CHANTIX® (varenicline tartrate) 8 USE IN SPECIFIC POPULATIONS

(varenicline tartrate)

Prescribing Information

8 USE IN SPECIFIC POPULATIONS

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 US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, 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 CHANTIX 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 who smoked during pregnancy (N=78,412) and with non-smoking pregnant women (N=806,438). The prevalence of major malformations, the primary outcome, was similar in all groups, including between smoking and non-smoking groups. The prevalence of adverse perinatal outcomes in the varenicline-exposed cohort was not greater than in the cohort of women who smoked, and differed somewhat between the three cohorts. The prevalences of the primary and secondary outcomes are shown in Table 6.

Table 6. Summary of Primary and Secondary Outcomes for Three Birth Cohorts
Outcome	Varenicline Cohort (n=335)	Smoking Cohort (n=78,412)	Non-Smoking Cohort (n=806,438)
* Included only live births in the cohorts. Prevalence among first trimester varenicline-exposed pregnancies (11/317 [3.5%]). † There was a lag in death data in Denmark, so the cohorts were smaller.
Major congenital malformation*	12 / 334 (3.6%)	3,382 / 78,028 (4.3%)	33,950 /804,020 (4.2%)
Stillbirth	1 (0.3%)	384 (0.5%)	2,418 (0.3%)
Small for gestational age	42 (12.5%)	13,433 (17.1%)	73,135 (9.1%)
Preterm birth	25 (7.5%)	6,173 (7.9%)	46,732 (5.8%)
Premature rupture of membranes	12 (3.6%)	4,246 (5.4%)	30,641 (3.8%)
Sudden infant death syndrome†	0/307 (0.0%)	51/71,720 (0.1%)	58/755,939 (<0.1%)

The study limitations include the inability to capture malformations in pregnancies that do not result in a live birth, and possible misclassification of outcome and of exposure to varenicline or to smoking.

Other small epidemiological studies of pregnant women exposed to varenicline did not identify an association with major malformations, consistent with the Danish and Swedish observational cohort study. Methodological limitations of these studies include small samples and lack of adequate controls.

Overall, available studies cannot definitely establish or exclude any varenicline-associated risk during pregnancy.

Animal Data

Pregnant rats and rabbits received varenicline succinate during organogenesis at oral doses up to 15 and 30 mg/kg/day, respectively. While no fetal structural abnormalities occurred in either species, maternal toxicity, characterized by reduced body weight gain, and reduced fetal weights occurred in rabbits at the highest dose (exposures 50 times the human exposure at the MRHD of 1 mg twice daily based on AUC). Fetal weight reduction did not occur in rabbits at exposures 23 times the human exposure at the MRHD based on AUC.

In a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate from organogenesis through lactation. Maternal toxicity, characterized by a decrease in body weight gain was observed at 15 mg/kg/day (36 times the human exposure at the MRHD based on AUC). However, decreased fertility and increased auditory startle response occurred in offspring at the highest maternal dose of 15 mg/kg/day.

8.2 Lactation

Risk Summary

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 [see Data]. However, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. The lack of clinical data during lactation precludes a clear determination of the risk of CHANTIX to an infant during lactation; however the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CHANTIX and any potential adverse effects on the breastfed child from CHANTIX or from the underlying maternal condition.

Clinical Considerations

Because there are no data on the presence of varenicline in human milk and the effects on the 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 infants.

Data

In a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate through gestation and lactation Mean serum concentrations of varenicline in the nursing pups were 5–22% of maternal serum concentrations.

8.4 Pediatric Use

CHANTIX 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 (0-24), was comparable to that noted for the same doses in the adult population. When 0.5 mg BID was given, steady-state daily exposure of varenicline was, on average, higher (by approximately 40%) in adolescent patients with bodyweight ≤55 kg compared to that noted in the adult population.

The efficacy and safety of varenicline was evaluated in a randomized, double-blind, placebo-controlled study of 312 patients aged 12 to 19 years, who smoked an average of at least 5 cigarettes per day during the 30 days prior to recruitment, had a score of at least 4 on the Fagerstrom Test for Nicotine Dependence scale, and at least one previous failed quit attempt. Patients were stratified by age (12 to 16 years of age, n=216 and 17 to 19 years of age, n=96) and by body weight (≤55 kg and >55 kg). Patients were randomized to one of two doses of varenicline, adjusted by weight to provide plasma levels in the efficacious range (based on adult studies) and placebo. Patients received treatment for 12 weeks, followed by a non-treatment period of 40 weeks, along with age-appropriate counseling throughout the study. Results from this study showed that varenicline, at either dose studied, did not improve continuous abstinence rates at weeks 9 through 12 of treatment compared with placebo in subjects 12 to 19 years of age. The varenicline safety profile in this study was consistent with that observed in adult studies.

8.5 Geriatric Use

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 65–75 years) for 7 consecutive days was similar to that of younger subjects. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Varenicline is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.2)].

