Vareniciline

Vareniciline is a smoking cessation agent belonging to a cholinergic-receptor agonist.

Vareniciline is used in the treatment of Smoking cessation and Dry eye disease.

Vareniciline is well absorbed from the gastrointestinal tract with bioavailability of approx 90%. It get distributed into tissues, including the brain with plasma protein binding of ≤20% with Minimal metabolism and get excreted via urine (approx 92% as unchanged drug, <10% as metabolites) with elimination half-life: Approx 24 hours.

The Tmax of varenicline was achieved at 2 to 4 hours after administration for each regimen after both single and multiple doses of varenicline and Cmax was about 8.27 (1.47) ng/ml Vareniciline shows common side effects like Headache, dizziness, Diarrhea, sore throat, runny nose, sneezing, joint pain, etc.

Vareniciline is available in tablets and nasal solution.

Vareniciline is available in India, Germany, Canada, France, USA

Varenicline is a highly selective and potent partial neuronal α₄β₂ nicotinic acetylcholine receptor agonist. It acts by preventing Vareniciline stimulation of the mesolimbic dopamine system, the neuronal mechanism underlying reward and reinforcement experienced during smoking. Additionally, it stimulates dopamine activity but to a much lesser extent than Vareniciline , leading to reduced craving and withdrawal symptoms.

Vareniciline is used in the treatment of Smoking cessation and Dry eye disease.

Vareniciline is approved for use in the following clinical indications

Smoking cessation: As an aid to smoking cessation treatment

Dry eye disease: Treatment of the signs and symptoms of dry eye disease.

Vareniciline is available in various strengths as 0.5 mg, 1 mg, 1 actuation delivers 0.03mg/0.05mL.

Vareniciline is available in the form of Tablets and Nasal solution.

• Dosage Adjustment in Kidney Patient

CrCl ≥30 mL/minute: No dosage adjustment necessary.

• CrCl <30 mL/minute: Initial: 0.5 mg once daily; maximum maintenance dose: 0.5 mg twice daily
• ESRD (receiving hemodialysis): Maximum dose: 0.5 mg once daily

• Dosage Adjustment in Hepatic impairment Patient

No Dosage Adjustment is necessary .

• Dosage Adjustment for Pediatric Patients:
• Smoking cessation: Adolescents ≥17 years: Note: Efficacy has not been established in patients <17 years of age; a randomized, double-blind, placebo-controlled trial including 216 pediatric patients 12 to 16 years of age showed that varenicline did not improve continuous abstinence rates; use is not recommended in pediatric patients ≤16 years of age. In another double-blind, placebo-controlled trial of 157 adolescents and young adults 14 to 19 years of age (mean age: 19.1 ± 1.5 years), the primary efficacy endpoint of end of treatment (week 12) abstinence was the same in both treatment and placebo groups at 8.9%; significant findings in secondary endpoints were observed, including higher weekly self-reported abstinence rates, and patients who achieved 7-day abstinence reported shorter time to achieve 7 days abstinence (39 days compared to 59 days with placebo).
• Days 1 to 3: Oral: 0.5 mg once daily.
• Days 4 to 7: Oral: 0.5 mg twice daily.

• Maintenance (≥ Day 8): Oral: 1 mg twice daily for 11 weeks; may consider a temporary or permanent dose reduction if usual dose is not tolerated. If patient successfully quits smoking at the end of the 12 weeks, may continue for another 12 weeks to help maintain success. Patients who are motivated to quit and do not succeed in stopping smoking during prior therapy, or who relapse after treatment, should be encouraged to make another attempt with varenicline once factors contributing to the failed attempt have been identified and addressed.

• Approaches to selecting a tobacco quit date: May either choose a fixed quit date (ie, start varenicline, then quit on day 8) or a flexible quit date (ie, start varenicline, then quit between days 8 to 35). Alternatively, a gradual quit date (ie, start varenicline and reduce smoking 50% by week 4, reduce an additional 50% by week 8, and continue reducing with a goal of complete abstinence by week 12) is acceptable.

