Sertraline 50mg Film-Coated Tablets

Sertraline 100mg Film-Coated Tablets

Each tablet contains 50mg of sertraline (as hydrochloride)

Each tablet contains 100mg of sertraline (as hydrochloride)

For excipients see 6.1

Film coated tablet

Sertraline 50mg Tablets are white film-coated oblong, biconvex tablets, scored on one side.

Sertraline 100mg Tablets are white film-coated oblong, biconvex tablets.

Sertraline is indicated for the treatment of symptoms of depressive illness, including accompanying symptoms of anxiety. Following satisfactory response, continuation with sertraline therapy is effective in preventing relapse of the initial episode of depression or recurrence of further depressive episodes, including accompanying symptoms of anxiety.

Sertraline is also indicated for the treatment of obsessive compulsive disorder (OCD). Following initial response, sertraline has been associated with sustained efficacy, safety and tolerability in up to two years treatment of OCD.

Sertraline is also indicated for the treatment of paediatric patients with OCD.

Clinical trials in post-traumatic stress disorder (PTSD) demonstrated efficacy in female patients but no evidence of efficacy was seen in males. Treatment with sertraline cannot normally therefore be recommended for male patients with PTSD. A therapeutic trial in males might on occasion be justified, but treatment should subsequently be withdrawn unless there is clear evidence of therapeutic benefit.

Sertraline is not indicated for use in children and adolescents under the age of 18 years with Major Depressive Disorder.

In particular, controlled clinical studies failed to demonstrate efficacy and do not support the use of sertraline in the treatment of children and adolescents with Major Depressive Disorder (See sections 4.3, Contra-Indications and 4.8, Undesirable effects).

Sertraline should be given as a single daily dose. Sertraline 50mg Tablets can be administered with or without food.

Adults

Depression (including accompanying symptoms of anxiety): The starting dose is 50mg daily and the usual antidepressant dose is 50mg daily. In some patients, doses higher than 50mg may be required.

Obsessive Compulsive Disorder: The starting dose is 50mg daily, and the therapeutic dose range is 50-200mg daily.

Post-Traumatic Stress Disorder: Treatment for PTSD should be initiated at 25mg/day. After one week, the dose should be increased to 50mg once daily. PTSD is a heterogeneous illness and some patient groups fulfilling the criteria for PTSD do not appear to be responsive to treatment with sertraline. Dosing should be reviewed periodically by the prescribing physician to determine response to therapy and treatment should be withdrawn if there is no clear evidence of efficacy.

Depression (including accompanying symptoms of anxiety), OCD and PTSD: In some patients doses higher than 50mg daily may be required. In patients with incomplete response but good toleration at lower doses, dosage adjustments should be made in 50mg increments over a period of weeks to a maximum of 200mg daily.

Once optimal therapeutic response is achieved the dose should be reduced, depending on therapeutic response, to the lowest effective level. Dosage during prolonged maintenance therapy should be kept at the lowest effective level, with subsequent adjustments depending on therapeutic response. The onset of therapeutic effect may be seen within seven days, although two to four weeks (and even longer in OCD) are usually necessary for full activity. A longer treatment period, even beyond 12 weeks in some cases, may be required in the case of a therapeutic trial in PTSD.

Use in children aged 6-17 years: Treatment should only be initiated by specialists. The safety and efficacy of sertraline has been established in paediatric OCD patients (aged 6-17). The administration of sertraline to paediatric OCD patients (aged 13-17) should commence at 50 mg/day. Therapy for paediatric OCD patients (aged 6-12) should commence at 25mg/day increasing to 50mg/day after 1 week. Subsequent doses may be increased in case of lack of response in 50mg/day increments up to 200mg/day as needed. However, the generally lower body weights of children compared to adults should be taken into consideration in advancing the dose from 50mg, in order to avoid excessive dosing. Given the 24 hour elimination half-life of sertraline, dose changes should not occur at intervals of less than one week.

The efficacy and safety of sertraline in children and adolescents under the age of 18 years with Major Depressive Disorder have not been established. Controlled clinical studies failed to demonstrate efficacy and do not support the use of sertraline in the treatment of children and adolescents with Major Depressive Disorder (See sections 4.3, Contra-Indications and 4.8, Undesirable effects).