No dosage adjustment is recommended for elderly patients.

8.6 Renal Impairment

Varenicline is substantially eliminated by renal glomerular filtration along with active tubular secretion. Dose reduction is not required in patients with mild-to-moderate renal impairment. For patients with severe renal impairment (estimated creatinine clearance <30 mL/min), and for patients with end-stage renal disease undergoing hemodialysis, dosage adjustment is needed [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Medication Guide

MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 6/2025
MEDICATION GUIDE CHANTIX® (CHANT-iks) (varenicline) Tablets
What is the most important information I should know about CHANTIX? When you try to quit smoking, with or without CHANTIX, you may have symptoms that may be due to nicotine withdrawal, including:
• urge to smoke • depressed mood • trouble sleeping • irritability		• frustration • anger • feeling anxious • difficulty concentrating	• restlessness • decreased heart rate • increased appetite • weight gain
Some people have even experienced suicidal thoughts when trying to quit smoking without medication. Sometimes quitting smoking can lead to worsening of mental health problems that you already have, such as depression. Some people have had serious side effects while taking CHANTIX to help them quit smoking, including: New or worse mental health problems, such as changes in behavior or thinking, aggression, hostility, agitation, depressed mood, or suicidal thoughts or actions. Some people had these symptoms when they began taking CHANTIX, and others developed them after several weeks of treatment, or after stopping CHANTIX. These symptoms happened more often in people who had a history of mental health problems before taking CHANTIX, than in people without a history of mental health problems. Stop taking CHANTIX and call your healthcare provider right away if you, your family, or caregiver notice any of these symptoms. Work with your healthcare provider to decide whether you should continue to take CHANTIX. In many people, these symptoms went away after stopping CHANTIX, but in some people symptoms continued after stopping CHANTIX. It is important for you to follow-up with your healthcare provider until your symptoms go away. Before taking CHANTIX, tell your healthcare provider if you have ever had depression or other mental health problems. You should also tell your healthcare provider about any symptoms you had during other times you tried to quit smoking, with or without CHANTIX.
What is CHANTIX? CHANTIX is a prescription medicine to help people stop smoking. Quitting smoking can lower your chances of having lung disease, heart disease or getting certain types of cancer that are related to smoking. CHANTIX has not been shown to be effective in children 16 years of age and under. CHANTIX should not be used in children 16 years of age and under. It is not known if CHANTIX is safe and effective when used with other stop smoking medicines.
Who should not take CHANTIX? Do not take CHANTIX if you have had a serious allergic or skin reaction to CHANTIX. Symptoms may include: • swelling of the face, mouth (tongue, lips, gums), throat or neck
• trouble breathing		• rash, with peeling skin	• blisters in your mouth
What should I tell my healthcare provider before taking CHANTIX? See "What is the most important information I should know about CHANTIX?" Before you take CHANTIX, tell your healthcare provider if you: • use other treatments to quit smoking. Using CHANTIX with a nicotine patch may cause nausea, vomiting, headache, dizziness, upset stomach, and tiredness to happen more often than if you just use a nicotine patch alone. • have kidney problems or get kidney dialysis. Your healthcare provider may prescribe a lower dose of CHANTIX for you. • have a history of seizures. • drink alcohol. • have heart or blood vessel problems. • have any other medical conditions. • are pregnant or plan to become pregnant. • are breastfeeding. It is not known if CHANTIX passes into breast milk. If you breastfeed and take CHANTIX, monitor your baby for seizures as well as spitting up or vomiting more than normal. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Your healthcare provider may need to change the dose of some of your medicines when you stop smoking. You should not use CHANTIX while using other medicines to quit smoking. Tell your healthcare provider if you use other treatments to quit smoking. Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine.
How should I take CHANTIX? • There are 3 ways that you can use CHANTIX to help you quit smoking. Talk to your healthcare provider about the following 3 ways to use CHANTIX: o Choose a quit date when you will stop smoking. Start taking CHANTIX 1 week (7 days) before your quit date. Take CHANTIX for 12 weeks. OR o Start taking CHANTIX before you choose a quit date. Pick a date to quit smoking that is between days 8 and 35 of treatment. Take CHANTIX for 12 weeks. OR o If you are sure that you are not able or willing to quit smoking right away, start taking CHANTIX and reduce smoking during the first 12 weeks of treatment, as follows:
	Weeks 1 through 4	Reduce your smoking to reach one-half of your starting daily number of cigarettes. Example: If you usually smoke 20 cigarettes each day, reduce your smoking to 10 cigarettes each day during weeks 1 through 4.
	Weeks 5 through 8	Reduce your smoking to reach one-quarter of your starting daily number of cigarettes. Example: If you usually smoked 20 cigarettes each day, reduce your smoking to 5 cigarettes each day during weeks 5 through 8.
