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  • CLASSES

    Antismoking Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Nicotine receptor agonist
    Used to promote smoking cessation
    Monitor closely for emerging or worsening suicidal thoughts/behavior, depression, or other changes in mood or behavior

    COMMON BRAND NAMES

    Chantix

    HOW SUPPLIED

    Chantix Oral Tab: 0.5mg, 1mg, 0.5-1mg

    DOSAGE & INDICATIONS

    For use as an adjunct to psychosocial interventions for tobacco cessation (smoking cessation).
    Oral dosage
    Adults

    Set a patient quit date to stop smoking. Initiate varenicline 1 week before the quit date, or, the patient can begin treatment and then quit smoking between Days 8 and 35 of varenicline treatment. Titrate the dose over a 1 week period starting with 0.5 mg PO once daily on Days 1 through 3, then 0.5 mg PO twice daily on Days 4 through 7, and finally 1 mg PO twice daily on day 8 until the end of treatment. Duration of therapy should be 12 weeks; patients who are successful after 12 weeks may be treated with an additional 12 week course to increase chances of long-term abstinence. Patients who are motivated to quit and tolerated the drug, but were unsuccessful or relapsed after treatment should be encouraged to make a second attempt once factors contributing to the failed attempt have been identified and addressed. FOR PATIENTS UNABLE OR UNWILLING TO QUIT SMOKING ABRUPTLY: Initiate varenicline treatment and have patient reduce smoking by 50% from baseline within the first 4 weeks, reduce smoking by an additional 50% in the next 4 weeks, and continue reducing with the goal of complete abstinence by 12 weeks. Continue varenicline for an additional 12 weeks, for a total of 24 weeks of treatment. Smoking cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided additional advice and support. Patients should be provided with appropriate supportive educational materials and counseling.

    MAXIMUM DOSAGE

    Adults

    1 mg PO twice daily.

    Elderly

    1 mg PO twice daily.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is necessary for patients with hepatic impairment.

    Renal Impairment

    CrCl 30 mL/minute or more: No dosage adjustment needed.
    CrCl less than 30 mL/minute: Initially, 0.5 mg once per day. Max: 0.5 mg PO twice daily.
     
    Intermittent hemodialysis
    Varenicline is removed by hemodialysis. A maximum dose of 0.5 mg PO once daily may be given if well tolerated in patients with end-stage renal disease on hemodialysis.

    ADMINISTRATION

    Oral Administration

    Administer varenicline after eating with a full glass of water.

    STORAGE

    Chantix:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Angioedema, serious rash

    Varenicline should be avoided in patients with a known hypersensitivity to varenicline or any component of the formulation. Life-threatening hypersensitivity reactions, including angioedema, have occurred. Clinical signs included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (throat and larynx). There were infrequent reports of life-threatening angioedema requiring emergent medical attention due to respiratory compromise. Rarely, serious skin reactions such as Stevens-Johnson syndrome and erythema multiforme have also been reported during postmarketing use of the drug. Patients should be instructed to discontinue the medication and seek immediate medical care if they experience a serious rash with mucosal lesions or any other signs of hypersensitivity.

    Behavioral changes, bipolar disorder, depression, psychiatric event, schizophrenia, suicidal ideation

