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Aliskiren Hemifumarate / Amlodipine Besylate

Pronunciation: AL-is-KYE-ren hem-i-FUE-ma-rate am-LOE-di-peen BES-i-late
Class: Antihypertensive combination

Trade Names

Tekamlo
- Tablets, oral aliskiren 150 mg/amlodipine 5 mg
- Tablets, oral aliskiren 150 mg/amlodipine 10 mg
- Tablets, oral aliskiren 300 mg/amlodipine 5 mg
- Tablets, oral aliskiren 300 mg/amlodipine 10 mg

Pharmacology

Aliskiren

Direct renin inhibitor, decreasing plasma renin activity and inhibiting conversion of angiotensinogen to angiotensin I. All agents that inhibit the renin-angiotensin-aldosterone system suppress the negative feedback loop, leading to a compensatory rise in plasma-renin concentration. Aliskiren blocks the clinical effect of increased renin levels.

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Amlodipine

Inhibits movement of calcium ions across cell membrane in systemic and coronary vascular smooth muscle.

Indications and Usage

Treatment of hypertension, alone or with other antihypertensive agents.

Contraindications

Concomitant use with angiotensin receptor blockers or ACE inhibitors in diabetic patients.

Dosage and Administration

Adults

PO aliskiren 150 mg/amlodipine 5 mg once daily initially. Titrate as needed after 2 to 4 wk of therapy (max, 300 mg/10 mg once daily).

General Advice

  • Because high-fat meals decrease the absorption of aliskiren/amlodipine, instruct patients to establish a pattern for taking with regard to meals.
  • May administer with some other antihypertensive agents. In patients with diabetes, use in combination with angiotensin receptor blockers or ACE inhibitors is contraindicated. Also avoid concomitant use in patients with moderate renal impairment (glomerular filtration rate [GFR] less than 60 mL/min).
  • Not recommended for use as initial therapy in patients with intravascular volume depletion.
  • The antihypertensive effect is largely attained within 1 to 2 wk.
  • Switch patients receiving aliskiren or amlodipine from separate tablets to a single tablet of aliskiren/amlodipine containing the same component doses.

Storage/Stability

Store between 59° and 86°F. Protect from heat and moisture.

Drug Interactions

ACE inhibitors, angiotensin receptor blockers

In patients with diabetes, use in combination with angiotensin receptor blockers or ACE inhibitors is contraindicated. Also avoid concomitant use in patients with moderate renal impairment (GFR less than 60 mL/min).

Aliskiren Atorvastatin

Aliskiren plasma concentrations may be elevated, increasing its effects and risk of adverse reactions. Use with caution.

Azole antifungal agents (eg, itraconazole, ketoconazole)

Aliskiren plasma concentrations may be elevated, increasing its effects and the risk of adverse reactions. Avoid coadministration of itraconazole and aliskiren. Monitor cardiac status and adjust dosage if needed. (See Amlodipine/Azole Antifungal Agents.)

Cyclosporine

Aliskiren plasma concentrations increased significantly. Avoid coadministration.

Food

Grapefruit juice, orange juice, and apple juice may decrease the plasma concentration and pharmacologic effects of aliskiren. If an interaction is suspected, instruct patients to avoid grapefruit juice, orange juice, and apple juice.

Loop diuretics (eg, furosemide)

The plasma concentrations and pharmacologic effects of loop diuretics may be reduced. Larger doses of loop diuretics may be needed.

Potassium preparations (eg, potassium supplements, salt substitutes containing potassium), potassium-sparing diuretics (eg, spironolactone)

The risk of hyperkalemia may be increased. Closely monitor serum potassium. Adjust treatment as needed.

Rifamycins (eg, rifampin)

Aliskiren plasma concentrations may be reduced, decreasing the pharmacologic effects. Monitor BP and adjust aliskiren dosage as needed.

Amlodipine Azole antifungal agents (eg, itraconazole, ketoconazole)

Amlodipine plasma concentrations may be elevated, increasing its effects and the risk of adverse reactions. Monitor cardiac status and adjust dosage if needed. (See Aliskiren/Azole Antifungal Agents.)

Conivaptan

Amlodipine plasma concentrations may be elevated, increasing its effects. Monitor patients closely for signs of extended pharmacologic effects of amlodipine.

Protease inhibitors (eg, ritonavir)

Amlodipine concentrations may be elevated, increasing its effects. Monitor patients closely. Adjust dosage as needed.

Sildenafil

Coadministration of amlodipine with sildenafil resulted in increased BP-lowering effect. Monitor BP.

Simvastatin

Simvastatin plasma concentrations may be elevated, increasing the risk of toxicity. Limit the dosage of simvastatin to 20 mg/day when amlodipine is coadministered.

Adverse Reactions

Cardiovascular

Hypotension.

Hematologic

Decreased Hgb and Hct.

Hypersensitivity

Angioedema requiring airway management and hospitalization (postmarketing).

Metabolic-Nutritional

Peripheral edema (9%); hyperkalemia (1%).

Renal

Elevated BUN and serum creatinine.

Precautions

Warnings

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue aliskiren/amlodipine as soon as possible.


Monitor

Ensure that volume and/or salt depletion have been corrected before initiating therapy. Evaluate renal function and measure serum electrolytes before stating therapy and periodically thereafter. Monitor BP and pulse at regular intervals.


Pregnancy

Category D . Can cause fetal and neonatal morbidity and death when administered to pregnant women.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution, starting at the low end of the dosing range.

Renal Function

May be at increased risk of acute renal failure. Consider withholding or discontinuing therapy in patients with a significant decrease in renal function. Avoid concomitant use of ACE inhibitors or angiotensin receptor blockers in patients with moderate renal impairment (GFR less than 60 mL/min).

Hepatic Function

Use with caution in patients with severe hepatic impairment.

Angioedema

Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with aliskiren and has necessitated hospitalization and intubation. Discontinue aliskiren/amlodipine in patients who develop angioedema; do not readminister to these patients.

CV effects

Rarely, initiation or change to the dose of a calcium channel blocker has resulted in the development of documented increased frequency, duration, or severity of angina or acute MI, particularly in patients with severe obstructive coronary artery disease.

Hyperkalemia

May be at increased risk of hyperkalemia.

Hypotension

Rarely, excessive fall in BP may occur. In patients with an activated renin-angiotensin-aldosterone system, such as volume-depleted and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. Correct these conditions prior to administration of aliskiren/amlodipine or start treatment under close medical supervision.

Overdosage

Symptoms

Aliskiren

Hypotension.

Amlodipine

Peripheral vasodilation with marked hypotension, reflex tachycardia.

Patient Information

  • Advise patients to establish a routine pattern for taking this medication with regard to meals. High-fat meals decrease absorption substantially.
  • Advise patients not to take potassium supplements or salt substitutes containing potassium without consulting their health care provider.
  • Inform patients that light-headedness can occur, especially during the first days of therapy, and that it should be reported to the health care provider. Advise patients that if syncope occurs, to discontinue the drug until they consult their health care provider.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, which may cause light-headedness and possible syncope.
  • Tell women of childbearing age about the consequences of exposure to drugs that act on the renin-angiotensin-aldosterone system. Discuss other treatment options with women planning to become pregnant. Ask these patients to report pregnancies to their health care provider as soon as possible.
  • Advise patients to immediately report swelling of the face, extremities, eyes, lips, or tongue, or difficulty swallowing or breathing to their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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