Diovan
Diovan
Generic Name
Diovan
Mechanism
- Blockade of AT1 receptors: Selectively antagonizes the Angiotensin‑II type‑1 (AT1) receptors on vascular smooth muscle, cardiac myocytes, and kidney tubules.
- Inhibition of vasoconstriction: Prevents angiotensin‑II‑mediated vasoconstriction, reducing systemic vascular resistance.
- Renal effects: Lowers sodium and water reabsorption, improving glomerular filtration.
- Neurohormonal modulation: Diminishes aldosterone release, suppresses sympathetic activity, and attenuates cardiac remodeling—beneficial in heart failure.
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Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral bioavailability ~25%. *Food decreases absorption*—take on an empty stomach for maximal effect. |
| Distribution | Protein‑bound ~88%; crosses cellular membranes; not significant blood‑brain barrier penetration. |
| Metabolism | Minimal hepatic metabolism (mainly hydrolysis); active metabolite *carboxy‑valsartan* (~3–5% systemic exposure). |
| Elimination | Renal excretion (~85%). Elimination half‑life: 6–9 h; 12 h in patients with renal impairment. |
| Drug interactions | ↓Co‑administration with CYP3A4 inhibitors (e.g., ketoconazole) modestly increases plasma valsartan. Potentiation with potassium‑sparing diuretics or ACE inhibitors can increase hyperkalemia risk. |
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Indications
- Hypertension: ≥25 mg daily, titrate to 160 mg per day.
- Heart failure with reduced ejection fraction (HFrEF): 2 mg/kg twice daily (max 320 mg/day) in stable patients.
- Post‑myocardial infarction: 8–16 mg twice daily to reduce mortality (per SAVOR‑TIMI 53).
- Proteus-associated nephropathy: Used adjunctively for renoprotection.
- Diabetic nephropathy: For slowing progression of albuminuria (off‑label, based on ARB benefit).
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Contraindications
- Contraindications:
- *Prior angiotensin‑II receptor blocker or ACE inhibitor hypersensitivity*.
- Pregnancy (Category D) – fetal toxicity; not recommended in lactation.
- Warnings:
- Hyperkalemia: Monitor in CKD or with potassium‑sparing agents.
- Renal dysfunction: Renal clearance declines with reduced GFR; dose adjustment required.
- Hypotension: Watch for orthostatic symptoms, especially when combined with diuretics or nitrates.
- ACE‑I stacking: Avoid simultaneous use of ACEi and ARB due to augmented risk of hyperkalemia, renal injury, and hypotension.
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Dosing
| Condition | Dose | Titration |
| Hypertension | 80 mg once daily → 160 mg once daily | Increase in 40‑80 mg increments after 2–4 weeks if BP uncontrolled |
| HFrEF | 2 mg/kg twice daily (max 320 mg/day) | Titrate every 4–6 weeks; monitor for signs of fluid overload |
| Post‑MI | 8–16 mg twice daily | Start low; may increase to 32 mg twice daily if tolerated |
| Renal disease | Start at 80 mg once daily; increase by 40‑80 mg increments | Watch serum creatinine & potassium |
• Take: orally, ideally at the same time each day, either with or without food (though faster absorption when fasting).
• Missed dose: Take ASAP; skip next dose if close to the next scheduled dose.
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Adverse Effects
| Category | Examples |
| Common | Dizziness, fatigue, cough (rare vs ACEi), mild orthostatic hypotension |
| Serious | Hyperkalemia, renal impairment, severe hypotension, angioedema (extremely rare), cough with ACEi overlapping, liver enzyme elevations |
• Monitor liver function tests if >3 × ULN ALT/AST occurs.
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Monitoring
| Parameter | Frequency | Target/Reference |
| BP & HR | At each visit (≥every 4 weeks) | <120/80 mmHg |
| Serum creatinine & BUN | Baseline, 1–2 weeks after dose change, then every 3 months | Stable or slight rise <30 % |
| Serum potassium | Baseline, 1–2 weeks after dose change, then every 3–6 months | 3.5–5.0 mmol/L |
| Urine albumin-to-creatinine ratio (HFrEF/diabetic nephropathy) | Baseline, then yearly | Improvement or stability |
| Liver function tests | Baseline; repeat if abnormal symptoms | ↑ <3 × ULN |
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Clinical Pearls
- “Drug holiday” for valsartan: In patients on potassium‑sparing diuretics prone to hyperkalemia, consider a brief 48‑hour drug holiday to re‑balance electrolytes before rechallenge.
- Co‑administration with ACE‑I: The SAVOR‑TIMI 53 trial showed no mortality benefit and greater adverse events—treat patients with hypertension using ARB *alone* or after ACE‑I discontinuation.
- Dose adjustment in elderly: Start at the lower end (80 mg) because pharmacokinetics shift; consider renal function rather than age alone.
- Cardiac remodeling endpoint: In HFrEF studies, 2 mg/kg BID achieved <30 % reduction in left‑ventricular mass index—a handy metric for echocardiographic follow‑up.
- Safety in hepatic impairment: No dose adjustment required for mild–moderate liver disease; contraindicated in severe hepatic failure due to increased serum concentrations (~2.5‑fold).
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