• Dosing: Kidney Impairment:

Pediatric

• Adolescents ≥17 years:
• CrCl ≥30 mL/minute: No dosage adjustment necessary.
• CrCl <30 mL/minute: Initial: 0.5 mg once daily; maximum maintenance dose: 0.5 mg twice daily.
• End-stage renal disease (ESRD) (receiving hemodialysis): Maximum maintenance dose: 0.5 mg once daily.

Take after eating and with a full glass of water to decrease gastric upset.

Vareniciline is contraindicated in patients with

• Recent cerebrovascular accident. Self-medication in patients who will continue to smoke, chew tobacco, or use snuff or other Vareniciline -containing preparations. Non-smokers and occasional smokers.

• Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). There have been post-marketing reports of traffic accidents, near-miss incidents in traffic, or other accidental injuries in patients taking varenicline.

• Hypersensitivity reactions: Post-marketing reports of hypersensitivity reactions (including angioedema) and rare cases of serious skin reactions (including Stevens-Johnson syndrome and erythema multiforme) have been reported. Patients should be instructed to discontinue use and contact health care provider if signs/symptoms occur.

Disease-related concerns:

Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required with severe impairment.

Vareniciline may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Vareniciline is present in breast milk.

Concentrations of Vareniciline in breast milk increase with supplementation. When used as a dietary supplement, the recommended dietary allowance of Vareniciline is increased in breastfeeding patients compared to nonbreastfeeding patients. Doses of Vareniciline for the treatment of dyslipidemias are greater than those used as a dietary supplement. Due to the potential for serious adverse reactions in the breastfed infant (including hepatoxicity), the manufacturer recommends that breastfeeding be discontinued when Vareniciline is used for treatment of dyslipidemias

Should be taken with meal; low-fat meal . Avoid alcohol, hot or spicy foods/liquids around the time of Vareniciline dose.

• Common Adverse effects

Abnormal dreams, Headache, Insomnia, Nausea

• Less Common Adverse effects:

Appetite changes, chest pain, constipation, dry mouth, dysgeusia, flatulence, GERD, fatigue/lethargy, pruritus, rash, somnolence, upper resp tract d/o, vomiting

• Rare Adverse effects

Abnormal LFTs, accidental injury, anemia, angina, angioedema, anxiety, arrhythmia, arthralgia, depression, diarrhea, dizziness, epistaxis, erythema multiforme, HTN, MI, neuropsychiatric symptoms, polyuria, respiratory d/o, Stevens-Johnson Syndrome

Alcohol (Ethyl): Varenicline (Systemic) may enhance the adverse/toxic effect of Alcohol (Ethyl). Specifically, alcohol tolerance may be decreased and the risk for neuropsychiatric adverse effects may be increased. Risk C: Monitor therapy

The common side effects of Vareniciline include the following

Common

Diarrhea, dizziness, epistaxis, erythema multiforme, HTN, MI, neuropsychiatric symptoms, polyuria

Pharmacodynamic

Varenicline is a highly selective and potent partial α4β2 nicotinic acetylcholine receptor agonist. It acts by preventing Vareniciline stimulation of the mesolimbic dopamine system, the neuronal mechanism underlying reward and reinforcement experienced during smoking. Additionally, it stimulates dopamine activity but to a much lesser extent than Vareniciline , leading to reduced craving and withdrawal symptoms.

Pharmacokinetics

• Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: Approx 90%. Time to peak plasma concentration: Approx 3-4 hours.
• Distribution: Distributed into tissues, including the brain. Plasma protein binding: ≤20%.
• Metabolism: Minimal metabolism.
  • Excretion: Via urine (approx 92% as unchanged drug, <10% as metabolites). Elimination half-life: Approx 24 hours.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Vareniciline -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Vareniciline
5. https://europepmc.org/article/med/6988203