Micardis HCT (Telmisartan, Hydrochlorothiazide)
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Micardis HCT (Telmisartan, Hydrochlorothiazide)

Micardis® HCT
(telmisartan and hydrochlorothiazide) 40 mg/12.5 mg 80 mg/12.5 mg and 80 mg/25 mg Tablets

WARNING

FETAL TOXICITY

  • When pregnancy is detected, discontinue MICARDIS HCT as soon as possible.
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (see WARNINGS, Fetal Toxicity).

DRUG DESCRIPTION

MICARDIS HCT tablets are a combination of telmisartan, an orally active angiotensin II antagonist acting on the AT1 receptor subtype, and hydrochlorothiazide, a diuretic.

Telmisartan, a non-peptide molecule, is chemically described as 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1Hbenzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Its empirical formula is C33H30N4O2, its molecular weight is 514.63, and its structural formula is:

Telmisartan Structural Formula Illustration

Telmisartan is a white to slightly yellowish solid. It is practically insoluble in water and in the pH range of 3 to 9, sparingly soluble in strong acid (except insoluble in hydrochloric acid), and soluble in strong base.

Hydrochlorothiazide is a white, or practically white, practically odorless, crystalline powder with a molecular weight of 297.74. It is slightly soluble in water, and freely soluble in sodium hydroxide solution. Hydrochlorothiazide is chemically described as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7sulfonamide 1,1-dioxide. Its empirical formula is C7H8ClN3O4S2, and its structural formula is:

Hydrochlorothiazide Structural Formula Illustration

MICARDIS HCT tablets are formulated for oral administration in three combinations of 40 mg/12.5 mg, 80 mg/12.5 mg, and 80 mg/25 mg telmisartan and hydrochlorothiazide, respectively. The tablets contain the following inactive ingredients: sodium hydroxide, meglumine, povidone, sorbitol, magnesium stearate, lactose monohydrate, microcrystalline cellulose, maize starch, sodium starch glycolate. As coloring agents, the 40 mg/12.5 mg and 80 mg/12.5 mg tablets contain ferric oxide red, and the 80 mg/25 mg tablets contain ferric oxide yellow. Micardis® HCT (telmisartan and hydrochlorothiazide) tablets are hygroscopic and require protection from moisture.

What are the possible side effects of hydrochlorothiazide and telmisartan (Micardis HCT)?

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.

In rare cases, hydrochlorothiazide and telmisartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have muscle pain, tenderness, or weakness especially if you also have fever, nausea or vomiting, and dark colored urine.

Stop using this medication and call your doctor at once if you have any other...

Read All Potential Side Effects and See Pictures of Micardis HCT »

What are the precautions when taking telmisartan, hydrochlorothiazide (Micardis HCT)?

Before taking this medication, tell your doctor or pharmacist if you are allergic to telmisartan or hydrochlorothiazide; 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: kidney disease (such as renal artery stenosis), liver disease, bile duct blockage, loss of too much body water and/or minerals (volume depletion, dehydration), untreated mineral imbalance (such as low or high potassium), gout, lupus.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such...

Read All Potential Precautions of Micardis HCT »

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Micardis® HCT (telmisartan and hydrochlorothiazide) tablets are indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy (see DOSAGE AND ADMINISTRATION).

DOSAGE AND ADMINISTRATION

The usual starting dose of telmisartan is 40 mg once a day; blood pressure response is dose related over the range of 20-80 mg. Patients with depletion of intravascular volume should have the condition corrected or telmisartan tablets should be initiated under close medical supervision (see WARNINGS, Hypotension in Volume-Depleted Patients). Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision (see PRECAUTIONS).

Hydrochlorothiazide is effective in doses of 12.5 mg to 50 mg once daily.

To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy. The side effects (see WARNINGS) of telmisartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of telmisartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects.

Micardis® HCT (telmisartan and hydrochlorothiazide) tablets may be administered with other antihypertensive agents.

MICARDIS HCT tablets may be administered with or without food.

Replacement Therapy

The combination may be substituted for the titrated components.

Dose Titration by Clinical Effect

MICARDIS HCT tablets are available as tablets containing either telmisartan 40 mg and hydrochlorothiazide 12.5 mg, or telmisartan 80 mg and hydrochlorothiazide 12.5 mg or 25 mg. A patient whose blood pressure is not adequately controlled with telmisartan monotherapy 80 mg (see above) may be switched to MICARDIS HCT tablets, telmisartan 80 mg/hydrochlorothiazide 12.5 mg once daily, and finally titrated up to 160/25 mg, if necessary.

A patient whose blood pressure is inadequately controlled by 25 mg once daily of hydrochlorothiazide may be switched to MICARDIS HCT (telmisartan 80 mg/hydrochlorothiazide 12.5 mg or telmisartan 80 mg/hydrochlorothiazide 25 mg) tablets once daily. The clinical response to MICARDIS HCT tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to 160/25 mg, if necessary. Those patients controlled by 25 mg hydrochlorothiazide but who experience hypokalemia with this regimen, may be switched to MICARDIS HCT (telmisartan 80 mg/hydrochlorothiazide 12.5 mg) tablets once daily, reducing the dose of hydrochlorothiazide without reducing the overall expected antihypertensive response.

