on the amount of fluid that you should drink. CRIXIVAN can cause kidney stones. Having enough fluids in your body should help reduce the chances of forming a kidney stone. Call your doctor or other health care provider if you develop kidney pains (middle to lower stomach or back pain) or blood in the urine.

Does CRIXIVAN cure HIV or AIDS?

CRIXIVAN does not cure HIV infection or AIDS and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using CRIXIVAN.

Avoid doing things that can spread HIV-1 infection.

  • Do not share needles or other injection equipment.
  • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
  • Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

Who should not take CRIXIVAN?

Do not take CRIXIVAN if you have had a serious allergic reaction to CRIXIVAN or any of its components.

What other medical problems or conditions should I discuss with my doctor?

Talk to your doctor if:

  • You are pregnant or if you become pregnant while you are taking CRIXIVAN. We do not yet know how CRIXIVAN affects pregnant women or their developing babies.
  • You are breastfeeding. Do not breastfeed. We do not know if CRIXIVAN can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Also talk to your doctor if you have:

Tell your doctor about any medicines you are taking or plan to take, including non-prescription medicines, herbal products including St. John's wort (Hypericum perforatum), or dietary supplements.

Can CRIXIVAN be taken with other medications?

MEDICINES YOU SHOULD NOT TAKE WITH CRIXIVAN

Oral VERSED® (midazolam) HALCION® (triazolam)
ORAP® (pimozide) XANAX® (alprazolam)
PROPULSID® (cisapride) REVATIO® (sildenafil for the treatment of pulmonary arterial hypertension)
CORDARONE® (amiodarone) UROXATRAL® (alfuzosin)
HISMANAL® (astemizole) Ergot medications (e.g., Wigraine®, Cafergot®, D.H.E. 45®, Migranal®, Ergotrate®, and Methergine®) ZOCOR®* (simvastatin) MEVACOR®* (lovastatin)

Taking CRIXIVAN with the above medications could result in serious or life-threatening problems (such as irregular heartbeat or excessive sleepiness).

In addition, you should not take CRIXIVAN with the following:

Rifampin, known as RIFADIN®, RIFAMATE®, RIFATER®, or RIMACTANE®.

There is also an increased risk of drug interactions between CRIXIVAN and LIPITOR® (atorvastatin) and CRESTOR® (rosuvastatin); talk to your doctor before you take any of these cholesterol-reducing drugs with CRIXIVAN.

Taking CRIXIVAN with REYATAZ® (atazanavir) is not recommended because they can both sometimes cause increased levels of bilirubin in the blood.

Taking CRIXIVAN with St. John's wort (Hypericum perforatum), an herbal product sold as a dietary supplement, or products containing St. John's wort is not recommended. Taking St. John's wort has been shown to decrease CRIXIVAN levels and may lead to increased viral load and possible resistance to CRIXIVAN or cross resistance to other antiretroviral drugs.

Before you take VIAGRA® (sildenafil), CIALIS® (tadalafil), or LEVITRA® (vardenafil) with CRIXIVAN, talk to your doctor about possible drug interactions and side effects. If you take any of these medicines together with CRIXIVAN, you may be at increased risk of side effects such as low blood pressure, visual changes, and penile erection lasting more than 4 hours, which have been associated with sildenafil, tadalafil, and vardenafil. If an erection lasts longer than 4 hours, you should seek immediate medical assistance to avoid permanent damage to your penis. Your doctor can explain these symptoms to you.

MEDICINES YOU CAN TAKE WITH CRIXIVAN

RETROVIR® (zidovudine, ZDV also called AZT) EPIVIR™ (lamivudine, 3TC)
ZERIT® (stavudine, d4T) isoniazid (INH)
BACTRIM®/SEPTRA® (trimethoprim/sulfamethoxazole) DIFLUCAN® (fluconazole)
BIAXIN® (clarithromycin) ORTHO-NOVUM 1/35® (oral contraceptive)
TAGAMET® (cimetidine) Methadone

VIDEX® (didanosine, ddI) — If you take CRIXIVAN with VIDEX, take them at least one hour apart.

MYCOBUTIN® (rifabutin) — If you take CRIXIVAN with MYCOBUTIN, your doctor may adjust both the dose of MYCOBUTIN and the dose of CRIXIVAN. NIZORAL® (ketoconazole) — If you take CRIXIVAN with NIZORAL, your doctor may adjust the dose of CRIXIVAN.

