Cleviprex (Clevidipine Butyrate)
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Cleviprex (Clevidipine Butyrate)

Cleviprex
(clevidipine) Injectable Emulsion, for Intravenous Use

DRUG DESCRIPTION

Cleviprex is a sterile, milky-white emulsion containing 0.5 mg/mL of clevidipine suitable for intravenous administration. Clevidipine is a dihydropyridine calcium channel blocker. Chemically, the active substance,clevidipine,is butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-l,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate. It is a racemic mixture with a molecular weight of 456.3 g/mol. Each enantiomer has equipotent antihypertensive activity. The structure and formula are:

Cleviprex
  (clevidipine)Structural Formula Illustration

Clevidipineis practically insoluble in water and is formulated in an oil-in-water emulsion. In addition to the active ingredient, clevidipine, Cleviprex contains soybean oil(200 mg/mL), glycerin (22.5 mg/mL), purified egg yolk phospholipids (12 mg/mL),oleic acid (0.3 mg/mL), disodium edetate (0.05 mg/mL), and sodium hydroxide to adjust pH. Cleviprex has a pH of 6.0 - 8.0 and is a ready-to-use emulsion.

What are the possible side effects of clevidipine (Cleviprex)?

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.

Call your doctor at once if you have a serious side effect such as:

  • feeling like you might pass out;
  • slow heart rate;
  • urinating less than usual or not at all;
  • drowsiness, confusion, mood changes, increased thirst, loss of appetite, vomiting;
  • feeling short of breath, even with mild exertion;
  • swelling, rapid weight gain; or
  • chest pain or heavy feeling, pain...

Read All Potential Side Effects and See Pictures of Cleviprex »

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Cleviprex is indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable.

DOSAGE AND ADMINISTRATION

Monitoring

Monitor blood pressure and heart rate continually during infusion,and then until vital signs are stable.Patients who receive prolonged Cleviprex infusions and are not transitioned to other antihypertensive therapies should be monitored for the possibility of rebound hypertension for at least 8 hours after the infusion is stopped. These patients may need follow-up adjustments in blood pressure control.

Recommended Dosing

Cleviprex is intended for intravenous use.Titrate drug to achieve the desired blood pressure reduction. Individualize dosage depending on the blood pressure to be obtained and theresponse of the patient.

Initial dose

Initiate the intravenous infusion of Cleviprex at 1-2 mg/hour.

Dose titration

The dose may be doubled at short (90 second) intervals initially. As the blood pressure approaches goal, the increase in doses should be less than doubling and the time between dose adjustments should be lengthened to every 5-10 minutes. An approximately 1-2 mg/hour increase will generally produce an additional 2-4 mmHg decrease in systolic pressure.

Maintenance dose

The desired therapeutic response for most patients occurs at doses of 4-6 mg/hour. Patients with severe hypertension may require doses up to 32 mg/hour, but there is limited experience at this dose rate.

Maximum dose

Most patients were treated with maximum doses of 16 mg/hour or less.There is limited short-term experience with doses up to 32 mg/hour.Because of lipid load restrictions, no more than 1000 mL or an average of 21 mg/hour of Cleviprex infusion is recommended per 24 hour period. In clinical trials, 55 hypertensive patients were treated with > 500mL of Cleviprex infusion per 24 hour period.There is little experience with infusion durations beyond 72 hours at any dose.

Transition to an oral antihypertensive agent

Discontinue Cleviprex or titrate downward while appropriate oral therapy is established. When an oral antihypertensive agent is being instituted, consider the lag time of onset of the oral agent's effect. Continue blood pressure monitoring until desired effect is achieved.

Special populations

Special populations were not specifically studied.In clinical trials, 78 patients with abnormal hepatic function(one or more of the following: elevatedserum bilirubin, AST/SGOT, ALT/SGPT) and 121patients with moderate to severe renalimpairment were treated with Cleviprex. An initial Cleviprex infusion rate of 1-2 mg/hour is appropriate in these patients.

Table 1 is a guideline for dosing conversion from mg/hour to mL/hour.

Table 1. Dose conversion

Dose (mg/hour) Dose (mL/hour)
1 2
2 4
4 8
6 12
8 16
10 20
12 24
14 28
16 32
18 36
20 40
22 44
24 48
26 52
28 56
30 60
32 64

Instructions for Administration

Maintainaseptic technique while handling Cleviprex. Cleviprex is a single-use parenteral product. Do not use if contamination is suspected. Once the stopper is punctured, use within 12 hours and discard any unused portion.