Patients with Renal Impairment

The usual regimens of therapy with Micardis® HCT (telmisartan and hydrochlorothiazide) tablets may be followed as long as the patient's creatinine clearance is > 30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so MICARDIS HCT tablets are not recommended.

Patients with Hepatic Impairment

MICARDIS HCT tablets are not recommended for patients with severe hepatic impairment. Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision using the 40/12.5 mg combination (see PRECAUTIONS).

HOW SUPPLIED

MICARDIS HCT tablets are available in three strengths as biconvex two-layered, oblong-shaped, uncoated tablets in three combinations of 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg telmisartan and hydrochlorothiazide, respectively. The hydrochlorothiazide layer is red in the 40 mg/12.5 mg and 80 mg/12.5 mg tablets, and yellow in the 80 mg/25 mg tablets, and all are unmarked. The telmisartan layer for all three strengths is white, but may contain red specks in the 40 mg/12.5 mg and 80 mg/12.5 mg tablets and yellow specks in the 80 mg/25 mg tablets. The telmisartan layer is marked with the Boehringer Ingelheim logo and H4 for the 40 mg/12.5 mg dose strength, H8 for the 80 mg/12.5 mg dose strength and H9 for the 80 mg/25 mg dose strength.

Tablets are provided as follows:

MICARDIS HCT tablets 40 mg/12.5 mg are individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0043-37).

MICARDIS HCT tablets 80 mg/12.5 mg are individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0044-37).

MICARDIS HCT tablets 80 mg/25 mg are individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0042-37).

Storage

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Tablets should not be removed from blisters until immediately before administration.

Address medical inquiries to (800) 542-6257 or (800) 459-9906 TTY.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877 USA. Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany. Revised: Revised: Dec. 2011

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Micardis® HCT (telmisartan and hydrochlorothiazide) tablets has been evaluated for safety in over 1700 patients, including 716 treated for over six months and 420 for over one year. In clinical trials with MICARDIS HCT tablets, no unexpected adverse events have been observed. Adverse experiences have been limited to those that have been previously reported with telmisartan and/or hydrochlorothiazide. The overall incidence of adverse experiences reported with the combination was comparable to placebo. Most adverse experiences were mild in intensity and transient in nature and did not require discontinuation of therapy.

Adverse events occurring at an incidence of 2% or more in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo, irrespective of their causal association, are presented in Table 1.

TABLE 1 : Adverse Events Occurring in ≥ 2% of Telmisartan/Hydrochlorothiazide (HCTZ) Patients*

  Telm/HCTZ
(N=414)
(%)
Placebo
(N=74)
(%)
Telm
(N=209)
(%)
HCTZ
(N=121)
(%)
Body as a whole
  Fatisue 3 1 3 3
  Influenza-like symptoms 2 1 2 3
Central/peripheral nervous system
  Dizziness 5 1 4 6
Gastrointestinal system
  Diarrhea 3 0 5 2
  Nausea 2 0 1 2
Respiratory system disorder
  Sinusitis 4 3 3 6
  Upper respiratory tract infection 8 7 7 10
* includes all doses of telmisartan (20-160 mg), hydrochlorothiazide (6.25-25 mg), and combinations thereof

The following adverse events were reported at a rate less than 2% in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo: back pain, dyspepsia, vomiting, tachycardia, hypokalemia, bronchitis, pharyngitis, rash, hypotension postural, abdominal pain.

Finally, the following adverse events were reported at a rate of 2% or greater in patients treated with telmisartan/hydrochlorothiazide, but were as, or more common in the placebo group: pain, headache, cough, urinary tract infection.

Adverse events occurred at approximately the same rates in men and women, older and younger patients, and black and non-black patients.

In controlled trials (n=1017), 0.3% of patients treated with Micardis® HCT (telmisartan and hydrochlorothiazide) tablets 40/12.5 mg, 80/12.5 mg or 80/25 mg discontinued due to orthostatic hypotension, and the incidence of dizziness was 4%, 7%, and 1%, respectively.

Telmisartan

Other adverse experiences that have been reported with telmisartan, without regard to causality, are listed below:

Autonomic Nervous System : impotence, increased sweating, flushing

Body as a Whole : allergy, fever, leg pain, malaise, chest pain

Cardiovascular : palpitation, dependent edema, angina pectoris, leg edema, abnormal ECG, hypertension, peripheral edema

CNS : insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoaesthesia

Gastrointestinal : flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specific gastrointestinal disorders

Metabolic : gout, hypercholesterolemia, diabetes mellitus

Musculoskeletal : arthritis, arthralgia, leg cramps, myalgia

Psychiatric : anxiety, depression, nervousness

Resistance Mechanism : infection, fungal infection, abscess, otitis media

Respiratory : asthma, rhinitis, dyspnea, epistaxis

Skin : dermatitis, eczema, pruritus

Urinary : micturition frequency, cystitis

Vascular : cerebrovascular disorder

Special Senses : abnormal vision, conjunctivitis, tinnitus, earache

A single case of angioedema was reported (among a total of 3781 patients treated with telmisartan).