RESCRIPTOR® (delavirdine) — If you take CRIXIVAN with RESCRIPTOR, your doctor may adjust the dose of CRIXIVAN.

SPORANOX® (itraconazole) — If you take CRIXIVAN with SPORANOX, your doctor may adjust the dose of CRIXIVAN.

SUSTIVA™ (efavirenz) — If you take CRIXIVAN with SUSTIVA, check with your doctor.

Intravenous VERSED® (midazolam) — If you take CRIXIVAN with Intravenous VERSED®, your doctor may adjust the dose of VERSED®.

Talk to your doctor about any medications you are taking.

Calcium Channel Blockers: Tell your doctor if you are taking calcium channel blockers (e.g., amlodipine, felodipine).

Antiarrhythmics: Tell your doctor if you are taking antiarrhythmics (e.g., quinidine). Anticonvulsants: Tell your doctor if you are taking anticonvulsants (e.g., phenobarbital, phenytoin, or carbamazepine).

Steroids: Tell your doctor if you are taking steroids (e.g., dexamethasone).

What are the possible side effects of CRIXIVAN?

Like all prescription drugs, CRIXIVAN can cause side effects. The following is not a complete list of side effects reported with CRIXIVAN when taken either alone or with other anti-HIV drugs. Do not rely on this leaflet alone for information about side effects. Your doctor can discuss with you a more complete list of side effects.

Some patients treated with CRIXIVAN developed kidney stones. In some of these patients this led to more severe kidney problems, including kidney failure or inflammation of the kidneys or kidney infection which sometimes spread to the blood. Drinking at least six 8-ounce glasses of liquids (preferably water) each day should help reduce the chances of forming a kidney stone ( see How should I take CRIXIVAN?). Call your doctor or other health care provider if you develop kidney pains (middle to lower stomach or back pain) or blood in the urine.

Some patients treated with CRIXIVAN have had rapid breakdown of red blood cells (hemolytic anemia) which in some cases was severe or resulted in death.

Some patients treated with CRIXIVAN have had liver problems including liver failure and death. Some patients had other illnesses or were taking other drugs. It is uncertain if CRIXIVAN caused these liver problems.

Diabetes and high blood sugar (hyperglycemia) have occurred in patients taking protease inhibitors. In some of these patients, this led to ketoacidosis, a serious condition caused by poorly controlled blood sugar. Some patients had diabetes before starting protease inhibitors, others did not. Some patients required adjustments to their diabetes medication. Others needed new diabetes medication.

In some patients with hemophilia, increased bleeding has been reported.

Severe muscle pain and weakness have occurred in patients taking protease inhibitors, including CRIXIVAN, together with some of the cholesterol-lowering medicines called “statins”. Call your doctor if you develop severe muscle pain or weakness.

Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the trunk. Loss of fat from the legs, arms and face may also happen. The cause and long term health effects of these conditions are not known at this time.

In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from opportunistic infections may occur when combination antiretroviral treatment is started.

Clinical Studies

Increases in bilirubin (one laboratory test of liver function) have been reported in approximately 14% of patients. Usually, this finding has not been associated with liver problems. However, on rare occasions, a person may develop yellowing of the skin and/or eyes.

Side effects occurring in 2% or more of patients included: abdominal pain, fatigue or weakness, low red blood cell count, flank pain, painful urination, feeling unwell, nausea, upset stomach, diarrhea, vomiting, acid regurgitation, increased or decreased appetite, back pain, headache, dizziness, taste changes, rash, itchy skin, yellowing of the skin and/or eyes, upper respiratory infection, dry skin, and sore throat.

Swollen kidneys due to blocked urine flow occurred rarely.

Marketing Experience

Other side effects reported since CRIXIVAN has been marketed include: allergic reactions; severe skin reactions; yellowing of the skin and/or eyes; heart problems including heart attack; stroke; abdominal swelling; indigestion; inflammation of the kidneys; decreased kidney function; inflammation of the pancreas; joint pain; depression; itching; hives; change in skin color; hair loss; ingrown toenails with or without infection; crystals in the urine; painful urination; numbness of the mouth and increased cholesterol.

Tell your doctor promptly about these or any other unusual symptoms. If the condition persists or worsens, seek medical attention.

How should I store CRIXIVAN capsules?

  • Keep CRIXIVAN capsules in the bottle they came in and at room temperature (59°-86°F).
  • Keep CRIXIVAN capsules dry by leaving the small desiccant in the bottle. Keep the bottle closed.

