INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo AROPAX 20 (tablet)
AROPAX 30 (tablet)

SCHEDULING STATUS:
S5

PROPRIETARY NAMES
(and dosage form):

AROPAX 20 (tablet)
AROPAX 30 (tablet)

COMPOSITION:
Each tablet contains
paroxetine hydrochloride equivalent to paroxetine 20 mg or 30 mg free base.

PHARMACOLOGICAL CLASSIFICATION:
A.1.2 Psychoanaleptics (Anti-depressants)

PHARMACOLOGICAL ACTION:
AROPAX
is a selective inhibitor of 5-hydroxytryptamine (5-HT, serotonin) uptake and its antidepressant action is thought to be related to its specific inhibition of 5-HT uptake in brain neurones. AROPAX is well absorbed after oral dosing and undergoes first pass metabolism.
The elimination half life is variable but is generally about 1 day. Steady state systemic levels are attained 7-14 days after starting treatment and pharmacokinetics do not appear to change during long-term therapy.
Further Information:
AROPAX
is chemically unrelated to the tricyclic or tetracyclic antidepressants. The principle metabolites of AROPAX are polar and conjugated products of oxidation and methylation. which are readily cleared. In view of their relative lack of pharmacological activity, it is most unlikely that they contribute to the therapeutic effects of AROPAX .
The metabolites of AROPAX do not compromise the selective action of AROPAX on neuronal 5-HT uptake. Animal studies indicate that AROPAX is well tolerated by the cardiovascular system.

INDICATIONS:
Depression:
Major depressive disorders, such as single episodes and recurrent depression with associated anxiety, especially where sedation is not required. Treatment at generally lower dosages may be continued for up to one year to prevent relapse and recurrence of further depressive episodes.
Panic Disorder:
Paroxetine has been shown to be effective in the treatment of panic disorder with and without agoraphobia. The combination of paroxetine and cognitive-behavioural therapy has been shown to be statistically significantly more effective than cognitive-behavioural therapy alone in the treatment of panic disorder. In a placebo-controlled trial, the efficacy of paroxetine in the treatment of panic disorder has been maintained for up to one year.
Obsessive Compulsive Disorder:
For the short-term treatment of severe disabling Obsessive Compulsive Disorder, where the obsessions or compulsions cause marked distress, are time-consuming or significantly interfere with social or occupational functioning.
Social Phobia:
Paroxetine has been shown to be effective in the treatment of Social Phobia.

CONTRA-INDICATIONS:
Known hypersensitivity to paroxetine and its excipients.
Monoamine oxidase (MAO) inhibitors:
AROPAX
should not be used in combination with MAO inhibitors or within 2 weeks of terminating treatment with MAO inhibitors. MAO inhibitors should not be introduced within 2 weeks of cessation of therapy with AROPAX .
Children:
The use of AROPAX in children cannot be recommended as safety and efficacy have not been established.
Use During Pregnancy and Lactation:
The safety of AROPAX in human pregnancy or lactation has not been established. AROPAX should not be used during pregnancy or by nursing mothers unless the potential benefit outweighs the possible risk.

WARNINGS:
History of mania:
AROPAX
should be used with caution in patients with a history of mania.
AROPAX should be used with caution in patients already receiving neuroleptics, since symptoms suggestive of Neuroleptic Malignant Syndrome cases have been reported with this combination.
Oral anticoagulants:
AROPAX
should be administered with great caution to patients receiving oral anticoagulants.
Preliminary data suggest that there may be a pharmacodynamic interaction between AROPAX and warfarin which may result in increased bleeding in the presence of unaltered prothrombin times.
Effects on ability to drive and use machines:
Patients should be cautioned about their ability to drive a car and operate machinery.
Alcohol:
The concomitant use of AROPAX and alcohol is not advised.

