Varenicline

Varenicline is an aid to smoking cessation treatment.

Overview

Varenicline is one of the most powerful drugs currently available to help a patient stop smoking. The drug acts as an agonist to a number of the brain’s nicotine receptors, with varying degrees of strength. Its effect is a partial stimulation of the receptors, which can dull some of the symptoms of nicotine withdrawal while simultaneously preventing actual nicotine from binding to the receptors. The one-two punch has the effect of alleviating nicotine cravings and making indulging those cravings less satisfying.

Buprenorphine, a drug approved by the FDA to treat opioid dependence, works in a similar fashion.

Varenicline is most commonly found in the prescription drug Chantix. Produced by Pfizer in several iterations, Chantix is currently the only form of varenicline approved for sale by the FDA.

Conditions Treated

  • Nicotine dependence

Type of Medicine

  • Nicotine cessation aid

Efficacy

Six clinical studies across more than 3500 separate participants measured the effectiveness of varenicline in treating nicotine dependence (helping the subject stop smoking). The studies ran for 12 weeks of the subjects taking varenicline, and a 40 week monitoring period (making a full year) to measure rates of relapse. Across the 12 weeks of taking the drug, placebo groups never got above 10% of their participants abstaining from smoking. The groups receiving the varenicline reported 30% abstinence rate, while some groups reported 50%+ abstinence rate. As the 12 weeks wore on, the abstinence rate in the varenicline groups reported steady increases in abstinence rate, while the abstinence rate in placebo groups remained flat. When studies compared 1 mg and 2 mg doses varenicline, the groups receiving 2 mgs of varenicline consistently reported higher abstinence rates.

Varenicline is a tool to help a patient stop smoking. In order to be effective it should be combined with some form of therapy and the desire and determination within the patient to stop smoking.

Side Effects

  • Nausea
  • Stomach pain
  • Indigestion
  • Constipation
  • Gas
  • Bloating
  • Vomiting
  • Unpleasant tastes
  • Changes in and/or loss of taste
  • Headaches
  • Weakness
  • Tiredness
  • Hyperventilation
  • Unusual/vivid dreams (similar to nicotine dreams)
  • Nightmares
  • Insomnia and other sleep problems
  • Dry mouth
  • Various symptoms of the common cold
  • Varenicline has been known to cause serious, sometimes fatal side effects. The following symptoms can be signs of these rare but dangerous side effects. Contact your doctor immediately if you experience:
  • Shortness of breath
  • Feelings of confusion
  • Hallucinations (auditory or visual)
  • Extreme stomach upset
  • Extreme vomiting
  • Seizures
  • Burning sensation in the feet or toes
  • Rogue or unusual leg pain
  • Signs of an allergic reaction:
  • Hives
  • Redness/rash
  • Itching
  • Skin damage/abnormalities
  • Hoarseness/difficulty talking
  • Tightness in the chest
  • Wheezing
  • Swelling of the head and/or neck
  • Toxic Epidermal Necrolysis (Stevens-Johnson Syndrome), a serious condition with potentially permanent or lethal consequences may occur while taking varenicline. Contact your doctor immediately if you experience:
  • Red or irritated eyes
  • Red, painful, blistered or peeling skin
  • Fever
  • Sores on your skin, eyes, mouth, or throat
  • Along with Toxic Epidermal Necrolysis, varenicline can cause angioedema, a harmful skin condition similar to hives. Angioedema brought on by varenicline has, in some cases, caused extreme swelling of the neck and throat, cutting off the patient's ability to breathe. Patients who experience swelling in these areas should take extra caution and inform their doctor immediately.
  • Heart attacks and strokes have occurred in people taking varenicline. Call your doctor immediately and seek medical help if you experience any of the symptoms of these incidents. The symptoms of a heart attack can include:
  • Chest pain which spreads to the arms, neck, jaw, back or stomach
  • Abnormal sweating
  • Feelings of sickness or vomiting
  • The symptoms of a stroke can include:
  • Changes in strength between one side of the body and the other
  • Changes in eyesight, speech, or balance
  • Changes in clear logical thought
  • Intense headache

Varenicline has also been known to cause sleepwalking, a condition that isn’t dangerous in of itself but can be dangerous. Call your doctor immediately if you begin to sleepwalk.