Hydrochlorothiazide

Other adverse experiences that have been reported with hydrochlorothiazide, without regard to causality, are listed below:

Body as a whole : weakness

Digestive : pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation

Hematologic : aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia

Hypersensitivity : purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions

Metabolic : hyperglycemia, glycosuria, hyperuricemia

Musculoskeletal : muscle spasm

Nervous System/Psychiatric : restlessness

Renal : renal failure, renal dysfunction, interstitial nephritis

Skin : erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis

Special Senses : transient blurred vision, xanthopsia

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Micardis® (telmisartan) tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to MICARDIS tablets. The most frequently spontaneously reported events include: headache, dizziness, asthenia, coughing, nausea, fatigue, weakness, edema, face edema, lower limb edema, angioneurotic edema, urticaria, hypersensitivity, sweating increased, erythema, chest pain, atrial fibrillation, congestive heart failure, myocardial infarction, blood pressure increased, hypertension aggravated, hypotension (including postural hypotension), hyperkalemia, syncope, dyspepsia, diarrhea, pain, urinary tract infection, erectile dysfunction, back pain, abdominal pain, muscle cramps (including leg cramps), myalgia, bradycardia, eosinophilia, thrombocytopenia, uric acid increased, abnormal hepatic function/liver disorder, renal impairment including acute renal failure, anemia, increased CPK, anaphylactic reaction, tendon pain (including tendonitis, tenosynovitis), drug eruption (toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), hypoglycemia (in diabetic patients), and angioedema (with fatal outcome).

Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers, including MICARDIS tablets.

Clinical Laboratory Findings

In controlled trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of Micardis® HCT (telmisartan and hydrochlorothiazide) tablets.

Hemoglobin and Hematocrit : Decreases in hemoglobin ( ≥ 2 g/dL) and hematocrit ( ≥ 9%) were observed in 1.2% and 0.6% of telmisartan/hydrochlorothiazide patients, respectively, in controlled trials. Changes in hemoglobin and hematocrit were not considered clinically significant and there were no discontinuations due to anemia.

Creatinine, Blood Urea Nitrogen (BUN) : Increases in BUN ( ≥ 11.2 mg/dL) and serum creatinine ( ≥ 0.5 mg/dL) were observed in 2.8% and 1.4%, respectively, of patients with essential hypertension treated with MICARDIS HCT tablets in controlled trials. No patient discontinued treatment with MICARDIS HCT tablets due to an increase in BUN or creatinine.

Liver Function Tests : Occasional elevations of liver enzymes and/or serum bilirubin have occurred. No telmisartan/hydrochlorothiazide treated patients discontinued therapy due to abnormal hepatic function.

Serum Electrolytes : See PRECAUTIONS.

Read the Micardis HCT (telmisartan, hydrochlorothiazide) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Telmisartan

Digoxin: When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. It is, therefore, recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing telmisartan to avoid possible over-or under-digitalization.

Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Cases have also been reported with angiotensin II receptor antagonists including telmisartan. Because lithium should not be used with diuretics, the use of lithium with telmisartan and hydrochlorothiazide is not recommended.

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving telmisartan and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDs including selective COX-2 inhibitors.

Ramipril and Ramiprilat: Co-administration of telmisartan 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state Cmax and AUC of ramipril 2.3 and 2.1 fold, respectively, and Cmax and AUC of ramiprilat 2.4 and 1.5 fold, respectively. In contrast, Cmax and AUC of telmisartan decrease by 31% and 16%, respectively. When co-administering telmisartan and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan.

Warfarin: Telmisartan administered for 10 days slightly decreased the mean warfarin trough plasma concentration; this decrease did not result in a change in International Normalized Ratio (INR).

Other Drugs: Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glibenclamide, simvastatin, hydrochlorothiazide or ibuprofen. Telmisartan is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.

Hydrochlorothiazide

When administered concurrently, the following drugs may interact with thiazide diuretics:

Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.

Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs: Additive effect or potentiation.

Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (e.g., norepinephrine): Possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to the muscle relaxant.

Lithium: Should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with Micardis® HCT (telmisartan and hydrochlorothiazide) tablets.

Non-steroidal anti-inflammatory drugs: In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when MICARDIS HCT tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Fetal Toxicity

Pregnancy Category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue MICARDIS HCT as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the reninangiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue MICARDIS HCT, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to MICARDIS HCT for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use).