DOSAGE AND DIRECTIONS FOR USE:
Depression:
The recommended dose is 20 mg daily. In some patients it may be necessary to increase the dose, which should be done gradually by 10 mg increments to a maximum of 50 mg daily, according to the patient's response.
Panic Disorder:
The recommended dose is 40 mg daily. Patients should be started on 10 mg/day and the dose increased weekly in 10 mg increments according to the patient's response. Some patients may benefit from having their dose increased up to a maximum of 60 mg/day.
A low initial starting dose is recommended to minimise the potential worsening of panic symptomatology which is generally recognised to occur early in the treatment of this disorder.
Obsessive Compulsive Disorder:
The recommended dose is 40 mg daily. Patients should start on 20 mg and the dose can be increased weekly in 10 mg increments. Some patients will benefit from having their dose increased up to a maximum of 60 mg/day.
Social Phobia:
The recommended dose is 20 mg daily. Some patients not responding to a 20 mg dose may benefit from having dose increases in 10 mg increments as required, up to a maximum of 40 mg/day according to the patient’s response.
General information:
It is recommended that AROPAX is administered once daily in the morning with food. The tablet should be swallowed rather than chewed.
Morning dosing with AROPAX does not affect either the quality or duration of sleep. Patients are likely to experience improved sleep as they respond to AROPAX therapy. Patients should be treated for a sufficient period to ensure that they are free from symptoms. This period may be several months for depression and for obsessive compulsive disorder and panic disorder can be even longer.
Elderly:
Increased plasma concentrations of AROPAX occur in elderly subjects. Dosing should commence at the adult starting dose and may be increased gradually by 10 mg increments up to 40 mg daily.
Renal/hepatic impairment:
Increased plasma concentrations of AROPAX occur in patients with severe renal impairment (creatinine clearance <30 mL/min) or severe hepatic impairment. Therefore, dosage should be restricted to the lower end of the dosage range.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Adverse experiences may decrease in intensity and frequency with continued treatment. The most commonly observed adverse effects associated with the use of AROPAX are: nausea, somnolence, sweating, tremor, asthenia, dry mouth, insomnia, constipation, dizziness, sexual dysfunction, dyspepsia, vomiting, diarrhoea, anxiety, decreased appetite and headaches. The following events have been reported less frequently: Bruising, rash, acute glaucoma, urinary retention, peripheral and facial oedema, neuroleptic malignant syndrome, confusion, “serotonergic syndrome” (symptoms may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, shivering, tachycardia, diarrhoea, inco-ordination, fever and tremor), symptoms suggestive of hyperprolactinaemia/galactorrhea and hyponatraemia (predominantly in the elderly) which is sometimes due to syndrome of inappropriate anti-diuretic hormone secretion (SIADH). Allergic reactions, such as angioedema, urticaria and skin rashes have been reported.
Elevations of hepatic enzymes have been reported. Post marketing reports of hepatic events (such as hepatitis, sometimes associated with jaundice and/or liver failure) have been received. Discontinuation of AROPAX should be considered if there is a prolonged elevation of liver function test results.
Abnormal bleeding predominantly of the skin and mucous membranes (mostly ecchymoses and purpura) has been reported. Manic reactions have been reported less frequently. Blurred vision has been reported.
There have been reports of extrapyramidal symptoms associated with the use of AROPAX and of aggravation of Parkinson's disease in patients taking AROPAX. AROPAX should therefore be avoided in patients with extrapyramidal disorders or who were using neuroleptic medication. Paroxetine should be used with caution in patients already receiving neuroleptics, since symptoms suggestive of Neuroleptic Malignant Syndrome cases have been reported with this combination.
Abrupt discontinuation may lead to withdrawal symptoms which include dizziness, sensory disturbances, sleep disturbance, insomnia, tremor, confusion, nausea and sweating. Confusion, convulsions and photosensitivity reactions have been observed.
Interactions:
The absorption and pharmacokinetics of AROPAX are not affected by food or antacids. The metabolism and pharmacokinetics of AROPAX may be affected by the induction or inhibition of drug metabolising enzymes. For example, cimetidine, a known drug metabolising inhibitor, can increase the bioavailability of paroxetine, and, phenytoin, a known drug metabolising inducer, can decrease it.
When AROPAX is to be co-administered with a known drug metabolising enzyme inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment of AROPAX is considered necessary when the medicine is to be co-administered with known drug metabolising enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effects (tolerability and efficacy).
Paroxetine inhibits the specific hepatic cytochrome P450 isozyme CYP2D6 responsible for the metabolism of debrisoquine and sparteine. This may lead to enhanced plasma levels of those co-administered drugs which are metabolised by this isozyme. Drugs metabolised by this isozyme include certain tricyclic antidepressants (e.g. nortriptyline, amitriptyline, imipramine and desipramine), phenothiazine neuroleptics (e.g. perphenazine and thioridazine ) and Type 1c antiarrhythmics (e.g. propafenone). Single dose studies in a limited number of healthy subjects has shown AROPAX does not increase the sedation and drowsiness associated with haloperidol, amylobarbitone or oxazepam, when given in combination. Co-administration with serotonergic medicines e.g. monoamine oxidase (MAO) inhibitors (see Contra-indications), and tryptophan medication may lead to an incidence of 5-HT associated effects (serotonergic syndrome).
Lithium: Since there is little clinical experience, and there have been reports of interaction of lithium with other 5-HT re-uptake inhibitors, the concurrent administration of AROPAX and lithium should be undertaken with caution. Lithium levels should be monitored.
Co-administration of AROPAX and phenytoin is associated with decreased plasma concentrations of paroxetine and increased adverse experiences (diarrhoea, indifference, imbalance, nervousness, ataxia and vertigo). No initial dosage adjustment of paroxetine is considered necessary when these agents are co-administered. Any subsequent adjustments should be guided by clinical effect. Co-administration of AROPAX with other anti-convulsants may also be associated with an increased incidence of adverse events. Daily administration of paroxetine increases significantly the plasma levels of procyclidine; other anti-cholinergic drugs may be similarly affected. If anticholinergic effects are seen, the dose of procyclidine should be reduced.
Anticoagulants/Warfarin: see WARNINGS.

