AMLODIPINE BESYLATE AND VALSARTAN
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.
Amlodipine is a dihydropyridine calcium channel blocker that inhibits the influx of calcium ions into vascular smooth muscle and cardiac muscle, causing vasodilation and reduced peripheral vascular resistance. Valsartan is an angiotensin II receptor blocker that selectively blocks the binding of angiotensin II to AT1 receptors, resulting in vasodilation and reduced aldosterone secretion.
| Metabolism | Amlodipine is extensively metabolized in the liver via cytochrome P450 3A4 (CYP3A4). Valsartan is minimally metabolized; about 20% is metabolized to a glucuronide conjugate via UDP-glucuronosyltransferase (UGT) 2B7, and it is not metabolized by CYP450 enzymes. |
| Excretion | Amlodipine: ~60% renal (10% as unchanged drug), ~20-25% biliary/fecal. Valsartan: ~83% fecal via biliary, ~13% renal (mainly unchanged). |
| Half-life | Amlodipine: 30-50 hours (terminal); Valsartan: 6-9 hours. Amlodipine's long half-life allows once-daily dosing; steady state achieved after 7-10 days. |
| Protein binding | Amlodipine: ~93% bound to plasma proteins; Valsartan: ~95% bound (mainly albumin). |
| Volume of Distribution | Amlodipine: ~21 L/kg (large Vd indicating extensive tissue distribution); Valsartan: ~17 L (not per kg; approx 0.24 L/kg assuming 70 kg). |
| Bioavailability | Amlodipine: ~64-90% after oral administration; Valsartan: ~25% (oral), high variability. |
| Onset of Action | Amlodipine: 2-4 hours after oral dose (gradual onset); Valsartan: ~2 hours (peak effect). |
| Duration of Action | Amlodipine: 24 hours (allows once-daily); Valsartan: 24 hours (once-daily dosing). Both maintain effect over 24-hour interval. |
Adults: initial combination therapy 5/160 mg (amlodipine/valsartan) orally once daily; titrate based on response, maximum 10/320 mg once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Not recommended for GFR <30 mL/min due to limited data. |
| Liver impairment | Child-Pugh A: no dose adjustment. Child-Pugh B: initial amlodipine dose 2.5 mg; combination product not recommended due to fixed doses. Child-Pugh C: contraindicated. |
| Pediatric use | Not established for patients <6 years. Age 6-16 years: initial 2.5/80 mg (amlodipine/valsartan) orally once daily; titrate based on response, maximum 5/320 mg once daily (weight ≥50 kg) or 5/160 mg once daily (weight <50 kg). |
| Geriatric use | Start at lowest available dose (e.g., 2.5/160 mg) due to higher incidence of hypotension; cautious titration. No specific dose adjustment per se, but sensitivity to antihypertensives is increased. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.
| FDA category | Contraindicated |
| Breastfeeding | Both amlodipine and valsartan are excreted in human milk in low concentrations. Amlodipine milk-to-plasma ratio (M/P) is approximately 1.0; valsartan M/P ratio is unknown due to absence of data. Risk of infant hypotension and renal effects from valsartan exposure. Consider alternative agents; if used, monitor infant for hypotension, oliguria, and hyperkalemia. |
| Teratogenic Risk |
■ FDA Black Box Warning
Warning: Fetal toxicity. Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
["Hypersensitivity to amlodipine, valsartan, or any component of the formulation","Concomitant use with aliskiren in patients with diabetes","Pregnancy (second and third trimesters)"]
| Precautions | ["Avoid use in pregnancy; discontinue if pregnancy occurs","Symptomatic hypotension, especially in patients with severe aortic stenosis or intravascular volume depletion","Worsening angina or myocardial infarction (rare, with calcium channel blockers)","Impaired renal function: monitor serum potassium and creatinine","Peripheral edema (common with amlodipine)"] |
| Food/Dietary |
Loading safety data…
| First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Fetal toxicity including oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal hypotension, hyperkalemia, and renal failure. Risk increases with prolonged exposure. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, serum electrolytes, and urine output. Fetal monitoring including ultrasound for amniotic fluid volume (oligohydramnios) and fetal growth. Neonatal monitoring for hypotension, hyperkalemia, and renal function. |
| Fertility Effects | No formal studies; animal studies do not suggest impaired fertility. Based on mechanism, angiotensin II receptor blockers may theoretically affect reproductive function but no human evidence of significant impact. |
| Avoid grapefruit and grapefruit juice; they can increase amlodipine serum concentrations and potentiate hypotensive effects. No significant food interactions with valsartan, but advise a low-salt diet as part of hypertension management. Alcohol may exacerbate hypotension; limit intake. |
| Clinical Pearls | Amlodipine/amlodipine besylate is a dihydropyridine calcium channel blocker; valsartan is an angiotensin II receptor blocker. This combination is indicated for hypertension not adequately controlled on monotherapy. The fixed-dose combination may improve compliance. Amlodipine can cause peripheral edema, which may be more common at higher doses and in older patients; adding valsartan may reduce the incidence of edema. Avoid use in pregnancy (due to valsartan) and in patients with bilateral renal artery stenosis. Monitor serum potassium and renal function periodically, especially in patients with renal impairment or on potassium-sparing diuretics. The maximum recommended dose is 10 mg/320 mg once daily. |
| Patient Advice | Take exactly as prescribed, usually once daily. Do not crush or chew tablets. · Do not use if pregnant or planning to become pregnant; stop and inform your doctor immediately if you become pregnant. · Avoid potassium supplements and salt substitutes containing potassium unless approved by your doctor. · Common side effects include swelling in ankles or feet, dizziness, flushing, and headache. Notify your doctor if swelling or dizziness is bothersome. · Do not stop taking this medication suddenly without consulting your doctor. · If you miss a dose, take it as soon as you remember unless it is near the time for your next dose. Do not double up. · Avoid grapefruit and grapefruit juice as they may increase amlodipine levels. |