Varenicline

Registered South African indications:

• Smoking cessation
  - Used as an aid in patients committed to stop smoking, in addition to a behaviour modification programme

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Moderate renal impairment (CrCl ≥30ml/min-≤50ml/min) with adverse reactions that are not tolerable
• Severe renal impairment (CrCl <30ml/min)
  - End-stage renal disease
• Porphyria
• Underlying psychiatric illness (e.g. depression)
• History of seizures or other conditions that potentially lower the seizure threshold
• Treatment discontinuation without dose tapering
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Smoking cessation

• Oral (tab): Day 1-3: 0.5mg, dly; Day 4-7: 0.5mg, 12hrly; Day 8 onwards: 1mg, 12hrly; Treatment duration: 12 weeks

---

The patient should set a date to stop smoking. Varenicline dosing should usually start at 1-2 weeks before this date

---

For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks treatment with varenicline at 1mg, 12hrly may be considered for the maintenance of abstinence

---

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. Patients should then continue taking varenicline for an additional 12 weeks for a total of 24 weeks of treatment

---

Patients who are motivated to quit and who did not succeed in stopping smoking during prior varenicline therapy, or who relapsed after treatment, may benefit from another quit attempt with varenicline

---

Patients who cannot tolerate adverse reactions of varenicline may have the dose lowered temporarily or permanently to 0.5mg, 12hrly

---

In smoking cessation therapy, risk for relapse to smoking is elevated in the period immediately following the end of treatment. In patients with a high risk of relapse, dose tapering may be considered

Not established for use in children

Pregnancy

• Caution; not recommended
• A moderate amount of data on pregnant women indicated no malformative or foetal/ neonatal toxicity of varenicline
• Animal studies have shown reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of varenicline during pregnancy

Breastfeeding

• Caution; not recommended
• It is unknown whether varenicline is excreted in human breast milk. Animal studies suggest that varenicline is excreted in breast milk
• A decision on whether to continue/ discontinue breastfeeding or to continue/ discontinue therapy with varenicline should be made taking into account the benefit of breastfeeding to the child and the benefit of varenicline therapy to the woman

Fertility 

• There is no clinical data on the effects of varenicline on fertility
• Non-clinical data revealed no hazard for humans based on standard male and female fertility studies in the rat

Renal Impairment

• Mild to moderate (CrCl ≥30-≤80ml/min): No adjustment recommended
  In patients with moderate renal impairment (CrCl ≥30ml/min-≤50ml/min) who experience adverse reactions that are not tolerable, dosing may be reduced to 1mg, dly
• Severe (CrCl <30ml/min): Caution; dose adjustment recommended
  Oral (tab): Day 1-3: 0.5mg, dly; Day 4 onwards: 1mg, dly
  Based on insufficient clinical experience in patients with end stage renal disease, treatment is not recommended in this patient population 

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Abnormal dreams
• Insomnia
• Suicidal ideation
• Aggression
• Panic reaction
• Abnormal thinking
• Restlessness
• Mood swings
• Depression
• Anxiety
• Hallucinations
• Increased libido
• Decreased libido
• Psychosis
• Somnambulism
• Abnormal behaviour
• Dysphoria
• Bradyphrenia
• Somnolence
• Dizziness
• Seizures
• Tremor
• Lethargy
• Hypoaesthesia
• Cerebrovascular accident  
• Hypertonia
• Dysarthria
• Abnormal coordination
• Circadian rhythm sleep disorder
• Transient loss of consciousness
• Fatigue

Cardiovascular Disorders

• Myocardial infarction
• Angina pectoris
• Tachycardia
• Palpitations
• Increased heart rate
• Atrial fibrillation
• Depressed electrocardiogram ST segment
• Decreased electrocardiogram T wave amplitude
• Increased blood pressure
• Hot flush
• Chest pain
• Chest discomfort

Respiratory Disorders

• Nasopharyngitis
• Bronchitis
• Sinusitis
• Dyspnoea
• Cough
• Upper respiratory tract inflammation
• Respiratory tract congestion
• Dysphonia
• Allergic rhinitis
• Throat irritation
• Sinus congestion
• Upper airway cough syndrome
• Rhinorrhoea
• Laryngeal pain
• Snoring

Gastrointestinal Disorders

• Dysgeusia
• Hypogeusia
• Nausea and vomiting
• Gastro-oesophageal reflux disease
• Constipation
• Diarrhoea
• Abdominal distension
• Abdominal pain
• Toothache
• Dyspepsia
• Flatulence
• Dry mouth
• Haematochezia
• Gastritis
• Changes in bowel habit
• Eructation
• Aphthous stomatitis
• Gingival pain
• Haematemesis
• Abnormal faeces
• Coated tongue

Hepatobiliary Disorders

• Abnormal hepatic function test

Genitourinary Disorders

• Pollakiuria
• Nocturia
• Glycosuria
• Polyuria
• Menorrhagia
• Vaginal discharge
• Sexual dysfunction
• Abnormal semen analysis

Endocrine and Metabolic Disorders

• Increased weight
• Decreased appetite
• Increased appetite
• Hyperglycaemia
• Diabetes mellitus
• Polydipsia
• Feeling cold
• Increased blood calcium

Musculoskeletal Disorders

• Arthralgia
• Myalgia
• Back pain
• Muscle spasms
• Musculoskeletal chest pain
• Joint stiffness
• Costochondritis

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Erythema
• Acne
• Hyperhidrosis
• Night sweats
• Severe cutaneous reactions
  - Stevens-Johnson syndrome
  - Erythema multiforme
• Angioedema
• Cyst

Immune, Blood and Lymphatic System Disorders

• Fungal infection
• Viral infection
• Decreased platelet count
• Fever
• Influenza-like illness
• Increased C-reactive protein

Sensory Disorders

• Conjunctivitis
• Eye pain
• Scotoma
• Scleral discolouration
• Mydriasis
• Photophobia
• Myopia
• Increased lacrimation
• Tinnitus

• Cimetidine
• Nicotine replacement therapy

Other interactions

• Alcohol

None routine

Additional observations

• Behavioral changes
• Psychiatric symptoms
  - Agitation
  - Depression
  - Suicidal behavior
  - Suicidal ideation

Effect of smoking cessation

• Physiological changes resulting from smoking cessation, with or without treatment with varenicline, 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

Varenicline binds with high affinity and selectivity at alpha-4 beta-2 neuronal nicotinic acetylcholine receptors, where it acts as a partial agonist. It has both agonist activity, with lower intrinsic efficacy than nicotine, and antagonist activities in the presence of nicotine. Electrophysiology studies in vitro and neurochemical studies in vivo have shown that varenicline binds to the α4β2 neuronal nicotinic acetylcholine receptors and stimulates receptor-mediated activity, but at a significantly lower level than nicotine. Nicotine competes for the same human α4β2 nAChR binding site for which varenicline has higher affinity. Therefore, varenicline can effectively block nicotine's ability to fully activate α4β2 receptors and the mesolimbic dopamine system, the neuronal mechanism underlying reinforcement and reward experienced upon smoking. Varenicline is highly selective and binds more potently to the α4β2 receptor subtype (Ki=0.15nM) than to other common nicotinic receptors (α3β4 Ki=84nM, α7 Ki= 620nM, α1βγδ Ki= 3,400nM), or to non-nicotinic receptors and transporters (Ki >1µM, except to 5-HT3 receptors: Ki=350nM).

Tablet 0.5mg & 1mg

• Champix starter pack (Pfizer) originator

Tablet 1mg

• Champix 1mg (Pfizer) originator