Aliskiren Hemifumarate / Amlodipine Besylate / Hydrochlorothiazide
Pronunciation: a-lis-KYE-ren hem-i-FUE-mar-ate/am-LOE-di-peen BES-i-late/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination
- Tablets, oral aliskiren 150 mg/amlodipine 5 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral aliskiren 300 mg/amlodipine 5 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral aliskiren 300 mg/amlodipine 5 mg/hydrochlorothiazide 25 mg
- Tablets, oral aliskiren 300 mg/amlodipine 10 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral aliskiren 300 mg/amlodipine 10 mg/hydrochlorothiazide 25 mg
Aliskiren is a direct renin inhibitor; it decreases plasma renin activity and inhibits the conversion of angiotensinogen to angiotensin I. Amlodipine is a calcium channel blocker; it inhibits influx of calcium ions into vascular smooth muscle and cardiac muscle. Hydrochlorothiazide is a thiazide diuretic; it enhances excretion of sodium and chloride and reduces plasma volume.
Indications and Usage
Treatment of hypertension.
Anuria; hypersensitivity to sulfonamide-derived drugs such as hydrochlorothiazide.
Dosage and AdministrationAdults
PO 1 tablet (aliskiren 150 or 300 mg/amlodipine 5 or 10 mg/hydrochlorothiazide 12.5 or 25 mg) per day. May increase the dosage after 2 wk (max, aliskiren 300 mg/amlodipine 10 mg/hydrochlorothiazide 25 mg).Elderly (75 years and older)
PO Initially, amlodipine 2.5 mg/day. However, this strength is not available in this combination product.Renal Function Impairment
PO For patients with CrCl less than 30 mL/min, this combination is not recommended.Hepatic Function Impairment
PO For patients with severe hepatic impairment, the initial dosage of amlodipine should be 2.5 mg/day. However, this strength is not available in this combination product. Increase hydrochlorothiazide dosage slowly.
- May be taken with or without food; however, it should be taken the same way every day with regard to food. High-fat meals decrease absorption substantially.
- Use the combination product for patients not adequately controlled on any two of the following: aliskiren, a dihydropyridine calcium channel blocker, thiazide diuretics.
- Use the combination product for patients who experience dose-limiting adverse reactions attributed to an individual component (while on any dual combination of the components of the product) and use a lower dose of that component to achieve similar blood pressure reductions.
- May substitute the combination product (at the same dose) for patients receiving the individual components from separate tablets.
Store between 59° and 86°F. Protect from heat and moisture.
No drug interaction studies have been conducted between aliskiren/amlodipine/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the aliskiren/amlodipine/hydrochlorothiazide combination.Aliskiren ACE inhibitors (eg, captopril)
The risk of hyperkalemia may be increased. Closely monitor serum potassium. (See Hydrochlorothiazide/ACE Inhibitors.)Atorvastatin
Coadministration of atorvastatin resulted in an approximate 50% increase in aliskiren C max and AUC after multiple dosing. Use with caution.Cyclosporine, itraconazole, ketoconazole
Aliskiren blood concentrations may be increased. Avoid concomitant use. (See Amlodipine/Azole Antifungal Agents.)Grapefruit juice
Grapefruit juice may decrease aliskiren plasma concentrations and pharmacologic effects. Patients taking aliskiren should avoid grapefruit products and take aliskiren with a liquid other than grapefruit juice. (See Amlodipine/Grapefruit Juice.)Irbesartan
Concurrent use of irbesartan decreased the aliskiren C max up to 50% after multiple dosing. Use with caution.Loop diuretics (eg, furosemide)
Plasma concentrations and pharmacologic effects of loop diuretics may be decreased by aliskiren. Larger doses of loop diuretics may be needed. (See Hydrochlorothiazide/Loop Diuretics.)Rifamycins (eg, rifampin)
Aliskiren plasma concentrations may be decreased, decreasing the pharmacologic effects and risk of adverse reactions.Verapamil
Aliskiren C max and AUC may be increased by approximately 2-fold. No dosage adjustment is necessary.Amlodipine Azole antifungal agents (eg, itraconazole, ketoconazole)
Amlodipine concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid concomitant use. (See Aliskiren/Cyclosporine, Itraconazole, Ketoconazole.)Conivaptan
Amlodipine plasma concentrations of may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Clinical monitoring for signs of extended pharmacologic effect of amlodipine is warranted.Diltiazem
Amlodipine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Closely monitor blood pressure.Grapefruit juice
Amlodipine bioavailability may be increased. Avoid concomitant use. (See Aliskiren/Grapefruit Juice.)Protease inhibitors (eg, indinavir, ritonavir)
The antihypertensive effects of amlodipine may be increased. Use with caution. Close clinical monitoring is warranted.Simvastatin
Concomitant therapy may increase the risk of myopathy, including rhabdomyolysis. Therefore, the dose of simvastatin should not exceed 20 mg/day.Hydrochlorothiazide ACE inhibitors (eg, captopril)
The risk of acute renal dysfunction may be increased. Monitor renal function. (See Aliskiren/ACE Inhibitors.)Adrenocorticotropic hormones, corticosteroids
Electrolyte depletion may be intensified, particularly hypokalemia. Laboratory monitoring is warranted.Alcohol, barbiturates, narcotics
Potentiation of orthostatic hypotension may occur. Monitor blood pressure.Antihypertensive agents
Additive or potentiation of hypotension effects may occur. Closely monitor blood pressure.Antineoplastic agents (eg, cyclophosphamide)
Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.Cholestyramine and colestipol resins
Hydrochlorothiazide absorption may be impaired. Separate the administration times by at least 4 hours, if not longer.Diazoxide
The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor blood pressure, blood glucose, and serum uric acid. If coadministration cannot be avoided, a decreased dosage of 1 or both agents may be required.Digoxin
Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Measure plasma concentrations of potassium and magnesium; supplement low levels.Dofetilide
Dofetilide plasma concentrations may be increased. Prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration of hydrochlorothiazide and dofetilide is contraindicated.Drugs that increase potassium concentrations (eg, potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium)
Serum potassium concentrations may be increased.Hypoglycemic agents, oral (eg, sulfonylureas), insulin
Hydrochlorothiazide may increase fasting blood glucose and decrease insulin secretion. The effect of oral hypoglycemic agents and insulin may be decreased. Monitor blood glucose and adjust the hypoglycemic dose as needed.Lithium
Lithium clearance may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Lithium generally should not be given with hydrochlorothiazide.Loop diuretics (eg, furosemide)
Hydrochlorothiazide and furosemide have synergistic effects that may result in profound diuresis and serious electrolyte abnormalities. Monitor for dehydration and electrolyte abnormalities during combined therapy. (See Aliskiren/Loop Diuretics.)Nondepolarizing muscle relaxants (eg, tubocurarine)
Possible increased responsiveness to the muscle relaxant because of diuretic-induced hypokalemia. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.NSAIDs (eg, ibuprofen, indomethacin)
The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide may be reduced. Monitor blood pressure and the diuretic response.Pressor amines (eg, norepinephrine)
Response to pressor amines may be decreased. Use with caution.Tretinoin
The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.
Dizziness, headache (4%).
Uric acid elevations (5%); ALT elevations (3%); changes in RBC count, hemoglobin, and hematocrit.
Hypokalemia (11%); peripheral edema (7%); hyperkalemia (3%).
Drugs that act directly on the renin-angiotensin-aldosterone system can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.
Periodically monitor electrolytes (eg, serum potassium) and blood pressure.
Category D . Drugs such as aliskiren that act directly on the renin-angiotensin-aldosterone system during the second and third trimesters can cause fetal and neonatal morbidity and death. In addition, first-trimester use of ACE inhibitors has been associated with birth defects in retrospective data. Thiazides can cross the placenta and are associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults. Discontinue therapy as soon as pregnancy is detected.
It is not known whether aliskiren or amlodipine is excreted in human milk. Hydrochlorothiazide is excreted in human milk. The molecular weight (about 567) for amlodipine is low enough that excretion into breast milk should be expected. A decision should be made whether to discontinue breast-feeding or discontinue this drug, taking into account the importance of the drug to the mother.
Safety and efficacy not established.
Use with caution. Use low initial dosage of amlodipine in patients 75 y and older.
May occur in patients with or without history of allergy or bronchial asthma; cross-sensitivity with sulfonamides may also occur. Hypersensitivity reactions may range from urticaria to anaphylaxis.
Use with caution. Do not use in patients with severe renal disease (CrCl less than 30 mL/min).
Minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx has been reported with aliskiren and may be fatal.
Increased frequency, duration, or severity of angina or acute MI has occurred rarely on initiation or change of dose with a calcium channel blocker. More common among patients with severe obstructive coronary artery disease.
Has been rarely reported. May occur in patients who are volume- or salt-depleted; use with caution.
Transient myopia and acute angle-closure glaucoma may occur. 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.
Systemic lupus erythematosus
Exacerbation or activation may occur.
Marked peripheral vasodilation and hypotension, reflex tachycardia.Hydrochlorothiazide
Excessive diuresis resulting in electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration.
- Advise patient to take once daily as prescribed.
- Advise patient to try to take each dose at about the same time each day.
- Advise patients to establish a routine pattern for taking the dose, either with or without a meal.
- Instruct patient to sit or lie down if experiencing dizziness or light-headedness when standing.
- Caution patient that inadequate fluid intake, or excessive perspiration, diarrhea, or vomiting can lead to a fall in BP, resulting in light-headedness or fainting.
- Caution patient to not take any potassium supplements or salt substitutes containing potassium unless advised by health care provider.
- Advise patient to avoid alcohol because of the risk of hypotension.
- Instruct patient to stop taking the product and immediately report any of these symptoms to health care provider: fainting; swelling of the face, lips, eyelids, or tongue.
- Tell women of childbearing age about the consequences of exposure of the fetus to this product. Instruct patient to inform health care provider as soon as possible if she becomes pregnant.
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