Apo-Varenicline

Varenicline tartrate.

APO-VARENICLINE 0.5 mg film-coated tablets are white to off-white, modified capsule shape, biconvex coated tablet. Engraved "APO" on one side and "VAR" over "0.5" on the other side.
Each 0.5 mg film-coated tablet contains 0.5 mg of varenicline (as tartrate).
APO-VARENICLINE 1 mg film-coated tablets are blue, modified capsule shape, biconvex coated tablet. Engraved "APO" on one side and "VAR" over "1" on the other side.
Each 1 mg film-coated tablet contains 1 mg of varenicline (as tartrate).
The active substance is varenicline.
Excipients/Inactive Ingredients: Nonmedicinal ingredients are anhydrous dibasic calcium phosphate, hydroxypropyl cellulose and magnesium stearate. The film-coating contains hydroxypropyl cellulose, hydroxypropyl methylcellulose, titanium dioxide and triacetin. The 1 mg tablet also contains indigotine aluminum lake 12-14% as a colouring agent.

APO-VARENICLINE contains the active substance varenicline. APO-VARENICLINE is a medicine which is used in adults to help them stop smoking.
APO-VARENICLINE can help to relieve the craving and withdrawal symptoms associated with stopping smoking.
APO-VARENICLINE can also reduce the enjoyment of cigarettes if the patient smokes when on treatment.

Always take this medicine exactly as prescribed. Patients must be advised to check with the doctor or pharmacist if they are not sure.
Patients are more likely to stop smoking if they are motivated to stop. The doctor and pharmacist can provide advice, support and sources of further information to help ensure the attempt to stop smoking is successful.
Before starting the course of APO-VARENICLINE, the patient should usually decide on a date in the second week of treatment (between day 8 and day 14) when the patient will stop smoking. If the patient is not willing or able to set a target quit date within 2 weeks, the patient may choose his/her own target quit date within 5 weeks after starting treatment.
APO-VARENICLINE comes as a white tablet (0.5 mg) and a blue tablet (1 mg). The patient starts with the white tablet and then usually go to the blue tablet. See the table as follows for the usual dosing instructions which should be followed from Day 1. (See table.)

Click on icon to see table/diagram/image

After 12 weeks of treatment, if the patient has stopped smoking, an additional 12 weeks of treatment with APO-VARENICLINE 1 mg film-coated tablets twice daily may be recommended to help avoid returning back to smoking.
Should the patient experience adverse effects that cannot be tolerated, the dose may temporarily or permanently reduced to 0.5 mg twice daily.
If the patient has problems with the kidneys, advise the patient to speak to the doctor before taking APO-VARENICLINE. A lower dose may be needed.
APO-VARENICLINE is for oral use.
The tablets should be swallowed whole with water and can be taken with or without food.
Forgotten intake of APO-VARENICLINE: A double dose should not be taken to make up for a forgotten tablet. It is important that the patient take APO-VARENICLINE regularly at the same time each day. If the patient forgets to take a dose, advise the patient to take it as soon as he/she remembers. If, it is within 3-4 hours before the next dose, the missed tablet should not be taken.
Stopping intake of APO-VARENICLINE: It has been shown in clinical trials that taking all doses of the medicine at the appropriate times and for the recommended duration of treatment described previously will increase the chances of stopping smoking. Therefore, unless the doctor instructs to stop treatment, advise the patient that it is important to keep taking APO-VARENICLINE, according to the instructions described in the table previously.
In smoking cessation therapy, risk of returning to smoking may be elevated in the period immediately following the end of treatment. The patient may temporarily experience increased irritability, urge to smoke, depression and/or sleep disturbances when the patient stops taking APO-VARENICLINE. The doctor may decide to gradually lower the dose of APO-VARENICLINE at the end of treatment.
Patients must be advised regarding any further questions on the use of this medicine.

If the patient accidentally takes more APO-VARENICLINE than prescribed, advise the patient to seek medical advice or go to the nearest hospital casualty department immediately. The patient must take the box of tablets with them.

APO-VARENICLINE should not be taken if the patient is allergic to varenicline or any of the other ingredients of this medicine (listed in Description).