    Patients should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness (e.g., schizophrenia, depression, bipolar disorder) during treatment with varenicline, due to serious neuropsychiatric symptoms reported during use of the drug. If neuropsychiatric symptoms develop, evaluate the patient for symptom severity and the extent to which the patient is benefiting from treatment, and consider dose reduction or discontinuation, or continued treatment with closer monitoring. In many cases, resolution of symptoms has occurred after discontinuation, although the symptoms can persist; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve Post-marketing reports have included mood or behavioral changes or a psychiatric event such as psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, panic, mania, depression, suicidal ideation, suicide attempt, and completed suicide in patients with or without a psychiatric history. Some reported cases may have been complicated by symptoms of nicotine withdrawal, such as depressed mood, in patients who stopped smoking, although most occurred during varenicline treatment. It should be noted that depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication.  Some reported neuropsychiatric 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 the drug and contact a healthcare provider immediately if agitation, depressed mood, suicidal ideation, suicidal behavior, or other behavioral changes that are not typical for the patient are observed. The boxed warning in the product labeling regarding serious neuropsychiatric effects was removed in December 2016 following results from the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES), which was a large, randomized, double-blind, active- and placebo-controlled smoking cessation clinical trial assessing varenicline, bupropion, and nicotine replacement therapy in patients with (n = 4003) and without (n = 3912) a history of a psychiatric disorder. In the non-psychiatric cohort, less patients receiving varenicline reported a serious neuropsychiatric event than patients receiving placebo (0.1% vs. 0.4%). There was a similar incidence of serious neuropsychiatric events between the psychiatric patients receiving varenicline or placebo (0.6% each). In the psychiatric cohort, there were more neuropsychiatric events reported in each treatment group than in the non-psychiatric cohort, and the incidence of events at endpoint was higher in psychiatric patients receiving each of the active treatments than placebo. Risk differences in the psychiatric cohort versus placebo were: 2.7% for varenicline, 2.2% for bupropion, and 0.4% for transdermal nicotine. More patients in the varenicline-treated psychiatric cohort had serious neuropsychiatric events involving a psychiatric hospitalization than in patients receiving placebo (0.5% vs. 0.2%).

    Complex sleep-related behaviors, driving or operating machinery, ethanol ingestion, ethanol intoxication

    Patients should be advised to use caution when driving or operating machinery or performing other tasks that require mental alertness until they know how varenicline will affect them. There have been reports of motor vehicle accidents, near-miss traffic incidents, and other accidental injuries during use of varenicline. In some cases, patients have experienced drowsiness, dizziness, loss of consciousness, or difficulty concentrating that resulted in impairment, or concern about potential impairment, in driving or operating machinery. There have also been postmarketing reports of patients experiencing increased effects of ethanol intoxication while taking varenicline. Some cases have described unusual and sometimes aggressive behavior, and have often been accompanied by amnesia of the events. Patients should be advised to reduce their amount of ethanol ingestion while taking varenicline until they know whether the drug affects their tolerance for alcohol. Instruct patients to discontinue varenicline and notify their healthcare provider if they experience somnambulism or other complex sleep-related behaviors. Somnambulism (sleep-walking) has been reported in patients taking varenicline, with some cases describing harmful behavior to self, others, or property.

    Seizures

    Seizures have been reported in patients treated with varenicline during clinical trials and post-marketing experience. 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. Weigh this potential risk against the potential benefits before prescribing varenicline in patients with a history of seizures or other factors that can lower the seizure threshold. Tell patients to discontinue varenicline and contact a healthcare provider immediately if they experience a seizure while on treatment.

    Cardiac disease, myocardial infarction or stroke

    A comprehensive evaluation of cardiovascular risk (i.e., randomized controlled trials and meta-analysis) suggests that varenicline may be associated with a small, increased risk of certain cardiovascular events, such as myocardial infarction or stroke, in patients with cardiac disease. However, because smoking is an independent major risk factor for cardiovascular disease, the health benefits of smoking cessation must be balanced with concerns of potential drug-related cardiac risks. In one smoking cessation trial of patients with stable cardiac disease, nonfatal myocardial infarction and nonfatal stroke occurred more frequently in patients using varenicline than placebo, but the difference was not statistically significant, and all-cause and cardiovascular mortality was lower in patients treated with varenicline. A meta-analysis showed an increased hazard ratio of 1.95 for Major Adverse Cardiovascular Events (MACE) with varenicline, which was not statistically significant. A large postmarketing neuropsychiatric safety outcome trial showed few MACE events; therefore, the findings did not significantly contribute to identifying the cardiac risk of varenicline. Patients should be instructed to seek medical attention if they experience new or worsening cardiac symptoms (such as those suggestive of myocardial infarction or stroke) while receiving varenicline.

