AdultPediatricDosage Forms & Strengths tablet 0.5mg 1mg Smoking Cessation Set a date to stop smoking and begin varenicline 1 week before this date Alternatively, the patient can begin varenicline and then quit smoking between days 8 and 35 of treatment Also see Administration Quit smoking date regimen Initiate regimen 1 week before quit smoking date Days 1-3: 0.5 mg PO qDay Days 4-7: 0.5 mg PO BID Day 8 to end of treatment: 1 mg PO BID If quitting is successful after 12 weeks, continue another 12 weeks at 1 mg q12hr Gradual approach to quitting For patients who are sure that they are not able or willing to quit abruptly, consider a gradual approach to quitting smoking with varenicline Begin dosing and reduce smoking by 50% from baseline within the first 4 weeks, by an additional 50% in the next 4 weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks Continue varenicline for an additional 12 weeks, for a total of 24 weeks of treatment Encourage patients to attempt quitting sooner if they feel ready Dosage Modifications Consider a temporary or permanent dose reduction in patients who cannot tolerate the adverse effects Renal impairment Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment required Severe (CrCl <30 mL/min): 0.5 mg PO qDay initially; may increase to 0.5 mg PO q12hr ESRD on hemodialysis: Not to exceed 0.5 mg PO qDay <18 years: Safety and efficacy not establishedInteraction CheckerEnter a drug name and vareniclineNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (0)Serious - Use Alternative (2)tafenoquinetafenoquine will increase the level or effect of varenicline by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.trilaciclibtrilaciclib will decrease the level or effect of varenicline by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities. Monitor Closely (10)dichlorphenamidedichlorphenamide and varenicline both decrease serum potassium. Use Caution/Monitor.erdafitiniberdafitinib increases levels of varenicline by increasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.ethanolvarenicline increases effects of ethanol by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration have resulted in some patients experiencing increased intoxicating effects of alcohol, sometimes associated with aggressive behavior and/or amnesia. Advise patients to reduce the amount of alcohol they consume while taking varenicline until they know whether it affects their tolerance for alcohol.famotidinefamotidine will increase the level or effect of varenicline by decreasing renal clearance. Use Caution/Monitor.ibuprofen/famotidineibuprofen/famotidine will increase the level or effect of varenicline by decreasing renal clearance. Use Caution/Monitor.nicotine inhaledvarenicline increases toxicity of nicotine inhaled by Other (see comment). Use Caution/Monitor. Comment: Varenicline is a partial agonist at the nicotinic Ach receptor; concomitant use with nicotine replacement therapy may increase adverse effects.nicotine intranasalvarenicline increases toxicity of nicotine intranasal by Other (see comment). Use Caution/Monitor. Comment: Varenicline is a partial agonist at the nicotinic Ach receptor; concomitant use with nicotine replacement therapy may increase adverse effects.nizatidinenizatidine will increase the level or effect of varenicline by decreasing renal clearance. Use Caution/Monitor.tobramycin inhaledtobramycin inhaled and varenicline both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicityvandetanibvandetanib increases levels of varenicline by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).Minor (2)cimetidinecimetidine increases levels of varenicline by decreasing renal clearance. Minor/Significance Unknown.isavuconazonium sulfateisavuconazonium sulfate will increase the level or effect of varenicline by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.cimetidineMinor (1)cimetidine increases levels of varenicline by decreasing renal clearance. Minor/Significance Unknown.dichlorphenamideMonitor Closely (1)dichlorphenamide and varenicline both decrease serum potassium. Use Caution/Monitor.erdafitinibMonitor Closely (1)erdafitinib increases levels of varenicline by increasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.ethanolMonitor Closely (1)varenicline increases effects of ethanol by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration have resulted in some patients experiencing increased intoxicating effects of alcohol, sometimes associated with aggressive behavior and/or amnesia. Advise patients to reduce the amount of alcohol they consume while taking varenicline until they know whether it affects their tolerance for alcohol.famotidineMonitor Closely (1)famotidine will increase the level or effect of varenicline by decreasing renal clearance. Use Caution/Monitor.ibuprofen/famotidineMonitor Closely (1)ibuprofen/famotidine will increase the level or effect of varenicline by decreasing renal clearance. Use Caution/Monitor.isavuconazonium sulfateMinor (1)isavuconazonium sulfate will increase the level or effect of varenicline by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.nicotine inhaledMonitor Closely (1)varenicline increases toxicity of nicotine inhaled by Other (see comment). Use Caution/Monitor. Comment: Varenicline is a partial agonist at the nicotinic Ach receptor; concomitant use with nicotine replacement therapy may increase adverse effects.nicotine intranasalMonitor Closely (1)varenicline increases toxicity of nicotine intranasal by Other (see comment). Use Caution/Monitor. Comment: Varenicline is a partial agonist at the nicotinic Ach receptor; concomitant use with nicotine replacement therapy may increase adverse effects.nizatidineMonitor Closely (1)nizatidine will increase the level or effect of varenicline by decreasing renal clearance. Use Caution/Monitor.tafenoquineSerious - Use Alternative (1)tafenoquine will increase the level or effect of varenicline