Varenicline

Varenicline is a medicine that can help adults quit smoking. It works by lowering the cravings and withdrawal symptoms associated with quitting, as well as the positive impacts of nicotine. This makes it easier for smokers to quit since it reduces both their desire to smoke and the reinforcement from nicotine. Varenicline was approved by the U.S. Food and Drug Administration (FDA) in 2006 for the treatment of smoking cessation. It is also approved in many other countries for the same indication.

BRAND NAMES

CHAMPIX: CHAMPIX contains the active substances varenicline. It is available in the form of film coated tablets with strengths of 0.5mg and 1mg. 

TYRVAYA: TYRVAYA is available in form of nasal spray. It contains the active ingredient varenicline tartrate 0.03mg.

MECHANISM OF ACTION

Varenicline acts as a partial agonist at the α4β2 nicotinic receptors in the brain. Varenicline binds to these receptors and provides some stimulation, mimicking the effects of nicotine. This helps to reduce cravings and withdrawal symptoms when quitting smoking. Varenicline also blocks nicotine from binding to these receptors. This means that when someone smokes while using varenicline, the nicotine has less of an effect, reducing its pleasurable impact and the drive to keep smoking.

PHARMACOKINETICS

Absorption:

Varenicline is quickly absorbed after oral intake, with about 90% bioavailability. Food does not significantly affect absorption, so it can be taken with or without meals.

Distribution:

It has a wide distribution in the body, with a large volume of distribution (~334 L). About 20% of it is bound to plasma proteins.

Metabolism:

Varenicline is processed in the liver, mainly through the CYP2A6 enzyme. The primary metabolite is inactive, and it is referred to as N-desmethyl varenicline.

Excretion:

Most of varenicline is excreted unchanged through the urine (about 92% of the dose). A small amount is eliminated in the feces and its half-life is approximately 24 hours, which supports once-daily dosing. It is primarily eliminated through the kidneys. In patients with renal issues, clearance may be slower, requiring dose adjustments.

DOSAGE AND ADMINISTRATION

Oral Formulation:

Initial dose: Start with 0.5 mg once daily for days 1 to 3, then increase to 0.5 mg twice daily from days 4 to 7. Start varenicline 1 week before quitting. Alternatively, start varenicline and stop smoking between days 8 and 35.

Maintenance: After day 8, take 1 mg twice daily for 11 weeks.

Long-Term Use: Treatment can be extended for up to 6 months or longer depending on patient needs, though further research is needed for long-term efficacy beyond 12 months.

Nasal Formulation:

Administer one spray in each nostril twice daily. If a dose is missed, continue with the next scheduled dose. Before the first use, prime the spray by delivering 7 actuations into the air. If not used for over 5 days, re-prime with 1 actuation. Do not shake the device. Take oral tablets with water to reduce gastric discomfort.

DRUG INTERACTIONS

• Nicotine: Combining with nicotine replacement may increase side effects (nausea, dizziness).
• Alcohol: Varenicline may enhance alcohol's effects, so limit intake.
• CYP450 Enzyme Inhibitors: Minimal interactions with drugs affecting this enzyme.
• Renal Impairment: Dose adjustments needed in patients with kidney issues.

CONTRAINDICATIONS

• Allergy: Avoid if allergic to varenicline or its components.
• Severe Renal Impairment: Not recommended without dose adjustments.
• Pregnancy/Breastfeeding: Avoid unless necessary due to limited safety data.
• Psychiatric Disorders: Use with caution in individuals with psychiatric history due to mood changes and suicidal thoughts.

SIDE EFFECTS

Common side effects

• Nausea (most frequent)
• Headache
• Insomnia
• Dizziness
• Fatigue
• Dry mouth

Severe side effects:

• Psychiatric effects: Mood swings, depression, anxiety, and suicidal thoughts or behavior.
• Cardiovascular issues: Increased risk of heart attack in individuals with existing heart conditions (use with caution).
• Severe allergic reactions: Rash, swelling, or breathing difficulties.
• Seizures: Rare but possible.

TOXICITY:

• Overdose: Symptoms include nausea, vomiting, increased heart rate, blood pressure, and seizures. Treatment is supportive care with monitoring and fluids.
• Chronic Toxicity: High doses can cause gastrointestinal issues, increased blood pressure/heart rate, and neuropsychiatric symptoms.
• Renal Impairment: Slower clearance in kidney issues, increasing the risk of toxicity.
• Psychiatric Effects: High doses may worsen depression, anxiety, and suicidal thoughts, especially in those with a mental health history.