Dosing and uses of Exforge (valsartan-amlodipine)
Adult dosage forms and strengths
amlodipine/valsartan
tablet
- 5mg/160mg
- 5mg/320mg
- 10mg/160mg
- 10mg/320mg
Hypertension
Initiate with 5 mg/160 mg PO qDay Or
Substitute for individually titrated components
May increase dose after at least 2 weeks, not to exceed 10 mg/day amlodipine and 320 mg/day valsartan
May be adminsitered concomitantly with other antihypertensive agents
Dosage modifications
Renal impairment
- Mild or moderate (CrCl >30 mL/min): Dose adjustment not necessary
- Severe (CrCl <30 mL/min): Not studied
Hepatic impairment
- Not recommended for initial therapy; amlodipine 2.5 mg is not an available strength with available dosage forms for this drug combination
- Amlodipine: Exposure is increased with hepatic insufficiency, consider decreasing dose
- Valsartan: Exposure increased with mild-to-moderate hepatic insufficiency does not require dosage adjustment; unknown for severe hepatic impairment
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Not recommended for initial therapy; amlodipine 2.5 mg is not an available strength with available dosage forms for this drug combination
Base initial dose on 2.5 mg of amlodipine PO qDay
No overall difference in the efficacy or safety of valsartan has been observed, but greater sensitivity of some older individuals cannot be ruled out
Exforge (valsartan-amlodipine) adverse (side) effects
>10%
Headache
Increased BUN (6-17%)
1-10%
Peripheral edema (5-8%)
Anxiety (3%)
Nasopharyngitis (4%)
Increased potassium (3%)
Upper respiratory infection (3%)
Dizziness (2%)
Somnolence (3%)
Diarrhea (3%)
Nausea (3%)
Abdominal pain (3%)
Cough (2%)
<1%
Orthostatic hypotension
Syncope
Visual disturbance
Tinnitus
Exanthema
Postmarketing Reports
Amlodipine
- Gynecomastia
- Jaundice and hepatic enzyme elevations
Valsartan
- Hypersensitivity: Angioedema (rare)
- Digestive: Elevated liver enzymes, hepatitis (rare)
- Renal: Impaired renal function, renal failure
- Clinical laboratory tests: Hyperkalemia
- Dermatologic: Alopecia, bullous dermatitis
- Blood and lymphatic: Thrombocytopenia (rare)
- Vascular: Vasculitis
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to valsartan, amlodipine or other ingredients
Pregnancy (2nd & 3rd trimesters): significant risk of fetal & neonatal morbidity & mortality
Anuria
Concomitant administration with aliskiren in patients with diabetes mellitus
Cautions
Use during the 2nd or 3rd trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Black box warnings)
Excessive hypotension may occur (rare); caution if volume/salt depleted, initiate cautiously in patients with heart failure, recent MI, or those undergoing surgery or dialysis
Worsening angina and acute MI may occur after starting or increasing amlodipine dose, particularly with severe obstructive CAd
Peripheral edema may occur within 2-3 weeks of starting therapy (amlodipine)
Use caution in heart failure, severe aortic stenosis (amlodipine), hepatic impairment, renal artery stenosis, or hypertrophic cardiomyopathy
Patients whose renal function may depend in part on the activity of the renin angiotensin system (e.g. patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion)
May cause hyperkalemia
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy; closely monitor blood pressure
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd & 3rd trimesters). During the second and third trimesters of pregnancy, these drugs have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death.
Lactation: discontinue drug or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
