Varenicline is indicated for use as an aid to smoking cessation treatment.

Varenicline binds with high affinity and selectivity at α4β2 neuronal nicotinic acetylcholinereceptors. The efficacy of Varenicline in smoking cessation is believed to be the result of varenicline's activity at α4β2 sub-type of the nicotinic receptor where its binding produces agonist activity, while simultaneously preventing nicotine binding to these receptors.

Electrophysiology studies in vitro and neurochemical studies in vivo have shown that varenicline binds to α4β2 neuronal nicotinic acetylcholine receptors and stimulates receptor-mediated activity, but at a significantly lower level than nicotine. Varenicline blocks the ability of nicotine to activate α4β2 receptors and thus to stimulate the central nervous mesolimbic dopamine system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking. Varenicline is highly selective and binds more potently to α4β2 receptors than to other common nicotinic receptors ( >500-fold α3β4, >3,500fold α7, >20,000-fold α1βγδ), or to non-nicotinic receptors and transporters (> 2,000-fold). Varenicline also binds with moderate affinity (Ki = 350 nM) to the 5-HT3 receptor.

Smoking cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided additional advice and support. Provide patients with appropriate educational materials and counseling to support the quit attempt.

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

The recommended dose of Varenicline is 1 mg twice daily following a 1-week titration as follows:

• Days 1-3: 0.5 mg once daily
• Days 4-7: 0.5 mg twice daily
• Day 8-end of treatment: 1 mg twice daily

Patients should be treated with Varenicline for 12 weeks. For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks treatment with Varenicline is recommended to further increase the likelihood of long-term abstinence.

For patients who are sure that they are not able or willing to quit abruptly, consider a gradual approach to quitting smoking with Varenicline. 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 Varenicline treatment for an additional 12 weeks, for a total of 24 weeks of treatment. Encourage patients to attempt quitting sooner if they feel ready

Patients who are motivated to quit, and who did not succeed in stopping smoking during prior Varenicline therapy for reasons other than intolerability due to adverse events or who relapsed after treatment, should be encouraged to make another attempt with Varenicline once factors contributing to the failed attempt have been identified and addressed.

Consider a temporary or permanent dose reduction in patients who cannot tolerate the adverse effects of Varenicline.

Varenicline should be taken orally after eating and with a full glass of water.

May increase intoxicating effects of alcohol.

Known hypersensitivity to varenicline or to any of the excipients in the product (microcrystalline cellulose, dibasic calcium phosphate, anhydrous, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, Opadry Blue/White and Opadry Clear).

Nasopharyngitis, bronchitis, sinusitis, increased wt, decreased &/or increased appetite, abnormal dreams, insomnia, headache, somnolence, dizziness, dysgeusia, dyspnea, cough, nausea, GERD, vomiting, constipation, diarrhea, abdominal distension & pain, toothache, dyspepsia, flatulence, dry mouth, rash, pruritus, arthralgia, myalgia, back pain, chest pain, fatigue, abnormal liver function test.

Use in Pregnancy: Category C. There are no adequate and well-controlled studies in pregnant women. Varenicline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 

Use in Lactation: It is unknown whether varenicline is excreted in human breast milk. Animal studies suggest that varenicline is excreted in breast milk. A decision on whether to discontinue breast-feeding or to discontinue therapy with varenicline should be made taking into account the benefit of breast-feeding to the child and the benefit of varenicline therapy to the woman

Discontinue use if changes in behavior or thinking, agitation or depressed mood, anxiety, psychosis, mood swings, aggressive behavior, agitation, depressed mood, suicidal ideation & behavior. Concomitant use in patients attempting to quit smoking. Patients with history of seizures or other conditions that potentially lower seizure threshold. Report if patients had history of psychiatric illness prior to initiation. Hypersensitivity reactions including angioedema, swelling of the face, mouth (tongue, lips, gums), neck (throat & larynx) & extremities. Severe cutaneous reactions including Stevens-Johnson syndrome & erythema multiforme (rare).

Special Precautions for Disposal and Other Handling: No special requirements for disposal.

Drugs used in substance dependence