Usage
Varenicline is prescribed for smoking cessation. It is classified as a nicotinic receptor partial agonist. Varenicline works by reducing nicotine cravings and withdrawal symptoms while also blocking the rewarding effects of nicotine from smoking.
Alternate Names
The International Nonproprietary Name (INN) is varenicline. A popular brand name is Chantix.
How It Works
Pharmacodynamics: Varenicline is a nicotinic acetylcholine receptor partial agonist. It selectively binds to the α4β2 nicotinic receptor subtype, stimulating dopamine release, but to a lesser degree than nicotine, thereby reducing cravings and withdrawal symptoms. When a person smokes while taking varenicline, the drug blocks nicotine from fully activating the receptors, reducing the sense of reward and satisfaction.
Pharmacokinetics: Varenicline is well absorbed after oral administration, reaching peak plasma concentrations within 3-4 hours. It has minimal metabolism in the liver, mainly by CYP2B6, but this pathway is not considered clinically significant. It’s primarily eliminated unchanged through renal excretion (approximately 92%), with a half-life of about 24 hours.
Mode of action: Varenicline binds with high affinity and selectivity to the α4β2 neuronal nicotinic acetylcholine receptors, where it acts as a partial agonist. It stimulates receptor activity but less so than nicotine resulting in lower levels of dopamine release. This helps alleviate withdrawal symptoms and cravings. If nicotine is introduced (through smoking) while varenicline is bound to the receptor, the drug acts as an antagonist, preventing nicotine from binding and producing its full rewarding effects.
Elimination pathways: Varenicline is primarily eliminated unchanged by the kidneys via glomerular filtration and active tubular secretion.
Dosage
Standard Dosage
Adults:
The standard dosage regimen involves a gradual titration over the first week:
- Days 1-3: 0.5 mg once daily
- Days 4-7: 0.5 mg twice daily
- Days 8 onwards: 1 mg twice daily
Treatment typically lasts for 12 weeks, with a possible extension to 24 weeks for patients who have successfully quit to further reduce the risk of relapse.
Children:
Varenicline is not recommended for use in patients under 18 years of age. Safety and efficacy have not been established in pediatric populations.
Special Cases:
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Elderly Patients: No dosage adjustment is necessary for healthy elderly patients. However, renal function should be monitored, as elderly patients are more prone to renal impairment.
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Patients with Renal Impairment:
- Mild to moderate impairment (creatinine clearance ≥ 30 mL/min): No dosage adjustment required.
- Severe impairment (creatinine clearance < 30 mL/min): 0.5 mg once daily initially, may be increased to 0.5 mg twice daily.
- End-stage renal disease (ESRD) requiring hemodialysis: Not to exceed 0.5 mg once daily.
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Patients with Hepatic Dysfunction: No dosage adjustment is necessary.
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Patients with Comorbid Conditions: Caution should be used in patients with a history of psychiatric illness (e.g., depression, schizophrenia, bipolar disorder) or seizures. Close monitoring for neuropsychiatric symptoms is essential. For patients with cardiovascular disease, careful evaluation of risks and benefits is needed.
Clinical Use Cases
Varenicline’s sole clinical use is as an aid to smoking cessation in adults. It is not indicated for other medical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose reductions may be necessary for patients who experience intolerable side effects, particularly nausea. Temporary or permanent reductions to 0.5 mg twice daily may be considered.
Side Effects
Common Side Effects:
Nausea, constipation, gas, vomiting, sleep disturbances (insomnia, abnormal dreams), headache, and changes in taste.
Rare but Serious Side Effects:
Neuropsychiatric symptoms (mood changes, depression, suicidal ideation, agitation, aggression), serious skin reactions (Stevens-Johnson syndrome), cardiovascular events (changes in heart rate, blood pressure), seizures, and angioedema.
Long-Term Effects:
The potential long-term effects of varenicline are still being studied. Neuropsychiatric symptoms are of particular concern and require ongoing monitoring even after treatment discontinuation.
Adverse Drug Reactions (ADR):
Serious neuropsychiatric events, severe skin reactions, cardiovascular events, and seizures.
