Micardis HCT
telmisartan and hydrochlorothiazide · Tablet · Oral
Uses
(telmisartan and hydrochlorothiazide) is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the classes to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with MICARDIS HCT. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy [see Clinical Studies (14) ]. MICARDIS HCT is not indicated for initial therapy for the treatment of hypertension [see Dosage and Administration (2.1) ]. MICARDIS HCT may be used alone or in combination with other antihypertensive agents. MICARDIS HCT is a combination of an angiotensin II receptor blocker (ARB) and a thiazide diuretic indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1 ) MICARDIS HCT is not indicated for initial therapy ( 1 )
Dosage and administration
Usual starting dose is 80 mg/12.5 mg once daily ( 2.1 ) Titrate up to 160 mg/25 mg as needed ( 2.1 ) Initiate patients with biliary obstructive disorders or hepatic insufficiency at 40 mg/12.5 mg ( 2.2 ) 2.1 Dosing Information Initiate a patient whose blood pressure is not adequately controlled with telmisartan monotherapy 80 mg on MICARDIS HCT, 80 mg/12.5 mg orally once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary. Initiate a patient whose blood pressure is not adequately controlled by 25 mg once daily of hydrochlorothiazide, or is controlled but who experiences hypokalemia with this regimen on MICARDIS HCT 80 mg/12.5 mg once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary. Patients titrated to the individual components (telmisartan and hydrochlorothiazide) may instead receive the corresponding dose of MICARDIS HCT. MICARDIS HCT may be administered with other antihypertensive drugs. 2.2 Dose Adjustment for Hepatic Impairment Initiate patients with biliary obstructive disorders or hepatic insufficiency under close medical supervision using the 40 mg/12.5 mg combination. MICARDIS HCT tablets are not recommended for patients with severe hepatic impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ]. 2.3 Important Administration Instructions MICARDIS HCT tablets should not be removed from blisters until immediately before administration.
Dosage forms and strengths
40 mg/12.5 mg, red and white tablets marked with the Boehringer Ingelheim logo and "H4" 80 mg/12.5 mg, red and white tablets marked with the Boehringer Ingelheim logo and "H8" 80 mg/25 mg, yellow and white tablets marked with the Boehringer Ingelheim logo and "H9" Tablets: 40 mg/12.5 mg, 80 mg/12.5 mg, 80 mg/25 mg ( 3 )
Contraindications
4 CONTRAINDICATIONS MICARDIS HCT is contraindicated: In patients who are hypersensitive to any component of this product [see Warnings and Precautions (5.5) ]. In patients with anuria. For co-administration with aliskiren in patients with diabetes [see Drug Interactions (7.4) ]. Hypersensitivity to telmisartan or any component ( 4 ) Anuria ( 4 ) Co-Administration with aliskiren in patients with diabetes ( 4 )
Warnings and precautions
Avoid fetal or neonatal exposure ( 5.1 ) Correct volume or salt depletion before initiating therapy. Observe for signs and symptoms of hypotension. ( 5.2 ) Monitor renal function and potassium in susceptible patients ( 5.3 ) Observe for clinical signs of fluid or electrolyte imbalance ( 5.4 ) Hypersensitivity Reaction ( 5.5 ) Acute Myopia and Secondary Angle-Closure Glaucoma ( 5.6 ) 5.1 Fetal Toxicity Telmisartan 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. Hydrochlorothiazide Thiazides cross the placental barrier and appear in cord blood. Adverse reactions include fetal or neonatal jaundice and thrombocytopenia [see Use in Specific Populations (8.1) ]. 5.2 Hypotension in Volume- or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initialization of treatment with MICARDIS HCT. Correct volume or salt depletion prior to administration of MICARDIS HCT. 5.3 Impaired Renal Function Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing oliguria, progressive azotemia, or acute renal failure on MICARDIS HCT. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on MICARDIS HCT. 5.4 Electrolytes and Metabolic Disorders Drugs, including telmisartan, that inhibit the renin-angiotensin system can cause hyperkalemia, particularly in patients with renal insufficiency, diabetes, or combination use with other angiotensin receptor blockers or ACE inhibitors and the concomitant use of other drugs that raise serum potassium levels [see Drug Interactions (7.1 , 7.4) ] . Hydrochlorothiazide can cause hypokalemia and hyponatremia. Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Hypomagnesemia can result in hypokalemia which may be difficult to treat despite potassium repletion. Monitor serum electrolytes periodically. In controlled trials using the telmisartan/hydrochlorothiazide combination treatment, no patient administered 40 mg/12.5 mg, 80 mg/12.5 mg, or 80 mg/25 mg experienced a decrease in potassium ≥1.4 mEq/L, and no patient experienced hyperkalemia. Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides. Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy. Because telmisartan decreases uric acid, telmisartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia. 5.5 Hypersensitivity Reaction Hydrochlorothiazide 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 [see Contraindications (4) ]. 5.6 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 acute 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. 5.7 Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus. 5.8 Postsympathectomy Patients The antihypertensive effects of hydrochlorothiazide may be enhanced in the postsympathectomy patient.
