Varenicline

Generic Name

Varenicline

Brand Names

Champix

Chantix

Champix Start

Tyrvaya (unrelated brand with different active ingredient)

Generic versions available in multiple countries following patent expiry

Drug Class

Partial agonist at the α4β2 nicotinic acetylcholine receptor

Smoking cessation aid

Nicotinic receptor modulator

Mechanism of Action

Varenicline is a selective partial agonist at the α4β2 subtype of the nicotinic acetylcholine receptor in the brain

Acts by binding to these receptors with high affinity

As a partial agonist it produces a moderate release of dopamine

Relieves nicotine cravings and withdrawal symptoms

At the same time it blocks nicotine from binding to these receptors

Prevents full dopamine stimulation by nicotine if the person smokes during therapy

Thus it reduces the rewarding and reinforcing effects of smoking

Indications

Aid to smoking cessation in adults

Used to increase the likelihood of quitting smoking

May be used as monotherapy or in combination with behavioral support programs

Off-label uses include

Smokeless tobacco cessation

Treatment of alcohol dependence

Assistance in e-cigarette withdrawal

Not officially approved for these off-label uses

Dosage and Administration

Initiation should begin 1 week before the chosen quit date

Alternatively patient may begin and choose a quit date between Day 8 and Day 35

Recommended dose

Days 1 to 3 05 mg once daily

Days 4 to 7 05 mg twice daily

Day 8 onward 1 mg twice daily

Total duration of treatment is 12 weeks

For patients who successfully quit an additional 12-week course may be offered to enhance abstinence

Should be taken with a full glass of water after food to reduce nausea

Dose adjustment not required for age sex or race

In patients with severe renal impairment starting dose should be 05 mg once daily

May be titrated cautiously to 1 mg daily if tolerated

Pharmacokinetics

Orally absorbed with peak plasma concentrations in 3 to 4 hours

Bioavailability is approximately 90 percent

Minimal plasma protein binding <20 percent

Not significantly metabolized

Eliminated primarily via renal excretion as unchanged drug

Half-life is approximately 24 hours

Excretion mainly through active tubular secretion

Contraindications

Known hypersensitivity to varenicline or any of its excipients

History of serious hypersensitivity or skin reactions including Stevens-Johnson syndrome

Concomitant use with bupropion or nicotine replacement therapy should be done cautiously due to additive side effects

Not approved for use in children or adolescents

Warnings and Precautions

Neuropsychiatric adverse effects including depression agitation hostility suicidal ideation have been reported

FDA previously issued a boxed warning which was later removed based on large-scale studies

Monitor mood behavior and mental health status during treatment

May impair ability to drive or operate machinery especially if experiencing dizziness or somnolence

Caution in patients with seizure disorders as seizures have occurred

May increase risk of cardiovascular events in patients with pre-existing cardiovascular disease

Monitor blood pressure in hypertensive patients

Can cause nausea which may be dose-dependent and dose-limiting

May exacerbate alcohol-related adverse effects including increased intoxication or aggressive behavior

Should be discontinued if serious psychiatric or behavioral changes occur

Adverse Effects

Very common

Nausea

Insomnia

Abnormal dreams

Headache

Common

Irritability

Depressed mood

Fatigue

Somnolence

Dry mouth

Constipation

Dyspepsia

Vomiting

Flatulence

Abnormal taste

Less common

Seizures

Mood swings

Aggression

Suicidal ideation

Skin rash

Hypersensitivity

Rare

Stevens-Johnson syndrome

Erythema multiforme

Angioedema

Serious neuropsychiatric events

Overdose

Limited data available

Symptoms may include nausea vomiting and behavioral changes

Supportive care is the mainstay of treatment

No specific antidote exists

Hemodialysis may aid removal due to low protein binding and renal elimination

Drug Interactions

Minimal drug interaction potential due to lack of significant hepatic metabolism

Does not inhibit or induce CYP450 enzymes

No known significant interaction with oral contraceptives digoxin or warfarin

Caution with alcohol due to reports of increased intoxication and behavioral effects

May enhance adverse effects when combined with other CNS-active agents such as bupropion SSRIs benzodiazepines

Combination with nicotine replacement therapy may lead to increased nausea headache and dizziness

Does not require dose adjustment when co-administered with other drugs commonly used in smoking cessation including nortriptyline or clonidine

Use in Special Populations

Pregnancy

Category C

Use only if potential benefits justify the risk

Limited human data but potential for fetal harm cannot be excluded

Animal studies show developmental toxicity

Not recommended unless no alternative exists

Lactation

Excreted in breast milk

Risk to infant is unknown

Breastfeeding should be discontinued or drug avoided

Geriatrics

No dosage adjustment required unless renal function is impaired

Renal Impairment

Dose should be reduced in moderate to severe renal impairment

Patients with creatinine clearance <30 mLmin should start at 05 mg once daily

Hepatic Impairment

No dose adjustment required

Pediatrics

Safety and effectiveness not established in patients under 18 years

Monitoring Parameters

Mental status and behavior for neuropsychiatric symptoms

Smoking status and abstinence rates

Tolerability especially nausea and sleep disturbances

Blood pressure in patients with cardiovascular comorbidities

Renal function in those with known impairment

Comparative Pharmacology

Compared to bupropion

Varenicline has higher efficacy in achieving smoking abstinence at 12 and 24 weeks

Lower risk of seizures compared to bupropion

Higher incidence of nausea

Compared to nicotine replacement therapy

More effective at promoting long-term abstinence

No nicotine exposure and fewer cravings in direct comparisons

However combination therapy may be considered in some patients

Compared to behavioral therapy alone

Pharmacological treatment with varenicline shows significantly better outcomes

Combining with behavioral interventions provides optimal benefit

Formulations Available

Tablets 05 mg and 1 mg

Starter packs available containing titration regimen

Packaged in blister packs or bottles depending on region

Available globally in branded and generic versions following patent expiry

Regulatory and Legal Status

Prescription-only medicine

Approved by FDA EMA and other global agencies for smoking cessation

Initially launched in 2006

FDA boxed warning was removed in 2016 following post-marketing safety studies

Classified as non-controlled substance

Included in national smoking cessation programs in many countries