by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.tobramycin inhaledMonitor Closely (1)tobramycin inhaled and varenicline both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicitytrilaciclibSerious - Use Alternative (1)trilaciclib will decrease the level or effect of varenicline by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities. vandetanibMonitor Closely (1)vandetanib increases levels of varenicline by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2). >10% Nausea (15-40%; dose related) Abnormal dreams Headache Insomnia 1-10% Appetite changes Chest pain Constipation Dry mouth Dyspepsia Dyspnea Flatulence Gastroesophageal reflux disease (GERD) Fatigue or lethargy Pruritus Rash Somnolence Rhinorrhea Vomiting Upper respiratory tract disorder Frequency Not Defined (selected) Abnormal liver function tests Anemia Anxiety Arrhythmia Arthralgia Depression Diarrhea Dizziness Epistaxis Hypertension Myocardial infarction (MI) Polyuria Respiratory disorder Postmarketing Reports Depression, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide, somnambulism Serious skin reactions, including Stevens-Johnson syndrome Cerebrovascular accident Seizures MI Cardiovascular: During nontreatment follow-up to 52 weeks, adjudicated events comparing patients with stable cardiovascular disease to premarket studies included need for coronary revascularization (2.0% vs 0.6%), hospitalization for angina pectoris (1.7% vs 1.1%), and new diagnosis of peripheral vascular disease (PVD) or admission for PVD procedure (1.4% vs 0.6%) Irritability Agitation Somnambulism Contraindications Documented hypersensitivity or skin reactions to drug or components of formulation Nonsmokers Cautions May cause nausea; reduce dose if nausea occurs Somnambulism reported, including cases describing harmful behavior to self, others, or property; instruct patients to discontinue varenicline and notify their healthcare professional Seizures reported; some patients had no history of seizures, whereas others had a history of seizure disorder that was remote or well-controlled; in most cases, the seizure occurred within the first month of therapy; use with caution in patients with history of seizures or with other factors that might lower seizure threshold May cause CNS depression; use caution when performing tasks requiring mental alertness, such as, operating heavy machinery or driving Hypersensitivity reactions reported, including angioedema Rare but serious skin reactions reported, including Stevens-Johnson Syndrome and erythema multiforme Neuropsychiatric adverse effects Serious neuropsychiatric adverse events reported; these postmarketing reports include 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 Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication; however, some of these adverse events occurred in patients taking varenicline who continued to smoke Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses Some neuropsychiatric adverse events, including unusual and sometimes aggressive behavior directed to oneself or others, may have been worsened by concomitant use of alcohol Advise patients and caregivers that the patient should stop taking varenicline and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical are observed, or if the patient develops suicidal ideation or suicidal behavior Alcohol interaction Patients should reduce amount alcohol they consume when initiating therapy until they know whether it increases intoxicating effects Postmarketing reports of patients experiencing increased intoxicating effects of alcohol while taking varenicline; some cases described unusual and sometimes aggressive behavior, and were often accompanied by amnesia for the events Cardiovascular risk May increase risk of cardiovascular events in patients with underlying cardiovascular disease; randomized, double-blind, placebo-controlled study of 700 patients treated with varenicline for smoking cessation found increases in risk of nonfatal MI, need for revascularization, angina pectoris, and peripheral vascular disease In FDA meta-analysis, varenicline (compared with placebo) showed nonsignificant increase in risk for major adverse cardiovascular events (ie, combined outcome of cardiovascular-related death, nonfatal heart attack, and nonfatal stroke); these events were uncommon in both groups Pregnancy Available data have not suggested increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke; smoking during pregnancy causes increased risks of orofacial clefts, premature rupture of membranes, placenta previa, placental abruption, ectopic pregnancy, fetal growth restriction and low birth weight, stillbirth, preterm delivery and shortened gestation, neonatal death, sudden infant death syndrome and reduction of lung function in infants; it is not known whether quitting smoking with varenicline during pregnancy reduces these risks Lactation Because there are no data on presence of varenicline in human milk and effects on breastfed infant, breastfeeding women should monitor their infant for seizures and excessive vomiting, which are adverse reactions that have occurred in adults that may be clinically relevant in breastfeeding infantsPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Agonist at nicotinic receptors; acts on mesolimbic dopamine system associated with nicotine addiction, where it prevents nicotine stimulation; stimulates nicotine activity but to lesser degree than nicotine does Absorption Completely absorbed Bioavailability: High Peak plasma time: 3-4 hr Distribution Protein bound: <20% Metabolism Minimally metabolized Elimination Excretion: Urine (92%) Half-life: 24 hr Excretion: Urine (92%) Oral Administration Take dose after eating with full glass of water Set date to stop smoking, and start varenicline 1 week before that date; alternatively, the patient can begin varenicline dosing and then quit smoking between days 8 and 35 of treatment 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