Side effects
The following adverse reactions are discussed elsewhere in labeling: Hypotension [see Warnings and Precautions (5.2) ] Renal Impairment [see Warnings and Precautions (5.3) ] Electrolytes and Metabolic Disorders [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥2% of patients) were upper respiratory tract infection, dizziness, sinusitis, diarrhea, fatigue, influenza-like symptoms, and nausea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. MICARDIS HCT has been evaluated for safety in more than 1700 patients, including 716 treated for hypertension for longer than 6 months and 420 for more than 1 year. Adverse reactions have been limited to those that have been previously reported with telmisartan and/or hydrochlorothiazide. Adverse reactions occurring at an incidence of ≥2% in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo, are presented in Table 1 [see Clinical Studies (14) ]. Table 1 Adverse Reactions Occurring at an Incidence of ≥2% in Patients Treated with Telmisartan/Hydrochlorothiazide and at a Greater Rate Than in Patients Treated with Placebo* * includes all doses of telmisartan (20 to 160 mg), hydrochlorothiazide (6.25 to 25 mg), and combinations thereof Telmisartan/Hydrochlorothiazide (n = 414) Placebo (n = 74) Telmisartan (n = 209) Hydrochlorothiazide (n = 121) Body as a whole Fatigue 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% Other adverse reactions observed for telmisartan/hydrochlorothiazide were: pain (including back and abdominal), dyspepsia, erythema, vomiting, bronchitis, and pharyngitis. Adverse reactions occurred at approximately the same rates in men and women, older and younger patients, and black and non-black patients. Telmisartan Other adverse events that have been reported with telmisartan are listed below: Autonomic Nervous System: impotence, increased sweating, flushing Body as a Whole: allergy, fever, leg pain, chest pain Cardiovascular: palpitation, angina pectoris, abnormal ECG, hypertension, peripheral edema Central Nervous System: insomnia, somnolence, migraine, paresthesia, involuntary muscle contractions, hypoesthesia Gastrointestinal: flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroesophageal reflux, toothache Hepato-biliary: elevations of liver enzymes or serum bilirubin Metabolic: gout, hypercholesterolemia, diabetes mellitus Musculoskeletal: arthritis, arthralgia, leg cramps, myalgia Psychiatric: anxiety, depression, nervousness Resistance Mechanism: 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 Hydrochlorothiazide Other adverse events that have been reported with hydrochlorothiazide 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 Musculoskeletal: muscle spasm Nervous System/Psychiatric: restlessness Renal: interstitial nephritis Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis Special Senses: transient blurred vision, xanthopsia Clinical Laboratory Findings 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 because of an increase in BUN or creatinine [see Warnings and Precautions (5.3) ] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of MICARDIS HCT. 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.
