Varenicline
FDA Drug Information • Also known as: Tyrvaya, Varenicline
- Brand Names
- Tyrvaya, Varenicline
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Varenicline tablets contain varenicline (as the tartrate salt), which is a partial nicotinic agonist selective for α 4 β 2 nicotinic acetylcholine receptor subtypes. Varenicline, as the tartrate salt, is a powder which is a white to off-white to slightly yellow solid with the following chemical name: 7,8,9,10-tetrahydro-6,10-methano-6 H -pyrazino[2,3- h][3]benzazepine, (2 R ,3 R )-2,3-dihydroxybutanedioate (1:1). It is freely soluble in water and very slightly soluble in methanol. Varenicline tartrate has a molecular weight of 361.35 Daltons, and a molecular formula of C 13 H 13 N 3
What Is Varenicline Used For?
1 INDICATIONS AND USAGE 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 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION 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. ( 2.1 ) Starting Week: 0.5 mg once daily on days 1 to 3 and 0.5 mg twice daily on days 4 to 7. ( 2.1 ) Continuing Weeks: 1 mg twice daily for a total of 12 weeks. ( 2.1 ) An additional 12 weeks of treatment is recommended for successful quitters to increase likelihood of long-term abstinence. ( 2.1 ) 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. ( 2.1 ) 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. ( 2.2 ) Consider dose reduction for patients who cannot tolerate adverse effects. ( 2.1 ) 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. ( 2.1 ) Provide patients with appropriate educational materials and counseling to support the quit attempt. ( 2.1 ) 2.1 Usual Dosage for Adults 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 tablets dosing one week before this date. Alternatively, the patient can begin varenicline tablets dosing and then quit smoking between days 8 and 35 of treatment. Varenicline tablets should be taken orally after eating and with a full glass of water. The recommended dose of varenicline tablets are 1 mg twice daily following a 1-week titration as follows: Days 1 to 3: 0.5 mg once daily Days 4 to 7: 0.5 mg twice daily Day 8 to end of treatment: 1 mg twice daily Patients should be treated with varenicline tablets 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 tablets are 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 tablets. Patients should begin varenicline tablets dosing and reduce smoking by 50% from baseline within the...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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 premarketing studies, the most common adverse events associated with varenicline (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal (vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting. The treatment discontinuation rate due to adverse events in patients dosed with 1 mg twice daily was 12% for varenicline, compared to 10% for placebo in studies of three months’ treatment. In this group, the discontinuation rates that are higher than placebo for the most common adverse events in varenicline-treated patients were as follows: nausea (3% vs. 0.5% for placebo), insomnia (1.2% vs. 1.1% for placebo), and abnormal dreams (0.3% vs. 0.2% for placebo). Smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. 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. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. During the premarketing development of varenicline, over 4500 subjects were exposed to varenicline, with over 450 treated for at least 24 weeks and approximately 100 for a year. Most study participants were treated for 12 weeks or less. The most common adverse event associated with varenicline treatment is nausea, occurring in 30% of patients treated at the recommended dose, compared with 10% in patients taking a comparable placebo regimen [see Warnings and Precautions (5.9) ] . Table 1 shows the adverse events for varenicline and placebo in the 12- week fixed dose premarketing studies with titration in the first week [Studies 2 (titrated arm only), 4, and 5]. Adverse events were categorized using the Medical Dictionary for Regulatory Activities (MedDRA, Version 7.1). MedDRA High Level Group Terms (HLGT) reported in ≥5% of patients in the varenicline 1 mg twice daily dose group, and more commonly than in the placebo group, are listed, along with subordinate Preferred Terms (PT) reported in ≥1% of varenicline patients (and at least 0.5% more frequent than placebo). Closely related Preferred Terms such as ‘Insomnia’, ‘Initial insomnia’, ‘Middle insomnia’, ‘Early morning awakening’ were grouped, but individual patients reporting two or more grouped events are only counted once. Table 1. Common Treatment Emergent AEs (%) in the Fixed-Dose, Placebo-Controlled Studies (HLGTs >5% of Patients in the 1 mg BID varenicline Group and More Commonly than Placebo and PT ≥1% in the 1 mg BID varenicline Group, and 1 mg BID varenicline at Least 0.5% More than Placebo) SYSTEM ORGAN CLASS High Level Group Term Preferred Term Varenicline 0.5 mg BID N=129 Varenicline 1 mg BID N=821 Placebo N=805 * Includes PTs Abdominal (pain, pain upper, pain...
Drug Interactions
7 DRUG INTERACTIONS 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. ( 7.2 ) 7.1 Use with Other Drugs for Smoking Cessation Safety and efficacy of varenicline in combination with other smoking cessation therapies have not been studied. Bupropion Varenicline (1 mg twice daily) did not alter the steady-state pharmacokinetics of bupropion (150 mg twice daily) in 46 smokers. The safety of the combination of bupropion and varenicline has not been established. Nicotine replacement therapy (NRT) Although co-administration of varenicline (1 mg twice daily) and transdermal nicotine (21 mg/day) for up to 12 days did not affect nicotine pharmacokinetics, the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue was greater for the combination than for NRT alone. In this study, eight of twenty-two (36%) patients treated with the combination of varenicline and NRT prematurely discontinued treatment due to adverse events, compared to 1 of 17 (6%) of patients treated with NRT and placebo. 7.2 Effect of Smoking Cessation on Other Drugs Physiological changes resulting from smoking cessation, with or without treatment with varenicline, may alter the pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) for which dosage adjustment may be necessary.
Contraindications
4 CONTRAINDICATIONS 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. ( 4 )
Pregnancy and Breastfeeding
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 animal studies, varenicline did not result in major malformations but caused decreased fetal weights in rabbits when dosed during organogenesis at exposures equivalent to 50 times the exposure at the maximum recommended human dose (MRHD). Additionally, administration of varenicline to pregnant rats during organogenesis through lactation produced developmental toxicity in offspring at maternal exposures equivalent to 36 times human exposure at the MRHD [see Data] . The estimated background risk of oral clefts is increased by approximately 30% in infants of women who smoke during pregnancy, compared to pregnant women who do not smoke. The background risk of other major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk 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. Data Human Data A population-based observational cohort study using the national registers of Denmark and Sweden compared pregnancy and birth outcomes among women exposed to varenicline (N=335, includes 317 first trimester exposed) with women...
Overdosage
10 OVERDOSAGE 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Varenicline tablets are supplied for oral administration in two strengths: 0.5 mg are capsular, biconvex, white, film-coated tablets debossed with ‘VA’ on one side and ‘0.5’ on the other side. 1 mg are capsular, biconvex, light blue, film-coated tablets debossed with ‘VA’ on one side and ‘1’ on the other side. Varenicline Tablets are supplied in the following package configurations: Packs Starting 4-week card: 0.5 mg x 11 tablets and 1 mg x 42 tablets NDC 59651-451-53 Continuing 4-week card: 1 mg x 56 tablets NDC 59651-418-55 Starting Month Box: 0.5 mg x 11 tablets and 1 mg x 42 tablets NDC 59651-451-53 Continuing Month Box: 1 mg x 56 tablets NDC 59651-418-55 Bottles 0.5 mg Bottles of 56 NDC 59651-417-56 1 mg Bottles of 56 NDC 59651-418-56 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.