Telmisartan And Hydrochlorothiazide
FDA Drug Information • Also known as: Micardis Hct, Telmisartan And Hydrochlorothiazide
- Brand Names
- Micardis Hct, Telmisartan And Hydrochlorothiazide
- Drug Class
- Thiazide Diuretic [EPC], Angiotensin 2 Receptor Blocker [EPC]
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue telmisartan and hydrochlorothiazide as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations ( 8.1 )] . Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) and Use in Specific Populations ( 8.1 )] . WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue telmisartan and hydrochlorothiazide as soon as possible. ( 5.1 , 8.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 , 8.1 )
Description
11 DESCRIPTION Telmisartan and hydrochlorothiazide tablets USP 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 molecular formula is C 33 H 30 N 4 O 2 , its molecular weight is 514.63, and its structural formula is: Telmisartan USP is a white or slightly yellowish, crystalline powder. It is sparingly soluble in methylene chloride, slightly soluble in methanol, practically insoluble in water. It dissolves in 1M sodium hydroxide. Hydrochlorothiazide USP is white or practically white, practically odorless, crystalline powder with a molecular weight of 297.74. It is slightly soluble in water, freely soluble in sodium hydroxide solution, in n-butylamine and in dimethylformamide; sparingly soluble in methanol; insoluble in ether, in chloroform and in dilute mineral acids. Hydrochlorothiazide is chemically described as 6-chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its molecular formula is C 7 H 8 ClN 3 O 4 S 2 , and its structural formula is: Telmisartan and hydrochlorothiazide tablets USP 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: colloidal silicon dioxide, hydroxypropyl cellulose, lactose monohydrate, mannitol, meglumine, povidone, sodium hydroxide pellets and sodium stearyl fumarate. In addition, the 40 mg/12.5 mg and 80 mg/12.5 mg tablets contain red ferric oxide and the 80 mg/25 mg tablets contain yellow ferric oxide. Telmisartan and hydrochlorothiazide tablets USP are hygroscopic and require protection from moisture. Meets USP dissolution test 3. Chemical Structure1 Chemical Structure2
What Is Telmisartan And Hydrochlorothiazide Used For?
1 INDICATIONS AND USAGE Telmisartan and hydrochlorothiazide tablets are 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 telmisartan and hydrochlorothiazide tablets. 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) ]. Telmisartan and hydrochlorothiazide tablets are not indicated for initial therapy for the treatment of hypertension [see Dosage and Administration (2.1) ]. Telmisartan and hydrochlorothiazide tablets may be used alone or in combination with other antihypertensive agents. Telmisartan and hydrochlorothiazide tablets are a...
Dosage and Administration
2 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 telmisartan and hydrochlorothiazide tablets, 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 telmisartan and hydrochlorothiazide tablets 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 telmisartan and hydrochlorothiazide tablets. Telmisartan and hydrochlorothiazide tablets 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. Telmisartan and hydrochlorothiazide 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 Telmisartan and hydrochlorothiazide tablets should not be removed from blisters until immediately before administration.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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 Aurobindo Pharma USA, Inc. at 1-866-850-2876 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. Telmisartan and hydrochlorothiazide 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,...
Drug Interactions
7 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 telmisartan and hydrochlorothiazide 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 telmisartan and hydrochlorothiazide 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 telmisartan and hydrochlorothiazide 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...
Contraindications
4 CONTRAINDICATIONS Telmisartan and hydrochlorothiazide tablets are 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 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Telmisartan and hydrochlorothiazide 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 telmisartan and hydrochlorothiazide 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...
Overdosage
10 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Telmisartan and hydrochlorothiazide tablets USP are available in three strengths as: 40 mg/12.5 mg tablet: white to off-white and red colored bilayered oblong shaped biconvex tablets debossed with “H” on one side and “71” on the other side. The white to off-white layer may contain red specks. Cartons of 30 (3 x 10) Unit-dose Tablets NDC 65862-976-03 80 mg/12.5 mg tablet: white to off-white and red colored bilayered oblong shaped biconvex tablets debossed with “H” on one side and “72” on the other side. The white to off-white layer may contain red specks. Cartons of 30 (3 x 10) Unit-dose Tablets NDC 65862-977-03 80 mg/25 mg tablet: white to off-white and yellow colored bilayered oblong shaped biconvex tablets debossed with “H” on one side and “76” on the other side. The white to off-white layer may contain yellow specks. Cartons of 30 (3 x 10) Unit-dose Tablets NDC 65862-978-03 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Tablets should not be removed from blisters until immediately before administration.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.