Drug interactions
Lithium: Risk of lithium toxicity ( 7.2 ) Non-steroidal anti-inflammatory drugs (NSAIDs): Reduced diuretic, natriuretic, and antihypertensive effects; increased risk of renal impairment ( 7.3 ) Dual blockade of renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.4 ) Antidiabetic drugs: Dosage adjustment may be required ( 7.6 ) Cholestyramine and colestipol: Reduced absorption of thiazides ( 7.7 ) 7.1 Agents Increasing Serum Potassium Co-administration of telmisartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. 7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of thiazide diuretics or angiotensin II receptor antagonists, including telmisartan. Monitor lithium levels in patients receiving MICARDIS HCT and lithium. 7.3 Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors Telmisartan 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 ARBs, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. The antihypertensive effect of ARBs may be attenuated by NSAIDs. Therefore, monitor renal function and blood pressure periodically in patients receiving MICARDIS HCT and NSAIDs. Hydrochlorothiazide Administration of a non-steroidal anti-inflammatory agent, including a selective COX-2 inhibitor, can reduce the diuretic, natriuretic, and antihypertensive effects of diuretics. Therefore, when MICARDIS HCT and non-steroidal anti-inflammatory agents including selective COX-2 inhibitors are used concomitantly, observe closely to determine if the desired effect of the diuretic is obtained. 7.4 Dual Blockade of the Renin-Angiotensin-Aldosterone System and Changes in Renal Function Dual blockade of the renin-angiotensin-aldosterone system (RAS) with angiotensin blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and renal impairment. The ONTARGET trial enrolled 25,620 patients ≥55 years old with atherosclerotic disease or diabetes with end-organ damage, randomizing them to telmisartan (ARB) only, ramipril (ACE inhibitor) only, or the combination, and followed them for a median of 56 months. Patients who received the combination of ARB and ACE inhibitor did not obtain any additional benefit (no additional reduction of risk of cardiovascular death, myocardial infarction, stroke, or hospitalization from heart failure) compared to ARB monotherapy or ACE inhibitor monotherapy, but experienced an increased incidence of renal dysfunction (e.g., acute renal failure) compared with monotherapy groups. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on MICARDIS HCT and other agents that affect the RAS. Do not co-administer aliskiren with MICARDIS HCT in patients with diabetes. Avoid concomitant use of aliskiren with MICARDIS HCT in patients with renal impairment (GFR <60 mL/min/1.73 m 2 ). 7.5 Digoxin When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. Monitor digoxin levels in patients taking concomitant MICARDIS HCT and digoxin. 7.6 Antidiabetic Drugs (Oral Agents and Insulin) Dosage adjustment of antidiabetic drugs may be required when co-administered with hydrochlorothiazide. 7.7 Cholestyramine and Colestipol Resins Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Stagger the dosage of hydrochlorothiazide and the resin such that hydrochlorothiazide is administered at least 4 hours before or 4 to 6 hours after the administration of the resin.
Use in specific populations
Lactation: Do not breastfeed during treatment with MICARDIS HCT ( 8.2 ) Severe Hepatic Impairment: Use not recommended ( 8.6 ) Severe Renal Impairment: Use not recommended ( 8.7 ) 8.1 Pregnancy Risk Summary MICARDIS HCT can cause fetal harm when administered to a pregnant woman. 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 (see Clinical Considerations ) . 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. Studies in rats and rabbits with telmisartan showed fetotoxicity only at maternally toxic doses (see Data ) . When pregnancy is detected, discontinue MICARDIS HCT as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal adverse reactions Telmisartan Use of drugs that act on the RAS in the second and third trimesters of pregnancy can result in the following: oligohydramnios, reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. In patients taking MICARDIS HCT during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If oligohydramnios is observed, discontinue MICARDIS HCT, unless it is considered lifesaving for the mother. 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. If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function [see Use in Specific Populations (8.4) ] . Hydrochlorothiazide Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults. Data Animal Data MICARDIS HCT A developmental toxicity study was performed in rats with telmisartan/hydrochlorothiazide doses of 3.2/1.0, 15/4.7, 50/15.6, and 0/15.6 mg/kg/day. Although the two higher dose combinations appeared to be more toxic (significant decrease in body weight gain) to the dams than either drug alone, there did not appear to be an increase in toxicity to the developing embryos. Telmisartan 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 of up to 45 mg/kg/day. In rabbits, embryo lethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed at 45 mg/kg/day (approximately 12 times the maximum recommended human dose [MRHD] of 80 mg on a mg/m 2 basis). In rats, maternally toxic (reduced body weight gain and food consumption) telmisartan doses of 15 mg/kg/day (approximately 1.9 times the MRHD on a mg/m 2 basis), administered during late gestation and lactation, were observed to produce adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, and decreased weight gain. The no-observed-effect doses for developmental toxicity in rats and rabbits, 5 and 15 mg/kg/day, respectively, are approximately 0.64 and 3.7 times, respectively, on a mg/m 2 basis, the MRHD of telmisartan (80 mg/day). Hydrochlorothiazide Studies in which hydrochlorothiazide was administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the MRHD), provided no evidence of harm to the fetus. Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. It accumulates in the amniotic fluid, with reported concentrations up to 19 times that in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women. The use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided. 8.2 Lactation Risk Summary There is no information regarding the presence of MICARDIS HCT or telmisartan in human milk, the effects on the breastfed infant or the effects on milk production.
