VARENICLINE UMEDICA

5 mg twice daily Day 8 – End of treatment: 1 mg twice daily The patient should set a date to stop smoking. 1). Patients should be treated with Varenicline for 12 weeks. 1). A gradual approach to quitting smoking with Varenicline should be considered for patients who are not able or willing to quit abruptly.

Patients should reduce smoking during the first 12 weeks of treatment and quit by the end of that treatment period. 1). 1). 5 mg twice daily. In smoking cessation therapy, risk for relapse to smoking is elevated in the period immediately following the end of treatment.

4). 2). Because elderly patients are more likely to have decreased renal function, prescribers should consider the renal status of an elderly patient. Renal impairment No dose adjustment is necessary for patients with mild (estimated creatinine clearance > 50 ml/min and ≤ 80 ml/min) to moderate (estimated creatinine clearance ≥ 30 ml/min and ≤ 50 ml/min) renal impairment.

For patients with moderate renal impairment who experience adverse reactions that are not tolerable, dosing may be reduced to 1 mg once daily. For patients with severe renal impairment (estimated creatinine clearance < 30 ml/min), the recommended dose of Varenicline is 1 mg once daily.

5 mg once daily for the first 3 days then increased to 1 mg once daily. 2). 2). 2). Method of administration Varenicline Umedica is for oral use and the tablets should be swallowed whole with water. Varenicline Umedica can be taken with or without food.

Summary of the safety profile Smoking cessation with or without treatment is associated with various symptoms. For example, dysphoric or depressed mood; insomnia, irritability, frustration or anger; anxiety; difficulty concentrating; restlessness; decreased heart rate; increased appetite or weight gain have been reported in patients attempting to stop smoking.

No attempt has been made in either the design or the analysis of the Varenicline studies to distinguish between adverse reactions associated with study drug treatment or those possibly associated with nicotine withdrawal. Adverse drug reactions are based on evaluation of data from pre-marketing phase 2-3 studies and updated based on pooled data from 18 placebo-controlled pre- and post-marketing studies, including approximately 5,000 patients treated with varenicline.

6%). In the majority of cases nausea occurred early in the treatment period, was mild to moderate in severity and seldom resulted in discontinuation. Tabulated summary of adverse reactions In the table below all adverse reactions, which occurred at an incidence greater than placebo are listed by system organ class and frequency (very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000)).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness System Organ Class Adverse Drug Reactions Infections and infestations Very common Nasopharyngitis Common Bronchitis, sinusitis Uncommon Fungal infection, viral infection Blood and lymphatic system disorders Rare Platelet count decreased Metabolism and nutrition disorders Common Weight increased, decreased appetite, increased appetite Uncommon Hyperglycaemia Rare Diabetes mellitus, polydipsia Psychiatric disorders Very common Abnormal dreams, insomnia Uncommon Suicidal ideation, aggression, panic reaction, thinking abnormal, restlessness, mood swings, depression*, anxiety*, hallucinations*, libido increased, libido decreased Rare Psychosis, somnambulism, abnormal behaviour, dysphoria, bradyphrenia Nervous system disorders Very common Headache Common Somnolence, dizziness, dysgeusia Uncommon Seizure, tremor, lethargy, hypoaesthesia Rare Cerebrovascular accident, hypertonia, dysarthria, coordination abnormal, hypogeusia, circadian rhythm sleep disorder Not known Transient loss of consciousness Eye disorders Uncommon Conjunctivitis, eye pain Rare Scotoma, scleral discolouration, mydriasis, photophobia, myopia, lacrimation increased Ear and labyrinth disorders Uncommon Tinnitus Cardiac disorders Uncommon Myocardial infarction, angina pectoris, tachycardia, palpitations, heart rate increased Rare Atrial fibrillation, electrocardiogram ST segment depression, electrocardiogram T wave amplitude decreased Vascular disorders Uncommon Blood pressure increased, hot flush Respiratory, thoracic and mediastinal disorders Common Dyspnoea, cough Uncommon Upper respiratory tract inflammation, respiratory tract congestion, dysphonia, rhinitis allergic, throat irritation, sinus congestion, upperairway cough syndrome, rhinorrhoea Rare Laryngeal pain, snoring Gastrointestinal disorders Very common Nausea Common Gastrooesophageal reflux disease, vomiting, constipation, diarrhoea, abdominal distension, abdominal pain, toothache, dyspepsia, flatulence, dry mouth Uncommon Haematochezia, gastritis, change of bowel habit, eructation, aphthous stomatitis, gingival pain Rare Haematemesis, abnormal faeces, tongue coated Skin and subcutaneous tissue disorders Common Rash, pruritus Uncommon Erythema, acne, hyperhidrosis, night sweats Rare Severe cutaneous reactions, including Stevens Johnson Syndrome and Erythema Multiforme, angioedema Musculoskeletal and connective tissue disorders Common Arthralgia, myalgia, back pain Uncommon Muscle spasms, musculoskeletal chest pain Rare Joint stiffness, costochondritis Renal and urinary disorders Uncommon Pollakiuria, nocturia Rare Glycosuria, polyuria Reproductive system and breast disorders Uncommon Menorrhagia Rare Vaginal discharge, sexual dysfunction General disorders and administration site conditions Common Chest pain, fatigue Uncommon Chest discomfort, influenza like illness, pyrexia, asthenia, malaise Rare Feeling cold, cyst Investigations Common Liver function test abnormal Rare Semen analysis abnormal, C-reactive protein increased, blood calcium Decreased * Frequencies are estimated from a post-marketing, observational cohort study Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Effect of smoking cessation Physiological changes resulting from smoking cessation, with or without treatment with Varenicline Umedica, may alter the pharmacokinetics or pharmacodynamics of some medicinal products, for which dosage adjustment may be necessary (examples include theophylline, warfarin and insulin).

As smoking induces CYP1A2, smoking cessation may result in an increase of plasma levels of CYP1A2 substrates. Neuropsychiatric symptoms Changes in behaviour or thinking, anxiety, psychosis, mood swings, aggressive behaviour, depression, suicidal ideation and behaviour and suicide attempts have been reported in patients attempting to quit smoking with Varenicline in the post-marketing experience A large randomised, double-blind, active and placebo-controlled study was conducted to compare the risk of serious neuropsychiatric events in patients with and without a history of psychiatric disorder treated for smoking cessation with varenicline, bupropion, nicotine replacement therapy patch (NRT) or placebo.

The primary safety endpoint was a composite of neuropsychiatric adverse events that have been reported in post-marketing experience. 1 Pharmacodynamics properties - Study in Subjects with and without a History of Psychiatric Disorder).

Depressed mood, rarely including suicidal ideation and suicide attempt, may be a symptom of nicotine withdrawal. Clinicians should be aware of the possible emergence of serious neuropsychiatric symptoms in patients attempting to quit smoking with or without treatment.

If serious neuropsychiatric symptoms occur whilst on varenicline treatment, patients should discontinue varenicline immediately and contact a healthcare professional for re- evaluation of treatment. g. depression). 1). 1). Care should be taken with patients with a history of psychiatric illness and patients should be advised accordingly.

Seizures 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 Umedica. Varenicline should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

1.