    Dialysis, renal failure, renal impairment

    Varenicline should be used cautiously in patients with renal impairment or renal failure. Varenicline is substantially excreted by the kidneys and the risk of toxic reactions is greater in patients with impaired renal function. Dosage adjustments are necessary in patients with CrCl less than 30 mL/minute and those with end-stage renal disease receiving dialysis.

    Geriatric

    No overall differences in safety or effectiveness were observed during clinical trials in geriatric patients vs. younger adults. Clinical experience has not identified differences in responses. However, greater sensitivity of some older patients cannot be ruled out. Geriatric patients are more likely to have decreased renal function. Since varenicline is known to be substantially excreted by the kidney and the risk of toxic reactions are greater in patients with impaired renal function, care should be taken in dose selection for the elderly; it may be useful to monitor renal function.

    Infants, pregnancy

    Available data have not suggested an increased risk for major birth defects in exposed infants following maternal exposure to varenicline during pregnancy compared with women who smoke. Overall, however, available study results cannot definitively establish or exclude any varenicline-associated risk during pregnancy. In one population-based observational study using national registries from Denmark and Sweden where pregnancy and birth outcomes were compared among women exposed to varenicline, women who smoked during pregnancy, and non-smoking pregnant women, the prevalence of major malformations was similar in all groups. The prevalence of other adverse perinatal outcomes in the varenicline-exposed cohort was not greater than in the cohort of women who smoked. Study limitations included the inability to capture malformations from pregnancies without a live birth and misclassifications of outcomes, varenicline exposure, or smoking exposure. Other small epidemiological studies did not identify an association between varenicline use during pregnancy and major malformations. 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 smoking cessation with varenicline during pregnancy reduces these risks. Non-pharmacologic smoking cessation efforts are used to help reduce the proportion of women who continue to smoke in late pregnancy, thereby reducing adverse perinatal outcomes. Nicotine replacement treatment is used during pregnancy only if the likelihood of smoking cessation justifies the potential risk of the treatment or the risk that the patient will continue to smoke. The potential effects of varenicline on labor and delivery are not known.

    Breast-feeding

    There are no data on the presence of varenicline in human milk, the effects on the breast-fed infant, or the effects on human milk production. In animal studies varenicline was present in milk of lactating rats. 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. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for varenicline and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. If varenecline use is required, breast-feeding 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 a breast-feeding infant. The decision of whether to use a pharmacologic method for smoking cessation in a woman who is breast-feeding should be evaluated in comparison to the risks associated with passive exposure of the infant to tobacco smoke. Nicotine replacement products may be considered as an alternate smoking cessation treatments to varenicline in breast-feeding mothers if supportive cessation interventions are ineffective. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children

    Varenicline is not recommended for children and adolescents because its efficacy in these populations has not been demonstrated. Varenicline did not improve continuous abstinence rates at weeks 9 through 12 of treatment compared to placebo in a randomized, double-blind study of 312 patients 12 to 19 years of age, who smoked an average of at least 5 cigarettes per day, had a Fagerstrom Test for Nicotine Dependence score of at least 4, and at least 1 previous failed attempt to quit. The safety profile of varenicline was similar to that of adults.[32296]

    ADVERSE REACTIONS

    Severe

    pancreatitis / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    atrial fibrillation / Early / Incidence not known
    stroke / Early / Incidence not known
    thrombosis / Delayed / Incidence not known
    atrial flutter / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    night blindness / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    cholecystitis / Delayed / Incidence not known
    suicidal ideation / Delayed / Incidence not known

    Moderate

    depression / Delayed / 0-11.0
    constipation / Delayed / 5.0-8.0
    hostility / Early / 0-2.0
    dyspnea / Early / 1.0-2.0
    euphoria / Early / 0-1.0
    gastritis / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    complex sleep-related behaviors / Early / Incidence not known
    amnesia / Delayed / Incidence not known
    dysarthria / Delayed / Incidence not known
    migraine / Early / Incidence not known
    psychosis / Early / Incidence not known
    hallucinations / Early / Incidence not known
    mania / Early / Incidence not known
    ethanol intoxication / Early / Incidence not known
    erythema / Early / Incidence not known
    hot flashes / Early / Incidence not known
    psoriasis / Delayed / Incidence not known
    atopic dermatitis / Delayed / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    angina / Early / Incidence not known
    palpitations / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    nephrolithiasis / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    nystagmus / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    photophobia / Early / Incidence not known
    cataracts / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    splenomegaly / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known