Pregnancy
8.1 Pregnancy Risk Summary MICARDIS HCT can cause fetal harm when administered to a pregnant woman. 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 (see Clinical Considerations ) . 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. Studies in rats and rabbits with telmisartan showed fetotoxicity only at maternally toxic doses (see Data ) . When pregnancy is detected, discontinue MICARDIS HCT as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal adverse reactions Telmisartan Use of drugs that act on the RAS in the second and third trimesters of pregnancy can result in the following: oligohydramnios, reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. In patients taking MICARDIS HCT during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If oligohydramnios is observed, discontinue MICARDIS HCT, unless it is considered lifesaving for the mother. 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. If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function [see Use in Specific Populations (8.4) ] . Hydrochlorothiazide Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults. Data Animal Data MICARDIS HCT A developmental toxicity study was performed in rats with telmisartan/hydrochlorothiazide doses of 3.2/1.0, 15/4.7, 50/15.6, and 0/15.6 mg/kg/day. Although the two higher dose combinations appeared to be more toxic (significant decrease in body weight gain) to the dams than either drug alone, there did not appear to be an increase in toxicity to the developing embryos. Telmisartan 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 of up to 45 mg/kg/day. In rabbits, embryo lethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed at 45 mg/kg/day (approximately 12 times the maximum recommended human dose [MRHD] of 80 mg on a mg/m 2 basis). In rats, maternally toxic (reduced body weight gain and food consumption) telmisartan doses of 15 mg/kg/day (approximately 1.9 times the MRHD on a mg/m 2 basis), administered during late gestation and lactation, were observed to produce adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, and decreased weight gain. The no-observed-effect doses for developmental toxicity in rats and rabbits, 5 and 15 mg/kg/day, respectively, are approximately 0.64 and 3.7 times, respectively, on a mg/m 2 basis, the MRHD of telmisartan (80 mg/day). Hydrochlorothiazide Studies in which hydrochlorothiazide was administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the MRHD), provided no evidence of harm to the fetus. Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. It accumulates in the amniotic fluid, with reported concentrations up to 19 times that in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women. The use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided.
Pediatric use
8.4 Pediatric Use Safety and effectiveness of MICARDIS HCT in pediatric patients have not been established. Neonates with a history of in utero exposure to MICARDIS HCT: If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.
Geriatric use
8.5 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant diseases or other drug therapy.
Overdosage
Telmisartan Limited data are available with regard to overdosage of telmisartan in humans. The most likely manifestations of overdosage with telmisartan are 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 hemofiltration and is not dialyzable. Hydrochlorothiazide The most common signs and symptoms observed in patients with a hydrochlorothiazide overdose 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 LD 50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.
