INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
XET 20 TABLETS

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

XET 20 TABLETS

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

PHARMACOLOGICAL CLASSIFICATION:
A 1.2 Psychoanaleptics (Antidepressants)

PHARMACOLOGICAL ACTION:
Paroxetine is a selective serotonin re-uptake inhibitor (SSRI). The antidepressant effect of paroxetine is thought to be related to its effect on serotonergic neurotransmission.
Pharmacokinetics:
After oral administration, paroxetine is readily absorbed from the gastrointestinal tract. Absorption is not influenced by the presence of food, milk or antacids. Paroxetine is highly protein bound (95%) and undergoes extensive first-pass metabolism in the liver where it is metabolised in part by cytochrome P450 2D6 (CYP2D6). The metabolites appear to be clinically inactive. The elimination half-life is about 24 hours, but there is wide intersubject variability. Steady-state is achieved in 7 to 14 days in most patients. Paroxetine is excreted renally (approximately 64%) and in the faeces (approximately 36%) mainly as inactive metabolites.

INDICATIONS:

•	Depression
•	Obsessive Compulsive Disorder (OCD)
•	Social phobia
•	Panic disorder

CONTRA-INDICATIONS:

•	Hypersensitivity to paroxetine or any of the ingredients of XET 20 TABLETS.
•	MAO Inhibitors: XET 20 TABLETS 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 XET 20 TABLETS.
•	Children under the age of 18 years (see WARNINGS and SIDE EFFECTS AND SPECIAL PRECAUTIONS).
•	Co-administration with thioridazine.

WARNINGS:
Safety and efficacy in children under 18 years have not been established. (See CONTRA-INDICATIONS and SIDE EFFECTS AND SPECIAL PRECAUTIONS).
Patients with major depressive disorder, both adults and children, may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medicines. This risk may persist until significant remission occurs. A causal role, however, for antidepressant medicines in inducing such behaviour has not been established. Patients being treated with XET 20 TABLETS should, nevertheless, be observed closely for clinical worsening and suicidality, especially at the beginning of a course of therapy, or at any time of dose changes, either increases or decreases.
Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric and non-psychiatric disorders.
The following symptoms have been reported in patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness, impulsivity, akathisia, hypomania, and mania). Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing XET 20 TABLETS, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
If the decision is made to discontinue treatment, XET 20 TABLETS should be tapered (See PRECAUTIONS and DOSAGE AND DIRECTIONS FOR USE).
XET 20 TABLETS should be used with caution in:-

•	Patients with a history of mania.
•	Patients already receiving neuroleptics, since symptoms suggestive of Neuroleptic Malignant Syndrome may occur with this combination.
•	Patients concomitantly treated with medicines that give an increased risk for bleeding, and in patients with a known tendency for bleeding or those with predisposing conditions. Treatment with XET 20 TABLETS may cause skin and mucous membrane bleedings.

Co-administration with risperidone may lead to increased toxicity thereof (see INTERACTIONS).
Patients should be cautioned about their ability to drive a car and operate machinery.
The concomitant use of XET 20 TABLETS and alcohol is not advised.

INTERACTIONS:
Cimetidine, a drug metabolising inhibitor, can increase the bioavailability of XET 20 TABLETS, whereas the drug metabolising inducer phenytoin can decrease it.
When XET 20 TABLETS 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 XET 20 TABLETS 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).
XET 20 TABLETS 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 medicines 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) risperidone, Type 1c antiarrhythmics (e.g. propafenone) and metoprolol.
Co-administration with risperidone may lead to increased toxicity thereof.
Interaction between XET 20 TABLETS and monoamine oxidase (MAO) inhibitors (See CONTRA-INDICATIONS), and also between XET 20 TABLETS and tryptophan medication may occur, resulting in a “serotonin syndrome”.
Concurrent administration of XET 20 TABLETS and lithium should be undertaken with caution. Lithium levels should be monitored.
Co-administration of XET 20 TABLETS 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 XET 20 TABLETS with anti-convulsants may be associated with an increased incidence of adverse events.
Daily administration of XET 20 TABLETS may significantly increase the plasma levels of procyclidine; other anti-cholinergic drugs may be similarly affected. If anti-cholinergic effects are seen, the dose of procyclidine should be reduced.
XET 20 TABLETS should be administered with great caution to patients receiving oral anticoagulants (See WARNINGS).
Co-administration of XET 20 TABLETS with warfarin may result in increased bleeding in the presence of unaltered prothrombin times.