Cleviprex is supplied in sterile, pre-mixed, ready-to-use 50 mL or 100 mL vials. Invert vial gently several times before use to ensure uniformity of the emulsion prior to administration. Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. Administer Cleviprex using aninfusion device allowing calibrated infusion rates. Commercially available standard plastic cannulae may be used to administer the infusion. Administer Cleviprex by a central line or a peripheral line.

Cleviprex should not be administered in the same line as other medications.

Cleviprex should not be diluted, but it can be administered with the following:

  • Water for Injection, USP
  • Sodium Chloride (0.9%) Injection, USP
  • Dextrose (5%) Injection, USP
  • Dextrose (5%) in Sodium Chloride (0.9%) Injection, USP
  • Dextrose (5%) in Ringers Lactate Injection, USP
  • Lactated Ringers Injection, USP
  • 10% amino acid

HOW SUPPLIED

Dosage Forms and Strengths

Cleviprex is a sterile, milky white injectable emulsion for intravenous use, available in the following two configurations:

  • 50 mL single use vial with 0.5 mg/mL clevidipine
  • 100 mL single use vial with 0.5 mg/mL clevidipine

Cleviprex (clevidipine)injectable emulsion is supplied as a sterile, milky white liquid emulsion product in single-use 50 mL or 100 mL glass vials at a concentration of 0.5 mg/mL of clevidipine.

NDC 65293-005-50: 50 mL vial
NDC 65293-005-00: 100 mL vial

Storage

Leave vials in cartons until use. Clevidipineis photosensitive and storage in cartons protects against photodegradation. Protection from light during administration is not required.

Store vials refrigerated at 2-8°C (36-46°F). Do notfreeze. Vials in cartons may be transferred to 25°C (77°F, USP controlled room temperature) for a period not to exceed 2 months.Upon transfer to room temperature, mark vials in cartons "This product was removed from the refrigerator on _/_/_ date.lt must be used or discarded 2 months after this date or the labeled expiration date (whichever date comes first)."Do not return to refrigerated storage after beginning room temperature storage.

Handling

Maintain aseptic technique while handling Cleviprex. Cleviprex is a single-use parenteral product that contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, for up to 12 hours, in the event of accidental contamination. However, Cleviprex can still support the growth of microorganisms, as it is not an antimicrobially preserved product under USP standards. Do not use if contamination is suspected. Once the stopper is punctured, use within 12 hours and discard any unused portion.

Cleviprex inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms, staphylococcus epidermidis and serratiamarcescens.

Manufactured by: Fresenius KabiAustria GmbH, Graz, Austria. Marketed by: The Medicines Company, Parsippany, New Jersey07054. For information call: 888-977-MDCO (6326). Revised: 07/2011

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The following risk is discussed elsewhere in the labeling:

Clinical Trials Experience

Cleviprex clinical development included 19 studies, with 99 healthy subjects and 1307 hypertensive patients who received at least one dose of clevidipine(1406 total exposures). Clevidipinewas evaluated in 15 studies in hypertensive patients: 1099 patients with perioperative hypertension, 126 with severe hypertension and 82 patients with essential hypertension.

The desired therapeutic response was achieved at doses of 4-6 mg/hour. Cleviprex wasinfused for < 24 hours in the majority of patients (n=l 199); it was infused as a continuous infusion in an additional 93 patients for durations between 24 and 72 hours.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Perioperative Hypertension

The placebo-controlled experience with Cleviprex in the perioperative setting was both small and brief (about 30 minutes). Table 2 shows treatment-emergent adverse reactions and the category of "any common adverse event" in ESCAPE-1 and ESCAPE-2 where the rate on Cleviprex exceeded the rate on placebo by at least 5% (common adverse reactions).

Table 2.Common adverse reactions in placebo-controlled perioperative studies.

  ESCAPE-1 ESCAPE-2
CLV
N=53(%)
PBO
N=51(%)
CLV
N=61(%)
PBO
N=49(%)
Any common adverse event 27(51%) 21 (41%) 32(53%) 24(49%)
Acute renal failure 5 (9%) 1 (2%) -- --
Atrial fibrillation -- -- 13(21%) 6(12%)
Nausea -- -- 13(21%) 6(12%)

Three randomized, parallel, open-label studies called ECLIPSE, with longer exposure in cardiac surgery patients define the adverse reactions for patients with perioperative hypertension.Each ECLIPSE study compared Cleviprex (n=752) to an active comparatonnitroglycerin (NTG, n=278), sodium nitroprusside (SNP, n=283), ornicardipine (NIC, n=193).The pooled mean maximum dose in these studies was 10 mg/hour and the mean duration of treatment was 8 hours.

