Telmisartan, Amlodipine, and Indapamide (Monograph)

Brand name: Widaplik
Drug class: Angiotensin II Receptor Antagonists

Introduction

Telmisartan, amlodipine, and indapamide (telmisartan/amlodipine/indapamide) is a fixed-combination preparation containing telmisartan (an angiotensin II receptor blocker), amlodipine (a dihydropyridine calcium channel blocker), and indapamide (a thiazide-like diuretic).

Uses for Telmisartan, Amlodipine, and Indapamide

Telmisartan, amlodipine, and indapamide has the following uses:

Telmisartan/amlodipine/indapamide is indicated for the treatment of hypertension in adult patients, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

Telmisartan, Amlodipine, and Indapamide Dosage and Administration

General

Telmisartan, amlodipine, and indapamide is available in the following dosage form(s) and strength(s):

Fixed-combination tablets (telmisartan/amlodipine/indapamide) in the following strengths:

• 10 mg/1.25 mg/0.625 mg

• 20 mg/2.5 mg/1.25 mg

• 40 mg/5 mg/2.5 mg

Dosage

Adults

Dosage and Administration

• Administer orally once daily.

• Swallow tablets whole. Do not cut, crush, or chew tablets. Telmisartan/amlodipine/indapamide may be taken with or without food.

• Correct imbalances of intravascular volume- or salt-depletion, before initiating therapy.

• Dosage must be individualized. For initial treatment of hypertension, start with telmisartan/amlodipine/indapamide (10 mg/1.25 mg/0.625 mg) or telmisartan/amlodipine/indapamide (20 mg/2.5 mg/1.25 mg) orally once daily.

• Dosage may be increased after 2 weeks to a maximum dose of 40 mg/5 mg/2.5 mg orally once daily to achieve more rapid blood pressure control.

• Almost all the antihypertensive effect is apparent within 2 weeks of initiating treatment.

Cautions for Telmisartan, Amlodipine, and Indapamide

Contraindications

• Known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan/amlodipine/indapamide, or to other sulfonamide-derived drugs, or to any other component of this product.

• Do not co-administer aliskiren with telmisartan/amlodipine/indapamide in patients with diabetes.

Warnings/Precautions

Warnings

Fetal Toxicity

Use of drugs that act on the renin-angiotensin-aldosterone 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/amlodipine/indapamide as soon as possible.

Hypotension

Telmisartan/amlodipine/indapamide can cause symptomatic hypotension. Patients with hypovolemia, salt depletion, or aortic stenosis are at increased risk. Monitor blood pressure and adjust dose as needed. Hypotension leading to worsening angina and acute myocardial infarction can develop after starting or increasing the dose of telmisartan/amlodipine/indapamide because of the amlodipine component, particularly in patients with severe obstructive coronary artery disease.

Electrolyte and Glucose Imbalances

Thiazide-like diuretics can cause hyponatremia, hypomagnesemia, and hypokalemia and can also alter serum glucose and affect insulin requirements. Drugs that inhibit the renin angiotensin-aldosterone system can cause hyperkalemia. Patients with renal impairment or heart failure are at increased risk for hyperkalemia. Monitor serum electrolytes and glucose periodically.

Impaired Renal Function

Inhibiting the renin-angiotensin-aldosterone system or diuresis can precipitate renal dysfunction, oliguria and acute renal failure. Patients with severe congestive heart failure or renal dysfunction are at increased risk. Monitor renal function periodically and adjust dose as needed.

Acute Angle-Closure Glaucoma, Acute Myopia, and Choroidal Effusion

Sulfonamide or sulfonamide-derivative drugs, like indapamide, can cause an idiosyncratic reaction resulting in acute angle-closure glaucoma and elevated intraocular pressure with or without a noticeable acute myopic shift and/or choroidal effusions. Symptoms may include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated, the angle-closure glaucoma may result in permanent visual field loss. The primary treatment is to discontinue telmisartan/amlodipine/indapamide 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.

Hyperuricemia

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide-like diuretics.

Specific Populations

Pregnancy

Telmisartan/amlodipine/indapamide can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin-aldosterone system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin-aldosterone system from other antihypertensive agents. Studies in rats and rabbits showed fetotoxicity only at maternally toxic doses of telmisartan. When pregnancy is detected, discontinue telmisartan/amlodipine/indapamide 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 malformations and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively.

Lactation

There is no information regarding the presence of telmisartan/amlodipine/indapamide in human milk, the effects on the breastfed infant, or the effects on milk production. Limited published studies report that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine on milk production. There is no information regarding the presence of telmisartan in human milk. Telmisartan is present in the milk of lactating rats. It is not known whether indapamide is excreted in human milk. Because of the potential for serious adverse reactions in the breastfed infant including hypotension, hyperkalemia and renal impairment, advise a nursing woman not to breastfeed during treatment with telmisartan/amlodipine/indapamide.

Pediatric Use

Safety and effectiveness of telmisartan/amlodipine/indapamide in pediatric patients have not been established.

Geriatric Use

In subgroup analysis in subjects ≥65 years of age (n= 176), the antihypertensive effect of telmisartan/amlodipine/indapamide was not substantially different compared to younger subjects; however, the number of elderly patients enrolled in both telmisartan/amlodipine/indapamide studies was small.

Hepatic Impairment

Because telmisartan, amlodipine and indapamide are hepatically cleared, initiate therapy at the lowest dose and titrate slowly. The use of thiazide-like diuretics may precipitate hepatic coma because of fluid shifts.

Renal Impairment

Renal impairment does not increase the AUC of telmisartan. Telmisartan is not removed from blood by hemodialysis. The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. The effect of renal impairment on the pharmacokinetics of indapamide is unknown.

Common Adverse Effects

The most common adverse reaction is symptomatic hypotension. Low sodium and potassium values were recorded more often with telmisartan/amlodipine/indapamide compared to placebo.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• NSAIDs: Increased risk of renal impairment and loss of anti-hypertensive effect.

• If simvastatin is co-administered with telmisartan/amlodipine/indapamide, do not exceed doses greater than 20 mg daily of simvastatin.

• Do not co-administer aliskiren with telmisartan/amlodipine/indapamide in patients with diabetes.

Actions

Mechanism of Action

The active ingredients of telmisartan/amlodipine/indapamide target 3 separate mechanisms involved in blood pressure regulation. Telmisartan blocks the vasoconstrictor and aldosterone-secreting 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. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Indapamide is a thiazide-like diuretic. Although the mechanism of action is not clear, indapamide appears to act principally on the distal convoluted tubules of the nephron. The drug enhances the excretion of sodium, chloride, and water by inhibiting the transport of sodium ions across the renal tubule.

Advice to Patients

• Advise the patient to read the FDA-approved patient labelling.

• Advise female patients of childbearing age about the consequences of exposure to telmisartan/amlodipine/indapamide during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible.

• Advise nursing women not to breastfeed during treatment with telmisartan/amlodipine/indapamide.

• 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.

• Advise patients to inform their healthcare provider if they experience signs or symptoms associated with hyperuricemia.

• Advise patients not to use potassium supplements or salt substitutes that contain potassium without consulting the prescribing healthcare provider.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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