PREGNANCY AND LACTATION:
The safety of XET 20 TABLETS in pregnancy or lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE:
It is recommended that XET 20 TABLETS is administered in the morning with food.
XET 20 TABLETS should be swallowed rather than chewed.
Depression: 20 mg daily. This dose can be increased gradually if needed 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. The initial starting dose is 10 mg daily, which may be increased by 10 mg increments. The maximum dose is 60 mg daily.
The low initial starting dose is recommended to minimise the potential worsening of panic symptoms when initiating treatment with XET 20 TABLETS.
Obsessive Compulsive Disorder: The recommended dose is 40 mg daily. The initial starting dose is 20 mg daily, which may be increased by 10 mg increments to a maximum of 60 mg daily.
Social Phobia: The recommended daily dose is 20 mg. This dose may be increased gradually if needed by 10 mg increments to a maximum of 60 mg according to the patient’s response.
Children: The safety and efficacy of XET 20 TABLETS in children under the age of 18 years have not been established. In children hostility, suicide ideation and self-harm may occur with XET 20 TABLETS.
Elderly: Elderly subjects may experience increased plasma concentrations with XET 20 TABLETS. Dosing should commence at the adult starting dose and may be increased gradually by 10 mg increments up to 40 mg daily.
Hepatic and renal impairment: Increased plasma concentrations of XET 20 TABLETS may occur in patients with severe renal impairment (creatinine clearance < 30 ml/min) or severe hepatic impairment. The dosage should therefore be restricted to the lower end of the dosage range.
Patients should be treated for a sufficient period to ensure that they remain free from symptoms. This may be several months or longer.
Abrupt discontinuation of XET 20 TABLETS should be avoided (See SIDE-EFFECTS AND SPECIAL PRECAUTIONS).

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Definition of frequencies:
Rare (=1/10 000, <1/1000)
Very rare (<1/10 000), including isolated reports.
Very common (=1/10)
Common (=1/100, <1/10)
Uncommon (=1/1000, <1/100)