There were many adverse events associated with the operative procedure in the clinical studies of Cleviprex and relatively few plausibly related to the drugs used to lower blood pressure. Thus, the ability to differentiate the adverse event profile between treatments is limited. The adverse events observed within one hour of the end of the infusion were similar in patients who received Cleviprex and in those who received comparator agents.There was no adverse reaction that was more than 2% more common on Cleviprex than on the average of all comparators.

Serious Adverse Events and Discontinuation - Perioperative Hypertension Studies

The incidence of adverse events leading to study drug discontinuation in patients with perioperative hypertension receiving Cleviprex was 5.9% versus 3.2% for all active comparators.For patients receiving Cleviprex and all active comparators the incidence of serious adverse events within one hour of drug infusion discontinuation was similar.

Severe Hypertension

The adverse events for patients with severe hypertension are based on anuncontrolled study in patients with severe hypertension (VELOCITY,n=126).

The common adverse reactions for Cleviprex in severe hypertension included headache (6.3%),nausea (4.8%), and vomiting (3.2%).The incidence of adverse events leading to study drug discontinuation for Cleviprex in severe hypertension was 4.8%.

Less Common Adverse Reactions in Patients with Severe or Essential Hypertension

Adverse reactions that were reported in < 1% of patients with severe or essential hypertension included:

Cardiac: myocardial infarction, cardiac arrest

Nervous system: syncope

Respiratory: dyspnea

Post-Marketing and Other Clinical Experience

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or to establish a casual relationship to drug exposure. The following adverse reactions have been identified during post-approval use of Cleviprex: increased blood triglycerides, ileus, hypersensitivity, hypotension, nausea, decreased oxygen saturation (possible pulmonary shunting) and reflex tachycardia.

Read the Cleviprex (clevidipine butyrate) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

No clinical drug interactionstudies were conducted. Clevidipine and its major dihydropyridine metabolite do not have the potential for blocking or inducing any CYP enzyme.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Need for Aseptic Technique

Use aseptic technique and discard any unused productwithin 12 hours of stopper puncture [see DOSAGE AND ADMINISTRATION].

Hypotension and Reflex Tachycardia

Cleviprex may produce systemic hypotension and reflex tachycardia.If either occurs, decrease the dose of Cleviprex. There is limited experience with short-duration therapy with beta-blockers as a treatment for Cleviprex-induced tachycardia.Beta-blocker use for this purpose is not recommended.

Lipid Intake

Cleviprex contains approximately 0.2 g of lipid per mL (2.0 kcal). Lipid intake restrictions may be necessary for patients with significant disorders of lipid metabolism. For these patients, a reduction in the quantity of concurrently administered lipids may be necessary to compensate for the amount of lipid infused as part of the Cleviprex formulation.

Negative Inotropy

Dihydropyridine calcium channel blockers can produce negative inotropic effects andexacerbateheart failure.Monitor heart failure patients carefully.

Beta-Blocker Withdrawal

Cleviprex is not a beta-blocker, does not reduce heart rate, and gives no protection against the effects of abrupt beta-blocker withdrawal. Beta-blockers should bewithdrawn only aftera gradual reduction indose.

Rebound Hypertension

Patients who receive prolonged Cleviprex infusions and are not transitioned to other antihypertensive therapies should be monitored for the possibility of rebound hypertension for at least 8 hours after the infusion is stopped.

