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It is marketed under the name Chantix and Champix. It is a prescription drug used to treat nicotine addiction.
It reduces cravings and decreases the pleasant effects of cigarettes and other tobacco products.
It is used to help people quit smoking when nicotine replacement therapy has not been effective or is not appropriate. Varenicline is intended to be used by adults in combination with smoking cessation education and counseling.
Varenicline works in the brain to reduce cravings and withdrawal symptoms . It is a high-affinity partial agonist for the nicotinic acetylcholine receptor α4β2 (NACH) subtype.
This leads to the release of dopamine in the nucleus accumbens when activated and therefore has the ability to reduce the feelings of craving and withdrawal caused by quitting smoking.
In this respect, it is similar to cytisine and different from the nicotinic antagonist bupropion and nicotine replacement therapies (NRTs) such as nicotine patches and nicotine gum.
Medical uses
Varenicline is used to stop smoking. In a 2009 meta-analysis, varenicline was found to be more effective than bupropion (odds ratio 1.40) and nicotine replacement therapies (odds ratio: 1.56).
A 2013 Cochrane review and network meta-analysis concluded that varenicline is the most effective drug for smoking cessation and that smokers were almost three times more likely to quit varenicline treatment than placebo.
Varenicline was more effective than bupropion or nicotine replacement therapy and as effective as the combination of nicotine replacement therapy for smoking cessation.
The United States Food and Drug Administration (US FDA) has approved the use of varenicline for up to twelve weeks. If you have successfully stopped smoking, you can continue for another twelve weeks.
Varenicline has not been tested in those under 18 years of age or in pregnant women, and therefore its use is not recommended by these groups.
Varenicline is considered a class C pregnancy drug, as animal studies have not shown an increased risk of birth defects, however, no human study data are available.
An observational study evaluating malformations related to varenicline exposure is currently underway, but has not yet had any results.
An alternative drug is preferred for smoking cessation while breastfeeding due to lack of information and based on animal studies on nicotine.
To increase your chances of success, use this drug with a smoking cessation program that includes education, support, and counseling.
Quitting smoking reduces the risk of heart and lung disease, as well as cancer. Varenicline works by blocking the effects of nicotine in the brain that make you want to smoke.
Discuss the risks and benefits of this drug with your doctor, as well as other ways to quit smoking (such as nicotine replacement therapy).
How to use varenicline
It is intended to be used in conjunction with smoking cessation education and counseling. There are 3 different approaches to setting a quit date (the “quit date”). Talk to your doctor or pharmacist about which method would be best for you.
In the fixed quit approach, start varenicline treatment 1 to 2 weeks before your scheduled quit date and continue for 12 weeks.
In the flexible quit approach, start taking varenicline, then set a quit date between weeks 2 and 5 after the start of treatment. Treatment should be continued for 12 weeks.
For those who succeed in quitting during this time, their doctor may recommend an additional 12-week treatment to reduce the risk that they will start smoking again.
In the gradual approach, start taking varenicline and decrease smoking with the goal of quitting at the end of 12 weeks.
If you can, you can quit smoking anytime before 12 weeks. Continue taking varenicline for an additional 12 weeks, for a total of 24 weeks of treatment.
Your doctor may suggest that you gradually decrease the dose of varenicline as you stop the medicine, to reduce the risk that you will start smoking again.
People who do not quit smoking during the first 12-week treatment are advised to try again once they have identified and addressed the factors that may have caused them problems quitting smoking.
Do not take this medicine if you are allergic to varenicline or any ingredient in the medication.
Do not take varenicline if you are using nicotine replacement therapy, such as patches, gum, or the nicotine inhaler.
The combination of varenicline and nicotine replacement therapy may cause more side effects than with varenicline alone and is unlikely to improve your chances of quitting smoking.
Varenicline dosage
The usual starting dose of varenicline is 0.5 mg once a day for the first 3 days, then 0.5 mg twice a day for the next 4 days, then continue with 0.5 mg twice a day or increase to 1 mg twice a day. day later.
The maximum dose of varenicline is 1 mg twice a day. Varenicline should be taken with a full glass of water after eating.
There are several ways to use varenicline. The first is to set a date to quit smoking before starting treatment with this drug.
Start taking varenicline as directed by your doctor, 1 week before your stop date.
When you first start taking this medication, take a 0.5 milligram tablet once a day for 3 days, then increase to a 0.5 milligram tablet twice a day for 4 days.
The dose is slowly increased to decrease the chance of side effects (such as nausea, unusual dreams). During this first week, it is okay to smoke.
Stop smoking on the quit date and start taking the dose prescribed by your doctor twice a day for the remainder of the 12-week treatment period.
The second way to use varenicline is to start taking the drug before choosing a date to quit smoking. Start with the 0.5 milligram tablets and increase the dose as directed by your doctor.
Pick a date to quit smoking between days 8 and 35 of treatment. Stop smoking on your chosen quit date. No matter which way you use varenicline, always follow your doctor’s instructions carefully.