	Weeks 9 through 12	Keep reducing your smoking until you are no longer smoking (you reach zero cigarettes each day).
	Aim to quit by the end of the 12th week of treatment, or sooner if you feel ready. Continue to take CHANTIX for another 12 weeks, for a total of 24 weeks of treatment. Starting CHANTIX before your quit date gives CHANTIX time to build up in your body. You can keep smoking during this time. Take CHANTIX exactly as prescribed by your healthcare provider.
• CHANTIX comes as a white tablet (0.5 mg) and a blue tablet (1 mg). You start with the white tablet and then usually go to the blue tablet. See the chart below for dosing instructions for adults.
	Day 1 to Day 3	o White tablet (0.5 mg) o Take 1 tablet each day
	Day 4 to Day 7	o White tablet (0.5 mg) o Take 1 in the morning and 1 in the evening
	Day 8 to end of treatment	o Blue tablet (1 mg) o Take 1 in the morning and 1 in the evening
• Make sure that you try to stop smoking on your quit date. If you slip-up and smoke, try again. Some people need to take CHANTIX for a few weeks for CHANTIX to work best. • Most people will take CHANTIX for up to 12 weeks. If you have completely quit smoking by 12 weeks, your healthcare provider may prescribe CHANTIX for another 12 weeks to help you stay cigarette-free. • Take CHANTIX after eating and with a full glass (8 ounces) of water. • This dosing schedule may not be right for everyone. Talk to your healthcare provider if you are having side effects such as nausea, strange dreams, or sleep problems. Your healthcare provider may want to reduce your dose. • If you miss a dose of CHANTIX, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Just take your next dose at your regular time.
What should I avoid while taking CHANTIX? • Use caution when driving or operating machinery until you know how CHANTIX affects you. CHANTIX may make you feel sleepy, dizzy, or have trouble concentrating, making it hard to drive or perform other activities safely. • Decrease the amount of alcoholic beverages that you drink during treatment with CHANTIX until you know if CHANTIX affects your ability to tolerate alcohol. Some people have experienced the following when drinking alcohol during treatment with CHANTIX:
	o increased drunkenness (intoxication)	o unusual or sometimes aggressive behavior o no memory of things that have happened
What are the possible side effects of CHANTIX? Serious side effects of CHANTIX may include: • See "What is the most important information I should know about CHANTIX?" • Seizures. Some people have had seizures during treatment with CHANTIX. In most cases, the seizures have happened during the first month of treatment with CHANTIX. If you have a seizure during treatment with CHANTIX, stop taking CHANTIX and contact your healthcare provider right away. • New or worse heart or blood vessel (cardiovascular) problems, mostly in people, who already have cardiovascular problems. Tell your healthcare provider if you have any changes in symptoms during treatment with CHANTIX. Get emergency medical help right away if you have any of the following symptoms of a heart attack, including: o chest discomfort (uncomfortable pressure, squeezing, fullness or pain) that lasts more than a few minutes, or that goes away and comes back o pain or discomfort in one or both arms, back, neck, jaw or stomach o shortness of breath, sweating, nausea, vomiting, or feeling lightheaded associated with chest discomfort • Sleepwalking can happen with CHANTIX, and can sometimes lead to behavior that is harmful to you or other people, or to property. Stop taking CHANTIX and tell your healthcare provider if you start sleepwalking. • Allergic reactions can happen with CHANTIX. Some of these allergic reactions can be life-threatening. • Serious skin reactions, including rash, swelling, redness, and peeling of the skin. Some of these skin reactions can become life-threatening. Stop taking CHANTIX and get medical help right away if you have any of the following symptoms: o swelling of the face, mouth (tongue, lips, and gums), throat or neck o trouble breathing o rash with peeling skin o blisters in your mouth The most common side effects of CHANTIX include: • nausea • sleep problems (trouble sleeping or vivid, unusual, or strange dreams) • constipation • gas • vomiting Tell your healthcare provider about side effects that bother you or that do not go away. These are not all the side effects of CHANTIX. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store CHANTIX? • Store CHANTIX at room temperature, between 68°F to 77°F (20°C to 25°C). • Keep CHANTIX and all medicines out of the reach of children.
General information about the safe and effective use of CHANTIX Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use CHANTIX for a condition for which it was not prescribed. Do not give your CHANTIX to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about CHANTIX that is written for healthcare professionals. For more information about CHANTIX and tips on how to quit smoking, go to www.CHANTIX.com or call 1-877-242-6849. If you are motivated to quit smoking and did not succeed during prior CHANTIX treatment for reasons other than side effects, or if you returned to smoking after treatment, speak with your healthcare provider about whether another course of CHANTIX therapy may be right for you.
What are the ingredients in CHANTIX? Active ingredient: varenicline tartrate Inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, Opadry® White (for 0.5 mg), Opadry® Blue (for 1 mg), and Opadry® Clear. LAB-0328-18.0

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