No teratogenic effects were observed when telmisartan was administered to pregnant rats at oral doses of up to 50 mg/kg/day and to pregnant rabbits at oral doses up to 45 mg/kg/day. In rabbits, embryolethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed at 45 mg/kg/day [about 12 times the maximum recommended human dose (MRHD) of 80 mg on a mg/m² basis]. In rats, maternally toxic (reduction in body weight gain and food consumption) telmisartan doses of 15 mg/kg/day (about 1.9 times the MRHD on a mg/m² basis), administered during late gestation and lactation, were observed to produce adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, decreased weight gain. Telmisartan has been shown to be present in rat fetuses during late gestation and in rat milk. The no observed effect doses for developmental toxicity in rats and rabbits, 5 and 15 mg/kg/day, respectively, are about 0.64 and 3.7 times, on a mg/m² basis, the maximum recommended human dose of telmisartan (80 mg/day).

Studies in which hydrochlorothiazide was administered to pregnant mice and rats during their periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively, provided no evidence of harm to the fetus.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Hypotension in Volume-Depleted Patients

Initiation of antihypertensive therapy in patients whose renin-angiotensin system are activated such as patients who are intravascular volume- or sodium-depleted, e.g., in patients treated vigorously with diuretics, should only be approached cautiously. These conditions should be corrected prior to administration of Micardis® HCT (telmisartan and hydrochlorothiazide) tablets. Treatment should be started under close medical supervision (see DOSAGE AND ADMINISTRATION). If hypotension occurs, the patients should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment which usually can be continued without difficulty once the blood pressure has stabilized.

Hydrochlorothiazide

Hepatic Impairment : Thiazide diuretics should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Hypersensitivity Reaction : Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.

Systemic Lupus Erythematosus : Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Lithium Interaction : Lithium generally should not be given with thiazides (see PRECAUTIONS: DRUG INTERACTIONS, Hydrochlorothiazide, Lithium).

Acute Myopia and Secondary Angle-Closure Glaucoma: Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

PRECAUTIONS

Serum Electrolytes

Telmisartan and Hydrochlorothiazide

In controlled trials using the telmisartan/hydrochlorothiazide combination treatment, no patient administered 40/12.5 mg, 80/12.5 mg or 80/25 mg had a decrease in potassium ≥ 1.4 mEq/L, and no patient experienced hyperkalemia. No discontinuations due to hypokalemia occurred during treatment with the telmisartan/hydrochlorothiazide combination. The absence of significant changes in serum potassium levels may be due to the opposing mechanisms of action of telmisartan and hydrochlorothiazide on potassium excretion on the kidney.

Hydrochlorothiazide

Periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient experiences excessive vomiting or receives parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.

Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.

The antihypertensive effects of the drug may be enhanced in the post sympathectomy patient.

If progressive renal impairment becomes evident consider withholding or discontinuing diuretic therapy.

Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.

Impaired Hepatic Function

Telmisartan

As the majority of telmisartan is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Micardis® HCT (telmisartan and hydrochlorothiazide) tablets should therefore be used with caution in these patients.

Impaired Renal Function

Telmisartan

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results may be anticipated in patients treated with telmisartan.

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen were observed. There has been no long-term use of telmisartan in patients with unilateral or bilateral renal artery stenosis but an effect similar to that seen with ACE inhibitors should be anticipated.

Hydrochlorothiazide

Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Dual Blockade of the Renin-angiotensin-aldosterone System

Telmisartan

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function (including acute renal failure) have been reported. Dual blockade of the renin-angiotensin-aldosterone system (e.g., by adding an ACE-inhibitor to an angiotensin II receptor antagonist) should include close monitoring of renal function.

The ONTARGET trial enrolled 25,620 patients > 55 years old with atherosclerotic disease or diabetes with end-organ damage, randomized them to telmisartan only, ramipril only, or the combination, and followed them for a median of 56 months. Patients receiving the combination of telmisartan and ramipril did not obtain any additional benefit on the composite endpoint of cardiovascular death, myocardial infarction, stroke and heart failure hospitalization compared to monotherapy, but experienced an increased incidence of clinically important renal dysfunction (e.g., acute renal failure) compared with groups receiving telmisartan alone or ramipril alone.

Co-administration of telmisartan and ramipril increases the exposure to both ramipril and ramiprilat by a factor of about 2 (see PRECAUTIONS: DRUG INTERACTIONS).

Concomitant use of telmisartan and ramipril is not recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Telmisartan and Hydrochlorothiazide

No carcinogenicity, mutagenicity, or fertility studies have been conducted with the combination of telmisartan and hydrochlorothiazide.

Telmisartan

There was no evidence of carcinogenicity when telmisartan was administered in the diet to mice and rats for up to 2 years. The highest doses administered to mice (1000 mg/kg/day) and rats (100 mg/kg/day) are, on a mg/m² basis, about 59 and 13 times, respectively, the maximum recommended human dose (MRHD) of telmisartan. These same doses have been shown to provide average systemic exposures to telmisartan > 100 times and > 25 times, respectively, the systemic exposure in humans receiving the MRHD (80 mg/day).

Genotoxicity assays did not reveal any telmisartan-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with Salmonella and E. coli (Ames), a gene mutation test with Chinese hamster V79 cells, a cytogenetic test with human lymphocytes, and a mouse micronucleus test.