Varenicline has been known to have neuropsychiatric effects. The FDA has added and removed a warning label from Chantix several times, but as of December 16, 2016, the label has been removed from the medication. The studied side effects include effects on mood, behavior, and suicidal thoughts/actions. Patients with preexisting conditions in these areas may be more at risk.

It is important to note that quitting smoking, with or without varenicline, can cause nicotine withdrawal symptoms, which include depression, agitation, and exacerbation of existing psychiatric disorders.

This is by no means a complete list of side effects and patients should contact their doctor right away if they begin to experience unusual symptoms. Side effects can be reported to the FDA at 1-800-FDA-1088.

Dosage

Patients are instructed to begin taking varenicline shortly before stopping smoking. In the case of Chantix, patients are instructed to pick a date to stop smoking and begin taking Chantix a week before that date.

Dosages usually begin at .5 mg daily, and build to 2 mg daily over the course of a week, divided into two 1 mg doses taken once in the morning and once at night. On average, steady state conditions will be reached within 4 days. Varenicline should only be taken orally.

Varenicline is prescribed in 12-week blocks. If patients succeed in quitting smoking by the end of the 12 weeks, they are encouraged to do another 12 weeks of the drug to decrease chances of relapse. Patients who fail to quit smoking by the end of the twelve weeks are encouraged to try again with varenicline when they’re able to.

The body does not build up a tolerance to varenicline. As a result, there is no need to increase dosage beyond the 2 mg daily maximum prescribed dose.

Varenicline is easiest on the body when taken after a meal and with a full 8 oz. glass of water.

In the event of a patient forgetting to take their dose, it is recommended they do so as soon as they remember. In the event that by the time they remember, it is nearly time for their next dose, they should simply wait to take their next dose. Patients are discouraged from taking two doses at once in an attempt to retroactively negate forgetting to take their last dose.

In both smokers and nonsmokers, single instance doses of 3mg have produced adverse reactions. In extremely rare cases, varenicline overdose can occur, requiring hospitalization.

Varenicline can cause mild dependency issues. Some patients have experienced adverse effects from abruptly ending their varenicline treatment. As much as 3% reported sleep problems.

Varenicline has not been properly evaluated for children (under 18 years of age) and cannot be described as safe.

Interactions

  • A series of studies ran on the interactions between varenicline and the following drugs, metformin, cimetidine, digoxin, warfarin, bupropion, and transdermal nicotine, found no meaningful interactions between the drugs and varenicline.
  • Due to the potential for drowsiness, dizziness, and other incapacitating side effects, patients taking varenicline are encouraged to refrain from driving and operating heavy machinery until they fully understand how varenicline affects them.
  • Varenicline is removed from the body by hemodialysis. Patients who rely on hemodialysis should consult with their doctor about the viability of using varenicline.

Drugs (The names listed below are the generic names for drugs)

  • In specific cases, varenicline can interact with lamotrigine (a medication often used to treat epilepsy). Patients taking lamotrigine should consult with their doctor about the risks of using the two drugs concurrently.
  • Dolutegravir (an antiretroviral used to treat HIV) can amplify the effects of varenicline in the blood. Special attention should be paid to the dosage of varenicline if the patient is currently taking dolutegravir, or is discontinuing their usage of dolutegravir.
  • Ranolazine (a heart medication commonly used to treat angina) can amplify the effects of varenicline. Special attention should be paid to the dosage of varenicline if the patient is currently taking ranolazine, or is discontinuing their usage of ranolazine.
  • Vandetanib (a medication used to treat some forms of thyroid cancer) can amplify the effects of varenicline. Special attention should be paid to the dosages in order to use the two drugs simultaneously, and in the event that patient stops taking either drug.
  • Nicotine, when used in tandem with varenicline, can amplify the effects and side effects of varenicline, including nausea, dizziness, vomiting, and headaches.
  • Varenicline can lower a patient’s tolerance for alcohol, and increase the likelihood of aggressive behavior and blackouts when drinking. Patients are encouraged to abstain from alcohol or limit their drinking until they fully understand how varenicline affects them.

