Aliskiren / Hydrochlorothiazide

Pronunciation: AL-is-KYE-ren/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Tekturna HCT
- Tablets, oral aliskiren 150 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral aliskiren 150 mg/hydrochlorothiazide 25 mg
- Tablets, oral aliskiren 300 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral aliskiren 300 mg/hydrochlorothiazide 25 mg

Pharmacology

Aliskiren

Decreases plasma renin activity and inhibits conversion of angiotensinogen to angiotensin I.

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Hydrochlorothiazide

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

For the treatment of hypertension.

Contraindications

Anuria; hypersensitivity to sulfonamide-derived drugs.

Dosage and Administration

Adults

PO Aliskiren 150 mg/hydrochlorothiazide 12.5 once daily initially. May increase the dosage after 2 to 4 weeks (max, aliskiren 300 mg/hydrochlorothiazide 25 mg once daily).

Renal Function Impairment
Adults

PO Dosage adjustment not necessary in patients with CrCl more than 30 mL/min; however, uptitrate slowly because thiazides may precipitate azotemia. Use is not recommended in patients with CrCl less than 30 mL/min.

Hepatic Function Impairment

PO Adjustment of the starting dose is not necessary; however, uptritrate slowly because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

General Advice

  • 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.
  • May administer with other antihypertensives.
  • Not recommended for use as initial therapy in patients with intravascular volume depletion.

Storage/Stability

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

Drug Interactions

No drug interaction studies have been conducted between aliskiren/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the aliskiren/hydrochlorothiazide combination.

Aliskiren Angiotensin antagonists (eg, ACE inhibitors [eg, captopril], angiotensin receptor blockers [eg, valsartan])

The risk of hyperkalemia may be increased. Closely monitor serum potassium. (See Hydrochlorothiazide/Angiotensin antagonists.)

Azole antifungal agents (eg, itraconazole, ketoconazole)

Aliskiren concentrations may be elevated, increasing the pharmacologic effects.

Cyclosporine

Aliskiren concentrations may be elevated, increasing the pharmacologic effects. Avoid concomitant use.

Drugs that increase potassium concentrations (eg, potassium supplements, salt substitutes containing potassium)

Serum potassium concentrations may be increased. Closely monitor serum potassium. Adjust treatment as needed.

Food (eg, apple juice, grapefruit juice, orange juice)

May decrease aliskiren plasma concentrations and pharmacologic effects. Advise patients taking aliskiren to avoid grapefruit products, orange juice, and apple juice.

Loop diuretics (eg, furosemide)

Plasma concentrations and pharmacologic effects of loop diuretics may be decreased. Larger doses of loop diuretics may be needed. (See Hydrochlorothiazide/Loop diuretics.)

Potassium-sparing diuretics (eg, spironolactone)

Serum potassium concentrations may be increased. Closely monitor serum potassium if coadministration cannot be avoided.

Rifamycins (eg, rifampin)

Pharmacologic effects and plasma concentrations of aliskiren may be reduced. Monitor BP and adjust aliskiren dosage as needed.

Hydrochlorothiazide Angiotensin antagonists (eg, ACE inhibitors [eg, captopril], angiotensin receptor blockers [eg, valsartan])

The risk of renal dysfunction may be increased. Monitor renal function, especially in elderly patients and in patients with renal impairment. If an adverse interaction is suspected, stop one or both agents. (See Aliskiren/Angiotensin antagonists.)

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur. Monitor BP.

Antihypertensive agents

Additive or potentiation of hypotensive effects. Closely monitor BP.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol resins

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide, reducing GI absorption up to 85% and 43%, respectively. Separate the administration times by as much as possible (at least 4 h). Adjust hydrochlorothiazide dose as needed.