This medication was prescribed for your particular condition. Do not use it for any other condition or give it to anybody else. Keep CRIXIVAN and all medicines out of the reach of children. If you suspect that more than the prescribed dose of this medicine has been taken, contact your local poison control center or emergency room immediately.

This leaflet provides a summary of information about CRIXIVAN. If you have any questions or concerns about either CRIXIVAN or HIV, talk to your doctor.

Last reviewed on RxList: 3/2/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Crixivan Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

INDINAVIR CAPSULE - ORAL

(in-DIN-uh-veer)

COMMON BRAND NAME(S): Crixivan

USES: This drug is used in combination with other HIV medications to help control HIV infection. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life.

Indinavir belongs to a class of drugs known as protease inhibitors. It may be given with ritonavir, another protease inhibitor, to increase ("boost") the levels of indinavir. This helps indinavir work better.

Indinavir is not a cure for HIV. It does not prevent the spread of HIV to others through sexual contact or blood contamination (such as sharing used needles).

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to prevent HIV infection after contact with the virus.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start taking indinavir and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth with a full glass of water (8 ounces or 240 milliliters) on an empty stomach (at least 1 hour before or 2 hours after food), usually 3 times daily or as directed by your doctor. If upset stomach occurs, you may take it with other liquids (such as non-fat milk, apple juice, coffee, tea) or with a light meal (such as dry toast with jelly, corn flakes with non-fat milk and sugar). Avoid taking this medication with a meal high in calories, fat, and protein since this may decrease its effect. If you are directed to take ritonavir with this medication, take them both at the same times.

To help decrease the risk of kidney stones while taking indinavir, drink at least 6 full glasses (8 ounces or 240 milliliters each) of water or other liquids throughout the day.

The dosage is based on your weight, liver function, medical condition, other medications, and response to treatment.

This medication works best when the amount of drug in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals. To help you remember, take it at the same times each day.

It is very important to continue taking this medication (and other HIV medications) exactly as prescribed by your doctor. Do not take more or less of this drug than prescribed or stop taking it (or other HIV medicines) even for a short time unless directed to do so by your doctor. Skipping or changing your dose without approval from your doctor may cause the amount of virus to increase, make the infection more difficult to treat, or worsen side effects.

Disclaimer

Crixivan Consumer (continued)

SIDE EFFECTS: Stomach pain, nausea, vomiting, heartburn, loss of appetite, or headache may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Some people may experience worsening of a previous medical condition (such as an old infection) as their immune systems improve, or develop new conditions because their immune systems have become overactive. This reaction may occur at any time (soon after starting HIV treatment or many months later). Tell your doctor right away if you have any serious side effects, including: unexplained weight loss, persistent muscle aches/weakness, joint pain, numbness/tingling of the hands/feet/arms/legs, severe tiredness, vision changes, severe/persistent headaches, signs of infection (such as fever, chills, trouble breathing, cough, non-healing skin sores), signs of an overactive thyroid (such as irritability, nervousness, heat intolerance, fast/pounding/irregular heartbeat, bulging eyes, unusual growth in the neck/thyroid known as a goiter), signs of a certain nerve problem known as Guillain-Barre Syndrome (such as difficulty breathing/swallowing/moving your eyes, drooping face, paralysis, slurred speech).

Tell your doctor immediately if any of these unlikely but serious side effects occur: yellowing eyes/skin.

Seek immediate medical attention if any of these rare but serious side effects occur: symptoms of a heart attack (such as chest/jaw/left arm pain, shortness of breath, unusual sweating), easy bruising/bleeding, persistent nausea/vomiting, stomach/abdominal pain, dark urine, decrease in the amount of urine.

Indinavir may cause kidney stones. Tell your doctor immediately if you have symptoms such as side or mid-back pain, pink/bloody urine, or pain with urination.

This medication may infrequently make your blood sugar level rise, which can cause or worsen diabetes. Tell your doctor immediately if you develop symptoms of high blood sugar such as increased thirst and urination. If you already have diabetes, check your blood sugar levels regularly. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

Changes in body fat may occur while you are taking this medication (such as increased fat in the upper back and stomach areas, decreased fat in the arms and legs). The cause and long-term effects of these changes are unknown. Discuss the risks and benefits of treatment with your doctor, as well as the possible use of exercise to reduce this side effect.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Crixivan (indinavir sulfate) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking indinavir, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood fat levels (cholesterol/triglycerides), diabetes, hemophilia, kidney problems (including kidney stones), heart problems (coronary artery disease, heart attack), liver problems.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Children may be more sensitive to the side effects of this drug, especially effects on the kidney (such as kidney stones).