Children aged less than six years: Sertraline is not recommended in children under six years of age since safety and efficacy have not been established. See also 'Pharmacological Properties'.

Use in the elderly: No special precautions are required. The usual adult dose is recommended. Several hundred elderly patients have participated in clinical studies with sertraline. The pattern and incidence of adverse reactions in the elderly is similar to that in younger patients.

Sertraline 50mg Tablets are for oral administration only.

Withdrawal symptoms seen on discontinuation of SSRI:Abrupt discontinuation should be avoided. When stopping treatment with SSRIs the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see section 4.4 Special Warnings and Special Precautions for Use and section 4.8 Undesirable Effects). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

Sertraline is contra-indicated in patients with a known hypersensitivity to sertraline or any of the excipients.

Monoamine oxidase inhibitors: Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), including the selective MAOI selegiline and the reversible MAOI (RIMA) moclobemide and in patients who have recently discontinued an SSRI and have been started on a MAOI.

Some cases presented with features resembling serotonin syndrome. Symptoms of a drug interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma.

Sertraline should not be used in combination with a MAOI. Sertraline may be started 14 days after discontinuing treatment with an irreversible MAOI and at least one day after discontinuing treatment with the reversible MAOI (RIMA), moclobemide. At least 14 days should elapse after discontinuing sertraline treatment before starting a MAOI or RIMA.

Use in hepatic impairment: There is insufficient clinical experience in patients with significant hepatic dysfunction and accordingly sertraline should not be used in such patients.

Concomitant use in patients taking pimozide is contra-indicated (see Section 4.5 - Interaction with other medicinal products and other forms of interaction.

Sertraline should not be used in children and adolescents under the age of 18 years with Major Depressive Disorder (See section 4.8, Undesirable effects) but are used to treat obsessive compulsive disorder (OCD) in children of six years and over (See Section 4.2. Posology and method of administration).

Monoamine oxidase inhibitors: See Section 4.3 Contra-indications.

Use in patients with renal or hepatic impairment: As with many other medications, sertraline should be used with caution in patients with renal and hepatic impairment (see Section 4.3 Contra-indications).

Since sertraline is extensively metabolised, excretion of unchanged drug in urine is a minor route of elimination. In patients with mild to moderate renal impairment (creatinine clearance 20-50ml/min) or severe renal impairment (creatinine clearance <20ml/min), single dose pharmacokinetic parameters were not significantly different compared with controls. However, steady state pharmacokinetics of sertraline have not been adequately studied in this patient population and caution is advised when treating patients with renal impairment.

Sertraline is extensively metabolised by the liver. A multiple dose pharmacokinetic study in subjects with mild, stable cirrhosis demonstrated a prolonged elimination half-life and approximately three-fold greater AUC and C_max in comparison with normal subjects. There were no significant differences in plasma protein binding observed between the two groups. The use of sertraline in patients with hepatic disease should be approached with caution. A lower or less frequent dose should be used in patients with hepatic impairment.

Diabetes: In patients with diabetes, treatment with an SSRI may alter glycaemic control, possibly due to improvement of depressive symptoms. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Seizures: Seizures are a potential risk with antidepressant or antiobsessional drugs. The drug should be discontinued in any patient who develops seizures. Sertraline should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Sertraline should be discontinued if there is an increase in seizure frequency.

Electroconvulsive therapy (ECT): Since there is little clinical experience of concurrent administration of sertraline and ECT, caution is advisable.

Mania: sertraline should be used with caution in patients with a history of mania/hypomania. Sertraline should be discontinued in any patient entering a manic phase.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which sertraline is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Use in children and adolescents under 18 years of age:

Sertraline should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

Haemorrhage: There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura with SSRIs.

Caution is advised in patients taking SSRIs, particularly in concomitant use with drugs known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, aspirin and non-steroidal anti-inflammatory drugs (NSAIDs)) as well as in patients with a history of bleeding disorders.

Psychomotor restlessness: The use of SSRIs has been associated with the development of psychomotor restlessness, which clinically may be very similar to akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental and it may be necessary to review the use of SSRIs.

Use in the elderly: Several hundred elderly patients have participated in clinical studies with sertraline. The pattern and incidence of adverse reactions in the elderly is similar to that in younger patients.

