Varenicline
Varenicline
Generic Name
Varenicline
Mechanism
- Varenicline is a *partial agonist* at neural α4β2 nicotinic acetylcholine receptors (nAChRs), the primary binding sites for nicotine in the brain.
- By binding to these receptors, it reduces nicotine withdrawal symptoms (e.g., irritability, anxiety, increased appetite) and blocks nicotine’s reinforcing effects, decreasing craving and the rewarding experience of smoking.
- The drug’s partial agonist activity produces a moderate depolarizing effect on the receptor, sufficient for relief of withdrawal but not enough to elicit the high associated with nicotine.
Pharmacokinetics
| Parameter | Details |
| Absorption | Oral bioavailability ≈ 61–71 % (food does not alter absorption significantly). Peak plasma concentrations at 2–4 h post‑dose. |
| Distribution | Volume of distribution ≈ 43 L. Highly protein‑bound (~ 95 %); crosses the blood–brain barrier. |
| Metabolism | Primarily via acetylation and hydrolysis; no major CYP450 involvement, so interaction potential is low. |
| Elimination | Renally excreted (≈ 70 % unchanged); other routes include hepatic and biliary. Half‑life ≈ 24 h (extending to 60–70 h in reduced renal function). |
| Dose Adjustment | No dosage adjustment needed for mild–moderate hepatic impairment; consider caution in severe renal impairment (CrCl < 30 mL/min). |
Indications
- Smoking cessation in adults and adolescents ≥ 12 yrs.
- Part of a treatment sequence after first‑line therapies (e.g., nicotine replacement, bupropion).
- Use is not recommended for nicotine abuse or addiction outside tobacco products.
Contraindications
- Absolute contraindication: Severe hepatic impairment (Child‑Pugh C).
- Warnings:
- Psychiatric disorders (depression, suicidal ideation, self‑harm behaviors). Discuss baseline mental status and monitor closely.
- Cardiovascular disease: Frontal‑wall ECG changes and QT prolongation possible; use with caution in patients with pre‑existing arrhythmias.
- Renal impairment: Use with caution; not studied in CrCl < 30 mL/min.
Dosing
| Week | Dose | Frequency |
| 0–1 | 0.5 mg (day 1) → 0.5 mg twice daily (day 2) | BID |
| 2–4 | 0.5 mg BID (days 8–14) | BID |
| 5–8 | 1.0 mg BID (days 15–56) | BID |
| 9–12 | 1.0 mg BID (days 57–84) | BID |
• Initiate *at least 10 days pre‑quit date* (“pre‑treatment moment”).
• Continue therapy for 12–16 weeks; may extend to 16 weeks in heavy smokers or comorbidities.
• Titration: Two‑step rise avoids peak plasma concentration (and nausea risk).
Adverse Effects
- GI: Nausea, vomiting, constipation, diarrhea (up to 20 % of patients).
- Sleep disturbances: Insomnia, vivid dreams, nightmares.
- Neurologic: Headache, dizziness, fatigue.
- Psychiatric: Depression, anxiety, irritability, self‑harm behavior; rarely, psychosis.
- Cardiac: Palpitations, tachycardia, possible QT prolongation (monitored in high‑risk patients).
- Rare: Severe allergic reactions, hypersensitivity.
Monitoring
- Baseline and periodic mental status exam; use PHQ‑9 or similar depression scale.
- Renal function: CrCl/BUN & creatinine before therapy & at 4‑12 week intervals if risk factors present.
- ECG (baseline, especially in arrhythmia history); re‑check if symptomatic.
- Weight: Document baseline; monitor for weight gain ≥ 5 % over 12 weeks.
- Adverse events: Provide a 24‑hr contact for severe reactions or suicidal ideation.
Clinical Pearls
- Pre‑treatment window: Starting *10 days before quit date* improves quit rates by 21 %.
- Dual therapy: In drastic smokers (≥ 20 cig/day), combine varenicline with nicotine patch or gum for the first 2–4 weeks.
- Counseling: Encourage patients to begin behavioral support (telephone counseling, mobile apps, or group therapy) alongside pharmacotherapy.
- Drug interaction savvy: *Varenicline* lacks significant CYP induction or inhibition; minimal interaction with most antidepressants or antihypertensives.
- Renal cautiousness: In CrCl 30–49 mL/min, avoid doubling dose; monitor for accumulation.
- Dietary advice: No special diet required; take with/without food – no food‑drug interaction.
- Gender considerations: No dose adjustment needed; meta‑analyses show similar efficacy in men and women.
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• *Keep this card handy for quick reference when prescribing or reviewing **varenicline* for smoking cessation. For in‑depth pharmacokinetic data and clinical trial outcomes, refer to the latest *American College of Physicians* guidelines and peer‑reviewed pharmacology journals.*