Advise the patient to talk to a doctor or pharmacist before taking APO-VARENICLINE.
There have been reports of depression, suicidal ideation and behaviour and suicide attempts in patients taking APO-VARENICLINE. If the patient is taking APO-VARENICLINE and develop agitation, depressed mood, changes in behaviour that are of concern to him/her or his/her family or if the patient develops suicidal thoughts or behaviours, the patient should stop taking APO-VARENICLINE and be advised to contact the doctor immediately for treatment assessment.
The effects of stopping smoking: The effects of changes in the body resulting from stopping smoking, with or without treatment with APO-VARENICLINE, may alter the way other medicines work. Therefore, in some cases an adjustment of the dose may be necessary. See Interactions for further details.
Psychiatric Symptoms: For some people, stopping smoking with or without treatment has been associated with an increased risk of experiencing changes in thinking or behaviour, feelings of depression and anxiety and can be associated with a worsening of psychiatric disorder. If the patient has a history of psychiatric disorder, advise the patient to discuss this with the doctor.
Serious neuropsychiatric symptoms have occurred in patients being treated with varenicline.
There have been reports of neuropsychiatric symptoms such as depressed mood, agitation, hallucinations, changes in behaviour or thinking, anxiety, psychosis, mood swings, aggressive behaviour, suicidal ideation and suicide in patients attempting to quit smoking while taking varenicline.
Patients and their families should be advised that the patient should stop taking varenicline and contact a health care professional immediately if changes in behaviour or thinking, agitation or depressed mood that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behaviour.
Heart symptoms: New or worse heart or blood vessel (cardiovascular) problems have been reported primarily in people who already have cardiovascular problems. Patients must be advised to inform the doctor if they have any changes in symptoms during treatment with APO-VARENICLINE. Advise patients to get emergency medical help right away if they have symptoms of a heart attack or stroke.
Seizures: Patients must be advised to inform the doctor if they have experienced seizures or have epilepsy before the start of APO-VARENICLINE treatment. Some people have reported seizures while taking APO-VARENICLINE.
In clinical trials and post-marketing experience there have been reports of seizures in patients with or without a history of seizures, treated with varenicline. Varenicline should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Hypersensitivity reactions: Patients must be advised to stop taking APO-VARENICLINE and to inform the doctor immediately if they experience any of the following signs and symptoms that may indicate a serious allergic reaction: swelling of the face, lips, tongue, gums, throat or body and/or difficulty breathing, wheezing.
Skin reactions: Potentially life-threatening skin rashes (Stevens-Johnson syndrome and Erythema Multiforme) have been reported with the use of APO-VARENICLINE. If the patients develops a rash or if the skin starts to peel or blister, advise the patient to stop taking APO-VARENICLINE and to seek emergency medical help.
Driving and using machines: APO-VARENICLINE may be linked with dizziness, sleepiness and transient loss of consciousness. The patient should not drive, operate complex machinery or engage in any other potentially hazardous activities until the patient knows whether this medicine affects the ability to perform these activities.
Use in Children: APO-VARENICLINE is not recommended for use in paediatric patients as efficacy was not demonstrated.