No drug-related effects on the reproductive performance of male and female rats were noted at 100 mg/kg/day (the highest dose administered), about 13 times, on a mg/m² basis, the MRHD of telmisartan. This dose in the rat resulted in an average systemic exposure (telmisartan AUC as determined on day 6 of pregnancy) at least 50 times the average systemic exposure in humans at the MRHD (80 mg/day).

Hydrochlorothiazide

Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) assay, in the Mouse Lymphoma Cell (mutagenicity) assay, and in the Aspergillus nidulans non-disjunction assay.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to mating and throughout gestation.

Nursing Mothers

It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Neonates with a history of in utero exposure to MICARDIS HCT

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

In the controlled clinical trials (n=1017), approximately 20% of patients treated with telmisartan/hydrochlorothiazide were 65 years of age or older, and 5% were 75 years of age or older. No overall differences in effectiveness and safety of telmisartan/hydrochlorothiazide were observed in these patients compared to younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Telmisartan

Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis.

Hydrochlorothiazide

The most common signs and symptoms observed in patients are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

CONTRAINDICATIONS

MICARDIS HCT tablets are contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan, hydrochlorothiazide, or any other component of this product (see ADVERSE REACTIONS).

Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan blocks the vasoconstrictor and aldosteronesecreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.

There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity ( > 3,000 fold) for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium salt and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.

The mechanism of the antihypertensive effect of thiazides is not fully understood.

Pharmacokinetics

General

Telmisartan

Following oral administration, peak concentrations (Cmax) of telmisartan are reached in 0.5-1 hour after dosing. Food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about 6% with the 40 mg tablet and about 20% after a 160 mg dose. The absolute bioavailability of telmisartan is dose dependent. At 40 and 160 mg the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20-160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan shows bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours. Trough plasma concentrations of telmisartan with once daily dosing are about 10-25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.

Hydrochlorothiazide

When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours.

Metabolism and Elimination

Telmisartan

Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose ( > 97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).

Telmisartan is metabolized by conjugation to form a pharmacologically inactive acylglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. After a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.

Total plasma clearance of telmisartan is > 800 mL/min. Terminal half-life and total clearance appear to be independent of dose.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. At least 61% of the oral dose is eliminated as unchanged drug within 24 hours.

Distribution

Telmisartan

Telmisartan is highly bound to plasma proteins ( > 99.5%), mainly albumin and α1-acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters, indicating additional tissue binding.

Hydrochlorothiazide

Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.

Special Populations

Pediatric : Telmisartan pharmacokinetics have not been investigated in patients < 18 years of age.

Geriatric : The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 65 years (see DOSAGE AND ADMINISTRATION).

Gender : Plasma concentrations of telmisartan are generally 2-3 times higher in females than in males. In clinical trials, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. No dosage adjustment is necessary.

Renal Insufficiency : Renal excretion does not contribute to the clearance of telmisartan. Based on modest experience in patients with mild-to-moderate renal impairment (creatinine clearance of 30-80 mL/min, mean clearance approximately 50 mL/min), no dosage adjustment is necessary in patients with decreased renal function. Telmisartan is not removed from blood by hemofiltration (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Hepatic Insufficiency : In patients with hepatic insufficiency, plasma concentrations of telmisartan are increased, and absolute bioavailability approaches 100% (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Drug Interactions

See PRECAUTIONS: DRUG INTERACTIONS.

Pharmacodynamics

Telmisartan

In normal volunteers, a dose of telmisartan 80 mg inhibited the pressor response to an intravenous infusion of angiotensin II by about 90% at peak plasma concentrations with approximately 40% inhibition persisting for 24 hours.

Plasma concentration of angiotensin II and plasma renin activity (PRA) increased in a dose-dependent manner after single administration of telmisartan to healthy subjects and repeated administration to hypertensive patients. The once-daily administration of up to 80 mg telmisartan to healthy subjects did not influence plasma aldosterone concentrations. In multiple dose studies with hypertensive patients, there were no clinically significant changes in electrolytes (serum potassium or sodium), or in metabolic function (including serum levels of cholesterol, triglycerides, HDL, LDL, glucose, or uric acid).

In 30 hypertensive patients with normal renal function treated for 8 weeks with telmisartan 80 mg or telmisartan 80 mg in combination with hydrochlorothiazide 12.5 mg, there were no clinically significant changes from baseline in renal blood flow, glomerular filtration rate, filtration fraction, renovascular resistance, or creatinine clearance.

Hydrochlorothiazide

After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours.

Clinical Trials

Telmisartan

The antihypertensive effects of telmisartan have been demonstrated in six principal placebo-controlled clinical trials, studying a range of 20-160 mg; one of these examined the antihypertensive effects of telmisartan and hydrochlorothiazide in combination. The studies involved a total of 1773 patients with mild to moderate hypertension (diastolic blood pressure of 95-114 mmHg), 1031 of whom were treated with telmisartan. Following once daily administration of telmisartan, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (SBP/DBP) 6-8/6 mmHg for 20 mg, 9-13/6-8 mmHg for 40 mg, and 12-13/7-8 mmHg for 80 mg. Larger doses (up to 160 mg) did not appear to cause a further decrease in blood pressure.

