THis is from the Summary of product characteristics, a legaly required document that is aggreed with the Medicines control agency
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Zyban is contraindicated in patients with hypersensitivity to bupropion or any of the excipients.
Zyban is contraindicated in patients with a current seizure disorder or any history of seizures.
Zyban is contraindicated in patients with a known central nervous system (CNS) tumour.
Zyban is contraindicated in patients who, at any time during treatment, are undergoing abrupt withdrawal from alcohol or any medicinal product known to be associated with risk of seizures on withdrawal (in particular benzodiazepines and benzodiazepine-like agents).
Zyban is contraindicated in patients with a current or previous diagnosis of bulimia or anorexia nervosa.
Zyban is contraindicated for use in patients with severe hepatic cirrhosis.
Concomitant use of Zyban and monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 14 days should elapse between discontinuation of irreversible MAOIs and initiation of treatment with Zyban. For reversible MAOIs, a 24 hour period is sufficient.
Zyban is contraindicated in patients with a history of bipolar disorder as it may precipitate a manic episode during the depressed phase of their illness.
Zyban should not be administered to patients being treated with any other medicinal product containing bupropion as the incidence of seizures is dose dependent.
4.4 Special warnings and precautions for use
Seizures
The recommended dose of Zyban must not be exceeded, since bupropion is associated with a dose-related risk of seizure. At doses up to the maximum recommended daily dose (300mg of Zyban daily), the incidence of seizures is approximately 0.1% (1/1,000).
There is an increased risk of seizures occurring with the use of Zyban in the presence of predisposing risk factors which lower the seizure threshold. Zyban must not be used in patients with predisposing risk factors unless there is a compelling clinical justification for which the potential medical benefit of smoking cessation outweighs the potential increased risk of seizure. In these patients, a maximum dose of 150mg daily should be considered for the duration of treatment.
All patients should be assessed for predisposing risk factors, which include:
• concomitant administration of other medicinal productsknown to lower the seizure threshold (e.g., antipsychotics, antidepressants, antimalarials, tramadol, theophylline, systemic steroids, quinolones and sedating antihistamines). For patients prescribed such medicinal products whilst taking Zyban, a maximum dose of150mg daily for the remainder of their treatment should be considered.
• alcohol abuse (see also 4.3 Contraindications)
• history of head trauma
• diabetes treated with hypoglycaemics or insulin
• use of stimulants or anorectic products.
Zyban should be discontinued and not recommenced in patients who experience a seizure while on treatment.
Interactions (see 4.5 Interaction with other medicinal products and other forms of interaction)
Due to pharmacokinetic interactions plasma levels of bupropion or its metabolites may be altered, which may increase the potential for undesirable effects (e.g. dry mouth, insomnia, seizures). Therefore care should be taken when bupropion is given concomitantly with medicinal products which can induce or inhibit the metabolism of bupropion.
Bupropion inhibits metabolism by cytochrome P450 2D6. Caution is advised when medicinal products metabolised by this enzyme are administered concomitantly.
Neuropsychiatry
Zyban is a centrally-acting noradrenaline (norepinephrine)/dopamine reuptake inhibitor and as such the pharmacology resembles that of some antidepressants. Neuropsychiatric reactions have been reported (see 4.8 Undesirable Effects). In particular, psychotic and manic symptomatology have been reported mainly in patients with a known history of psychiatric illness.
Depressed mood may be a symptom of nicotine withdrawal. Depression, rarely including suicidal ideation, has been reported in patients undergoing a smoking cessation attempt. These symptoms have also been reported during Zyban treatment, and generally occurred early during the treatment course. Clinicians should be aware of the possible emergence of significant depressive symptomatology in patients undergoing a smoking cessation attempt, and should advise patients accordingly.
Data in animals suggest a potential for drug abuse. However, studies on abuse liability in humans and extensive clinical experience show that bupropion has low abuse potential.
Hypertension
In clinical practice, hypertension, which in some cases may be severe (see 4.8 Undesirable Effects) and require acute treatment, has been reported in patients receiving bupropion alone and in combination with nicotine replacement therapy. This has been observed in patients with and without pre-existing hypertension. A baseline blood pressure should be obtained at the start of treatment with subsequent monitoring, especially in patients with pre-existing hypertension. Consideration should be given to discontinuation of Zyban if a clinically significant increase in blood pressure is observed.
Limited clinical trial data suggest that higher smoking cessation rates may be achieved by the combination use of Zyban together with Nicotine Transdermal System (NTS). However, a higher rate of treatment-emergent hypertension was noted in the combination therapy group. If combination therapy with a NTS is used, caution must be exercised and weekly monitoring of blood pressure is recommended. Prior to initiation of combination therapy prescribers should consult the prescribing information of the relevant NTS.
4.8 Undesirable effects
The list below provides information on the undesirable effects identified from clinical experience, categorised by incidence and System Organ Class body system. It is important to note that smoking cessation is often associated with nicotine withdrawal symptoms (e.g. agitation, insomnia, tremor, sweating), some of which are also recognised as adverse events associated with Zyban.
Undesirable effects are ranked under headings of frequency using the following convention; very common (>1/10); common (>1/100, 1/1,000, 1/10000,