Varenicline Tartrate is a nicotinic receptor partial agonist indicated as an aid to smoking cessation treatment.

Varenicline binds with high affinity and selectivity to α4β2 neuronal nicotinic acetylcholine receptors. Its effectiveness in smoking cessation is believed to result from partial agonist activity at α4β2 receptors, while also preventing nicotine from binding to these receptors.

Electrophysiological and neurochemical studies show that varenicline stimulates receptor-mediated activity at a lower level than nicotine. It blocks nicotine-induced activation of α4β2 receptors and reduces stimulation of the mesolimbic dopamine system, which is associated with reinforcement and reward from smoking. Varenicline is highly selective, binding more strongly to α4β2 receptors than to other nicotinic receptors (>500-fold α3β4, >3,500-fold α7, >20,000-fold α1βγδ), and also shows minimal binding to non-nicotinic receptors and transporters. It also binds with moderate affinity to the 5-HT3 receptor (Ki = 350 nM).

Begin Varenicline dosing one week before the date set by the patient to stop smoking. Alternatively, the patient can begin Varenicline dosing and then quit smoking between days 8 and 35 of treatment.

Starting Week: 0.5 mg once daily on days 1-3 and 0.5 mg twice daily on days 4-7.

Continuing Weeks: 1 mg twice daily for a total of 12 weeks.

An additional 12 weeks of treatment is recommended for successful quitters to increase likelihood of long-term abstinence.

Consider a gradual approach to quitting smoking with Varenicline for patients who are sure that they are not able or willing to quit abruptly. Patients should begin Varenicline dosing and reduce smoking by 50% from baseline within the first four weeks, by an additional 50% in the next four weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks. Continue treatment for an additional 12 weeks, for a total of 24 weeks.

Severe Renal Impairment (estimated creatinine clearance less than 30 mL/min): Begin with 0.5 mg once daily and titrate to 0.5 mg twice daily. For patients with end-stage renal disease undergoing hemodialysis, a maximum of 0.5 mg daily may be given if tolerated.

Consider dose reduction for patients who cannot tolerate adverse effects.

Another attempt at treatment is recommended for those who fail to stop smoking or relapse when factors contributing to the failed attempt have been addressed.

Provide patients with appropriate educational materials and counseling to support the quit attempt.

Pediatric Use: Varenicline is not recommended for use in pediatric patients 16 years of age or younger because its efficacy in this population was not demonstrated.

Other Smoking Cessation Therapies: The safety and efficacy of varenicline in combination with other smoking cessation therapies have not been established. Co-administration with transdermal nicotine resulted in a high rate of treatment discontinuation due to adverse effects.

Effect of Smoking Cessation on Other Drugs: Smoking cessation may alter the pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin), requiring dose adjustment.

History of serious hypersensitivity or severe skin reactions to Varenicline Tartrate.

The most common adverse reactions (>5% and at least twice the placebo rate) include nausea, abnormal dreams, constipation, flatulence, and vomiting.

Available data do not suggest an increased risk of major birth defects compared with women who smoke. Smoking during pregnancy is associated with maternal, fetal, and neonatal risks. There are no adequate data regarding the presence of varenicline in human milk or its effects on breastfed infants. In animal studies, varenicline was detected in the milk of lactating rats.

Neuropsychiatric Adverse Events: Postmarketing reports include mood changes (depression, mania), psychosis, hallucinations, paranoia, aggression, anxiety, suicidal ideation, and suicide-related behavior. Patients should be monitored and advised to discontinue varenicline if such symptoms occur.

Seizures: Seizures have been reported. Use with caution in patients with a history of seizures or other risk factors.

Alcohol Interaction: Alcohol effects may be increased. Patients should reduce alcohol intake until individual response is known.

Accidental Injury: Dizziness and reduced attention may occur. Caution is advised when driving or operating machinery.

Cardiovascular Events: Patients with cardiovascular disease may have an increased risk of events; monitor for new or worsening symptoms.

Somnambulism: Sleepwalking has been reported; discontinue use if it occurs.

Angioedema & Hypersensitivity: Rare but serious reactions may occur; discontinue immediately if symptoms develop.

Serious Skin Reactions: Discontinue at the first sign of rash with mucosal involvement.

Nausea: The most common adverse effect; dose reduction may help manage symptoms.

Drugs used in substance dependence

Store below 30°C, protected from light and moisture. Keep out of the reach of children.