Use in Children: More than 250 paediatric OCD patients have been exposed to sertraline in completed and ongoing studies. The safety profile of sertraline in these paediatric studies is comparable to that observed in the adult OCD studies. The efficacy of sertraline in paediatric patients with depression or panic disorder has not been demonstrated in controlled trials. Safety and effectiveness in paediatric patients below the age of six have not been established.

There is limited knowledge with respect to an effect on sexual development in children.

Sodium content: Sertraline 50mg Tablets contain approximately 0.3mg of sodium per tablet. To be taken into consideration by patients on a controlled sodium diet.

Withdrawal symptoms seen on discontinuation of SSRI treatment:

The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache are the most commonly reported reactions. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within two weeks, though in some individuals they may be prolonged (two to three months or more). It is therefore advised that SSRIs should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see "Withdrawal Symptoms Seen on Discontinuation of SSRIs", Section 4.2 Posology and Method of Administration).

Monoamine oxidase inhibitors: See Section 4.3 Contra-indications.

Centrally active medication: Caution is advised if sertraline is administered with other centrally active medication. In particular, SSRIs have the potential to interact with tricyclic antidepressants leading to an increase in plasma levels of the tricyclic antidepressant. A possible mechanism for this interaction is the inhibitory effect of SSRIs on the CYP2D6 isoenzyme. There is variability among the SSRIs in the extent to which they inhibit the activity of CYP2D6. The clinical significance of this depends on the extent of inhibition and the therapeutic index of the co-administered drug. In formal interaction studies, chronic dosing with sertraline 50mg daily showed minimal elevation (mean 23-37%) of steady state plasma desipramine levels (a marker of CYP2D6 isoenzyme activity).

Pimozide: Increased pimozide levels have been demonstrated in a study of a single low dose of pimozide (2mg) with sertraline coadministration. These increased levels were not associated with any changes in ECG. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide, concomitant use of pimozide and sertraline is contra-indicated.

Alcohol: In 11 healthy subjects administered sertraline (200mg daily) for nine days, there was no adverse effect on cognitive or psychomotor performance relative to placebo, following a single dose of 500mg/kg alcohol. However, the concomitant use of sertraline and alcohol in depressed patients is not recommended.

Lithium and tryptophan: In placebo-controlled trials in normal volunteers, the co-administration of sertraline and lithium did not significantly alter lithium pharmacokinetics. Co-administration of sertraline with lithium did result in an increase in tremor relative to placebo, indicating a possible pharmacodynamic interaction. There have been other reports of enhanced effects when SSRIs have been given with lithium or tryptophan and therefore the concomitant use of SSRIs with these drugs should be undertaken with caution.

Serotonergic drugs: There is limited controlled experience regarding the optimal timing of switching from other antidepressant or antiobsessional drugs to sertraline. Care and prudent medical judgement should be exercised when switching, particularly from long-acting agents. The duration of washout period which should intervene before switching from one selective serotonin reuptake inhibitor (SSRI) to another has not been established.

Until further data are available, serotonergic drugs, such as tramadol, sumatriptan or fenfluramine, should not be used concomitantly with sertraline, due to a possible enhancement of 5-HT associated effects.

St John's Wort: Concomitant use of the herbal remedy St John's Wort (Hypericum perforatum) in patients receiving SSRIs should be avoided since there is a possibility of serotonergic potentiation.

Drugs that affect platelet function, such as NSAIDs: See Section 4.4 Special warnings and precautions for use (Haemorrhage)'.

Other drug interactions: Since sertraline is bound to plasma proteins, the potential of sertraline to interact with other plasma protein bound drugs should be borne in mind.

Formal drug interaction studies have been performed with sertraline. Co-administration of sertraline (200mg daily) with diazepam or tolbutamide resulted in small, statistically significant changes in some pharmacokinetic parameters. Co-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline had no effect on the beta-adrenergic blocking ability of atenolol. No interaction with sertraline (200mg daily) was observed with glibenclamide or digoxin.

Co-administration of sertraline (200mg daily) with warfarin resulted in a small but statistically significant increase in prothrombin time, the clinical significance of which is unknown. Accordingly, prothrombin time should be carefully monitored when sertraline therapy is initiated or stopped.

Sertraline (200mg daily), did not potentiate the effects of carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy subjects.