Pheochromocytoma

There is no information to guide use of Cleviprex in treating hypertension associated with pheochromocytoma.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Clevidipine displayed positive genotoxic potentials in vitro in the Ames test, mouse lymphoma thymidine kinase locus assay, and chromosomal aberration assay but not in vivo in the mouse micronucleus test. Formaldehyde, a metabolite of clevidipine, a known genotoxicant in vitro and a probable human carcinogen, appears to be at least partially responsible for the positives in vitro results. Long-term studies for evaluation of carcinogenic potential have not been performed with clevidipine due to the intended short-term duration of human use. There were no adverse effects on fertility or mating behavior of male rats at clevidipine doses of up to 55 mg/kg/day, approximately equivalent to the maximum recommended human dose (MRHD) of 504 mg/day (21 mg/hour x 24 hours) on a body surface area basis. Female rats demonstrated pseudopregnancy and changes in estrus cycle at doses as low as 13 mg/kg/day (about 1/4th the MRHD); however, doses of up to 55 mg/kg/day did not affect mating performance or fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of Cleviprex use in pregnant women. In animal studies, clevidipine caused increases in maternal and fetal mortality and length of gestation.Cleviprex should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There was decreased fetal survival when pregnant rats and rabbits were treated with clevidipine during organogenesis at doses 0.7 times (on a body surface area basis) the maximum recommended human dose (MRHD) in rats and 2 times the MRHD in rabbits.

In pregnant rats dosed with clevidipine during late gestation and lactation, there were dose-related increases in maternal mortality, length of gestation and prolonged parturition at doses greater than or equal to 1/6 of the MRHD based on body surface area. When offspring of these dams were mated, they had a conception rate lower than that of controls. Clevidipine has been shown to cross the placenta in rats [see Nonclinical Toxicology].

Labor and Delivery

Cleviprex in the labor and delivery setting has not been establishedassafe and effective.Other calcium channel blockers suppress uterine contractions in humans.Pregnant rats treated with clevidipine during late gestation had an increased rate of prolonged parturition.

Nursing Mothers

It is not known whether clevidipine is excreted in human milk. Because many drugs are excreted in human milk, consider possible infant exposure when Cleviprex is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Cleviprex in children under 18 years of age have not been established.

Geriatric Use

Of the 1406 subjects (1307with hypertension) treated with Cleviprex in clinical studies, 620 were ≥ 65 years of age and 232 were ≥ 75 years of age. No overall differences in safety or effectiveness were observed between these and younger patients.Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, for an elderly patient doses should betitrated cautiously, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There has been no experience of overdosage in human clinical trials. In clinical trials, doses of Cleviprex up to 106 mg/hour or 1153 mg maximum total dose were administered. The expected major effects of overdose would be hypotension and reflex tachycardia.

Discontinuation of Cleviprex leads to a reduction in antihypertensive effects within 5 to 15 minutes [see CLINICAL PHARMACOLOGY]. In case of suspected overdosage, Cleviprex should be discontinued immediately and the patient's blood pressure should be supported.

CONTRAINDICATIONS

Known Allergy

Cleviprex is contraindicated in patients with allergies to soybeans, soy products, eggs, or egg products.

Defective Lipid Metabolism

Cleviprex is contraindicated in patients with defective lipid metabolism such as pathologic hyperlipemia, lipoid nephrosis, or acute pancreatitis if it is accompanied by hyperlipidemia.

Severe Aortic Stenosis

Cleviprex is contraindicated in patients with severeaortic stenosis because afterload reduction can be expected to reduce myocardial oxygen delivery.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Clevidipine is a dihydropyridine L-type calcium channel blocker. L-type calcium channels mediate the influx of calcium during depolarization in arterialsmooth muscle. Experiments in anesthetized rats and dogs show that clevidipinereduces mean arterial blood pressure by decreasing systemic vascular resistance.Clevidipinedoes not reduce cardiac filling pressure (pre-load), confirming lack of effects on the venous capacitance vessels.

Pharmacodynamics

Cleviprex is titrated to the desired reduction in blood pressure. The effect of Cleviprex appears to plateau at approximately 25% of baseline systolic pressure. The infusion rate for which half the maximal effect is observed is approximately 10 mg/hour.

Onset of Effect: In the perioperative patient population, Cleviprexproduces a 4-5% reduction in systolic blood pressurewithin 2-4 minutes after starting a 0.4 mcg/kg/min infusion (approximately 1-2 mg/hr).

Maintenance of Effect: In studies up to 72 hours of continuous infusion, there was no evidence of tolerance or hysteresis.

Offset of Effect: In most patients, full recovery of blood pressure is achieved in 5-15 minutes after the infusion is stopped.

In studies up to 72 hours of continuous infusion, in patients that were not transitioned to other antihypertensive therapies, there was some evidence of rebound hypertension following Cleviprex discontinuation.

Hemodynamics: Cleviprex causes a dose-dependent decrease in systemic vascular resistance.