Contraindications
Hypersensitivity to varenicline, history of serious skin reactions (e.g., Stevens-Johnson syndrome), and, generally, use in children under 18 years of age.
Drug Interactions
Clinically significant interactions are limited. Concomitant use with other medications primarily necessitates monitoring for changes in their effects, especially those metabolized by CYP1A2. Some examples include theophylline, warfarin, and insulin.
Interactions with alcohol and other smoking cessation therapies (bupropion, nicotine replacement therapy) are also possible. They may increase the risk of side effects, and caution is advised.
Pregnancy and Breastfeeding
Varenicline is classified as Pregnancy Category B3, and it is not recommended during pregnancy. Although studies have not conclusively linked varenicline to birth defects, the risks outweigh the benefits compared to other smoking cessation methods.
It is not known if varenicline is present in breast milk. Due to the potential for adverse reactions in infants, it is recommended that breastfeeding be discontinued or the drug avoided during breastfeeding. If the decision is made to continue breastfeeding, close monitoring of the infant for any adverse reactions is advised.
Drug Profile Summary
- Mechanism of Action: Nicotinic acetylcholine receptor partial agonist.
- Side Effects: Nausea, insomnia, abnormal dreams, constipation, headache, neuropsychiatric symptoms (rare but serious).
- Contraindications: Hypersensitivity to varenicline, serious skin reactions.
- Drug Interactions: Limited, monitoring recommended for drugs metabolized by CYP1A2.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: Titrate up to 1 mg twice daily; special adjustments for renal impairment. Not recommended for children.
- Monitoring Parameters: Smoking status, weight, blood pressure, heart rate, and signs of neuropsychiatric symptoms.
Popular Combinations
Varenicline is typically used as monotherapy. Combination with other smoking cessation medications is generally not recommended due to the potential for increased side effects without significantly improved efficacy.
Precautions
- Assess for history of psychiatric illness and monitor carefully during treatment.
- Evaluate renal function, especially in elderly patients.
- Advise patients about potential neuropsychiatric side effects, including suicidal ideation.
- Monitor for skin reactions.
- Caution patients about potential interactions with alcohol and other drugs.
- Advise patients about the potential for impaired driving ability due to side effects like dizziness and sleepiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Varenicline?
A: Adults: 0.5 mg once daily for days 1-3, then 0.5 mg twice daily for days 4-7, then 1 mg twice daily. Dosage adjustments are needed for patients with severe renal impairment. Not recommended for children.
Q2: How does Varenicline work?
A: Varenicline is a nicotinic receptor partial agonist. It reduces craving and withdrawal symptoms while blocking the rewarding effects of nicotine.
Q3: What are the most common side effects?
A: Nausea, constipation, sleep disturbances, headache, and changes in taste.
Q4: Are there any serious side effects I should be aware of?
A: Yes. Serious neuropsychiatric events (mood changes, depression, suicidal ideation), severe skin reactions, cardiovascular events, and seizures are rare but serious side effects.
Q5: Can Varenicline be used during pregnancy or breastfeeding?
A: No, it is generally not recommended due to potential risks to the fetus or infant.
Q6: How long is a typical course of Varenicline treatment?
A: 12 weeks, with a possible extension to 24 weeks for patients who have successfully quit.
Q7: Does Varenicline interact with other medications?
A: Clinically significant interactions are limited, but it’s important to monitor the effects of other drugs when taken concomitantly, particularly drugs metabolized by CYP1A2, and alcohol, bupropion, or NRT.
Q8: What should I do if a patient experiences nausea while taking Varenicline?
A: Dose reduction to 0.5 mg twice daily may be considered. Advising the patient to take the medication with food may also help.
Q9: What precautions should be taken in patients with psychiatric history?
A: Patients with pre-existing psychiatric disorders require close monitoring for worsening or new neuropsychiatric symptoms.
Q10: How effective is Varenicline compared to other smoking cessation therapies?
A: In clinical trials, Varenicline has shown higher quit rates compared to placebo and some other smoking cessation aids. However, individual responses vary, and comprehensive support and counseling are essential for all smoking cessation therapies.