Special Precautions for Use:
Cardiac Condition:
Administration of paroxetine to patients with a serious cardiovascular disorder such as (unstable) angina pectoris, poorly monitored cardiac decompensation, ventricular rhythm disorder and acute myocardial infarction, has not been studied and must therefore be avoided. If antidepressant medication is nevertheless indicated for such patients, paroxetine should be administered with caution.
Epilepsy:
AROPAX
should be used with caution in patients with epilepsy.
Seizures:
Seizures may occur in patients treated with AROPAX.
AROPAX should be discontinued in any patient who develops seizures.
Electro-Convulsive Therapy (ECT):
There is little clinical experience of the concurrent administration of AROPAX and electro-convulsive therapy.
Glaucoma:
AROPAX
infrequently causes mydriasis and should be used with caution in patients with narrow angle glaucoma.
Hyponatraemia:
Hyponatraemia has been reported, predominantly in the elderly. The hyponatraemia generally reverses on discontinuation of AROPAX.
Skin and mucous membrane bleedings have been reported following treatment with AROPAX. AROPAX should therefore be used with caution in patients concomitantly being treated with medicines that give an increased risk for bleeding and in patients with a known tendency for bleeding or those with predisposing conditions.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Experience of AROPAX overdosage has indicated that, in addition to those symptoms mentioned under side-effects, vomiting, dilated pupils, fever, blood-pressure changes, headache, involuntary muscle contractions, agitation, anxiety and tachycardia have been reported. Events such as coma or ECG changes have occasionally been reported and less frequently a fatal outcome, but generally when AROPAX was taken in conjunction with other psychotropic drugs, with or without alcohol. No specific antidote is known. Treatment of overdose is supportive and symptomatic. The stomach should be emptied either by the induction of emesis, lavage or both. Following evacuation, 20 to 30 grams of activated charcoal may be administered every 4 to 6 hours during the first 24 hours after ingestion. Supportive care, with frequent monitoring of vital signs and careful observation is indicated.

IDENTIFICATION:
AROPAX 20 : A white, film coated, oval shaped, biconvex tablet, engraved AROPAX 20 on one side and a break bar on the other.
AROPAX 30 : A blue, film coated, oval shaped, biconvex tablet, engraved AROPAX 30 on one side and a break bar on the other.

PRESENTATION:
AROPAX 20 : Cartons containing 28 blister packed tablets in strips of 14.
AROPAX 30 : Cartons containing 28 blister packed tablets in strips of 14.

STORAGE INSTRUCTIONS:
AROPAX
blister packs should be stored at room temperature (Below 30°C).
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
AROPAX
20: Y/1.2/419
AROPAX 30: Y/1.2/420

ZIMBABWE:
AROPAX
20: 98/13.2.1/3441 PP10

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
GlaxoSmithKline South Africa (Pty) Ltd
57 Sloane Street
Bryanston
2021

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
19/05/1999

GSK logo

P3720/0803

Good Old Printing CT: 592 3868

Updated on this site: May 2004
Source: Community Pharmacy

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