Heart Rate: An increase in heart rate is a normal response to vasodilation and decrease in blood pressure; in some patients these increases in heart rate may be pronounced [see WARNINGS AND PRECAUTIONS].

Electrophysiologic Effects: In healthy volunteers, clevidipine or its major carboxylic acid metabolite, at therapeutic and supratherapeutic concentrations (approximately 2.8 times steady-state), did not prolongcardiac repolarization.

Pharmacokinetics

Clevidipineis rapidly distributed and metabolized resulting in a very short half-life. The arterial blood concentration of clevidipinedeclines in a multi-phasic pattern following termination of the infusion. The initial phase half-life is approximately 1 minute, and accounts for 85-90% of clevidipineelimination. The terminal half-life is approximately 15 minutes.

Distribution: Clevidipine is > 99.5% bound to proteins in plasma at 37°C.The steady-state volume of distribution was determined to be 0.17 L/kg in arterial blood.

Metabolism and Elimination: Clevidipine rapidly metabolized by hydrolysis of the ester linkage, primarily by esterases in the blood and extravascular tissues, making its elimination unlikely to be affected by hepatic or renal dysfunction. The primary metabolitesarethe carboxylic acid metabolite and formaldehydeformed by hydrolysis of the ester group. The carboxylic acid metabolite is inactive as an antihypertensive. This metabolite is further metabolized by glucuronidation or oxidation to the corresponding pyridine derivative. The clearance of the primarydihydropyridine metabolite is 0.03 L/h/kg and the terminal half-life is approximately 9 hours.

In vitro studies show that clevidipineand its metabolite at the concentrations achieved in clinical practice will not inhibit or induce any CYP enzyme.

In a clinical study with radiolabeled clevidipine, 83% of the drug was excreted in urine and feces. The major fraction, 63-74% is excreted in the urine, 7-22% in the feces. More than 90% of the recovered radioactivity is excreted within the first 72 hours of collection.

Developmental Toxicology

When pregnant rats were dosed with clevidipine during late gestation and lactation, there were dose-related increases in mortality, length of gestation and prolonged parturition at dose levels as low as 13 mg/kg/day (about 1/4th the maximum recommended human dose of 504 mg/day (21 mg/hour x 24 hours) on a body surface area basis).When offspring of these dams were mated, they had a conception rate lower than that of controls.Clevidipine crosses the placental membrane in this species and doses of 35 or more mg/kg/day (about 0.7 times the MRHD) administered during organogenesis adversely affected fetal survival.Fetal survival was also adversely affected when pregnant rabbits were treated during organogenesis with 55 mg/kg/day (about twice the MRHD on a body surface area basis).

Clinical Studies

Perioperative Hypertension

Cleviprexwas evaluated in twodouble-blind, randomized, parallel, placebo-controlled, multicenter trials of cardiac surgery patients—pre-operative use in ESCAPE-1 (n=105) and post-operative use in ESCAPE-2 (n=l 10).Patients were undergoingcoronary artery bypass grafting, with or without valve replacement.Inclusion in ESCAPE-1 requireda systolic pressure ≥ 160 mmHg.In ESCAPE-2, the entry criterion was systolic pressure of ≥ 140 mmHg within 4 hours of the completed surgery.The mean baseline blood pressure was 178/77mmHg in ESCAPE -1 and 150/71 mmHg in ESCAPE 2.The population of both studies included 27% females and 47% patients older than age 65.

Cleviprex was infused in ESCAPE-1 preoperatively for 30 minutes, until treatment failure, or until induction of anesthesia, whichever came first.Cleviprex was infused in ESCAPE-2 postoperatively for a minimum of 30 minutes unless alternative therapy was required.The maximum infusion time allowed in the ESCAPE studies was 60 minutes.

In both studiesinfusion of Cleviprex was started at a dose of 1- 2 mg/hourand was titrated upwards, as tolerated, in doubling increments every 90 seconds up to an infusion rate of 16 mg/hourin order to achieve the desired blood pressure-lowering effect. At doses above 16 mg/hour increments were 7 mg/hour. The average Cleviprex infusion rate in ESCAPE-1 was 15.3 mg/hourand in ESCAPE-2 it was 5.1 mg/hour.The mean duration of exposure in the same ESCAPE studies was 30 minutes for the Cleviprex treated patients.

