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

Logo PROHEXAL

FLAP 4

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

PROHEXAL

ProHexal™ 20 (capsules)
ProHexal™ 20T (film coated dispersible tablets)
ProHexal™ 40T (film coated dispersible tablets)

COMPOSITION
ProHexal TM 20 - each capsule contains 20 mg
Fluoxetine as the hydrochloride.
ProHexal TM 20T - each tablet contains 20 mg Fluoxetine as the hydrochloride
ProHexal TM 40T - each tablet contains 40 mg Fluoxetine as the hydrochloride

PHARMACOLOGICAL CLASSIFICATION
A 1.2 Psychoanaleptics (antidepressants)

PHARMACOLOGICAL ACTION
Fluoxetine acts as an antidepressant by inhibiting the neuronal uptake of serotonin in the central nervous system. Fluoxetine is classed as a Selective Serotonin Reuptake Inhibitor (SSRI).
Pharmacokinetics: Because of the long elimination half-lives of the parent drug (2-3 days) and its major active metabolite, norfluoxetine (7 to 9 days), changes in dose will not be fully reflected in plasma for several weeks (approximately 4 half-lives). This should be taken into consideration during dose titration or cessation of treatment.

INDICATIONS
Major depression, i.e. a single episode and recurrent depression, with associated anxiety.
Bulimia nervosa: Fluoxtine has been shown to significantly decrease binge-eating and purging activity.
Obsessive compulsive disorder: Fluoxetine is indicated for the treatment of obsessive-compulsive disorder. The obsessions or compulsions must be experienced as intrusive, markedly distressing, time consuming or interfere significantly with the person’s social or occupational functioning.

CONTRA-INDICATIONS
- Hypersensitivity to fluoxetine or any of the ingredients of this formulation.
- Severe renal failure. (GFR <10 mL/min).
- Monoamine oxidase inhibitors.(MAOI’s). Fluoxetine should not be used in combination with MAOI’s or within 14 days of discontinuing therapy with a MAOI.
The concomitant use of these 2 medicines has led to serious and sometimes fatal reactions e.g. hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs and mental status changes that include extreme agitation progressing to delirium and coma.
Some cases can present with features resembling neuroleptic malignant syndrome.
At least 5 weeks should be allowed after stopping fluoxetine hydrochloride therapy, before initiating MAOI therapy.
Porphyria - there is insufficient data available.
Pregnancy - safety has not been established.
Paediatrics - safety of use in children has not been established.
Nursing mothers - safety of use during breast-feeding has not been established.

WARNINGS
Fluoxetine should be discontinued should a rash or allergic phenomena occur.

