Varenicline

Varenicline tablets are indicated for use as an aid to smoking cessation treatment. Varenicline tablets are a nicotinic receptor partial agonist indicated for use as an aid to smoking cessation treatment. ( 1 and 2.1 )

• Begin varenicline tablets dosing one week before the date set by the patient to stop smoking
• Alternatively, the patient can begin varenicline tablets dosing and then quit smoking between days 8 and 35 of treatment
• Starting Week: 0.5 mg once daily on days 1 to 3 and 0.5 mg twice daily on days 4 to 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 tablets for patients who are sure that they are not able or willing to quit abruptly
• Patients should begin varenicline tablets 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. …

Varenicline tablets 0.5 mg are capsular, biconvex, white, film-coated tablets debossed with ‘VA’ on one side and ‘0.5’ on the other side. Varenicline tablets 1 mg are capsular, biconvex, light blue, film-coated tablets debossed with ‘VA’ on one side and ‘1’ on the other side. Tablets: 0.5 mg and 1 mg ( 3 )

• Varenicline is not recommended for use
• In pediatric patients 16 years of age or younger because its efficacy in this population was not demonstrated
• Single and multiple-dose pharmacokinetics of varenicline have been investigated
• In pediatric patients aged 12 to 17 years old (inclusive) and were approximately dose-proportional over the 0.5 mg to 2 mg daily dose range studied
• Steady-state systemic exposure in adolescent patients of bodyweight >55 kg, as assessed by AUC (0 to 24), was comparable to that noted for the same doses in the adult population. …

A combined single- and multiple-dose pharmacokinetic study demonstrated that the pharmacokinetics of 1 mg varenicline given once daily or twice daily to 16 healthy elderly male and female smokers (aged 65 to 75 years) for 7 consecutive days was similar to that of younger subjects. …

• See FDA-approved patient labeling (Medication Guide) Initiate Treatment and Continue to Attempt to Quit if Lapse Instruct patients to set a date to quit smoking and to initiate varenicline tablets treatment one week before the quit date
• Alternatively, the patient can begin varenicline tablets dosing and then set a date to quit smoking between days 8 and 35 of treatment
• Encourage patients to continue to attempt to quit if they have early lapses after quit day [see Dosage and Administration ]
• For patients who are sure that they are not able or willing to quit abruptly, a gradual approach to quitting smoking with varenicline tablets may be considered. …

• Varenicline tablets are contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline tablets
• History of serious hypersensitivity or skin reactions to varenicline tablets

Based on varenicline characteristics and clinical experience to date, varenicline has no clinically meaningful pharmacokinetic drug interactions [see Clinical Pharmacology (12.3) ]. 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. ( 7.1 ) Effect of Smoking Cessation on Other Drugs: Pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) may be altered, necessitating dose adjustment. …

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. ( 5.1 ) Seizures: New or worsening seizures have been observed in patients taking varenicline. …

The following serious adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the labeling: Neuropsychiatric Adverse Events including Suicidality [see Warnings and Precautions (5.1) ] Seizures [see Warnings and Precautions (5.2) ] Interaction with Alcohol [see Warnings and Precautions (5.3) ] Accidental Injury [see Warnings and Precautions (5.4) ] Cardiovascular Events [see Warnings and Precautions (5.5) ] Somnambulism [see Warnings and Precautions (5.6) ] Angioedema and Hypersensitivity Reactions [see Warnings and Precautions (5.7) ] Serious Skin Reactions [see Warnings and Precautions (5.8) ] In the placebo-controlled premarketin …

8.1 Pregnancy Risk Summary Available data have not suggested an increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke [see Data]. Smoking during pregnancy is associated with maternal, fetal, and neonatal risks (see Clinical Considerations) . …

In case of overdose, standard supportive measures should be instituted as required. Varenicline has been shown to be dialyzed in patients with end-stage renal disease [see Clinical Pharmacology (12.3) ], however, there is no experience in dialysis following overdose.

9.1 Controlled Substance Varenicline is not a controlled substance. 9.3 Dependence Humans Fewer than 1 out of 1,000 patients reported euphoria in clinical trials with varenicline. At higher doses (greater than 2 mg), varenicline produced more frequent reports of gastrointestinal disturbances such as nausea and vomiting. There is no evidence of dose-escalation to maintain therapeutic effects in clinical studies, which suggests that tolerance does not develop. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.