Approximately 4% of Cleviprex-treated subjects in ESCAPE-1 and 41% in ESCAPE-2 were on concomitant vasodilators during the first 30 minutes of Cleviprex administration.

Cleviprex lowered blood pressure within 2-4 minutes.The change in systolic blood pressure over 30 minutes for ESCAPE-1 (preoperative) and ESCAPE-2 (postoperative) are shown in Figure 1 and 2.

Figure 1. Mean change in systolic blood pressure (mmHg) during 30-minute infusion, ESCAPE-1 (preoperative)

Mean change in systolic blood pressure (mmHg) during 30-minute infusion, ESCAPE-1 (preoperative) - Illustration

Figure 2. Mean change in systolic blood pressure (mmHg) during 30-minute infusion, ESCAPE-2 (postoperative)

Mean change in systolic blood pressure (mmHg) during 30-minute infusion, ESCAPE-2 (postoperative) - Illustration

The change in heart rate over 30 minutes for ESCAPE-1 (preoperative) and ESCAPE-2 (postoperative) are shown in Figure 3 and 4.

Figure 3. Mean change in heart rate(bpm) during 30-minute infusion, ESCAPE-1 (preoperative)

Mean change in heart rate(bpm) during 30-minute infusion, ESCAPE-1 (preoperative) - Illustration

Figure 4. Mean change in heart rate (bpm)during 30-minute infusion, ESCAPE-2 (postoperative)

Mean change in heart rate (bpm)during 30-minute infusion, ESCAPE-2 (postoperative) - Illustration

In three Phase 3 open-label clinical trials (ECLIPSE), 1512 patients were randomized to receive Cleviprex, nitroglycerin (perioperative hypertension), sodium nitroprusside (perioperative hypertension), or nicardipine (postoperative hypertension), for the treatment of hypertension in cardiac surgery. The mean exposure in the ECLIPSE studies was 8 hours at 4.5 mg/hour for the 752 patients who were treated with Cleviprex. Blood pressure control was assessed by measuring the magnitude and duration of SBP excursions outside the predefined pre- and post-operative SBP target range of 75-145 mmHg and the predefined intra-operative SBP range of 65-135 mmHg. In general, blood pressure control was similar with the four treatments.

Severe Hypertension

Cleviprexwas evaluated in an open-label, uncontrolledclinical trial (VELOCITY) in 126 patients with severe hypertension (SBP > 180 mmHg or diastolic blood pressure [DBP] > 115 mmHg). Cleviprex infusion was initiated at 2 mg/hour and up-titrated every 3 minutes, doubling up to a maximum dose of 32 mg/hour as required toachieve a prespecified target blood pressure range within 30 minutes (primary endpoint). The transition to oral antihypertensive therapy was assessed for up to 6hours following cessation of Cleviprex infusion.

The blood pressure effect in this study is shown in Figure 5. The average infusion rate was9.5 mg/hour.The mean duration of Cleviprex exposure was 21 hours.

Figure 5.Mean percent change in SBP (%) during the first 30 minutes of infusion, VELOCITY (severe hypertension)

Mean percent change in SBP (%) during the first 30 minutes of infusion, VELOCITY (severe hypertension) - Illustration

Oral antihypertensive therapy was instituted 1 hour prior to the anticipated cessation of Cleviprex infusion. Transition to oral antihypertensive therapy within 6 hours after discontinuing Cleviprex infusion was successful in 91% (115/126) of patients. No patient had IV antihypertensive therapy reinstituted following transition to oral therapy.

Essential Hypertension

Cleviprex was evaluated ina randomized, placebo-controlled, single-blind, parallel 72-hour continuous infusion study in 61 mild to moderate essential hypertensives.The mean baseline blood pressure was 151/86 mmHg.

Subjects were randomized to placebo or to 2, 4, 8, or 16 mg/hour. Doses above 2 mg/hour were started at 2 mg/hour and force-titrated in 2-fold increments at 3-minute intervals.Blood pressure, heart rate,and blood levels of clevidipinewere measured during the infusion period. Blood levels were monitored 1 hour after the infusion was discontinued. Blood pressure and heart rate were monitored for 8 hours and also at 96 hoursafter the termination of infusion. Systolic blood pressure effect was relatedto the concentration of clevidipine and plateaued at higher measured concentrations, with the maximal effect estimated at 25% of baseline systolic blood pressure. The estimated infusion rate necessary to achieve half of this maximal effect was approximately 10 mg/hour.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

