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Aliskiren Hemifumarate / Valsartan

Pronunciation: AL-is-KYE-ren hemi-FUE-ma-rate/val-SAR-tan
Class: Antihypertensive combination

Trade Names

Valturna
- Tablets, oral aliskiren hemifumarate 150 mg/valsartan 160 mg
- Tablets, oral aliskiren hemifumarate 300 mg/valsartan 320 mg

Pharmacology

Aliskiren

Direct renin inhibitor; decreases plasma renin activity and inhibits conversion of angiotensinogen to angiotensin I. All agents that inhibit the renin-angiotensin 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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Valsartan

Antagonizes the effect of angiotensin II (vasoconstriction and aldosterone secretion) by blocking the angiotensin II receptor in vascular smooth muscle and the adrenal gland, producing decreased BP.

Indications and Usage

For the treatment of hypertension.

Contraindications

None well documented.

Dosage and Administration

Adults

PO Aliskiren 150 mg/valsartan 160 mg once daily initially. May titrate up to aliskiren 300 mg/valsartan 320 mg per day if BP remains uncontrolled after 2 to 4 wk (max, aliskiren 300 mg/valsartan 320 mg per day).

General Advice

  • May administer with other antihypertensive agents.
  • The antihypertensive effect is usually attained within 2 wk.
  • Not recommended for use as initial therapy in patients with intravascular volume depletion.
  • A routine pattern should be established for taking this medication with regard to meals. High-fat meals decrease absorption substantially.

Storage/Stability

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

Drug Interactions

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

ACE inhibitors (eg, captopril)

The risk of hyperkalemia and renal dysfunction may be increased. Monitor renal function and serum potassium, especially in diabetic patients.

Atorvastatin

Coadministration of atorvastatin resulted in an approximate by 50% increase in aliskiren C max and AUC after multiple dosing. Use with caution.

Azole antifungals (eg, itraconazole)

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

Cyclooxygenase 2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen, indomethacin)

Coadministration may result in deterioration of renal function, including acute renal failure, especially in patients with renal impairment or volume depletion, or in elderly patients. Also, the antihypertensive effect of valsartan may be reduced by NSAIDs. Monitor renal function and BP.

Cyclosporine

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

Food

When taken with food, the mean AUC and C max of aliskiren decreased by 76% and 88%, respectively. Grapefruit juice, orange juice, and apple juice may decrease aliskiren plasma concentrations and pharmacologic effects; avoid coadministration.

Lithium

Lithium plasma concentrations may be elevated, increasing its pharmacologic effects and the risk of toxicity. Monitor lithium levels; adjust the lithium dosage as needed.

Loop diuretics (eg, furosemide)

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

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

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

Rifamycins (eg, rifampin)

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

Transporters

The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter organic anion–transporting polypeptide OATP1B1 and the hepatic efflux transporter multidrug resistance protein 2. Coadministration of inhibitors of the uptake transporter (cyclosporine, rifampin) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.

Trimethoprim

The risk of hyperkalemia may be increased, especially in elderly patients. Monitor serum potassium concentrations and clinical response. Consider alternative antibiotic treatment in elderly patients.

Adverse Reactions

CNS

Fatigue (3%); vertigo (1%).

Dermatologic

Rash (1%); severe cutaneous adverse reactions, including Stevens-Johnson syndrome and TEN (postmarketing).

Genitourinary

UTI (1%); elevated creatinine (up to 1%); elevated BUN.

Lab Tests

Hyperkalemia (4%); decreased Hgb and/or Hct; decreased RBC.

Respiratory

Cough, nasopharyngitis (3%); upper respiratory tract infection (1%).

Miscellaneous

Diarrhea, influenza (1%); angioedema requiring airway management and hospitalization, peripheral edema (postmarketing).

Precautions

Warnings

When pregnancy is detected, discontinue aliskiren/valsartan as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and 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 . Use 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.

Lactation

Undetermined. Breast-feeding is not recommended.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Renal Function

In studies of ACE inhibitors in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported; expect similar results with valsartan.

Hepatic Function

Patients with mild to moderate hepatic impairment, including patients with biliary obstructive disorder, showed lower valsartan Cl (higher AUCs).

Special Risk Patients

Initiate therapy cautiously in patients with heart failure or recent MI and in patients undergoing surgery or dialysis.

Angioedema

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

Hypotension

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

Hyperkalemia

May occur.

Renal effects

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may occur, particularly in volume-depleted patients. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria or progressive azotemia and (rarely) acute renal failure and/or death. In addition, some patients with heart failure developed increases in BUN and serum creatinine.

Overdosage

Symptoms

Bradycardia, circulatory collapse, depressed level of consciousness, hypotension, shock, tachycardia.

Patient Information

  • Inform 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.
  • Caution patients that light-headedness can occur, especially during the first few days of therapy, and that it should be reported to the prescribing health care provider. Inform patients that if syncope occurs, therapy should be discontinued until the health care provider has been consulted.
  • Caution patients that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, light-headedness, and possible syncope.
  • Tell female patients of childbearing potential about the consequences of exposure to aliskiren/valsartan during pregnancy. Discuss treatment options with female patients 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 in swallowing or breathing to their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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