Pregnancy: Although animal studies did not provide any evidence of teratogenicity, the safety of sertraline during human pregnancy has not been established. As with all drugs sertraline should only be used in pregnancy if the potential benefits of treatment to the mother outweigh the possible risks to the developing foetus.

Lactation: Sertraline is known to be excreted in breast milk. Its effects on the nursing infant have not yet been established. If treatment with sertraline is considered necessary, discontinuation of breast-feeding should be considered.

Clinical pharmacology studies have shown that sertraline has no effect on psychomotor performance. However, since antidepressant or antiobsessional drugs may impair the abilities required to perform potentially hazardous tasks such as driving a car or operating machinery, the patient should be cautioned accordingly. Sertraline should not be administered with benzodiazepines or other tranquillizers in patients who drive or operate machinery.

Side-effects which occurred significantly more frequently with sertraline than placebo in multiple dose studies were: nausea, diarrhoea/loose stools, anorexia, dyspepsia, tremor, dizziness, insomnia, somnolence, increased sweating, dry mouth and sexual dysfunction (principally ejaculatory delay in males).

The side-effect profile commonly observed in double-blind, placebo-controlled studies in patients with OCD and PTSD was similar to that observed in patients with depression.

Post-marketing spontaneous reports include the following:

Cardiovascular: Blood pressure disturbances including postural hypotension, tachycardia.

Eye disorders: Abnormal vision.

Gastro-intestinal: Vomiting, abdominal pain.

Nervous system: Amnesia, headache, drowsiness, movement disorders, paraesthesia, hypoaesthesia, depressive symptoms, hallucinations, aggressive reaction, agitation, anxiety, psychosis, depersonalisation, nervousness, panic reaction and signs and symptoms associated with serotonin syndrome which include fever, rigidity, confusion, agitation, diaphoresis, tachycardia, hypertension and diarrhoea.

There have also been reports of manic reaction, although this phenomenon may be part of the underlying disease.

Cases of suicidal ideation and suicidal behaviours have been reported during sertraline therapy or early after treatment discontinuation (see section 4.4).

Convulsions (Seizures): Sertraline should be discontinued in any patient who develops seizures (See Section 4.4 Special warnings and precautions for use').

Musculoskeletal: Arthralgia, myalgia.

Hepatic/pancreatic: Rarely, pancreatitis and serious liver events (including hepatitis, jaundice and liver failure). Asymptomatic elevations in serum transaminases (SGOT and SGPT) have been reported in association with sertraline administration (0.8 – 1.3%), with an increased risk associated with the 200mg daily dose. The abnormalities usually occurred within the first one to nine weeks of drug treatment and promptly diminished upon drug discontinuation.

Renal & urinary disorders: Urinary retention.

Reproductive: Hyperprolactinemia, galactorrhoea, menstrual irregularities, anorgasmy.

Skin and allergic reactions: Rash (including rare reports of erythema multiforme, photosensitivity), angioedema, ecchymoses, pruritus and anaphylactoid reactions.

Metabolic: Rare cases of hyponatremia have been reported and appeared to be reversible when sertraline was discontinued. Some cases were possibly due to the syndrome of inappropriate antidiuretic hormone secretion. The majority of reports were associated with older patients, and patients taking diuretics or other medications.

Haematologic: There have been rare reports of altered platelet function and/or abnormal clinical laboratory results in patients taking sertraline. While there have been reports of thrombocytopenia, abnormal bleeding or purpura in several patients taking sertraline, it is unclear whether sertraline had a causative role. See also Section 4.4 'Special warnings and precautions for use'.

General: Malaise.

Other: Withdrawal reactions have been reported with sertraline. Common symptoms include dizziness, paraesthesia, headache, anxiety and nausea. Abrupt discontinuation of treatment with sertraline should be avoided. The majority of symptoms experienced on withdrawal of sertraline are non-serious and self-limiting.

Rare: psychomotor restlessness/akathisia (see section 4.4 Special Warnings and Precautions for Use)

Adverse events from paediatric clinical trials: In paediatric clinical trials in depression the following adverse events were reported at a frequency of at least 2% of patients and occurred at a rate of at least twice that of placebo: dry mouth (2.1% vs 0.5%), hyperkinesia (2.6% vs 0.5%), tremor (2.1% vs 0%), diarrhoea (9.5% vs 1.6%), vomiting (4.2% vs 1.1%), agitation (6.3% vs 1.1%), anorexia (5.3% vs 1.1%) and urinary incontinence (2.1% vs 0%).

