United States - English - NLM (National Library of Medicine)

par pharmaceutical, inc. - varenicline tartrate (unii: 82269asb48) (varenicline - unii:w6hs99o8zo) - varenicline tablets are indicated for use as an aid to smoking cessation treatment. varenicline tablets are contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline tablets. 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 2-4% 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 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 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) 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%) *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. 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. 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 varenicline to an infant during lactation; however the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for varenicline and any potential adverse effects on the breastfed child from varenicline 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. 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 (0-24), 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. 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. 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. 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)]. varenicline is not a controlled substance. 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. abrupt discontinuation of varenicline was associated with an increase in irritability and sleep disturbances in up to 3% of patients. this suggests that, in some patients, varenicline may produce mild physical dependence which is not associated with addiction. in a human laboratory abuse liability study, a single oral dose of 1 mg varenicline did not produce any significant positive or negative subjective responses in smokers. in non-smokers, 1 mg varenicline produced an increase in some positive subjective effects, but this was accompanied by an increase in negative adverse effects, especially nausea. a single oral dose of 3 mg varenicline uniformly produced unpleasant subjective responses in both smokers and non-smokers. animals studies in rodents have shown that varenicline produces behavioral responses similar to those produced by nicotine. in rats trained to discriminate nicotine from saline, varenicline produced full generalization to the nicotine cue. in self-administration studies, the degree to which varenicline substitutes for nicotine is dependent upon the requirement of the task. rats trained to self-administer nicotine under easy conditions continued to self-administer varenicline to a degree comparable to that of nicotine; however in a more demanding task, rats self-administered varenicline to a lesser extent than nicotine. varenicline pretreatment also reduced nicotine self-administration.

Australia - English - Department of Health (Therapeutic Goods Administration)

arrotex pharmaceuticals pty ltd - varenicline tartrate, quantity: 1.71 mg (equivalent: varenicline, qty 1 mg) - tablet, film coated - excipient ingredients: microcrystalline cellulose; calcium hydrogen phosphate; hypromellose; triacetin; hyprolose; titanium dioxide; indigo carmine aluminium lake; magnesium stearate - varenicline tablets are indicated as an aid to smoking cessation in adults over the age of 18 years.

New Zealand - English - Medsafe (Medicines Safety Authority)

pfizer new zealand limited - varenicline tartrate 0.85mg equivalent to 0.5 mg varenicline;  ;  ; varenicline tartrate 1.71mg equivalent to 1 mg varenicline - combination - 0.5 mg and 1 mg - active: varenicline tartrate 0.85mg equivalent to 0.5 mg varenicline     excipient: calcium hydrogen phosphate colloidal silicon dioxide croscarmellose sodium magnesium stearate microcrystalline cellulose opadry clear ys-2-19114-a opadry white ys-1-18202 active: varenicline tartrate 1.71mg equivalent to 1 mg varenicline excipient: calcium hydrogen phosphate colloidal silicon dioxide croscarmellose sodium magnesium stearate microcrystalline cellulose opadry blue 03b90547 opadry clear ys-2-19114-a - an aid to smoking cessation

United States - English - NLM (National Library of Medicine)

leading pharma, llc - varenicline tartrate (unii: 82269asb48) (varenicline - unii:w6hs99o8zo) - varenicline tablets  is indicated for use as an aid to smoking cessation treatment. varenicline tablets is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline tablets. 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 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 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 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. 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 varenicline to an infant during lactation; however the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for varenicline and any potential adverse effects on the breastfed child from varenicline 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. 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 (0-24), 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. 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. 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)]. varenicline is not a controlled substance. 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. abrupt discontinuation of varenicline was associated with an increase in irritability and sleep disturbances in up to 3% of patients. this suggests that, in some patients, varenicline may produce mild physical dependence which is not associated with addiction. in a human laboratory abuse liability study, a single oral dose of 1 mg varenicline did not produce any significant positive or negative subjective responses in smokers. in non-smokers, 1 mg varenicline produced an increase in some positive subjective effects, but this was accompanied by an increase in negative adverse effects, especially nausea. a single oral dose of 3 mg varenicline uniformly produced unpleasant subjective responses in both smokers and non-smokers. animals studies in rodents have shown that varenicline produces behavioral responses similar to those produced by nicotine. in rats trained to discriminate nicotine from saline, varenicline produced full generalization to the nicotine cue. in self-administration studies, the degree to which varenicline substitutes for nicotine is dependent upon the requirement of the task. rats trained to self-administer nicotine under easy conditions continued to self-administer varenicline to a degree comparable to that of nicotine; however in a more demanding task, rats self-administered varenicline to a lesser extent than nicotine. varenicline pretreatment also reduced nicotine self- administration.

Canada - English - Health Canada

genmed a division of pfizer canada ulc - varenicline (varenicline tartrate); varenicline (varenicline tartrate) - kit - 0.5mg; 1mg - varenicline (varenicline tartrate) 0.5mg; varenicline (varenicline tartrate) 1mg - miscellaneous autonomic drugs

Canada - English - Health Canada

apotex inc - varenicline (varenicline tartrate); varenicline (varenicline tartrate) - kit - 0.5mg; 1mg - varenicline (varenicline tartrate) 0.5mg; varenicline (varenicline tartrate) 1mg - miscellaneous autonomic drugs

Canada - English - Health Canada

teva canada limited - varenicline (varenicline tartrate); varenicline (varenicline tartrate) - tablet - 0.5mg; 1mg - varenicline (varenicline tartrate) 0.5mg; varenicline (varenicline tartrate) 1mg - miscellaneous autonomic drugs

Australia - English - Department of Health (Therapeutic Goods Administration)

arrotex pharmaceuticals pty ltd - varenicline tartrate, quantity: 1.71 mg (equivalent: varenicline, qty 1 mg) - tablet, film coated - excipient ingredients: calcium hydrogen phosphate; hypromellose; triacetin; hyprolose; titanium dioxide; indigo carmine aluminium lake; sodium stearylfumarate; croscarmellose sodium - varenicline tablets are indicated as an aid to smoking cessation in adults over the age of 18 years.

United States - English - NLM (National Library of Medicine)

ascend laboratories, llc - varenicline tartrate (unii: 82269asb48) (varenicline - unii:w6hs99o8zo) - varenicline tablet is indicated for use as an aid to smoking cessation treatment. varenicline tablet is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline tablets. 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

Australia - English - Department of Health (Therapeutic Goods Administration)

arrotex pharmaceuticals pty ltd - varenicline tartrate, quantity: 1.71 mg (equivalent: varenicline, qty 1 mg) - tablet, film coated - excipient ingredients: microcrystalline cellulose; calcium hydrogen phosphate; hypromellose; triacetin; hyprolose; titanium dioxide; indigo carmine aluminium lake; magnesium stearate - varenicline tablets are indicated as an aid to smoking cessation in adults over the age of 18 years.