Varenicline Tartrate (varenicline tartrate)

Dosage of varenicline tartrate is expressed in terms of varenicline.

No dosing information is available for this tab.

Smoking cessation, with or without varenicline, can alter the pharmacokinetics or pharmacodynamics of drugs such as theophylline, warfarin, and insulin, potentially requiring dosage adjustment.

Based on its pharmacologic properties and clinical data, varenicline has no clinically significant pharmacokinetic drug interactions.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Varenicline/Ethyl Alcohol

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism of this interaction has not been described.

CLINICAL EFFECTS: Concurrent use of varenicline and alcohol-containing products may result in increased intoxicating effects of alcohol, aggressive behavior and/or amnesia.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be advised that varenicline can change the way they react to alcohol. Case reports have described decreased alcohol tolerance, sometimes associated with aggressive behavior and/or amnesia with alcohol consumption which was previously tolerated. Patients and providers should be aware of unsuspected sources of alcohol such as medications. Reduce the use of non-essential alcohol containing drugs (e.g. cough and cold products) when possible. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (2): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation - For comparison, the US National Institute on Alcohol Abuse and Alcoholism definition of a Standard Drink (e.g. 12oz of 5% beer, 5oz of 12% wine) contains 14 grams of alcohol.

DISCUSSION: A search of the FDA Adverse Event Reporting System (FAERS) identified 48 cases of adverse events due to the combination of varenicline and alcohol.(1) Aggressive behavior was described in 37 cases. In these cases, the amount of alcohol consumed was insufficient to explain the event. More than half of the patients involved described their behavior as a significant change from their behavior prior to varenicline treatment. In 16 of the 37 cases, patients reported no or impaired memory of the event; most of these cases were also associated with physical harm to a person and/or property. Decreased alcohol tolerance was observed in 11 cases in patients who consumed quantities of alcohol which previously did not cause adverse effects. Outcomes included an automobile accident leading to arrest and a significant facial injury. Most of the patients in these cases described poor memory of their experience.

*Known history of serious hypersensitivity reactions or skin reactions to varenicline.

There are no contraindication contraindications for this drug.

• Bipolar disorder
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Depression
• Schizophrenia
• Seizure disorder
• Suicidal ideation

• Acute coronary syndrome
• Acute myocardial infarction
• Alcohol intoxication
• Alcohol use disorder
• Angina
• Cerebrovascular accident
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Peripheral vascular disease
• Transient cerebral ischemia

Adverse events reported in >5% of patients receiving varenicline and at twice the incidence of placebo include nausea, abnormal (e.g., vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting.

Less Frequent

• Angina

Rare or Very Rare

• Abnormal hepatic function tests
• Accidental injury
• Acute myocardial infarction
• Acute pancreatitis
• Alcohol intolerance
• Anemia
• Angioedema
• Cardiac arrhythmia
• Cerebrovascular accident
• Diabetes mellitus
• Drug-induced psychosis
• Erythema multiforme
• Homicidal ideation
• Hypersensitivity drug reaction
• Hypertension
• Manic disorder
• Seizure disorder
• Stevens-johnson syndrome
• Suicidal
• Suicidal ideation
• Thrombotic disorder
• Transient cerebral ischemia
• Unconsciousness

More Frequent

• Constipation
• Dream disorder
• Flatulence
• Headache disorder
• Insomnia
• Nausea
• Vomiting

Less Frequent

• Acute abdominal pain
• Anorexia
• Drowsy
• Dyspepsia
• Dyspnea
• Fatigue
• Gastroesophageal reflux disease
• General weakness
• Hyperhidrosis
• Increased appetite
• Lethargy
• Malaise
• Nightmares
• Pruritus of skin
• Rhinorrhea
• Skin rash
• Upper respiratory infection
• Xerostomia

Rare or Very Rare

• Acne vulgaris
• Aggressive behavior
• Agitation
• Allergic rhinitis
• Arthralgia
• Asthma
• Back pain
• Behavioral disorders
• Chest pain
• Concentration difficulty
• Cramps
• Delusional disorder
• Depression
• Diarrhea
• Disturbance of attention
• Dizziness
• Drug-induced hot flash
• Dry skin
• Dysgeusia
• Eczema
• Edema
• Epistaxis
• Erectile dysfunction
• Flu-like symptoms
• Flushing
• Hallucinations
• Hostility
• Hyperglycemia
• Increased urinary frequency
• Libido changes
• Lymphadenopathy
• Menstrual disorder
• Mood changes
• Myalgia
• Nocturia
• Palpitations
• Panic disorder
• Paranoid disorder
• Peripheral vascular disease
• Polyuria
• Psoriasis
• Skin photosensitivity
• Sleep disorder
• Sleep walking disorder
• Symptoms of anxiety
• Tinnitus
• Toothache
• Urticaria
• Vertigo
• Visual changes
• Weight gain

No enhanced messaging available.

Efficacy of varenicline was not established in patients <=16 years of age; its use in this age group is not recommended. Weight-adjusted varenicline dosages for 12 weeks did not improve abstinence rates versus placebo; safety was consistent with adult studies. In pediatric patients 12-17 years of age, varenicline pharmacokinetics were approximately dose-proportional over the 0.5-2 mg daily range. Systemic exposure in adolescents weighing >55 kg was comparable to that observed in adults, while exposure was approximately 40% higher in those weighing <=55 kg compared with adults, at a dosage of 0.5 mg twice daily.

Available data do not indicate an increased risk of major congenital malformations or miscarriage when varenicline is used during pregnancy, compared to women who smoke. In a population-based cohort study from Denmark and Sweden, 335 pregnancies exposed to varenicline (317 during the first trimester) were compared with over 78,000 pregnancies in women who smoked and over 800,000 pregnancies in non-smokers. The rate of major congenital malformations was similar across all groups (3.6% varenicline versus 4.3% smokers versus 4.2% non-smokers). Rates of adverse perinatal outcomes (stillbirth, small for gestational age, preterm birth, and premature rupture of membranes) in the varenicline-exposed group were similar to or lower than those observed in women who smoked during pregnancy and were generally comparable to rates in non-smokers. Available studies cannot confirm or rule out varenicline-related risks during pregnancy.

In animal reproductive studies, varenicline therapy did not result in any major malformations; however, there was some evidence of maternal toxicity, developmental toxicity, and decreased fetal weight when pregnant rats and rabbits were administered varenicline during the period of organogenesis at maternal exposures 36-50 times the exposure at the maximum recommended human dose.

Smoking during pregnancy is associated with known risks to the mother, fetus, and newborn infant; however, it is not known whether smoking cessation with varenicline may reduce these risks.

It is not known whether the drug is distributed into human milk or if the drug has any effects on the breast-fed infant or on milk production. Because data on varenicline excretion in human milk and its effects on infants are lacking, breastfeeding women should monitor their infants for seizures or excessive vomiting; these are adverse effects reported in adults that may also be relevant in infants.

No dosage adjustment is needed in geriatric patients; however, due to age-related decreases in renal function, dosage reduction should be considered and renal function monitored.

In a combined single- and multiple-dose study of 16 healthy male and female smokers (65-75 years of age) who received varenicline 1 mg once or twice daily for 7 consecutive days, the pharmacokinetic profile was similar to that observed in younger adults. No differences in safety or effectiveness were observed between elderly and younger patients, and other clinical experience has not identified differences in response; however, increased sensitivity in some older patients cannot be ruled out.

Varenicline is substantially excreted by the kidneys. Because geriatric patients are more likely to have decreased renal function, dosage should be selected cautiously; it may be useful to monitor renal function in such patients.