Upon initiation of antihypertensive treatment with telmisartan, blood pressure was reduced after the first dose, with a maximal reduction by about 4 weeks. With cessation of treatment with telmisartan tablets, blood pressure gradually returned to baseline values over a period of several days to one week. During long-term studies (without placebo control) the effect of telmisartan appeared to be maintained for up to at least one year. The antihypertensive effect of telmisartan is not influenced by patient age, gender, weight or body mass index. Blood pressure response in black patients (usually a low-renin population) is noticeably less than that in Caucasian patients. This has been true for most, but not all, angiotensin II antagonists and ACE inhibitors. The onset of antihypertensive activity occurs within 3 hours after administration of a single oral dose. At doses of 20, 40, and 80 mg, the antihypertensive effect of once daily administration of telmisartan is maintained for the full 24-hour dose interval. With automated ambulatory blood pressure monitoring and conventional blood pressure measurements, the 24-hour trough-to-peak ratio for 40-80 mg doses of telmisartan was 70-100% for both systolic and diastolic blood pressure. The incidence of symptoma tic orthostasis after the first dose in all controlled trials was low (0.04%).

There were no changes in the heart rate of patients treated with telmisartan in controlled trials.

Telmisartan and Hydrochlorothiazide

In controlled clinical trials with over 2500 patients, 1017 patients were exposed to telmisartan (20 to 160 mg) and concomitant hydrochlorothiazide (6.25 to 25 mg). These trials included one factorial trial with combinations of telmisartan (20, 40, 80, 160 mg, or placebo) and hydrochlorothiazide (6.25, 12.5, 25 mg and placebo). Four other studies of at least six months duration allowed add-on of hydrochlorothiazide for patients who either were not adequately controlled on the randomized monotherapy dose or had not achieved adequate response after completing the up-titration of telmisartan.

The combination of telmisartan and hydrochlorothiazide resulted in additive placebo-adjusted decreases in systolic and diastolic blood pressure at trough of 16-21/9-11 mmHg for doses between 40/12.5 mg and 80/25 mg, compared to 9-13/7-8 mmHg for telmisartan 40 mg to 80 mg and 4/4 mmHg for hydrochlorothiazide 12.5 mg alone.

In active controlled studies, the addition of 12.5 mg hydrochlorothiazide to titrated doses of telmisartan in patients who did not achieve or maintain adequate response with telmisartan monotherapy further reduced systolic and diastolic blood pressure.

The antihypertensive effect was independent of age or gender.

There was essentially no change in heart rate in patients treated with the combination of telmisartan and hydrochlorothiazide in the placebo controlled trial.

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to MICARDIS HCT during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

Symptomatic Hypotension

A patient receiving Micardis® HCT (telmisartan and hydrochlorothiazide) tablets should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patients should be told that if syncope occurs, MICARDIS HCT tablets should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Potassium Supplements

A patient receiving MICARDIS HCT tablets should be told not to use potassium supplements or salt substitutes that contain potassium without consulting the prescribing physician.

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to MICARDIS HCT during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

Symptomatic Hypotension

A patient receiving Micardis® HCT (telmisartan and hydrochlorothiazide) tablets should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patients should be told that if syncope occurs, MICARDIS HCT tablets should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Potassium Supplements

A patient receiving MICARDIS HCT tablets should be told not to use potassium supplements or salt substitutes that contain potassium without consulting the prescribing physician.

Last reviewed on RxList: 1/30/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Micardis HCT 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.

TELMISARTAN/HYDROCHLOROTHIAZIDE - ORAL

(TEL-mi-SAR-tan/HYE-droe-KLOR-oh-THYE-a-zide)

COMMON BRAND NAME(S): Micardis HCT

WARNING: This drug can cause serious (possibly fatal) harm to an unborn baby if used during pregnancy. Therefore, it is important to prevent pregnancy while taking this medication. Consult your doctor for more details and to discuss the use of reliable forms of birth control while taking this medication. If you are planning pregnancy, become pregnant, or think you may be pregnant, contact your doctor immediately.

USES: This medication is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This product contains 2 medications: telmisartan and hydrochlorothiazide. Telmisartan belongs to a class of drugs called angiotensin receptor blockers. It works by relaxing blood vessels so blood can flow more easily. Hydrochlorothiazide is a "water pill" (diuretic). It increases the amount of urine you make, especially when you first start the medication. It also helps to relax the blood vessels so that blood can flow more easily.

These medications are used together when 1 drug alone is not controlling your blood pressure. Your doctor may direct you to start taking the individual medications first, and then switch you over to this combination product if this is the best dose combination for you.

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 treat heart failure and to help protect the kidneys from damage due to diabetes.

HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually once daily. Do not remove the medication from the blister pack until right before using. It is best to avoid taking this medication within 4 hours of your bedtime to avoid having to get up to urinate. Consult your doctor or pharmacist if you have questions about your dosing schedule.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick. It may take up to 4 weeks before you get the full benefit of this drug.

