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Varenicline

Chantix

Nicotinic Partial AgonistGeneric availableTDM data

Varenicline binds with high affinity and selectivity at the alpha4-beta2 neuronal nicotinic acetylcholine receptor, where it acts as a partial agonist — providing modest dopamine release to reduce craving and withdrawal, while simultaneously blocking nicotine from binding and reducing the reinforcing effects of smoking.

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FDA-Approved Indications

  • Aid to smoking cessation treatment in adults

What Sets This Drug Apart

  • Most effective single-agent pharmacotherapy for smoking cessation — NNT ~8-10 vs placebo at 6 months
  • Nausea in ~30% of patients — the most common side effect and primary reason for discontinuation
  • Minimal drug-drug interaction potential — 92% renally eliminated unchanged, no CYP involvement
  • FDA removed neuropsychiatric boxed warning in 2016 after EAGLES trial (N=8144) showed no signal vs NRT or placebo
  • Unique mechanism — partial agonist at alpha4beta2 nAChR provides craving relief while blocking nicotine reward