    Mild

    nausea / Early / 16.0-40.0
    insomnia / Early / 9.0-19.0
    headache / Early / 11.0-19.0
    abnormal dreams / Early / 8.0-13.0
    vomiting / Early / 1.0-11.0
    irritability / Delayed / 0-11.0
    libido decrease / Delayed / 1.0-10.0
    emotional lability / Early / 1.0-10.0
    flatulence / Early / 6.0-9.0
    dysgeusia / Early / 5.0-8.0
    anxiety / Delayed / 0-8.0
    abdominal pain / Early / 5.0-7.0
    fatigue / Early / 4.0-7.0
    agitation / Early / 0-7.0
    xerostomia / Early / 4.0-6.0
    dyspepsia / Early / 5.0-5.0
    appetite stimulation / Delayed / 3.0-4.0
    drowsiness / Early / 3.0-3.0
    rash / Early / 1.0-3.0
    anorexia / Delayed / 1.0-2.0
    lethargy / Early / 1.0-2.0
    nightmares / Early / 1.0-2.0
    gastroesophageal reflux / Delayed / 1.0-1.0
    pruritus / Rapid / 0-1.0
    rhinorrhea / Early / 0-1.0
    eructation / Early / Incidence not known
    weight gain / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    restlessness / Early / Incidence not known
    dizziness / Early / Incidence not known
    restless legs syndrome (RLS) / Delayed / Incidence not known
    psychomotor impairment / Early / Incidence not known
    somnambulism / Early / Incidence not known
    parosmia / Delayed / Incidence not known
    tremor / Early / Incidence not known
    paranoia / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    acne vulgaris / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    syncope / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    back pain / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    musculoskeletal pain / Early / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    nocturia / Early / Incidence not known
    polyuria / Early / Incidence not known
    xerophthalmia / Early / Incidence not known
    ocular irritation / Rapid / Incidence not known
    ocular pain / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    epistaxis / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known
    fever / Early / Incidence not known
    chills / Rapid / Incidence not known

