DIOVAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIOVAN (DIOVAN).
Angiotensin II receptor antagonist (ARB) that selectively blocks the binding of angiotensin II to the AT1 receptor, thereby inhibiting vasoconstriction, aldosterone secretion, and renal sodium reabsorption.
| Metabolism | Primarily glucuronidation via UGT1A3, UGT2B7, and UGT1A8; minor CYP2C9 oxidation; unchanged drug eliminated in feces (83%) and urine (13%). |
| Excretion | Primarily biliary/fecal (83% of dose) as unchanged drug; renal excretion accounts for 13% (mostly unchanged). |
| Half-life | Terminal elimination half-life: approximately 6 hours (range 4–8 hours) in healthy adults; not significantly altered in renal or hepatic impairment. |
| Protein binding | Highly protein-bound (95%), primarily to albumin. |
| Volume of Distribution | Volume of distribution at steady state (Vdss): approximately 17 L (0.24 L/kg for 70 kg adult); indicates limited extravascular distribution. |
| Bioavailability | Oral bioavailability: approximately 25% (range 10–35%); food reduces absorption by about 40% (Cmax and AUC decrease). |
| Onset of Action | Oral: onset of antihypertensive effect within 2 hours; peak effect at 4–6 hours. |
| Duration of Action | Duration of antihypertensive effect is approximately 24 hours with once-daily dosing; trough-to-peak ratio >60%. |
| Molecular Weight | 435.5 |
80-320 mg orally once daily; initial dose 80 mg; titrate to 160-320 mg daily based on response.
| Dosage form | CAPSULE |
| Renal impairment | No adjustment required for GFR ≥30 mL/min; for GFR <30 mL/min, use with caution; no data for dialysis. |
| Liver impairment | Mild to moderate (Child-Pugh A/B): no adjustment; severe (Child-Pugh C): contraindicated. |
| Pediatric use | 1-16 years: weight-based, initial 1.3 mg/kg/day (max 40 mg) orally, titrate up to 2.7 mg/kg/day (max 160 mg); 6-16 years: 80-160 mg once daily if weight ≥35 kg. |
| Geriatric use | Initial dose 80 mg once daily; titrate slowly; monitor renal function and blood pressure closely due to increased sensitivity. |
| 1st trimester | Avoid in first trimester due to potential teratogenicity; alternative antihypertensive recommended. |
| 2nd trimester | Contraindicated in second trimester due to fetal renal toxicity, oligohydramnios, and skull ossification defects. |
| 3rd trimester | Contraindicated in third trimester due to severe fetal and neonatal renal dysfunction, oligohydramnios, and hypotension. |
Clinical note
Comprehensive clinical and safety monograph for DIOVAN (DIOVAN).
| Placental transfer | Crosses placenta; fetal exposure is significant, especially in second and third trimesters, with documented risks of fetotoxicity. |
| Breastfeeding | Limited data; present in breast milk in low concentrations. Caution advised due to potential adverse effects on neonatal renal function. Consider alternative agents, especially when nursing preterm or infants with renal impairment. |
■ FDA Black Box Warning
When used during pregnancy, drugs that act directly on the renin-angiotensin system (RAS) can cause injury and even death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
| Serious Effects |
Pregnancy (especially second and third trimesters)History of hypersensitivity to valsartan or any ACE inhibitor/Angiotensin II Receptor Blocker (ARB)Coadministration with aliskiren in patients with diabetes mellitus
| Precautions | Fetal toxicity (see black box warning), Hypotension in volume- or salt-depleted patients, Monitor renal function; risk of acute renal failure in patients with renal artery stenosis, Hyperkalemia, especially in patients with renal impairment or on potassium supplements, Avoid concomitant use with aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min) |
| Food/Dietary | No significant food interactions; however, avoid high-potassium foods in large amounts (e.g., bananas, oranges, tomatoes) if also on potassium-sparing agents. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category D for 2nd and 3rd trimesters. First trimester: limited data, potential risk of fetal renal dysfunction and oligohydramnios; second and third trimesters: associated with oligohydramnios, fetal renal impairment, skull ossification defects, and neonatal hypotension, hyperkalemia, and anuria. |
| Fetal Monitoring | Serial ultrasound monitoring for fetal growth and amniotic fluid volume (especially oligohydramnios); fetal renal function assessment via biophysical profile; maternal blood pressure and renal function (serum creatinine, potassium) monitoring. |
| Fertility Effects | No direct evidence of impaired fertility in humans; animal studies show no adverse effects on fertility. However, angiotensin II receptor blockers may theoretically interfere with reproductive hormone pathways; clinical significance unclear. |
| Clinical Pearls | Monitor serum potassium and renal function, especially in elderly or volume-depleted patients. Adjust dose cautiously when used with NSAIDs or potassium supplements. Avoid use in pregnancy (second and third trimesters). Titrate dose slowly in patients with hepatic impairment. Consider switching from ACE inhibitor if cough develops. |
| Patient Advice | Do not stop taking this medication without consulting your doctor. · Avoid potassium supplements and salt substitutes containing potassium. · If you miss a dose, take it as soon as you remember; if near next dose, skip it and resume regular schedule. · Report symptoms like swelling of face/lips, difficulty breathing, or lightheadedness immediately. · Store at room temperature away from moisture and heat. · Take with or without food, but consistently either way. |