Telmisartan and Hydrochlorothiazide: Package Insert and Label Information

TELMISARTAN AND HYDROCHLOROTHIAZIDE- hydrochlorothiazide and telmisartan tablet
Lupin Pharmaceuticals, Inc.

WARNING: FETAL TOXICITY

  • When pregnancy is detected, discontinue telmisartan and hydrochlorothiazide tablets 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)].

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.

2 DOSAGE AND ADMINISTRATION

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 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.

3 DOSAGE FORMS AND STRENGTHS

  • 40 mg/12.5 mg: supplied as oval shaped, biconvex, bilayer, uncoated tablets; where hydrochlorothiazide layer is red coloured and telmisartan layer is white to off-white in colour but may have red specks; debossed with ‘M31’ on one side and ‘LU’ on other side.
  • 80 mg/12.5 mg: supplied as capsule shaped, biconvex, bilayer, uncoated tablets; where hydrochlorothiazide layer is red coloured and telmisartan layer is white to off-white in colour but may have red specks; debossed with ‘M32’ on one side and ‘LU’ on other side.
  • 80 mg/25 mg: supplied as capsule shaped, biconvex, bilayer, uncoated tablets; where hydrochlorothiazide layer is yellow coloured and telmisartan layer is white to off-white in colour but may have yellow specks; debossed with ‘M33’ on one side and ‘LU’ on other side.

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)].

5 WARNINGS AND PRECAUTIONS

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 telmisartan and hydrochlorothiazide tablets 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 telmisartan and hydrochlorothiazide tablets. Correct volume or salt depletion prior to administration of telmisartan and hydrochlorothiazide tablets.

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 telmisartan and hydrochlorothiazide tablets. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on telmisartan and hydrochlorothiazide tablets.

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.

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)]

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 tablets 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-likesymptoms 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 tractinfection 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 telmisartan and hydrochlorothiazide tablets in controlled trials. No patient discontinued treatment with telmisartan and hydrochlorothiazide tablets because of an increase in BUN or creatinine [see Warnings and Precautions (5.3)].

Page 1 of 4 1 2 3 4

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2021. All Rights Reserved.