Description
11 DESCRIPTION MICARDIS HCT tablets are a combination of telmisartan, an orally active angiotensin II antagonist acting on the AT 1 receptor subtype, and hydrochlorothiazide, a thiazide diuretic. Telmisartan, a non-peptide molecule, is chemically described as 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Its empirical formula is C 33 H 30 N 4 O 2 , its molecular weight is 514.63, and its structural formula is: 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-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C 7 H 8 ClN 3 O 4 S 2 , and its structural formula is: 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, and 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 tablets are hygroscopic and require protection from moisture. Chemical Structure Chemical Structure
Mechanism of action
12.1 Mechanism of Action MICARDIS HCT MICARDIS HCT is a combination of two drugs with antihypertensive properties: a thiazide diuretic, hydrochlorothiazide, and an angiotensin II receptor blocker (ARB), telmisartan. Telmisartan 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 aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 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 AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000-fold) for the AT 1 receptor than for the AT 2 receptor. Telmisartan does not inhibit ACE (kininase II) nor does it 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 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 co-administration of an ARB tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is not fully understood.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING MICARDIS HCT is available in three strengths as biconvex two-layered, oblong-shaped, uncoated tablets containing telmisartan and hydrochlorothiazide: 40 mg/12.5 mg tablet: red and white (may contain red specks) marked with the Boehringer Ingelheim company symbol and "H4"; individually blister-sealed in cartons of 30 tablets as 3 × 10 cards (NDC 0597-0043-37) 80 mg/12.5 mg tablet: red and white (may contain red specks) marked with the Boehringer Ingelheim company symbol and "H8"; individually blister-sealed in cartons of 30 tablets as 3 × 10 cards (NDC 0597-0044-37) 80 mg/25 mg tablet: yellow and white (may contain yellow specks) marked with the Boehringer Ingelheim company symbol and "H9"; individually blister-sealed in cartons of 30 tablets as 3 × 10 cards (NDC 0597-0042-37) Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Tablets should not be removed from blisters until immediately before administration.
Storage
Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Tablets should not be removed from blisters until immediately before administration.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Pregnancy Advise female patients of childbearing age about the consequences of exposure to MICARDIS HCT during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . Lactation Advise nursing women not to breastfeed during treatment with MICARDIS HCT [see Use in Specific Populations (8.2) ]. Symptomatic Hypotension and Syncope Advise patients that lightheadedness can occur, especially during the first days of therapy, and to report it to their healthcare provider. Inform patients 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. Advise patients to contact their healthcare provider if syncope occurs [see Warnings and Precautions (5.2) ] . Potassium Supplements Advise patients not to use potassium supplements or salt substitutes that contain potassium without consulting the prescribing healthcare provider [see Warnings and Precautions (5.4) and Drug Interactions (7.1) ]. Acute Myopia and Secondary Angle-Closure Glaucoma Advise patients to discontinue MICARDIS HCT and seek immediate medical attention if they experience symptoms of Acute Myopia or Secondary Angle-Closure Glaucoma [see Warnings and Precautions (5.6) ] . Non-melanoma Skin Cancer Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening.
Label text from the FDA structured product label by Boehringer Ingelheim Pharmaceuticals, Inc. (revised Dec 31, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Telmisartan in 3 products
- Hydrochlorothiazide in 3 products
Micardis HCT NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0597-0042 | Telmisartan 80 mg/1; Hydrochlorothiazide 25 mg/1 Tablet | Boehringer Ingelheim Pharmaceuticals, Inc. | NDA |
| 0597-0043 | Telmisartan 40 mg/1; Hydrochlorothiazide 12.5 mg/1 Tablet | Boehringer Ingelheim Pharmaceuticals, Inc. | NDA |
| 0597-0044 | Telmisartan 80 mg/1; Hydrochlorothiazide 12.5 mg/1 Tablet | Boehringer Ingelheim Pharmaceuticals, Inc. | NDA |
Frequently asked questions
What is Micardis HCT used for?
(telmisartan and hydrochlorothiazide) is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the classes to which…
What are the side effects of Micardis HCT?
The following adverse reactions are discussed elsewhere in labeling: Hypotension [see Warnings and Precautions (5.2) ] Renal Impairment [see Warnings and Precautions (5.3) ] Electrolytes and Metabolic Disorders [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥2% of patients) were upper respiratory tract infection, dizziness, sinusitis, diarrhea, fatigue, influenza-like… See the full label for the complete list.
Who makes Micardis HCT?
Micardis HCT is listed by 1 labeler in the FDA NDC directory, including Boehringer Ingelheim Pharmaceuticals, Inc..