Suicidal thoughts and suicide attempts were mainly observed in clinical trials with Major Depressive Disorder.

Sertraline has been evaluated in paediatric OCD patients aged 6 to 17 in a 12 week placebo-controlled study. Therapy for paediatric OCD patients (aged 6-12) commenced at 25mg/day increasing to 50mg/day after 1 week. Side-effects which occurred significantly more frequently with sertraline than placebo were: headache, insomnia, agitation [6-12 years]; insomnia, anorexia, tremor [13-17 years]. Most were of mild to moderate severity. There is limited evidence of efficacy and safety beyond 12 weeks of treatment.

Withdrawal symptoms seen on discontinuation of SSRI treatment:

Discontinuation of SSRIs (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache are themost commonly reported reactions. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when SSRI treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see section 4.2 Posology and Method of Administration and section 4.4 Special Warnings and Special Precautions for use).

On the evidence available, sertraline has a wide margin of safety in overdose. Overdoses of sertraline alone of up to 8g have been reported. Deaths involving overdoses of sertraline in combination with other drugs and/or alcohol have been reported. Therefore, any overdosage should be treated aggressively.

Symptoms of overdose include serotonin-mediated side-effects such as somnolence, gastrointestinal disturbances (such as nausea and vomiting), tachycardia, tremor, agitation and dizziness. Less frequently reported was coma.

No specific therapy is recommended and there are no specific antidotes to sertraline. Establish and maintain an airway, ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdose. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Due to the large volume of distribution of sertraline, forced diuresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be of benefit.

Pharmacotherapeutic Group: Monoamine oxidase inhibitors, non-selective

ATC Code: N06A F

Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) uptake in vitro and in vivo, but is without affinity for muscarinic, serotonergic, dopaminergic, adrenergic, histaminergic, gamma-aminobutyric acid (GABA) or benzodiazepine receptors.

Sertraline is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals.

Unlike tricyclic antidepressants, no weight gain is observed with treatment for depression.

Sertraline has not been observed to produce physical or psychological dependence.

Sertraline exhibits dose proportional pharmacokinetics over a range of 50-200mg. After oral administration of sertraline in man, peak blood levels occur at about 4.5 - 8.4 hours. Daily doses of sertraline achieve steady-state after one week. Sertraline has a plasma half-life of approximately 26 hours with a mean half-life for young and elderly adults ranging from 22-36 hours. Sertraline is approximately 98% bound to plasma proteins. The principal metabolite, N-desmethylsertraline, is inactive in in vivo models of depression and has a half-life of approximately 62-104 hours. Sertraline and N-desmethylsertraline are both extensively metabolised in man and the resultant metabolites excreted in faeces and urine in equal amounts. Only a small amount (<0.2%) of unchanged sertraline is excreted in the urine.

The pharmacokinetics of sertraline in paediatric OCD patients have been shown to be comparable with adults (although paediatric patients metabolise sertraline with slightly greater efficiency). However, lower doses may be advisable for paediatric patients given their lower body weights (especially 6-12 years), in order to avoid excessive plasma levels.

A clear relationship between sertraline concentration and the magnitude of therapeutic response has not been established.

The pharmacokinetics of sertraline in elderly patients are similar to younger adults.

Food does not significantly change the bioavailability of sertraline tablets.

Extensive chronic safety evaluation studies in animals show that sertraline is generally well tolerated at doses that are appreciable multiples of those that are clinically effective.

Tablet core

Microcrystalline cellulose

Dibasic calcium phosphate dihydrate

Hydroxypropylcellulose

Sodium starch glycolate

Magnesium stearate

Tablet coating

None

Two years

Do not store above 25°C.

Keep out of the reach and sight of children.

PVC/PVDC/aluminium foil opaque blister packs containing 7, 14, 28, 30 or 100^* tablets.

^*Not all pack sizes may be marketed

No special requirements.

Wockhardt UK Ltd

Ash Road North

Wrexham

LL13 9UF

UK

50mg - PL 29831/0184

100mg - PL 29831/0183

2^nd November 2007

January 2009.