  • Advise patients with underlying hypertension that they require continued follow up for their medical condition, and, if applicable, encourage patients to continue taking their oral antihypertensive medication(s) as directed.
  • Advise patients to contact a healthcare professional immediately for any of the following signs of a new hypertensive emergency: neurological symptoms, visual changes, or evidence of congestive heart failure.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

  • Advise patients with underlying hypertension that they require continued follow up for their medical condition, and, if applicable, encourage patients to continue taking their oral antihypertensive medication(s) as directed.
  • Advise patients to contact a healthcare professional immediately for any of the following signs of a new hypertensive emergency: neurological symptoms, visual changes, or evidence of congestive heart failure.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

Cleviprex
(clevidipine) Injectable Emulsion, for Intravenous Use

DRUG DESCRIPTION

Cleviprex is a sterile, milky-white emulsion containing 0.5 mg/mL of clevidipine suitable for intravenous administration. Clevidipine is a dihydropyridine calcium channel blocker. Chemically, the active substance,clevidipine,is butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-l,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate. It is a racemic mixture with a molecular weight of 456.3 g/mol. Each enantiomer has equipotent antihypertensive activity. The structure and formula are:

Cleviprex
  (clevidipine)Structural Formula Illustration

Clevidipineis practically insoluble in water and is formulated in an oil-in-water emulsion. In addition to the active ingredient, clevidipine, Cleviprex contains soybean oil(200 mg/mL), glycerin (22.5 mg/mL), purified egg yolk phospholipids (12 mg/mL),oleic acid (0.3 mg/mL), disodium edetate (0.05 mg/mL), and sodium hydroxide to adjust pH. Cleviprex has a pH of 6.0 - 8.0 and is a ready-to-use emulsion.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

Cleviprex
(clevidipine) Injectable Emulsion, for Intravenous Use

DRUG DESCRIPTION

Cleviprex is a sterile, milky-white emulsion containing 0.5 mg/mL of clevidipine suitable for intravenous administration. Clevidipine is a dihydropyridine calcium channel blocker. Chemically, the active substance,clevidipine,is butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-l,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate. It is a racemic mixture with a molecular weight of 456.3 g/mol. Each enantiomer has equipotent antihypertensive activity. The structure and formula are:

Cleviprex
  (clevidipine)Structural Formula Illustration

Clevidipineis practically insoluble in water and is formulated in an oil-in-water emulsion. In addition to the active ingredient, clevidipine, Cleviprex contains soybean oil(200 mg/mL), glycerin (22.5 mg/mL), purified egg yolk phospholipids (12 mg/mL),oleic acid (0.3 mg/mL), disodium edetate (0.05 mg/mL), and sodium hydroxide to adjust pH. Cleviprex has a pH of 6.0 - 8.0 and is a ready-to-use emulsion.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

Cleviprex
(clevidipine) Injectable Emulsion, for Intravenous Use

DRUG DESCRIPTION

Cleviprex is a sterile, milky-white emulsion containing 0.5 mg/mL of clevidipine suitable for intravenous administration. Clevidipine is a dihydropyridine calcium channel blocker. Chemically, the active substance,clevidipine,is butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-l,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate. It is a racemic mixture with a molecular weight of 456.3 g/mol. Each enantiomer has equipotent antihypertensive activity. The structure and formula are:

Cleviprex
  (clevidipine)Structural Formula Illustration

Clevidipineis practically insoluble in water and is formulated in an oil-in-water emulsion. In addition to the active ingredient, clevidipine, Cleviprex contains soybean oil(200 mg/mL), glycerin (22.5 mg/mL), purified egg yolk phospholipids (12 mg/mL),oleic acid (0.3 mg/mL), disodium edetate (0.05 mg/mL), and sodium hydroxide to adjust pH. Cleviprex has a pH of 6.0 - 8.0 and is a ready-to-use emulsion.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

Cleviprex Patient Information Including Side Effects

Brand Names: Cleviprex

Generic Name: clevidipine (Pronunciation: kle VID a peen)

What is clevidipine (Cleviprex)?

Clevidipine is in a group of drugs called calcium channel blockers. Clevidipine relaxes (widens) blood vessels and improves blood flow.

Clevidipine is an injectable medication that is used to treat high blood pressure (hypertension) in people who cannot take medicine by mouth.

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

What are the possible side effects of clevidipine (Cleviprex)?