Diseases

Varenicline is filtered out of the body by the liver. As a result, patients with extreme renal impairment should use caution when taking varenicline. It is recommended that patients with extreme renal impairment take no more than .5 mg of varenicline daily.

  • Patients with mild or moderate renal impairment should exercise caution while taking varenicline, but no adverse reactions have been observed in patients with mild to moderate renal impairment.
  • The elderly, due to increased likelihood of renal impairment, should use care when choosing a dosage.
  • Varenicline has been observed in some patients to create or exacerbate symptoms of cardiovascular diseases. Ischemic and hemorrhagic events have occurred in rare cases. Patients with a history of cardiovascular disease should use caution when considering taking varenicline and should be monitored for new or worsening signs of cardiovascular disease.
  • Varenicline is known to exacerbate pre-existing mental conditions. Patients with a history of mental illness, including depression and suicidal tendencies, should use extreme caution while taking varenicline. Mentally ill patients on varenicline should be monitored for changes including changes in behavior, hostility, aggression, depression, and suicidal thoughts/tendencies.
  • Varenicline has been known to cause seizures. Patients with epilepsy or who are predisposed to epilepsy should exercise caution when deciding to take varenicline.

Warnings

Varenicline has not been evaluated for use by patients under 18 years old. As such, it cannot be deemed safe for those under 18 years old.

Varenicline has not been evaluated for use by pregnant or breastfeeding women. As such, it cannot be deemed safe for either pregnant women or breastfeeding women. The adverse effects of smoking during pregnancy or while breastfeeding must be kept in mind. Women who do take varenicline while breastfeeding their child are advised to monitor the baby for both seizures and vomiting. It’s important to remember that smoking can also cause adverse effects on children while in the womb and while being breastfed.

Chantix, a form of varenicline made available by Pfizer, featured a boxed warning on the risks of suicide and the exacerbation of mental illnesses as recently as December of 2016. The black warning box was removed, in concurrence with the FDA and a review board of their experts, at that time. Nevertheless, patients taking varenicline should be aware that suicidal thoughts and tendencies suffered while taking varenicline may be caused by the drug. In 2013, Pfizer set aside nearly three million dollars to settle almost 3,000 cases against them, many over mental changes perceived to have been caused by the drug.

Storage

  • Varenicline is best when stored at room temperature, or between 68 and 77 degrees Fahrenheit (between 20 and 25 degrees Celsius).
  • Due to the potential danger it poses, varenicline should be stored out of the reach of children.

Summary

Nicotine dependence is a notoriously difficult condition to break out of. Almost any increase in abstinence rates would be notable, making varenicline’s 30%+ abstinence rates impressive. The drug's two-step method, where it both cuts down on the desire to smoke and cuts down on the enjoyment of smoking, can give many smokers the edge they need to finally overcome their addiction to nicotine.

Varenicline is simple to take and, in comparison to smoking cigarettes, relatively easy on the body. The drug interacts with only a handful of other drugs, and those interactions are mild at worst. Varenicline interacts with a small handful of relatively uncommon diseases, and the instances of major interactions are extremely rare. As a result, varenicline tends to be a very forgiving drug, especially to the otherwise healthy population.

For those living with pre-existing conditions, this is less the case. For those with cardiovascular disease, epilepsy, and mental problems, varenicline poses a far greater risk. Most importantly, the complications that these can bring are far harder to justify when compared with smoking, especially because varenicline is far from 100% effective in stopping patients from smoking. Given the complications possible, it is paramount that a patient consult with their doctor about all the possible interactions and all the patient's pre-existing conditions.

For many people, the ease of use for varenicline, combined with its extremely low instance of serious side effects will make the drug an attractive augment to their own willpower in the fight against cigarette addiction. For others, fighting with more than just a desire to smoke, the risks may simply be too high.

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