During pregnancy, this medication should be used only when clearly needed. However, it is now normal to prescribe HIV medicines for pregnant women with HIV. This has been shown to decrease the risk of giving HIV to the baby. Indinavir may be part of that treatment. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. Because breast milk can transmit HIV, do not breast-feed.

Disclaimer

Crixivan Consumer (continued)

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this drug include: amiodarone, atazanavir, certain benzodiazepines (alprazolam, midazolam, triazolam), conivaptan, eletriptan, ergot alkaloids (such as dihydroergotamine, ergonovine, ergotamine, methylergonovine), pimozide, ranolazine, rifampin, certain "statin" cholesterol drugs (lovastatin, simvastatin), St. John's wort.

Other medications can affect the removal of indinavir from your body, which may affect how indinavir works. Examples include rifabutin, venlafaxine, certain anti-seizure drugs (carbamazepine, phenytoin, phenobarbital), certain azole fungal medications (ketoconazole, itraconazole), among others.

Indinavir can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include trazodone, certain calcium channel blockers (such as nifedipine, felodipine, nicardipine), certain drugs that weaken the immune system (cyclosporine, tacrolimus, sirolimus), drugs to treat erectile dysfunction/pulmonary hypertension (such as sildenafil, vardenafil), salmeterol, among others.

This document does not contain all possible drug interactions. Keep a list of all the products you use. Share the list with your doctor and pharmacist to lessen your risk for serious medication problems.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: To reduce the risk of spreading HIV to others, always use effective barrier protections (such as latex or polyurethane condoms, dental dams) during all sexual activity. Consult your doctor or pharmacist for more details.

Do not share this medication with others.

Laboratory and/or medical tests (such as liver tests, viral load, T-cell counts, triglycerides/cholesterol, blood sugar) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Keep all medical and laboratory appointments.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised April 2012. Copyright(c) 2012 First Databank, Inc.

Crixivan Patient Information Including Side Effects

Brand Names: Crixivan

Generic Name: indinavir (Pronunciation: in DIN a veer)

What is indinavir (Crixivan)?

Indinavir is an antiviral medication in a group of HIV medicines called protease (PRO-tee-ayz) inhibitors. Indinavir prevents human immunodeficiency virus (HIV) cells from multiplying in your body.

Indinavir is used to treat HIV, which causes acquired immunodeficiency syndrome (AIDS). Indinavir is not a cure for HIV or AIDS.

Indinavir may also be used for other purposes not listed in this medication guide.

Crixivan 200 mg

white, imprinted with CRIXIVAN, 200 mg

Crixivan 400 mg

white, imprinted with CRIXIVAN, 400 mg

What are the possible side effects of indinavir (Crixivan)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking indinavir and call your doctor at once if you have any of these serious side effects:

  • fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;
  • pale or yellowed skin, dark colored urine, fever, confusion or weakness;
  • increased urination or extreme thirst;
  • pain in your side or lower back, blood in your urine;
  • easy bruising or bleeding;
  • signs of a new infection, such as fever or chills, cough, or flu symptoms; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • mild nausea, vomiting, diarrhea, bloating;
  • numbness or tingling, especially around your mouth;
  • tired feeling;
  • headache, mood changes; or
  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Crixivan (indinavir sulfate) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about indinavir (Crixivan)?

Do not take indinavir with amiodarone (Cordarone, Pacerone), cisapride (Propulsid), pimozide (Orap), alprazolam (Xanax), oral midazolam (Versed), triazolam (Halcion), or an ergot medicine such as Ergomar, Cafergot, Wigraine, D.H.E. 45, Migranal, Methergine.

These drugs can cause life-threatening side effects if you use them while you are taking indinavir.

There are many other medicines that can interact with indinavir. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

HIV/AIDS is usually treated with a combination of different drugs. To best treat your condition, use all of your medications as directed by your doctor. Do not change your doses or medication schedule without advice from your doctor. Every person with HIV or AIDS should remain under the care of a doctor.

Taking indinavir will not prevent you from passing HIV to other people through unprotected sex or sharing of needles. Talk with your doctor about safe methods of preventing HIV transmission during sex, such as using a condom and spermicide. Sharing drug or medicine needles is never safe, even for a healthy person.

Side Effects Centers

Crixivan Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking indinavir (Crixivan)?

Do not take this medication if you are allergic to indinavir.

