Varenicline Tartrate
Indications
Varenicline Tartrate is a nicotinic receptor partial agonist indicated for use as an aid to smoking cessation treatment.
Pharmacology
Varenicline binds with high affinity and selectivity at α4β2 neuronal nicotinic acetylcholine receptors. 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, >3,500-fold 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.
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, >3,500-fold 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.
Dosage & Administration
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.
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.
Interaction
Other Smoking Cessation Therapies: Safety and efficacy in combination with other smoking cessation therapies has not been established. Coadministration of varenicline and transdermal nicotine resulted in a high rate of discontinuation due to adverse events.
Effect of Smoking Cessation on Other Drugs: Pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) may be altered, necessitating dose adjustment.
Effect of Smoking Cessation on Other Drugs: Pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) may be altered, necessitating dose adjustment.
Contraindications
History of serious hypersensitivity or skin reactions to Varenicline Tartrate.
Side Effects
Most common adverse reactions (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal (e.g., vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting.
Pregnancy & Lactation
Available data have not suggested an increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke. Smoking during pregnancy is associated with maternal, fetal, and neonatal risks. There are no data on the presence of varenicline in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies varenicline was present in milk of lactating rats.
Precautions & Warnings
Neuropsychiatric Adverse Events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with Varenicline for the occurrence of such symptoms and instruct them to discontinue Varenicline and contact a healthcare provider if they experience such adverse events.
Seizures: New or worsening seizures have been observed in patients taking Varenicline. Varenicline should be used cautiously in patients with a history of seizures or other factors that can lower the seizure threshold.
Interaction with Alcohol: Increased effects of alcohol have been reported. Instruct patients to reduce the amount of alcohol they consume until they know whether Varenicline affects them.
Accidental Injury: Accidental injuries (e.g., traffic accidents) have been reported. Instruct patients to use caution driving or operating machinery until they know how Varenicline may affect them.
Cardiovascular Events: Patients with underlying cardiovascular (CV) disease may be at increased risk of CV events; however, these concerns must be balanced with the health benefits of smoking cessation. Instruct patients to notify their healthcare providers of new or worsening CV symptoms and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction (MI) or stroke.
Somnambulism: Cases of somnambulism have been reported in patients taking Varenicline. Some cases described harmful behavior to self, others, or property. Instruct patients to discontinue Varenicline and notify their healthcare provider if they experience somnambulism.
Angioedema and Hypersensitivity Reactions: Such reactions, including angioedema, infrequently life-threatening, have been reported. Instruct patients to discontinue Varenicline and immediately seek medical care if symptoms occur.
Serious Skin Reactions: Rare, potentially life-threatening skin reactions have been reported. Instruct patients to discontinue Varenicline and contact a healthcare provider immediately at first appearance of skin rash with mucosal lesions.
Nausea: Nausea is the most common adverse reaction (up to 30% incidence rate). Dose reduction may be helpful.
Seizures: New or worsening seizures have been observed in patients taking Varenicline. Varenicline should be used cautiously in patients with a history of seizures or other factors that can lower the seizure threshold.
Interaction with Alcohol: Increased effects of alcohol have been reported. Instruct patients to reduce the amount of alcohol they consume until they know whether Varenicline affects them.
Accidental Injury: Accidental injuries (e.g., traffic accidents) have been reported. Instruct patients to use caution driving or operating machinery until they know how Varenicline may affect them.
Cardiovascular Events: Patients with underlying cardiovascular (CV) disease may be at increased risk of CV events; however, these concerns must be balanced with the health benefits of smoking cessation. Instruct patients to notify their healthcare providers of new or worsening CV symptoms and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction (MI) or stroke.
Somnambulism: Cases of somnambulism have been reported in patients taking Varenicline. Some cases described harmful behavior to self, others, or property. Instruct patients to discontinue Varenicline and notify their healthcare provider if they experience somnambulism.
Angioedema and Hypersensitivity Reactions: Such reactions, including angioedema, infrequently life-threatening, have been reported. Instruct patients to discontinue Varenicline and immediately seek medical care if symptoms occur.
Serious Skin Reactions: Rare, potentially life-threatening skin reactions have been reported. Instruct patients to discontinue Varenicline and contact a healthcare provider immediately at first appearance of skin rash with mucosal lesions.
Nausea: Nausea is the most common adverse reaction (up to 30% incidence rate). Dose reduction may be helpful.
Therapeutic Class
Drugs used in substance dependence
Storage Conditions
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