If you are unable or unwilling to quit smoking right away, your doctor may prescribe a third way to take varenicline. Follow your doctor’s instructions carefully and cut down on your smoking as directed.
If this medicine comes in a dosage pack, carefully follow the directions on the dosage pack.
There are two types of dosage packs: a starter pack and a continuous pack, each with different strengths of this drug.
If this medicine comes in a bottle, carefully follow your doctor’s instructions on the prescription label. If you have any questions about how to take this medicine, talk to your doctor or pharmacist.
Take this medicine by mouth after eating and with a full glass of water. Dosage is based on your medical condition and response to treatment.
Do not increase your dose or take this medicine more often than prescribed. Your condition will not improve any faster, and your risk of side effects will increase. Do not take more than 1 milligram twice a day.
If you miss a dose, and it is within a few hours of the missed dose, take it as soon as possible and continue on your regular schedule.
Take this medicine regularly to get the most benefit from it. To help you remember, take it at the same time (s) every day.
Tell your doctor if you continue to smoke after a few weeks of treatment. If you can’t quit after 12 weeks of treatment, talk to your doctor.
If you are successful and do not smoke cigarettes after 12 weeks of treatment, your doctor may recommend another 12 weeks of varenicline treatment.
Side effects
Mild nausea is the most common side effect and is seen in about 30% of people taking varenicline, although this rarely (<3%) results in discontinuation of the drug.
Other less common side effects include headache, trouble sleeping, and nightmares.
Rare side effects reported by people taking varenicline compared to placebo include changes in taste, vomiting, abdominal pain, flatulence, and constipation.
It has been estimated that for every five subjects taking varenicline in maintenance doses, there will be an event of nausea, and for every 24 and 35 subjects treated, there will be an event of constipation and flatulence, respectively.
Gastrointestinal side effects lead to drug discontinuation in 2% to 8% of people using varenicline.
The incidence of nausea is dose dependent: the incidence of nausea was higher in people taking a higher dose (30%) versus placebo (10%) compared to people taking a smaller dose (16%) versus placebo (eleven%).
Tell your doctor right away if you have any serious side effects, including: burning sensation in your feet / toes, unusual pain in your legs when walking.
Stop taking varenicline and seek medical attention right away if you have very serious side effects, including:
- Seizures, symptoms of a heart attack (such as pain in the chest, jaw, left arm, shortness of breath, unusual sweating).
- Signs of a stroke (such as weakness on one side of the body, slurred speech, sudden vision changes, confusion), behavior that is harmful to self / others / property.
- In rare cases, varenicline can cause serious mental / mood changes, even after stopping the drug.
Allergic reaction
In rare cases, some people may develop severe allergic reactions and skin reactions to this drug.
Signs of an allergic reaction include a severe rash, skin changes, hives, swelling of the face or throat, or trouble breathing. If this occurs, seek immediate medical attention.
Behavior or mood swings
Some people taking this medicine experience erratic or aggressive behavior, agitation, depressed mood, or thoughts of hurting themselves or others.
If you experience any changes in your mood or behavior or if your friends or family notice any of these changes while taking this medicine, stop taking this medicine and contact your doctor immediately.
Mental health problems
If you have any type of mental health problem or a history of mental health problems, including schizophrenia, bipolar disorder, and major depressive disorder.
Talk to your doctor about how this medicine can affect your medical condition, how it can affect your health, the dosage and effectiveness of this medicine, and if any special monitoring is needed.
If you experience new or worse mood or behavior changes while taking varenicline, or if your friends or family notice any of these changes while taking this medicine, stop taking this medicine and contact your doctor immediately.
Depression and suicide
In 2007, the US Food and Drug Administration announced that it had received post-marketing reports of:
Thoughts of suicide and occasional suicidal behavior, erratic behavior, and drowsiness among people using varenicline to quit smoking.
In 2009, the U.S. Food and Drug Administration required varenicline to carry a warning stating that the drug should be discontinued if any of these symptoms are experienced.
A 2014 systematic review found no evidence of an increased risk of suicide.
Other analyzes have reached the same conclusion and found no increased risk of neuropsychiatric side effects with varenicline.
In a post-marketing surveillance study, no evidence of an increased risk of cardiovascular events, depression or self-harm was found with varenicline replacement therapy versus nicotine.
In 2016, the Food and Drug Administration removed the black box warning. People are still advised to stop taking the drug if they “notice side effects on mood, behavior, or thinking.”
Nicotine replacement therapy
Varenicline should be tried as a smoking cessation therapy only after a trial of nicotine replacement therapy has been unsuccessful.
People who use nicotine replacement therapy at the same time as varenicline may experience an increase in side effects.
The safety and efficacy of taking this drug with other smoking cessation therapies, such as nicotine replacement therapy, have not been established.
Nicotine withdrawal
Nicotine withdrawal symptoms can occur even when using varenicline.
Seizures
There have been reports of seizures by people taking this drug. They have been reported by people with seizure disorders and some without a history of seizures.