If you also take certain drugs to lower your cholesterol (bile acid-binding resins such as cholestyramine or colestipol), take this product at least 2 hours before or at least 4 hours after these medications.

Tell your doctor if your condition does not improve or if it worsens (such as your blood pressure readings remain high or increase).

Disclaimer

Micardis HCT Consumer (continued)

SIDE EFFECTS: Dizziness and lightheadedness may occur as your body adjusts to the medication. Tiredness and diarrhea may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

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.

This medication may cause a loss of too much body water (dehydration) and salt/minerals. Tell your doctor right away if you have any symptoms of dehydration or mineral loss, including: extreme thirst, very dry mouth, muscle cramps, weakness, fast/irregular heartbeat, confusion.

Tell your doctor right away if you have any serious side effects, including: fainting, unusual change in the amount of urine (not including the normal increase in urine when you first start this drug), toe/joint pain, muscle weakness, decrease in vision, eye pain.

A very serious allergic reaction to this drug is rare. However, get medical help right away 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 Micardis HCT (telmisartan, hydrochlorothiazide) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to telmisartan or hydrochlorothiazide; 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: kidney disease (such as renal artery stenosis), liver disease, bile duct blockage, loss of too much body water and/or minerals (volume depletion, dehydration), untreated mineral imbalance (such as low or high potassium), gout, lupus.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Too much sweating, diarrhea, or vomiting may cause loss of too much body water (dehydration) and increase your risk of dizziness or lightheadedness. Report prolonged diarrhea or vomiting to your doctor. Be sure to drink enough fluids to prevent dehydration unless your doctor directs you otherwise.

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

If you have diabetes, this medication may affect your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst and urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

This product may increase or decrease the potassium levels in your blood. Before using potassium supplements or salt substitutes that contain potassium, consult your doctor or pharmacist.

Hydrochlorothiazide may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Older adults may be more sensitive to the side effects of this drug, especially dizziness and kidney effects.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details. (See also Warning section.)

This medication passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Micardis HCT Consumer (continued)

DRUG INTERACTIONS: See also How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: aliskiren, dofetilide, lithium, drugs that may affect your potassium level (including other diuretics/"water pills" such as spironolactone, birth control products that contain drospirenone), ramipril.

Check the labels on all your medicines (such as cough-and-cold products, diet aids, or NSAIDs such as ibuprofen, naproxen) because they may contain ingredients that could increase your blood pressure or worsen your heart failure. Ask your pharmacist for more details.

This product may interfere with certain laboratory tests (including parathyroid test, protein-bound iodide test), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

OVERDOSE: If overdose is suspected, contact a 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. Symptoms of overdose may include: fast heartbeat, severe dizziness, fainting.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as kidney function, blood mineral levels including potassium) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Lifestyle changes that may help this medication work better include stress reduction programs, exercise, and dietary changes. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Have your blood pressure checked regularly while taking this medication. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

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 away from light and moisture. Do not store in the bathroom. Keep all medications 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.

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

Micardis HCT Patient Information Including Side Effects

Brand Names: Micardis HCT

Generic Name: hydrochlorothiazide and telmisartan (Pronunciation: hye droe klor oh THYE a zide and TEL mi SAR tan)

What is hydrochlorothiazide and telmisartan (Micardis HCT)?

Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

Telmisartan is in a group of drugs called angiotensin II receptor antagonists. Telmisartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.

The combination of hydrochlorothiazide and telmisartan is used to treat high blood pressure (hypertension).

Hydrochlorothiazide and telmisartan may also be used for other purposes not listed in this medication guide.

Micardis 25 mg-80 mg

oblong, white/yellow, imprinted with LOGO H9

What are the possible side effects of hydrochlorothiazide and telmisartan (Micardis HCT)?

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.

In rare cases, hydrochlorothiazide and telmisartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have muscle pain, tenderness, or weakness especially if you also have fever, nausea or vomiting, and dark colored urine.

Stop using this medication and call your doctor at once if you have any other serious side effects, such as:

  • eye pain, vision problems;
  • feeling light-headed, fainting;
  • swelling, rapid weight gain;
  • fast or pounding heartbeats;
  • urinating less than usual, or not at all;
  • jaundice (yellowing of the skin or eyes); or
  • dry mouth, increased thirst, drowsiness, restless feeling, confusion, increased urination, fast heart rate, fainting, or seizure (convulsions).

Less serious side effects may include:

  • stomach pain, diarrhea;
  • back pain;
  • headache, tired feeling, dizziness;
  • skin rash;
  • stuffy nose, sore throat; or
  • dry cough.

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 Micardis HCT (telmisartan, hydrochlorothiazide) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about hydrochlorothiazide and telmisartan (Micardis HCT)?

Do not use this medication if you are allergic to hydrochlorothiazide or telmisartan, or if you are unable to urinate.

