Varenicline

Pronunciation: (var-EN-i-kleen TAR-trate)
Class: Smoking deterrent

Trade Names

Chantix
- Tablets 0.5 mg
- Tablets 1 mg

Champix (Canada)

Pharmacology

Binds with high affinity and selectivity to neuronal nicotinic acetylcholine receptors, which produces agonist activity while preventing nicotine binding to receptors.

Pharmacokinetics

Absorption

Absorption is virtually complete and exhibits linear pharmacokinetics. C _max occurs within 3 to 4 h. Steady state is reached within 4 days.

Distribution

Plasma protein binding is 20% or less.

Metabolism

Minimal metabolism occurs.

Elimination

Elimination half-life is approximately 24 h. Excretion is 92% unchanged in the urine.

Special Populations

Renal Function Impairment
Mild Renal Function Impairment (CrCl > 50 mL/min to ≤ 80 mL/min)

Pharmacokinetics unchanged.

Moderate Renal Function Impairment (CrCl ≥ 30 mL/min to ≤ 50 mL/min)

Drug exposure increased 1.5-fold.

Severe Renal Function Impairment (CrCl < 30 mL/min)

Drug exposure increased 2.1-fold.

End-Stage Renal Disease

Drug exposure increased 2.7-fold.

Hepatic Function Impairment

Pharmacokinetics should not be affected.

Elderly

Pharmacokinetics in elderly patients (65 to 75 yr of age) are similar to that of younger patients.

Gender

Pharmacokinetics not affected.

Race

Pharmacokinetics not affected.

Smoking status

Pharmacokinetics not affected.

Indications and Usage

Aid to smoking cessation.

Contraindications

None well documented.

Dosage and Administration

Adults

PO 1 mg twice daily subsequent to the following titration: 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.

Severe Renal Impairment (CrCl < 30 mL/min)
Adults

PO Start with 0.5 mg once daily, then titrate as needed to a max of 0.5 mg twice daily.

End-stage renal disease undergoing hemodialysis

0.5 mg once daily max.

General Advice

Should be taken after eating and with a full glass of water.
Consider dosage reduction in patients unable to tolerate the adverse reactions.
Treat for 12 wk. For patients who have successfully stopped smoking after 12 wk, an additional 12-wk course may increase the likelihood of long-term abstinence.
Encourage patients who do not succeed in stopping smoking after 12 wk of initial therapy or who relapse to make another attempt once factors contributing to the failure have been identified and addressed.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Cimetidine

Coadministration increased the systemic exposure of varenicline by 29%.

Transdermal nicotine

The incidence of adverse reactions may be increased with coadministration.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (at least 1%).

CNS

Headache, insomnia (19%); abnormal dreams (13%); dysgeusia (8%); fatigue/malaise/asthenia (7%); sleep disorder (5%); increased appetite (4%); somnolence (3%); decreased appetite/anorexia, lethargy, nightmare (2%); anxiety, depression, disturbances in attention, dizziness, emotional disorder, irritability, restlessness, sensory disturbance (frequent); aggression, agitation, anxiety, delusions, depression, hallucinations, homicidal ideation, hostility, mania, panic, paranoia, psychosis, suicidal ideation, suicide attempt, suicide (postmarketing).

Dermatologic

Rash (3%); pruritus (1%); hot flush, hyperhidrosis (frequent); serious skin reactions (eg, erythema multiforme, Stevens-Johnson syndrome) (postmarketing).

EENT

Rhinorrhea (1%).

GI

Nausea (30%); flatulence (9%); constipation (8%); abdominal pain (7%); dry mouth (6%); dyspepsia, vomiting (5%); gastroesophageal reflux disease (1%); diarrhea, gingivitis, thirst (frequent).

Genitourinary

Menstrual disorder, polyuria (frequent).

Lab Tests

LFT abnormalities (frequent).

Musculoskeletal

Arthralgia, back pain, muscle cramp, musculoskeletal pain, myalgia (frequent).

Respiratory

Upper respiratory tract disorder (7%); dyspnea (2%); epistaxis (frequent).

Miscellaneous

Chest pain, edema, influenza-like illness (frequent); hypersensitivity reactions, including angioedema (postmarketing).

Precautions

Warnings

Serious neuropsychiatric events, including but not limited to depression, suicidal ideation, suicide attempt, and completed suicide, have been reported in patients taking varenicline. Some reported cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking.

All patients being treated with varenicline should be observed for neuropsychiatric symptoms, including changes in behavior, hostility, agitation, depressed mood, and suicide-related events such as ideation, behavior, and attempted suicide. These symptoms, as well as worsening of preexisting psychiatric illness and completed suicide, have been reported in some patients attempting to quit smoking while taking varenicline in the postmarketing experience. Symptoms were reported during and after discontinuation of varenicline treatment in patients with and without preexisting psychiatric disease.

Advise patients and caregivers that the patient should stop taking varenicline and contact a health care provider immediately if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.

Weigh the risks of varenicline against the benefits of its use.

Monitor

Observe patients for neuropsychiatric symptoms, including agitation, changes in behavior, depressed mood, suicidal behavior, and suicidal ideation.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased renal function.

Hypersensitivity

Hypersensitivity reactions, including angioedema, have been reported.

Renal Function

Use with caution. Dose reduction and monitoring are recommended in patients with severe renal impairment.

Neuropsychiatric symptoms and suicidality

Serious neuropsychiatric symptoms, including depression and, rarely, suicidal ideation, have been reported.

Skin reactions

Rare but serious skin reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported.

Overdosage

Symptoms

None well documented.

Patient Information

Instruct patient to set a date to quit smoking and to initiate varenicline treatment 1 wk before the date.
Advise patient to take the dose after eating and with a full glass of water.
Instruct patient on the recommended dosage regimen.
Inform patient that the adverse reactions (eg, nausea, insomnia) from treatment are usually transient and to notify health care provider if the reactions are persistently bothersome so that dosage modification can be considered.
Provide patient with educational material and necessary counseling to support smoking cessation.
Inform patient that some medications may require dose adjustment after smoking cessation.
Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding because of the risks of smoking. Explain risks and benefits of smoking cessation.
Instruct patients and caregivers to stop the product and contact health care provider if agitation, depressed mood, or changes in behavior that are not typical for the patient are observed, or if suicidal ideation or suicidal behavior develops.
Advise patients to use caution while driving or operating machinery or engaging in other potentially hazardous activities until they know how varenicline may affect them.
Inform patients that they may experience vivid, unusual, or strange dreams during treatment.
Advise patients to stop taking the drug if a skin reaction rash with mucosal lesions occurs and to contact a health care provider immediately.
Instruct patients to discontinue the drug and to immediately seek medical care if angioedema, with swelling of the mouth, face (eg, lip, gum, tongue), and neck (eg, larynx, pharynx) occur.