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Varenicline is a brand name for Varenicline. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Varenicline tablets are indicated for use as an aid to smoking cessation treatment. Varenicline tablets are a nicotinic receptor partial agonist indicated for use as an aid to smoking cessation treatment. ( 1 and 2.1 )
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Begin varenicline tablets dosing one week before the date set by the patient to stop smoking. Alternatively, the patient can begin varenicline tablets dosing and then quit smoking between days 8 and 35 of treatment.
5 mg twice daily on days 4 to 7. 1 ) Continuing Weeks: 1 mg twice daily for a total of 12 weeks. 1 ) An additional 12 weeks of treatment is recommended for successful quitters to increase likelihood of long-term abstinence. 1 ) Consider a gradual approach to quitting smoking with varenicline tablets for patients who are sure that they are not able or willing to quit abruptly.
Patients should begin varenicline tablets dosing and reduce smoking by 50% from baseline within the first four weeks, by an additional 50% in the next four weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks.
Continue treatment for an additional 12 weeks, for a total of 24 weeks. 5 mg twice daily. 5 mg daily may be given if tolerated. 2 ) Consider dose reduction for patients who cannot tolerate adverse effects. 1 ) Another attempt at treatment is recommended for those who fail to stop smoking or relapse when factors contributing to the failed attempt have been addressed.
1 ) Provide patients with appropriate educational materials and counseling to support the quit attempt. 1 Usual Dosage for Adults Smoking cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided additional advice and support.
Provide patients with appropriate educational materials and counseling to support the quit attempt. The patient should set a date to stop smoking. Begin varenicline tablets dosing one week before this date. Alternatively, the patient can begin varenicline tablets dosing and then quit smoking between days 8 and 35 of treatment.
Varenicline tablets should be taken orally after eating and with a full glass of water. 5 mg twice daily Day 8 to end of treatment: 1 mg twice daily Patients should be treated with varenicline tablets for 12 weeks. For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks treatment with varenicline tablets are recommended to further increase the likelihood of long-term abstinence.
For patients who are sure that they are not able or willing to quit abruptly, consider a gradual approach to quitting smoking with varenicline tablets. Patients should begin varenicline tablets dosing and reduce smoking by 50% from baseline within the first four weeks, by an additional 50% in the next four weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks.
8) ] In the placebo-controlled premarketing studies, the most common adverse events associated with varenicline (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal (vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting.
The treatment discontinuation rate due to adverse events in patients dosed with 1 mg twice daily was 12% for varenicline, compared to 10% for placebo in studies of three months’ treatment. In this group, the discontinuation rates that are higher than placebo for the most common adverse events in varenicline-treated patients were as follows: nausea (3% vs.
2% vs. 3% vs. 2% for placebo). Smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. , vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
During the premarketing development of varenicline, over 4500 subjects were exposed to varenicline, with over 450 treated for at least 24 weeks and approximately 100 for a year. Most study participants were treated for 12 weeks or less.
9) ] . Table 1 shows the adverse events for varenicline and placebo in the 12- week fixed dose premarketing studies with titration in the first week [Studies 2 (titrated arm only), 4, and 5]. 1). 5% more frequent than placebo). Closely related Preferred Terms such as ‘Insomnia’, ‘Initial insomnia’, ‘Middle insomnia’, ‘Early morning awakening’ were grouped, but individual patients reporting two or more grouped events are only counted once.
5 WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide.
Observe patients attempting to quit smoking with varenicline for the occurrence of such symptoms and instruct them to discontinue varenicline and contact a healthcare provider if they experience such adverse events. 1 ) Seizures: New or worsening seizures have been observed in patients taking varenicline.
Varenicline should be used cautiously in patients with a history of seizures or other factors that can lower the seizure threshold. 2 ) Interaction with Alcohol: Increased effects of alcohol have been reported. Instruct patients to reduce the amount of alcohol they consume until they know whether varenicline affects them.
, traffic accidents) have been reported. Instruct patients to use caution driving or operating machinery until they know how varenicline may affect them. 4 ) Cardiovascular Events: Patients with underlying cardiovascular (CV) disease may be at increased risk of CV events; however, these concerns must be balanced with the health benefits of smoking cessation.
Instruct patients to notify their healthcare providers of new or worsening CV symptoms and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction (MI) or stroke. 1 ) Somnambulism: Cases of somnambulism have been reported in patients taking varenicline.
Some cases described harmful behavior to self, others, or property. Instruct patients to discontinue varenicline and notify their healthcare provider if they experience somnambulism. 2 ) Angioedema and Hypersensitivity Reactions: Such reactions, including angioedema, infrequently life-threatening, have been reported.