If the patient is pregnant or breast-feeding, thinks that she may be pregnant or is planning to have a baby, she must be advised to ask the doctor or pharmacist for advice before taking this medicine. It is preferable to avoid the use of APO-VARENICLINE while pregnant. Advise the patient to talk to the doctor if she is intending to become pregnant.
Although it was not studied, APO-VARENICLINE may pass into breast milk. Advise the patient to ask the doctor or pharmacist for advice before taking APO-VARENICLINE.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Giving up smoking with or without treatment can cause various symptoms. These could include changes of mood (like feeling depressed, irritable, frustrated or anxious), sleeplessness, difficulty concentrating, decreased heart rate and increased appetite or weight gain.
Patients should be aware of the possible emergence of serious neuropsychiatric symptoms, such as agitation, depressed mood, or changes in behaviour during a quit attempt with or without APO-VARENICLINE and should be advised to contact a doctor or pharmacist if they experience such symptoms.
Serious side effects of either an uncommon or rare frequency have occurred in people attempting to quit smoking with APO-VARENICLINE: seizure, stroke, heart attack, suicidal thoughts, loss of contact with reality and unable to think or judge clearly (psychosis), changes in thinking or behaviour (such as aggression and abnormal behaviour). There have also been reports of severe skin reactions including Erythema Multiforme (a type of rash) and Stevens-Johnson Syndrome (a serious illness with blistering of the skin, mouth, around the eyes or genitals) and serious allergic reactions including angioedema (swelling of the face, mouth, or throat).
Very common: may affect more than 1 in 10 people: Inflammation of the nose and throat, abnormal dreams, difficulty sleeping, headache; Nausea.
Common: may affect up to 1 in 10 people: Chest infection, inflammation of the sinuses; Increased weight, decreased appetite, increased appetite; Sleepiness, dizziness, changes in the way things taste; Shortness of breath, cough; Heartburn, vomiting, constipation, diarrhoea, feeling bloated, abdominal pain, toothache, indigestion, flatulence, dry mouth; Skin rash, itching; Joint ache, muscle ache, back pain; Chest pain, tiredness.
Uncommon: may affect up to 1 in 100 people: Fungal infection, viral infection; Feeling of panic, difficulty thinking, restlessness, mood swings, depression, anxiety, hallucinations, changes in sex drive; Seizure, tremor, feeling sluggish, less sensitive to touch; Conjunctivitis, eye pain; Ringing in the ears; Angina, rapid heart rate, palpitations, increased heart rate; Increased blood pressure, hot flush; Inflammation of nose, sinuses and throat, congestion of nose, throat and chest, hoarseness, hay fever, throat irritation, congested sinuses, excess mucous from nose causing cough, runny nose; Red blood in stools, irritated stomach, change of bowel habit, belching, mouth ulcers, pain in the gums; Reddening of the skin, acne, increased sweating, night sweats; Muscle spasms, chest wall pain; Abnormally frequent urination, urination at night; Increased menstrual flow; Chest discomfort, flu like illness, fever, feeling weak or unwell; High blood sugar; Heart attack; Suicidal thoughts; Changes in thinking or behaviour (such as aggression).
Rare: may affect up to 1 in 1,000 people: Excessive thirst; Feeling unwell or unhappy, slow thinking; Stroke; Increased muscle tension, difficulty with speech, difficulty with coordination, reduced sense of taste, altered sleep pattern; Disturbed vision, eyeball discolouration, dilated pupils, sensitivity to light, shortsightedness, watery eyes; Irregular heart beat or heart rhythm disturbances; Throat pain, snoring; Blood in vomit, abnormal stools, coated tongue; Stiff joints, rib pain; Glucose in urine, increased urine volume and frequency; Vaginal discharge, changes in sexual ability; Feeling cold, cyst; Diabetes; Sleep walking; Loss of contact with reality and unable to think or judge clearly (psychosis); Abnormal behaviour; Severe skin reactions including Erythema Multiforme (a type of rash) and Stevens-Johnson Syndrome (a serious illness with blistering of the skin, mouth, around the eyes or genitals); Serious allergic reactions including angioedema (swelling of the face, mouth, or throat).
Not known: Transient loss of consciousness.
Reporting of side effects: In case of any side effects, advise the patient to talk to the doctor or pharmacist. This includes any possible side effects not listed in this monograph. By reporting side effects, it can help provide more information on the safety of this medicine.
Result of a meta-analysis: Cardiovascular events: In a trial of patients with stable cardiovascular disease (CVD) certain cardiovascular events were reported more frequently in patients treated with varenicline. A meta-analysis of 15 clinical trials, which included the smoking cessation trial of patients with stable CVD, had similar results.
Subjects with Cardiovascular Disease: A meta-analysis of 15 clinical trials of ≥ 12 weeks treatment duration, including 7002 patients (4190 varenicline, 2812 placebo), was conducted to systematically assess the cardiovascular safety of varenicline. The study in patients with stable cardiovascular disease described previously was included in the meta-analysis. The key cardiovascular safety analysis included occurrence and timing of a composite endpoint of Major Adverse Cardiovascular Events (MACE), defined as cardiovascular death, nonfatal MI, and nonfatal stroke. These events included in the endpoint were adjudicated by a blinded, independent committee. Overall, a small number of MACE occurred during treatment in the trials included in the meta-analysis (varenicline 7 [0.17%]; placebo 2 [0.07%]). Additionally, a small number of MACE occurred up to 30 days after treatment (varenicline 13 [0.31%]; placebo 6 [0.21%]).
The meta-analysis showed that exposure to Varenicline resulted in a hazard ratio for MACE of 2.83 (95% confidence interval from 0.76 to 10.55, p=0.12) for patients during treatment and 1.95 (95% confidence interval from 0.79 to 4.82, p=0.15) for patients up to 30 days after treatment. These are equivalent to an estimated increase of 6.5 MACE events and 6.3 MACE events per 1,000 patient-years, respectively of exposure. The hazard ratio for MACE was higher in patients with cardiovascular risk factors in addition to smoking compared with that in patients without cardiovascular risk factors other than smoking. There were similar rates of all-cause mortality (varenicline 6 [0.14%]; placebo 7 [0.25%]) and cardiovascular mortality (varenicline 2 [0.05%]; placebo 2 [0.07%]) in the varenicline arms compared with the placebo arms in the meta-analysis.

Patients must be advised to inform the doctor or pharmacist if they are taking, have recently taken or might take any other medicines.
In some cases as a result of stopping smoking, with or without APO-VARENICLINE, an adjustment of the dose of other medicines may be necessary. Examples include theophylline (a medicine to treat breathing problems), warfarin (a medicine to reduce blood clotting), and insulin (a medicine to treat diabetes). If in doubt, advise the patient to consult the doctor or pharmacist.
If the patient has severe kidney disease, the patient should avoid taking cimetidine (a medicine used for gastric problems) at the same time as APO-VARENICLINE as this may cause increased blood levels of APO-VARENICLINE.
Use of APO-VARENICLINE with other therapies for smoking cessation: Advise the patient to consult the doctor before using APO-VARENICLINE in combination with other smoking cessation therapies.
APO-VARENICLINE with food and drink: There have been some reports of increased intoxicating effects of alcohol in patients taking APO-VARENICLINE. However, it is not known if APO-VARENICLINE actually increases alcohol intoxication.
There is limited clinical data on any potential interaction between alcohol and varenicline. There have been post marketing reports of increased intoxicating effects of alcohol in patients treated with varenicline.

Do not throw away any medicines via wastewater or household waste. Ask the pharmacist how to throw away medicines no longer used. These measures will help protect the environment.

Store below 25°C.

Drugs Used in Substance Dependence

N07BA03 - varenicline ; Belongs to the class of drugs used in the management of nicotine dependence.

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