Before using hydrochlorothiazide and telmisartan, tell your doctor if you have congestive heart failure, kidney or liver disease, glaucoma, asthma, low or high blood levels of potassium, gout, lupus, diabetes, or an allergy to sulfa drugs or penicillin.

Avoid drinking alcohol. It can lower your blood pressure and may increase some of the side effects of hydrochlorothiazide and telmisartan.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

Do not use potassium supplements or salt substitutes while you are taking hydrochlorothiazide and telmisartan, unless your doctor has told you to.

In rare cases, hydrochlorothiazide and telmisartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have muscle pain, tenderness, or weakness especially if you also have fever, nausea or vomiting, and dark colored urine.

Side Effects Centers

Micardis HCT Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking hydrochlorothiazide and telmisartan (Micardis HCT)?

Do not use this medication if you are allergic to hydrochlorothiazide or telmisartan, or if you are unable to urinate.

Before using hydrochlorothiazide and telmisartan, tell your doctor if you have:

  • kidney disease;
  • liver disease;
  • congestive heart failure;
  • glaucoma;
  • asthma or allergies;
  • low or high levels of magnesium or potassium in your blood;
  • gout;
  • lupus,
  • diabetes; or
  • an allergy to sulfa drugs or penicillin.

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

FDA pregnancy category D. This medication can cause harm to an unborn baby. Do not use this medication without telling your doctor if you are pregnant. Telmisartan may cause injury and even death to the unborn baby if you take it during the second and third trimesters of pregnancy. Use an effective form of birth control. Stop using this medication and tell your doctor right away if you become pregnant during treatment.

It is not known whether hydrochlorothiazide and telmisartan passes into breast milk. Do not take this medication without first talking to your doctor if you are breast-feeding a baby.

How should I take hydrochlorothiazide and telmisartan (Micardis HCT)?

Take this medication 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.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Take this medication with a full glass (8 ounces) of water.

To be sure this medication is helping your condition, your blood pressure will need to be checked on a regular basis. Do not miss any scheduled appointments.

Hydrochlorothiazide can interfere with the results of a thyroid test. Tell any doctor who treats you that you are using this medication.

If you are being treated for high blood pressure, keep using this medication even if you feel fine. High blood pressure often has no symptoms.

Store hydrochlorothiazide and telmisartan at room temperature away from moisture and heat.

Side Effects Centers

Micardis HCT Patient Information including If I Miss a Dose

What happens if I miss a dose (Micardis HCT)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Micardis HCT)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include fast or slow heartbeat, feeling light-headed, or fainting.

What should I avoid while taking hydrochlorothiazide and telmisartan (Micardis HCT)?

Avoid drinking alcohol. It can lower your blood pressure and may increase some of the side effects of hydrochlorothiazide and telmisartan.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

Do not use potassium supplements or salt substitutes while you are taking hydrochlorothiazide and telmisartan, unless your doctor has told you to.

What other drugs will affect hydrochlorothiazide and telmisartan (Micardis HCT)?

Before taking hydrochlorothiazide and telmisartan, tell your doctor if you are using any of the following drugs:

  • any other blood pressure medications;
  • digoxin (digitalis, Lanoxin, Lanoxicaps);
  • a blood thinner such as warfarin (Coumadin, Jantoven);
  • steroids (prednisone and others);
  • lithium (Eskalith, Lithobid);
  • cholestyramine (Prevalite, Questran) or colestipol (Colestid);
  • insulin or diabetes medications you take by mouth;
  • a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Luminal, Solfoton);
  • any other diuretics, such as amiloride (Midamor), bumetanide (Bumex), chlorthalidone (Hygroton, Thalitone), ethacrynic acid (Edecrin), furosemide (Lasix), hydrochlorothiazide (HCTZ, HydroDiuril), indapamide (Lozol), metolazone (Mykrox, Zarxolyn), spironolactone (Aldactone), triamterene (Dyrenium, Maxzide, Dyazide), torsemide (Demadex), and others;
  • aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil), diclofenac (Voltaren), diflunisal (Dolobid), etodolac (Lodine), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis), ketorolac (Toradol), mefenamic acid (Ponstel), meloxicam (Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), piroxicam (Feldene), and others;
  • a muscle relaxer such as baclofen (Lioresal), carisoprodol (Soma), cyclobenzaprine (Flexeril), dantrolene (Dantrium), metaxalone (Skelaxin), or methocarbamol (Robaxin), orphenadrine (Norflex), or tizanidine (Zanaflex);
  • a narcotic medication such as hydrocodone (Lortab, Vicodin), hydromorphone (Dilaudid, Palladone), levorphanol (Levo-Dromoran), meperidine (Demerol), methadone (Methadose), morphine (Kadian, MS Contin), oxycodone (OxyContin), oxymorphone (Numorphan), or propoxyphene (Darvon, Darvocet).

This list is not complete and there may be other drugs that can interact with hydrochlorothiazide and telmisartan. 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.

Where can I get more information?

Your pharmacist can provide more information about hydrochlorothiazide and telmisartan.


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: 4.01. Revision date: 7/6/2011.

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