Corticotropin, corticosteroids

Electrolyte depletion may be intensified, particularly hypokalemia. Laboratory monitoring of serum potassium is warranted.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood and urine glucose, and serum uric acid. If coadministration cannot be avoided, a decreased dosage of one or both agents may be required.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose patients to digitalis-induced arrhythmias. Measure plasma concentrations of potassium and magnesium; supplement low levels. Prevent further losses with dietary management.

Dofetilide

Dofetilide plasma concentrations may be increased and/or hypokalemia may occur. Prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Hypoglycemic agents, oral (eg, sulfonylureas)

Hydrochlorothiazide may increase fasting blood glucose. The effect of oral hypoglycemic agents may be decreased. Monitor blood glucose and adjust the hypoglycemic dose as needed.

Insulin

Hydrochlorothiazide may increase fasting blood glucose and decrease insulin secretion. The effect of insulin may be decreased. Monitor blood glucose and adjust the insulin dose as needed.

Lithium

Lithium Cl may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Generally, do not give lithium with diuretics. If coadministration is necessary, closely monitor lithium levels and for signs of lithium toxicity. Adjust the lithium dose as needed.

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. Titrate dosage with small or intermittent doses. (See Aliskiren/Loop diuretics.)

Nondepolarizing muscle relaxants (eg, tubocurarine)

Possible increased responsiveness to the muscle relaxant due to 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 BP and the diuretic response. If an interaction is suspected, it may be necessary to discontinue the NSAID. Also, acute renal failure has been reported on rare occasions. Monitor renal function.

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.

Adverse Reactions

CNS

Dizziness (2%); asthenia, vertigo (1%).

GI

Diarrhea (2%).

Lab Tests

Elevated BUN (12%); hyperuricemia, hypokalemia (2%); elevated ALT, elevated creatinine, hyperkalemia (1%).

Respiratory

Cough (1%).

Miscellaneous

Influenza (2%); arthralgia (1%); angioedema, peripheral edema (postmarketing).

Precautions

Warnings

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


Monitor

Correct volume and/or salt depletion before initiating therapy. Evaluate renal function and measure serum electrolytes before starting therapy and periodically thereafter. Monitor BP and pulse on a regular basis.


Pregnancy

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

Lactation

Thiazides appear in human breast milk; it is not known if aliskiren is excreted in human milk.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Hypersensitivity

May occur in patients with or without a history of allergy or bronchial asthma; cross-sensitivity with sulfonamides may also occur. Hypersensitivity reactions may range from urticaria to anaphylaxis.

Renal Function

Do not use in patients with severe renal impairment (glomerular filtration rate less than 30 mL/min). Cumulative effects of hydrochlorothiazide may develop in patients with impaired renal function.

Hepatic Function

Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Angioedema

Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx has been reported with aliskiren and may be fatal.

Electrolyte imbalance

Hyperkalemia or hypokalemia may occur.

Hypotension

Decreases in BP may occur, especially in salt- or volume-depleted patients. Correct volume and salt depletion before initiating therapy.

Ocular effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma.

Systemic lupus erythematosus

Exacerbation or activation may occur.

Overdosage

Symptoms

Dehydration, electrolyte depletion (hypochloremia, hypokalemia, hyponatremia), hypotension.

Patient Information

  • Advise women of childbearing age about the consequences of exposure to drugs that act on the renin-angiotensin system. Discuss other treatment options with women planning to become pregnant. Ask patients to report pregnancies to their health care provider as soon as possible.
  • Caution patients that light-headedness can occur, especially during the first few days of therapy, and to report it to their prescribing health care provider. Inform patients that if syncope occurs, therapy should be discontinued until their health care provider has been consulted.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, with the same consequences of light-headedness and possible syncope.
  • Advise patients not to use potassium supplements or salt substitutes containing potassium without consulting their health care provider.
  • Advise patients to establish a routine pattern for taking aliskiren/hydrochlorothiazide with regard to meals. High-fat meals decrease absorption substantially.

Copyright © 2009 Wolters Kluwer Health.

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