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Amlodipine / Valsartan
Pronunciation: am-LOE-di-peen/val-SAR-tan
Class: Antihypertensive combination

Trade Names
Exforge
- Tablets, oral amlodipine 5 mg/valsartan 160 mg
- Tablets, oral amlodipine 10 mg/valsartan 160 mg
- Tablets, oral amlodipine 5 mg/valsartan 320 mg
- Tablets, oral amlodipine 10 mg/valsartan 320 mg

Pharmacology
Amlodipine

Inhibits movement of calcium ions across cell membranes in systemic and coronary
vascular smooth muscle.
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 Amlodipine 5 mg/valsartan 160 mg once daily initially. May increase after 1 to 2 wk

to a maximum dosage of amlodipine 10 mg/valsartan 320 mg once daily.
Elderly

PO Initially, amlodipine 2.5 mg once daily. Because this is a fixed-dose combination

tablet, therapy with amlodipine/valsartan may not be appropriate initial therapy in elderly
patients.
Renal Function Impairment
Adults

PO Titrate slowly.
Hepatic Function Impairment
Adults

PO Initially, amlodipine 2.5 mg once daily. Because this is a fixed-dose combination

tablet, therapy with amlodipine/valsartan may not be appropriate initial therapy in
patients with hepatic impairment; titrate slowly.
General Advice

May be taken with or without food.

May be administered with other antihypertensive agents.

Patients not adequately controlled on amlodipine (or another dihydropyridine calcium

channel blocker) alone or valsartan (or another angiotensin II receptor blocker) alone may be
switched to amlodipine/valsartan.

May be substituted for individually titrated components.

Not indicated for initial therapy in volume-depleted patients.

Storage/Stability
Store between 59 and 86F; protect from moisture.

Drug Interactions
No drug interaction studies have been conducted with amlodipine/valsartan. The
following interactions are based on drug interactions involving each component of the
amlodipine/valsartan combination.
ACE inhibitors (eg, captopril)

Coadministration may increase the risk of hyperkalemia and renal dysfunction. Consider
monotherapy. If coadministration cannot be avoided, closely monitor renal function and
serum potassium.
Aliskiren

The risk of hyperkalemia may be increased with coadministration, especially in diabetic

patients. Furthermore, addition of aliskiren to amlodipine/valsartan in diabetic patients
may increase the risk of nonfatal stroke, renal complications, and hypotension.
Coadministration is not recommended in diabetic patients.
Azole antifungal agents (eg, itraconazole, ketoconazole)

Azole antifungals may increase the plasma concentrations and pharmacologic effects of
amlodipine. If an interaction is suspected, consider decreasing the dosage.
Conivaptan

Plasma concentrations of amlodipine may be increased. Clinical monitoring for signs of

an extended pharmacologic effect of amlodipine is warranted.
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, those who are volume depleted, or
elderly patients. In addition, the antihypertensive effect of valsartan may be reduced by
NSAIDs. Monitor renal function and BP.
Drugs that increase potassium concentrations (eg, potassium supplements, salt
substitutes)

Serum potassium concentrations may be increased. Closely monitor serum potassium.

Adjust treatment as needed.
Lithium

Lithium plasma concentrations may be elevated, increasing its pharmacologic effects.

Monitor lithium levels; adjust dose accordingly.
Potassium-sparing diuretics (eg, amiloride)

The risk of hyperkalemia may be increased, especially in high-risk patients (eg, renal
impairment, type 2 diabetes). Closely monitor serum potassium and renal function.
Adjust therapy as needed.
Protease inhibitors (eg, indinavir, ritonavir)

The antihypertensive effects of amlodipine may be increased. Use with caution and
monitor clinical response. Reduce dosage as needed.
Sildenafil

Coadministration resulted in increased BP-lowering effect. Monitor BP.

Simvastatin

Plasma concentrations and pharmacologic effects of simvastatin may be increased. The

daily dose of simvastatin should not exceed 20 mg when amlodipine is coadministered.
Transporters

The results from an in vitro study with human liver tissue indicate that valsartan is a
substrate of the hepatic uptake transporter organic aniontransporting 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 is increased, especially in elderly patients. Monitor serum

potassium concentrations and clinical response. Consider alternative antibiotic
treatment. Adjust the antihypertensive dose as needed.

Adverse Reactions
Cardiovascular

Hypotension (6%); vasculitis (postmarketing).

Genitourinary

Increased BUN (6%); increased creatinine (4%); gynecomastia, renal impairment

(postmarketing).
Hepatic

Elevated liver enzymes, hepatitis, jaundice (postmarketing).

Metabolic

Peripheral edema (5%); hyperkalemia (3%).

Respiratory

Nasopharyngitis (4%); cough, upper respiratory tract infection (3%).

Miscellaneous

Dizziness (2%); alopecia, angioedema, rhabdomyolysis, thrombocytopenia

(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 . Use of drugs that act on the renin-angiotensin 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 therapy as soon as possible.
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 may occur. Valsartan would be
expected to behave similarly.
Hepatic Function

Use with caution.

Special Risk Patients

Initiate therapy cautiously in patients with heart failure, recent MI, or severe aortic
stenosis, and in patients undergoing surgery or dialysis.
Cardiovascular effects

Increased frequency, duration, or severity of angina or acute MI may occur. Use with
caution in patients with heart failure or severe aortic stenosis.
Hyperkalemia

May occur.
Hypotension

Decreases in BP may occur, especially in salt- or volume-depleted patients. Volume and

salt depletion should be corrected before initiating therapy.

Renal effects

Changes in renal function may occur, especially in volume-depleted patients. Oliguria

and/or progressive azotemia and (rarely) acute renal failure and/or death may occur in
patients whose renal function may depend on the activity of renin-angiotensinaldosterone system (eg, patients with severe CHF).

Overdosage
Symptoms

Bradycardia, circulatory collapse, depressed consciousness, hypotension, peripheral

vasodilation, shock, tachycardia.

Patient Information

Inform 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 these 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 that it should be reported to their 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, excessive perspiration, diarrhea, or

vomiting can lead to an excessive fall in BP, light-headedness, and possible syncope.

Advise patients not to take potassium supplements or salt substitutes containing

potassium without consulting their health care provider.

Copyright 2009 Wolters Kluwer Health.