4 CONTRAINDICATIONS Varenicline tablets are contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline tablets. History of serious hypersensitivity or skin reactions to varenicline tablets.
( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Continue varenicline tablets treatment for an additional 12 weeks, for a total of 24 weeks of treatment. 5) ]. Patients who are motivated to quit, and who did not succeed in stopping smoking during prior varenicline tablets therapy for reasons other than intolerability due to adverse events or who relapsed after treatment, should be encouraged to make another attempt with varenicline tablets once factors contributing to the failed attempt have been identified and addressed.
Consider a temporary or permanent dose reduction in patients who cannot tolerate the adverse effects of varenicline tablets. 2 Dosage in Special Populations Patients with Impaired Renal Function No dosage adjustment is necessary for patients with mild to moderate renal impairment.
5 mg once daily. 5 mg twice daily. 3) ] . Elderly and Patients with Impaired Hepatic Function No dosage adjustment is necessary for patients with hepatic impairment. 5) ] .
Table 1. , nausea was reported in 40% of patients treated with varenicline 1 mg twice daily in a one year study, compared to 8% of placebo-treated patients). Following is a list of treatment-emergent adverse events reported by patients treated with varenicline during all premarketing clinical trials and updated based on pooled data from 18 placebo-controlled pre- and postmarketing studies, including approximately 5,000 patients treated with varenicline.
0. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening.
Blood and Lymphatic System Disorders. Infrequent: anemia, lymphadenopathy. Rare: leukocytosis, splenomegaly, thrombocytopenia. Cardiac Disorders. Infrequent: angina pectoris, myocardial infarction, palpitations, tachycardia. Rare: acute coronary syndrome, arrhythmia, atrial fibrillation, bradycardia, cardiac flutter, cor pulmonale, coronary artery disease, ventricular extrasystoles.
Ear and Labyrinth Disorders. Infrequent: tinnitus, vertigo. Rare: deafness, Meniere’s disease. Endocrine Disorders. Infrequent: thyroid gland disorders. Eye Disorders. Infrequent: conjunctivitis, eye irritation, eye pain, vision blurred, visual impairment.
Rare: blindness transient, cataract subcapsular, dry eye, night blindness, ocular vascular disorder, photophobia, vitreous floaters. Gastrointestinal Disorders. Frequent: diarrhea, toothache. Infrequent: dysphagia, eructation, gastritis, gastrointestinal hemorrhage, mouth ulceration.
Rare: enterocolitis, esophagitis, gastric ulcer, intestinal obstruction, pancreatitis acute. General Disorders and Administration Site Conditions. Frequent: chest pain. Infrequent: chest discomfort, chills, edema, influenza-like illness, pyrexia.
Hepatobiliary Disorders. Rare: gall bladder disorder. Investigations. Frequent: liver function test abnormal, weight increased. Infrequent: electrocardiogram abnormal. Rare: muscle enzyme increased, urine analysis abnormal. Metabolism and Nutrition Disorders.
Infrequent: diabetes mellitus, hypoglycemia. Rare: hyperlipidemia, hypokalemia. Musculoskeletal and Connective Tissue Disorders. Frequent: arthralgia, back pain, myalgia. Infrequent: arthritis, muscle cramp, musculoskeletal pain. Rare: myositis, osteoporosis.
Nervous System Disorders. Frequent: disturbance in attention, dizziness. Infrequent: amnesia, convulsion, migraine, parosmia, syncope, tremor. Rare: balance disorder, cerebrovascular accident, dysarthria, mental impairment, multiple sclerosis, VII th nerve paralysis, nystagmus, psychomotor hyperactivity, psychomotor skills impaired, restless legs syndrome, sensory disturbance, transient ischemic attack, visual field defect.
Psychiatric Disorders. Infrequent: dissociation, libido decreased, mood swings, thinking abnormal. Rare: bradyphrenia, disorientation, euphoric mood. Renal and Urinary Disorders. Infrequent: nocturia, pollakiuria, urine abnormality. Rare: nephrolithiasis, polyuria, renal failure acute, urethral syndrome, urinary retention.
Reproductive System and Breast Disorders. Frequent : menstrual disorder. Infrequent: erectile dysfunction. Rare: sexual dysfunction. Respiratory, Thoracic and Mediastinal Disorders. Frequent: respiratory disorders. Infrequent: asthma, epistaxis, rhinitis allergic, upper respiratory tract inflammation.
Rare: pleurisy, pulmonary embolism. Skin and Subcutaneous Tissue Disorders. Infrequent: acne, dry skin, eczema, erythema, hyperhidrosis, urticaria. Rare: photosensitivity reaction, psoriasis. Vascular Disorders. Infrequent: hot flush. Rare: thrombosis.
