INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
DEPAROC 20 mg TABLET

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form)

DEPAROC 20 mg TABLET

COMPOSITION
Each tablet contains:
Paroxetine hydrochloride anhydrate equivalent to paroxetine 20 mg.

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 DEPAROC 20 MG.
•	MAO Inhibitors: DEPAROC 20 MG 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 DEPAROC 20 MG.
•	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 DEPAROC 20 MG 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 DEPAROC 20 MG, 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, DEPAROC 20 MG dosage should be tapered (See PRECAUTIONS and DOSAGE AND DIRECTIONS FOR USE).
DEPAROC 20 MG 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 increase the risk of bleeding, and in patients with a known tendency for bleeding or those with predisposing conditions. Treatment with DEPAROC 20 MG may cause skin and mucous membrane bleeding.

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 DEPAROC 20 MG and alcohol is not advised.

INTERACTIONS
Cimetidine, a drug metabolising inhibitor, can increase the bioavailability of DEPAROC 20 MG, whereas the drug metabolising inducer phenytoin can decrease it.
When DEPAROC 20 MG 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 DEPAROC 20 MG 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).
DEPAROC 20 MG 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 DEPAROC 20 MG and monoamine oxidase (MAO) inhibitors (See CONTRA-INDICATIONS), and also between DEPAROC 20 MG and tryptophan medication may occur, resulting in a “serotonin syndrome”.
Concurrent administration of DEPAROC 20 MG and lithium should be undertaken with caution. Lithium levels should be monitored.
Co-administration of DEPAROC 20 MG 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 DEPAROC 20 MG with anti-convulsants may be associated with an increased incidence of adverse events.
Daily administration of DEPAROC 20 MG 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.
DEPAROC 20 MG should be administered with great caution to patients receiving oral anticoagulants (See WARNINGS).
Co-administration of DEPAROC 20 MG with warfarin may result in increased bleeding in the presence of unaltered prothrombin times.

PREGNANCY AND LACTATION
The safety of DEPAROC 20 MG in pregnancy or lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE
It is recommended that DEPAROC 20 MG is administered in the morning with food.
DEPAROC 20 MG 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 DEPAROC 20 MG.
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 DEPAROC 20 MG in children under the age of 18 years have not been established. In children, hostility, suicidal ideation and self-harm may occur with DEPAROC 20 MG.
Elderly: Elderly subjects may experience increased plasma concentrations with DEPAROC 20 MG. 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 DEPAROC 20 MG 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 DEPAROC 20 MG should be avoided (See SIDE-EFFECTS AND SPECIAL PRECAUTIONS).

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects:
Definition of frequencies:
Rare (>1/10 000, <1/1 000)
Very rare (<1/10 000), including isolated reports.
Very common (>1/10)
Common (>1/100, <1/10)
Uncommon (>1/1 000, <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 the 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:	asthaenia.
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 DEPAROC 20 MG 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 DEPAROC 20 MG treatment

Common:	dizziness, sensory disturbances, sleep disturbances, anxiety, headache.
Uncommon:	agitation, nausea, tremor, confusion, sweating, diarrhoea.

Abrupt discontinuation of DEPAROC 20 MG 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 DEPAROC 20 MG treatment is no longer required, gradual discontinuation by dose tapering be carried out (See DOSAGE AND DIRECTIONS FOR USE).
Cardiac Condition:
Administration of DEPAROC 20 MG 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, DEPAROC 20 MG should be administered with caution.
Epilepsy:
DEPAROC 20 MG should be used with caution in patients with epilepsy.
Seizures:
Seizures may occur in patients treated with DEPAROC 20 MG.
DEPAROC 20 MG should be discontinued in any patient who develops seizures.
Electro-Convulsive Therapy (ECT):
Clinical experience of the concurrent administration of DEPAROC 20 MG and electroconvulsive therapy is lacking.
Hyponatraemia:
Hyponatraemia, which is generally reversible on discontinuation of DEPAROC 20 MG, may occur predominantly in the elderly.
Glaucoma:
DEPAROC 20 MG 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
White convex film coated tablets embossed “P2”with a breakline on one side and “G”on the other.

PRESENTATION
White plastic bottles with white child resistant caps, induction inner seal and desiccant, containing, 28 film coated tablets.

STORAGE INSTRUCTIONS
Store below 25°C in well closed containers protected from light.
KEEP OUT OF THE REACH OF CHILDREN.

REGISTRATION NUMBER
37/1.2/0595

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton
2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT
9 March 2005

574994/050419

68459
UNIPRINT

New addition to this site: September 2005
Source: Pharmaceutical Industry
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