If you have a seizure disorder, talk with your doctor about how this medication may affect your medical condition, how your medical condition may affect the dosage and effectiveness of this medication, and if any special monitoring is needed.
If you experience seizures while taking this drug, stop the drug immediately and get medical attention.
Cardiovascular disease
Varenicline may increase the risk of cardiovascular-related side effects in people with cardiovascular disease (conditions that affect the heart or blood vessels).
In June 2011, the US Food and Drug Administration issued a safety announcement that varenicline may be associated with “a small and increased risk of certain adverse cardiovascular events in people with cardiovascular disease.”
An earlier review from 2011 found an increased risk of cardiovascular events compared to placebo.
Expert comments in the same journal raised questions about the review methodology, concerns that were echoed by the European Medicines Agency and subsequent reviews.
Of particular concern were ‘the low number of observed events, the types of events counted, the higher dropout rate in people who received placebo, the lack of information on the timing of the events, and the exclusion of studies in which no one had an event.
If you have cardiovascular disease, such as heart disease or high blood pressure, talk with your doctor about how this drug may affect your medical condition, how your medical condition may affect the dosage and effectiveness of this drug, and if any special monitoring is needed. .
Talk to your doctor if you experience new or worsening cardiovascular-related symptoms, such as new or worsening chest pain, new or worse leg pain when walking, shortness of breath, or shortness of breath.
Diabetes
People with diabetes who quit smoking often experience changes in their blood sugar control. This is the result of eliminating the effect of nicotine in the body.
If you have diabetes, talk with your doctor about how quitting smoking may affect your medical condition, how your medical condition may affect the dosage and effectiveness of this medication, and if any special monitoring is needed.
You may be asked to check your blood sugar levels more often.
Drowsiness or reduced alertness
This medicine may affect the mental or physical abilities necessary to drive or operate machinery.
Some people find that it causes drowsiness, dizziness, or decreased ability to concentrate. Avoid driving, operating machinery, or performing other dangerous tasks until you have determined how varenicline affects you.
Renal function
Kidney disease or reduced kidney function can cause this drug to build up in the body, causing side effects.
If you have reduced kidney function or kidney disease, talk with your doctor about how this drug may affect your medical condition, how your medical condition may affect the dosage and effectiveness of this drug, and if any special monitoring is needed.
If you have kidney disease, a lower dose of this drug may be prescribed. Your doctor will monitor you while you are taking this medicine.
Alcohol
It is recommended that people reduce the amount of alcohol they drink. Drinking alcohol while taking varenicline can increase the risk of developing mood disorders or behavior changes.
This can occur whether there is a history of psychiatric disorder or not. Alcohol can increase the risk of experiencing these mood or behavior changes.
Precautions
Before taking varenicline, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems.
Before using this medicine, tell your doctor or pharmacist your medical history, especially of:
Kidney disease, mental / mood disorders (such as schizophrenia, bipolar disorder, depression), heart / blood vessel disease such as coronary artery disease, peripheral vascular disease, stroke, or seizure.
This medicine can make you dizzy, sleepy, lose consciousness, or make it hard to concentrate.
Marijuana and drug use can worsen these effects. Don’t drive or do anything that requires alertness until you can safely do so. Talk to your doctor if you are using any drugs.
This drug can also make you more sensitive to alcohol, even more drunkenness, unusual behavior, and limited or no recollection of things that happened.
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medicine, contact your doctor immediately.
It is not known whether varenicline passes into breast milk. If you are a nursing mother and you are taking this medicine, it may affect your baby. Talk to your doctor about whether you should continue to breastfeed.
The safety and effectiveness of this drug have not been established for children, seniors are more likely to experience side effects when taking this drug.
Mechanism of action
Varenicline exhibits full agonism at α7 nicotinic acetylcholine receptors and is a partial agonist at a4, 2, a3, 4, and a6 b2 subtypes. Furthermore, it is a weak agonist at α3β2-containing receptors.
Partial agonism of varenicline at α4β2 receptors rather than full agonism of nicotine produces less dopamine-releasing effect than nicotine.
This competitive binding of α4β2 reduces the ability of nicotine to bind and stimulate the mesolimbic dopamine system, similar to the method of action of buprenorphine in the treatment of opiate addiction.
Pharmacokinetics
Most of the active compound is excreted by the kidneys (92-93%). A small proportion is glucuronidated, oxidized, N-formylated, or conjugated to a hexose. The elimination half-life is approximately 24 hours.
History
The use of the Cytisus plant as a substitute for smoking during World War II led to its use as a smoking cessation aid in Eastern Europe and the extraction of cytisine. Cytisine analogs led to varenicline at Pfizer.
Varenicline received a ‘priority review’ by the US Food and Drug Administration in February 2006, shortening the usual review period from 10 months to 6 months due to its demonstrated efficacy in clinical trials and the perceived lack of safety.
Drug agency approval occurred on May 11, 2006. On August 1, 2006, varenicline was released for sale in the United States and on September 29, 2006, it was approved for sale in the European Union. .