Blood and lymphatic system disorders:
Uncommon: Abnormal bleeding, predominantly of the skin and mucous membranes (mostly ecchymosis, but also in the gastrointestinal tract, central nervous system and eye).
Endocrine disorders:
Very rare: Syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
Psychiatric disorders:
Common: Somnolence, insomnia.
Uncommon: Confusion, hallucinations.
Rare: Manic reactions.
Immune system disorders:
Very rare: Allergic reactions (including urticaria and angioedema).
Metabolism and nutrition disorders:
Common: Decreased appetite.
Rare:         Hyponatraemia.
Hyponatraemia, which may occur predominantly in elderly patients, is sometimes due to syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
Nervous system disorders:
Common: Dizziness, tremor.
Uncommon: Extrapyramidal disorders.
Rare: Convulsions.
Very rare: Serotonin syndrome (symptoms may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, shivering, tachycardia and tremor).
Extrapyramidal disorders may occur in patients using neuroleptic medication.
General disorders and administration site conditions:
Common: Asthenia.
Very rare: Peripheral oedema.
Eye disorders:
Common: Blurred vision.
Very rare: Acute glaucoma.
Respiratory, thoracic and mediastinal disorders
Common: Yawning.
Renal and urinary disorders
Uncommon: Urinary retention.
Reproductive system and breast disorders
Very common: Sexual dysfunction.
Rare: Hyperprolactinaemia/ galactorrhoea.
Gastrointestinal disorders
Very common: Nausea.
Common: Constipation, diarrhoea, dry mouth.
Hepato-biliary disorders
Rare: Elevation of hepatic enzymes.
Very rare: Hepatic events (such as hepatitis, sometimes associated with jaundice and/ or liver failure).
Elevation of hepatic enzymes may occur. Hepatic events, which may be fatal (such as hepatitis, sometimes associated with jaundice, and/or liver failure) may occur. Discontinuation of XET 20 TABLETS should be considered if there is prolonged elevation of liver function test results.
Skin and subcutaneous tissue disorders
Common: Sweating.
Uncommon: Skin rashes.
Very rare: Photosensitivity reactions.
Symptoms seen on discontinuation of XET 20 TABLETS treatment
Common: Dizziness, sensory disturbances, sleep disturbances, anxiety, headache.
Uncommon: Agitation, nausea, tremor, confusion, sweating, diarrhoea.
Abrupt discontinuation of XET 20 TABLETS may lead to withdrawal symptoms such as dizziness, sensory disturbances, (including paraesthesia and electric shock sensations), sleep disturbances, insomnia, tremor, confusion, agitation or anxiety, headache, nervousness, vertigo, nausea and sweating. It is therefore advised that when XET 20 TABLETS treatment is no longer required, gradual discontinuation by dose tapering be carried out (See DOSAGE AND DIRECTIONS FOR USE, and SPECIAL PRECAUTIONS).

Special precautions:
Safety and efficacy in children under 18 years of age have not been established. (See CONTRA-INDICATIONS and DOSAGE AND DIRECTIONS FOR USE).
Cardiac Condition:
Administration of XET 20 TABLETS 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, XET 20 TABLETS should be administered with caution.
Epilepsy:
XET 20 TABLETS should be used with caution in patients with epilepsy.
Seizures:
Seizures may occur in patients treated with XET 20 TABLETS.
XET 20 TABLETS should be discontinued in any patient who develops seizures.
Electro-Convulsive Therapy (ECT):
Clinical experience of the concurrent administration of XET 20 TABLETS and electro-convulsive therapy is lacking.
Hyponatraemia:
Hyponatraemia, which is generally reversible on discontinuation of XET 20 TABLETS, may occur predominantly in the elderly.
Glaucoma:
XET 20 TABLETS may cause mydriasis and should be used with caution in patients with narrow angle glaucoma.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
(See SIDE EFFECTS AND SPECIAL PRECAUTIONS)
Symptoms of overdose:
Vomiting, dilated pupils, fever, blood pressure changes, headache, involuntary muscle contractions, agitation, anxiety, tachycardia, coma and ECG changes.
Treatment of overdose:
Treatment is symptomatic and supportive.
There is no specific antidote. To decrease absorption, the stomach should be emptied by gastric lavage or induction of emesis or both. This should be followed by administration of 20 to 30 g of activated charcoal every four to six hours during the first 24 hours after ingestion. Frequent monitoring of vital signs and careful observation is recommended.

IDENTIFICATION:
Blue coloured, smooth, round, biconvex film coated tablets, with breakline on one side and plain on the other side.

PRESENTATION:
PVC/Aluminium blister packs of 30 tablets packed in an outer carton. Each blister strip contains 10 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C in the original outer container. Protect from light. Do not remove the blister from the outer carton until required for use.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
XET 20 TABLETS: 39/1.2/0216

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
ZYDUS HEALTHCARE SA (PTY) LTD
Adrina Building, First Floor
32 –34 Klinkenberg Road
Van Der Hoff Park
Potchefstroom
2531

DATE OF PUBLICATION OF THE PACKAGE INSERT:
17 March 2005

New addition to this site: January 2008
Source: Pharmaceutical Industry

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