Do not take indinavir with amiodarone (Cordarone, Pacerone), cisapride (Propulsid), pimozide (Orap), alprazolam (Xanax), oral midazolam (Versed), triazolam (Halcion), or ergot medicines such as ergotamine (Ergomar, Cafergot), dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), or methylergonovine (Methergine).

These drugs can cause life-threatening side effects if you use them while you are taking indinavir.

Before taking indinavir, tell your doctor if you are allergic to any drugs, or if you have:

  • liver disease;
  • kidney disease, or a history of kidney stones;
  • diabetes;
  • a bleeding disorder such as hemophilia; or
  • high cholesterol or triglycerides.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take indinavir.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. HIV can be passed to the baby if the mother is not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection while you are pregnant.

Your name may need to be listed on an antiviral pregnancy registry when you start using this medication.

You should not breast-feed while you are using indinavir. Women with HIV or AIDS should not breast-feed at all. Even if your baby is born without HIV, you may still pass the virus to the baby in your breast milk.

How should I take indinavir (Crixivan)?

Take indinavir exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Take indinavir with a full glass (8 ounces) of water or skim milk. You may also drink juice, coffee, or tea with this medication. Drink at least 6 glasses of water each day to prevent kidney stones while you are taking indinavir.

Indinavir should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal.

If you prefer to take the medication with food, eat only a light meal, such as dry toast with jelly, or corn flakes with skim milk and sugar. Avoid eating a high-fat meal.

It is important to use indinavir regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis. Your liver function may also need to be tested. Do not miss any scheduled visits to your doctor.

HIV/AIDS is usually treated with a combination of different drugs. To best treat your condition, use all of your medications as directed by your doctor. Be sure to read the medication guide or patient instructions provided with each of your medications. Do not change your doses or medication schedule without advice from your doctor. Every person with HIV or AIDS should remain under the care of a doctor.

Store indinavir at room temperature away from moisture and heat. Keep the capsules in their original container, along with the packet of moisture-absorbing preservative that comes with indinavir capsules.

Side Effects Centers

Crixivan Patient Information including If I Miss a Dose

What happens if I miss a dose (Crixivan)?

Take the missed dose as soon as you remember and take your next dose at the regularly scheduled time. If you are more than 2 hours late in taking your indinavir, skip the missed dose and take the next regularly scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Crixivan)?

Seek emergency medical attention if you think you have used too much of this medicine. Symptoms of an indinavir overdose may include nausea, vomiting, diarrhea, lower back pain, and blood in your urine.

What should I avoid while taking indinavir (Crixivan)?

If you also take didanosine, take it 1 hour before or after you take indinavir, on an empty stomach.

Taking indinavir will not prevent you from passing HIV to other people through unprotected sex or sharing of needles. Talk with your doctor about safe methods of preventing HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

What other drugs will affect indinavir (Crixivan)?

Before taking indinavir, tell your doctor if you are using:

  • injectable midazolam (Versed);
  • fluticasone (Advair, Flonase, Flovent);
  • St. John's wort;
  • antibiotics such as clarithromycin (Biaxin), itraconazole (Sporanox), ketoconazole (Nizoral), rifabutin (Mycobutin), or rifampin (Rifadin, Rimactane, Rifater);
  • antidepressants such as trazodone (Desyrel), and others;
  • a calcium channel blocker such as amlodipine (Caduet, Lotrel, Norvasc), diltiazem (Tiazac, Cartia, Dilacor), felodipine (Plendil), nifedipine (Procardia, Adalat), or verapamil (Calan, Covera, Isoptin, Verelan);
  • cholesterol-lowering medicine such as atorvastatin (Lipitor), lovastatin (Mevacor, Altocor), rosuvastatin (Crestor), or simvastatin (Zocor);
  • drugs that weaken the immune system, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune), or tacrolimus (Prograf);
  • heart rhythm medications such as quinidine (Quinaglute, Quinidex);
  • insulin or diabetes medication you take by mouth;
  • medicines to treat erectile dysfunction, such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra);
  • other HIV /AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), lopinavir/ritonavir (Kaletra), or ritonavir (Norvir); or
  • seizure medications such as carbamazepine (Carbatrol, Tegretol), phenobarbital (Luminal, Solfoton), or phenytoin (Dilantin).

This list is not complete and there are many other medicines that can interact with indinavir. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

Where can I get more information?

Your pharmacist can provide more information about indinavir.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 8.03. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

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