Varenicline has also been studied in postmarketing trials including (1) a trial conducted in patients with chronic obstructive pulmonary disease (COPD), (2) a trial conducted in generally healthy patients (similar to those in the premarketing studies) in which they were allowed to select a quit date between days 8 and 35 of treatment (“alternative quit date instruction trial”), (3) a trial conducted in patients who did not succeed in stopping smoking during prior varenicline therapy, or who relapsed after treatment (“re-treatment trial”), (4) a trial conducted in patients with stable cardiovascular disease, (5) a trial conducted in patients with stable schizophrenia or schizoaffective disorder, (6) a trial conducted in patients with major depressive disorder, (7) a postmarketing neuropsychiatric safety outcome trial in patients without or with a history of psychiatric disorder, (8) a non-treatment extension of the postmarketing neuropsychiatric safety outcome trial that assessed CV safety, (9) a trial in patients who were not able or willing to quit abruptly and who were instructed to quit gradually (“gradual approach to quitting smoking trial”).
Adverse events in the trial of patients with COPD (1), in the alternative quit date instruction trial (2), and in the gradual approach to quitting smoking trial (9) were similar to those observed in premarketing studies. In the re-treatment trial (3), the profile of common adverse events was similar to that previously reported, but, in addition, varenicline-treated patients also commonly reported diarrhea (6% vs.
4% in placebo-treated patients), depressed mood disorders and disturbances (6% vs. 1%), and other mood disorders and disturbances (5% vs. 2%). In the trial of patients with stable cardiovascular disease (4), more types and a greater number of cardiovascular events were reported compared to premarketing studies, as shown in Table 1 and in Table 2 below.
Table 2. 6 In the trial of patients with stable schizophrenia or schizoaffective disorder (5), 128 smokers on antipsychotic medication were randomized 2:1 to varenicline (1 mg twice daily) or placebo for 12 weeks with 12-week non-drug follow-up.
The most common treatment emergent adverse events reported in this trial are shown in Table 3 below. Table 3. Common Treatment Emergent AEs (%) in the Trial of Patients with Stable Schizophrenia or Schizoaffective Disorder Varenicline 1 mg BID N=84 Placebo N=43 Adverse Events ≥10% in the varenicline group Nausea 24 14 Headache 11 19 Vomiting 11 9 Psychiatric Adverse Events ≥5% and at a higher rate than in the placebo group Insomnia 10 5 For the trial of patients with major depressive disorder (6), the most common treatment emergent adverse events reported are shown in Table 4 below.
Additionally, in this trial, patients treated with varenicline were more likely than patients treated with placebo to report one of events related to hostility and aggression (3% vs. 1%). Table 4. 4 Restlessness 2 2 In the trial of patients without or with a history of psychiatric disorder (7), the most common adverse events in subjects treated with varenicline were similar to those observed in premarketing studies.
Most common treatment-emergent adverse events reported in this trial are shown in Table 5 below. Table 5. Treatment Emergent Common AEs (%) in the Trial of Patients without or with a History of Psychiatric Disorder Varenicline 1 mg BID Placebo Adverse Events ≥10% in the varenicline group Entire study population, N 1982 1979 Nausea 25 7 Headache 12 10 Psychiatric Adverse Events ≥2% in any treatment group Non-psychiatric cohort, N 975 982 Abnormal dreams 8 4 Agitation 3 3 Anxiety 5 6 Depressed mood 3 3 Insomnia 10 7 Irritability 3 4 Sleep disorder 3 2 Psychiatric cohort, N 1007 997 Abnormal dreams 12 5 Agitation 5 4 Anxiety 8 6 Depressed mood 5 5 Depression 5 5 Insomnia 9 7 Irritability 5 7 Nervousness 2 3 Sleep disorder 3 2 In the non-treatment extension of the postmarketing neuropsychiatric safety outcomes trial that assessed CV safety (8), the most common adverse events in subjects treated with varenicline and occurring up to 30 days after last dose of treatment were similar to those observed in premarketing studies.
2 Postmarketing Experience The following adverse events have been reported during post-approval use of varenicline. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
1) ] . 2) ]. There have been postmarketing reports of patients experiencing increased intoxicating effects of alcohol while taking varenicline. 3) ] . 7) ] . 8) ]. There have been reports of myocardial infarction (MI) and cerebrovascular accident (CVA) including ischemic and hemorrhagic events in patients taking varenicline.
In the majority of the reported cases, patients had pre-existing cardiovascular disease and/or other risk factors. 5) ] . There have been reports of hyperglycemia in patients following initiation of varenicline. 6) ] .
Instruct patients to discontinue varenicline and immediately seek medical care if symptoms occur. 2 ) Serious Skin Reactions: Rare, potentially life-threatening skin reactions have been reported. Instruct patients to discontinue varenicline and contact a healthcare provider immediately at first appearance of skin rash with mucosal lesions.