    DRUG INTERACTIONS

    Cimetidine: (Minor) Inhibitors of OCT2 (e.g., cimeditine) may increase the exposure of varenicline but these changes may not necessitate a dose adjustment of varenicline as the increase in systemic exposure is not expected to be clinically meaningful. Administration cimetidine (300 mg four times daily), with varenicline (2 mg single dose) to 12 smokers increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance. In vitro studies demonstrated the active renal secretion of varenicline is mediated by the human organic cation transporter OCT2. Another H2 antagonist may be preferable to cimetidine in patients taking varenicline.
    Ethanol: (Major) Patients should be advised to reduce the amount of alcohol they ingest while taking varenicline until they know whether the drug affects their tolerance for ethanol. Some reported neuropsychiatric events, including unusual and sometimes aggressive behavior directed to oneself or others, may have been worsened by a patient's concomitant use of alcohol. There have been postmarketing reports of patients experiencing increased ethanol intoxication while taking varenicline. Some cases described unusual and sometimes aggressive behavior, and were often accompanied by amnesia for the events.
    Lamotrigine: (Minor) Inhibitors of OCT2 (e.g., lamotrigine) may increase the exposure of varenicline but these changes may not necessitate a dose adjustment of varenicline as the increase in systemic exposure is not expected to be clinically meaningful. Administration of a known OCT2 inhibitor with varenicline (2 mg single dose) to 12 smokers increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance. In vitro studies demonstrated the active renal secretion of varenicline is mediated by the human organic cation transporter OCT2.
    Ranolazine: (Minor) Inhibitors of OCT2 (e.g., ranolazine) may increase the exposure of varenicline but these changes may not necessitate a dose adjustment of varenicline as the increase in systemic exposure is not expected to be clinically meaningful. Administration of a known OCT2 inhibitor with varenicline (2 mg single dose) to 12 smokers increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance. In vitro studies demonstrated the active renal secretion of varenicline is mediated by the human organic cation transporter OCT2.
    Tafenoquine: (Minor) Inhibitors of OCT2 (e.g., tafenoquine) may increase the exposure of varenicline but these changes may not necessitate a dose adjustment of varenicline as the increase in systemic exposure is not expected to be clinically meaningful. Administration of a known OCT2 inhibitor with varenicline (2 mg single dose) to 12 smokers increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance. In vitro studies demonstrated the active renal secretion of varenicline is mediated by the human organic cation transporter OCT2. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 substrates in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Available data have not suggested an increased risk for major birth defects in exposed infants following maternal exposure to varenicline during pregnancy compared with women who smoke. Overall, however, available study results cannot definitively establish or exclude any varenicline-associated risk during pregnancy. In one population-based observational study using national registries from Denmark and Sweden where pregnancy and birth outcomes were compared among women exposed to varenicline, women who smoked during pregnancy, and non-smoking pregnant women, the prevalence of major malformations was similar in all groups. The prevalence of other adverse perinatal outcomes in the varenicline-exposed cohort was not greater than in the cohort of women who smoked. Study limitations included the inability to capture malformations from pregnancies without a live birth and misclassifications of outcomes, varenicline exposure, or smoking exposure. Other small epidemiological studies did not identify an association between varenicline use during pregnancy and major malformations. 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 smoking cessation with varenicline during pregnancy reduces these risks. Non-pharmacologic smoking cessation efforts are used to help reduce the proportion of women who continue to smoke in late pregnancy, thereby reducing adverse perinatal outcomes. Nicotine replacement treatment is used during pregnancy only if the likelihood of smoking cessation justifies the potential risk of the treatment or the risk that the patient will continue to smoke. The potential effects of varenicline on labor and delivery are not known.

    MECHANISM OF ACTION

    Mechanism of Action: Varenicline is a partial agonist at alpha4-beta2 neuronal nicotinic acetylcholine receptors (nAChRs). These receptors are believed to be the site whereby nicotine exerts its effects. Similar to most abused substances, nicotine increases dopamine release in the nucleus accumbens and prefrontal cortex. Cravings for nicotine are stimulated by low levels of mesolimbic dopamine during periods of abstinence. Varenicline is effective because it partially stimulates alpha4-beta2 receptors to produce a modest level of mesolimbic dopamine thereby diminishing nicotine cravings and withdrawal symptoms. This mesolimbic dopamine level is lower than that produced by nicotine. Varenicline also has the added benefit of blocking the effects of nicotine by occupying receptor sites. By blocking receptors, varenicline reduces the pharmacologic reward of nicotine in cases where a patient relapses and uses tobacco. Varenicline is highly selective and binds more potently to alpha4-beta2 receptors than to other common nicotinic receptors (alpha3-beta4, alpha7, alpha1-beta-gamma-delta) or to non-nicotinic receptors and transporters. Varenicline also binds with moderate affinity to 5-HT3 (serotonin) receptors.

    PHARMACOKINETICS

    Varenicline is administered orally. Twenty percent or less of varenicline is plasma protein bound and is independent of both age and renal function. Metabolism is minimal. Approximately 92% of an administered dose is excreted unchanged in the urine. Elimination via the kidneys is primarily through glomerular filtration along with active tubular secretion by the human organic cation transporter, OCT2. The elimination half-life is about 24 hours.[32296]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none
    Based on in vitro studies, varenicline does not inhibit cytochrome P450 enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/5. It does not induce CYP1A2 or CYP3A4.[32296]

    Oral Route

    Varenicline is almost completely absorbed, and systemic availability is high with oral administration. Cmax occurs within 3 to 4 hours and steady-state is reached in about 4 days after multiple doses. Food or time-of-day do not affect varenicline oral bioavailability.[32296]