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.

Call your doctor at once if you have a serious side effect such as:

  • feeling like you might pass out;
  • slow heart rate;
  • urinating less than usual or not at all;
  • drowsiness, confusion, mood changes, increased thirst, loss of appetite, vomiting;
  • feeling short of breath, even with mild exertion;
  • swelling, rapid weight gain; or
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling.

Less serious side effects may include:

  • headache; or
  • mild nausea.

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 Cleviprex (clevidipine butyrate) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about clevidipine (Cleviprex)?

You should not receive this medication if you are allergic to clevidipine, eggs, or soy products. You also should not receive clevidipine if you have high cholesterol or triglyceride levels in your blood, pancreatitis with high cholesterol or triglycerides, a kidney disorder called lipoid nephrosis, or severe narrowing of the aortic valve in your heart (aortic stenosis).

Before you receive clevidipine, tell your doctor if you have food allergies, pancreatitis, pheochromocytoma (an adrenal gland tumor), heart disease, or a history of high cholesterol.

In an emergency situation, it may not be possible before you are treated to tell your caregivers about any health conditions you have or if you are pregnant or breast-feeding. However, make sure any doctor caring for you afterward knows that you have received this medication.

Tell your doctor about all other heart or blood pressure medications you are using.

Side Effects Centers

Cleviprex Patient Information including How Should I Take

What should I discuss with my healthcare provider before I receive clevidipine (Cleviprex)?

You should not receive this medication if you are allergic to clevidipine, eggs, or soy products. If possible, before you receive clevidipine, tell your doctor if you have:

  • high cholesterol or triglyceride levels in your blood;
  • pancreatitis with high cholesterol or triglycerides;
  • a kidney disorder called lipoid nephrosis; or
  • severe narrowing of the aortic valve in your heart (aortic stenosis).

If you have certain conditions, you may need a dose adjustment or special tests to safely receive this medication. If possible before you receive clevidipine, tell your doctor if you have:

  • food allergies;
  • pancreatitis;
  • pheochromocytoma (an adrenal gland tumor);
  • heart disease; or
  • a history of high cholesterol.

FDA pregnancy category C. It is not known whether clevidipine is harmful to an unborn baby. Before you receive this medication, tell your doctor if you are pregnant.

It is not known whether clevidipine passes into breast milk or if it could harm a nursing baby. Before you receive this medication, tell your doctor if you are breast-feeding a baby.

In an emergency situation, it may not be possible before you are treated with clevidipine to tell your caregivers if you are pregnant or breast-feeding. However, make sure any doctor caring for your pregnancy or your baby knows that you have received this medication.

How is clevidipine given (Cleviprex)?

Clevidipine is given as an injection through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection. You will continue to receive clevidipine until you are able to take blood pressure medication orally (by mouth).

Your blood pressure and heart rate will be watched closely while you are receiving clevidipine. Your blood pressure may also need to be checked often for several hours after you stop receiving this medication.

While you are being treated for high blood pressure, keep using your prescribed medications even if you feel fine. High blood pressure often has no symptoms, so you may not know when your blood pressure is high.

You may need to use blood pressure medication for the rest of your life. Call your doctor at once if you have any signs of dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).

Clevidipine may be only part of a complete program of treatment that also includes a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you must avoid to help control your condition.

Store clevidipine at room temperature away from moisture, heat, and light.

Side Effects Centers

Cleviprex Patient Information including If I Miss a Dose

What happens if I miss a dose (Cleviprex)?

Since clevidipine is given as needed by a healthcare professional, it is not likely that you will miss a dose.

What happens if I overdose (Cleviprex)?

Seek emergency medical attention if you think you have received too much of this medication.

Overdose symptoms may include slow heartbeats, severe dizziness, and fainting.

What should I avoid while receiving clevidipine (Cleviprex)?

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

What other drugs will affect clevidipine (Cleviprex)?

Tell your doctor about all other heart or blood pressure medications you are using.

Tell your doctor if you are also taking a beta-blocker drug (such as Blocadren, Corgard, Inderal, Normodyne, Tenormin, Toprol, Trandate, Zebeta, and others). You should not suddenly stop taking the beta-blocker. Stopping a beta-blocker too quickly can cause serious heart problems that will not be prevented by clevidipine.

There may be other drugs that can interact with clevidipine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about clevidipine.


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: 1.03. Revision date: 12/15/2010.

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