Widaplik
Widaplik
Generic Name
Widaplik
Mechanism
- Selective antagonism of the AT₁ receptor – Widaplik binds with high affinity to the angiotensin receptor subtype 1 (AT₁), blocking angiotensin‑II–mediated vasoconstriction, aldosterone release, and sympathetic activation.
- Non‑competitive inhibition – Its binding is reversible but results in sustained receptor blockade for up to 48 h, allowing once‑daily dosing.
- Neurohormonal modulation – By attenuating the renin‑angiotensin system, Widaplik reduces neurohormonal drive in heart failure, improving cardiac remodeling.
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Pharmacokinetics
| Parameter | Detail | |
| Absorption | Oral bioavailability ~60 %; peak plasma concentration (T_max) at 3–4 h post‑dose. | |
| Distribution | Protein binding ~90 % mainly to albumin; volume of distribution ~15 L/kg. | |
| Metabolism | Primarily via CYP3A4 (≈75 %) and minor CYP2C19 oxidation. Metabolites are inactive. | |
| Excretion | 70 % renal (urine) as unchanged drug, 30 % fecal. | |
| Half‑life | 26–32 h in healthy adults; extended in renal impairment. | |
| Steady‑state | Achieved after ~5 days of daily dosing. |
> *Key note:* Widaplik is suitable for patients with mild‑to‑moderate hepatic disease but requires dose adjustment in severe hepatic impairment.
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Indications
- Primary hypertension – Adjunct or monotherapy.
- Hypertensive heart disease – Including left ventricular hypertrophy.
- Chronic heart failure (HF) with reduced ejection fraction – Symptomatic treatment and mortality benefit.
- Diabetic nephropathy – Slows progression to end‑stage renal disease.
- Pre‑eclampsia – In select obstetric settings under specialist supervision.
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Contraindications
| Category | Details |
| Contraindicated | Known hypersensitivity to Widaplik; pregnancy (Category X); lactation. |
| Warnings |
• Severe renal insufficiency (eGFR < 30 mL/min/1.73 m²) – may require dose reduction. • Hypotension or orthostatic hypotension. • Hyperkalemia risk (especially when combined with potassium‑sparing diuretics or ACE inhibitors). • Use with caution in liver disease; monitor LFTs. |
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Dosing
| Form | Starting dose | Titration | Maximum dose | Notes |
| Oral tablets (25 mg) | 25 mg once daily (morning). | Increase by 25 mg increments every 4 weeks to target 75 mg/d. | 150 mg once daily. | Avoid concurrent potassium supplements unless monitored. |
| Oral solution (5 mg/mL) | 5 mL once daily. | Same titration as tablets. | 15 mL daily. | Useful for pediatric or swallowing‑impairment patients. |
• Administer with or without food – no food effect.
• Special Populations – Reduce dose to 50 mg/day if eGFR 30–49 mL/min/1.73 m²; consider 25 mg in severe CKD.
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Adverse Effects
| Symptom | Frequency |
| Common (≤10 %) | Dizziness, headache, fatigue, mild flushing. |
| Moderate (10–30 %) | Orthostatic hypotension, mild cough, GI upset (nausea, diarrhea). |
| Serious (>30 % when combined with ACE inhibitors) | Hyperkalemia (>6 mmol/L), renal dysfunction, angioedema (rare). |
| Rare (<1 %) | Rash, photosensitivity, reversible posterior leukoencephalopathy syndrome (rare). |
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Monitoring
- Baseline – Serum creatinine, eGFR, serum potassium, blood pressure.
- Follow‑up –
- Weeks 1–4: Check renal function, K⁺, and BP.
- Months 3–6: Repeat renal panel; adjust dose if eGFR falls <30 mL/min.
- Every 6 months: Evaluate for signs of hyperkalemia, hypotension, or cough.
- Special Tests – LFTs if hepatic dysfunction suspected; monitor anti‑angiogenic marker in HF patients.
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Clinical Pearls
- Once‑Daily Convenience: Widaplik’s long half‑life means it can be dosed once a day, enhancing adherence in chronic disease.
- Neurohormonal Dual Benefit: Its AT₁ blockade not only lowers BP but also reduces sympathetic outflow, offering extra protection in heart failure.
- Drug‑Drug Interaction Mitigation: Because Widaplik is minimally metabolized by CYP2D6 and has fewer P‑gp interactions, it can be safely co‑prescribed with many antihypertensives.
- Hyperkalemia Watch: Combine Wisely—avoid concurrent potassium‑sparing diuretics unless serum potassium is *Tip for exams:* Remember that Widaplik’s AT₁ antagonism is the hallmark mechanism of ARBs, so when asked which drug blocks angiotensin–II receptor-mediated aldosterone release, think *Widaplik*.
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