2 ) Nausea: Nausea is the most common adverse reaction (up to 30% incidence rate). Dose reduction may be helpful. 2) ] . These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide.
Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication.
However, some of these adverse events occurred in patients taking varenicline who continued to smoke. Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses.
2) ]. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking varenicline and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.
The healthcare provider should evaluate the severity of the symptoms and the extent to which the patient is benefiting from treatment, and consider options including dose reduction, continued treatment under closer monitoring, or discontinuing treatment.
In many postmarketing cases, resolution of symptoms after discontinuation of varenicline was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.
The neuropsychiatric safety of varenicline was evaluated in a randomized, double-blind, active and placebo-controlled study that included patients without a history of psychiatric disorder (non-psychiatric cohort, N=3912) and patients with a history of psychiatric disorder (psychiatric cohort, N=4003).
In the non-psychiatric cohort, varenicline was not associated with an increased incidence of clinically significant neuropsychiatric adverse events in a composite endpoint comprising anxiety, depression, feeling abnormal, hostility, agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, and irritability.
In the psychiatric cohort, there were more events reported in each treatment group compared to the non-psychiatric cohort, and the incidence of events in the composite endpoint was higher for each of the active treatments compared to placebo: Risk Differences (RDs) (95%CI) vs.
0) for transdermal nicotine. 4% of placebo-treated patients. 5% involving psychiatric hospitalization. 10) ] . 2 Seizures During clinical trials and the postmarketing experience, there have been reports of seizures in patients treated with varenicline.
Some patients had no history of seizures, whereas others had a history of seizure disorder that was remote or well-controlled. In most cases, the seizure occurred within the first month of therapy. Weigh this potential risk against the potential benefits before prescribing varenicline in patients with a history of seizures or other factors that can lower the seizure threshold.
2) ]. 3 Interaction with Alcohol There have been postmarketing reports of patients experiencing increased intoxicating effects of alcohol while taking varenicline. Some cases described unusual and sometimes aggressive behavior, and were often accompanied by amnesia for the events.
2) ] . 4 Accidental Injury There have been postmarketing reports of traffic accidents, near-miss incidents in traffic, or other accidental injuries in patients taking varenicline. In some cases, the patients reported somnolence, dizziness, loss of consciousness or difficulty concentrating that resulted in impairment, or concern about potential impairment, in driving or operating machinery.
Advise patients to use caution driving or operating machinery or engaging in other potentially hazardous activities until they know how varenicline may affect them. 5 Cardiovascular Events A comprehensive evaluation of cardiovascular (CV) risk with varenicline suggests that patients with underlying CV disease may be at increased risk; however, these concerns must be balanced with the health benefits of smoking cessation.
CV risk has been assessed for varenicline in randomized controlled trials (RCT) and meta-analyses of RCTs. In a smoking cessation trial in patients with stable CV disease, CV events were infrequent overall; however, nonfatal myocardial infarction (MI) and nonfatal stroke occurred more frequently in patients treated with varenicline compared to placebo.
8) ] . 82). In the large postmarketing neuropsychiatric safety outcome trial, an analysis of adjudicated MACE events was conducted for patients while in the trial and during a 28-week non-treatment extension period. Few MACE events occurred during the trial; therefore, the findings did not contribute substantively to the understanding of CV risk with varenicline.
10) ]. 6 Somnambulism Cases of somnambulism have been reported in patients taking varenicline. Some cases described harmful behavior to self, others, or property. 2) ] . 2) , Patient Counseling Information (17) ] . Clinical signs included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (throat and larynx).
There were infrequent reports of life-threatening angioedema requiring emergent medical attention due to respiratory compromise. Instruct patients to discontinue varenicline and immediately seek medical care if they experience these symptoms.
2) ]. As these skin reactions can be life-threatening, instruct patients to stop taking varenicline and contact a healthcare provider immediately at the first appearance of a skin rash with mucosal lesions or any other signs of hypersensitivity.
9 Nausea Nausea was the most common adverse reaction reported with varenicline treatment. Nausea was generally described as mild or moderate and often transient; however, for some patients, it was persistent over several months. The incidence of nausea was dose-dependent.
Initial dose-titration was beneficial in reducing the occurrence of nausea. For patients treated to the maximum recommended dose of 1 mg twice daily following initial dosage titration, the incidence of nausea was 30% compared with 10% in patients taking a comparable placebo regimen.
5 mg twice daily following initial titration, the incidence was 16% compared with 11% for placebo. Approximately 3% of patients treated with varenicline 1 mg twice daily in studies involving 12 weeks of treatment discontinued treatment prematurely because of nausea.
For patients with intolerable nausea, a dose reduction should be considered.