DOSAGE AND DIRECTIONS FOR USE
Changes in the dose will not be reflected in plasma for several weeks.
ProHexal may be administered with or without food.
Note that ProHexal tablets are dispersible and may be taken dissolved in a small quantity of water, or may be swallowed whole, with water.
Major depressive episodes - 20 mg per day is recommended, to be dosed in the morning.
Doses of above 80 mg per day are not recommended.
Bulimia nervosa - 60 mg per day is recommended.
Obsessive compulsive disorder - 20 to 60 mg per day is recommended
Dose should be individualised, within the recommended dosage.
Fluoxetine should be administered with caution in the elderly, particularly if they have systemic illness or are receiving multiple medications for concomitant diseases.
Patients should be monitored during the first two weeks of therapy, since a clinical response is not always evident during this time period.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
The following have been observed
Asthenia, fever, palpitations, vision disturbances.
Gastro-intestinal tract
Nausea, diarrhoea, dry mouth, appetite loss, dyspepsia, vomiting.
Nervous system
Headache, nervousness, insomnia, drowsiness, anxiety, tremor, dizziness, fatigue, decreased libido, seizures, hypomania and mania, abnormal dreams and agitation.
Respiratory system
Dyspnoea, pulmonary inflammatory processes of varying histopathology and/or fibrosis.
Skin and appendages
Rash or urticaria may develop - see Warnings. Systemic events related to vasculitis, have developed, especially in patients with a rash, less frequently death has occurred. Serum sickness, sweating and anaphalactoid reactions have occurred.
Urogenital system
Sexual dysfunction (delayed or inhibited orgasm)
Endocrine system
Hypothyroidism. Hyponatraemia, which could possibly be due to inappropriate anti-diuretic hormone secretion.
Elevated serum transaminase has been reported.
Aplastic anaemia, cerebral vascular accident, confusion, dyskinesia, ecchymoses, eosinophilia, pneumonia, gastro-intestinal haemorrhage, hyperprolactinaemia, movement disorders, neuroleptic malignant syndrome like episodes, pancreatitis, suicidal thoughts, pancytopaenia, immune related haemolytic anaemia, thrombocytopaenia, thrombocytopaenic purpura, vaginal bleeding following withdrawal.
Precautions
Fluoxetine should be administered with extreme caution to patients suffering from epilepsy, or with a history of such disorders, due to its epileptogenic effect.
Fluoxetine should be discontinued in any patient who develops seizures
Since fluoxetine undergoes hepatic metabolism and renal excretion it should be used with caution in patients suffering from hepatic or renal failure.
A lower dose or alternate day dosing is recommended in patients with significant hepatic dysfunction or mild to moderate renal failure.(GFR 10 - 50 mL/min).
Use with extreme caution in patients suffering from acute cardiac disease.
Fluoxetine may cause undesirable loss of mass.
Fluoxetine may alter blood glucose control in diabetic patients e.g. hypoglycaemia has occurred during therapy, with hyperglycaemia occurring following discontinuation of therapy. Adjust insulin or oral antidiabetic agent dosing as necessary.
Patients should be warned that their ability to perform tasks e.g. driving a motor vehicle etc. may be impaired.
Interactions
Fluoxetine should not be given concomitantly with monamine oxidase inhibitors (MAOI’s) - severe reactions including hypertension, convulsions and hyperpyrexia have been reported. See Contra-indications.
Central nervous system (CNS) depressants - e.g. alcohol and barbiturates may lead to additive sedation and depression.
Tricyclic antidepressants - blood levels may be elevated significantly thus leading to the possibility of toxicity.
Enhancement of serotonergic effects may occur if fluoxetine is given with tryptophan or lithium. There have also been reports of fluoxetine causing both increased and decreased concentrations of lithium. Lithium levels should be monitored. The half-life of concurrently administered diazepam may be prolonged. Fluoxetine is bound to plasma proteins and concurrent administration may alter plasma concentrations of other plasma protein bound medicines (eg. Warfarin, digitoxin), or conversely, fluoxetine binding may be changed by other agents.
There have been greater than 2-fold increases of previously stable plasma levels of other anti-depressants when fluoxetine has been administered in combination with these agents.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Treatment is symptomatic and supportive.
Since fluoxetine has a large volume of distribution, forced diuresis, dialysis, haemoperfusion and exchange transfusion are of little benefit.

IDENTIFICATION
ProHexal™ 20
- Hard shell size 3 capsule , cap and body is opaque green, filled with a homogenous white powder.
ProHexal™ 20T - White, round film coated tablet, one side with a snap-tab score and the other side convex. Slight smell of fruit and peppermint.
ProHexal 40T - White, round film coated tablet, with a facet divisible into quarters. Slight smell of fruit and peppermint.

PRESENTATION
ProHexal™ 20
- capsules are supplied in white opaque PP securitainers, containing 30 or 100 capsules each.
ProHexal™ 20T –tablets are supplied in aluminium/aluminium blisters.
10 blisters per blister card.
3 blister cards per carton (30’s).
ProHexal™ 40T - tablets are supplied in aluminium/aluminium blisters.
10 blisters per blister card.
3 blister cards per carton (30’s).

STORAGE CONDITIONS
Store below 25°C in the original container. Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS
ProHexal™ 20
(capsules) - 31/1.2/0638
ProHexal™ 20T (film coated dispersible tablets)- 32/1.2/0103
ProHexal™ 40T (film coated dispersible tablets) - 32/1.2/0104

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Hexal Pharma (SA)(PTY)LTD
46 Mahogany Road
Mahogany Ridge
Pinetown
3610

DATE OF PUBLICATION OF THIS PACKAGE INSERT
January 2001

        FLAP4

Updated on this site: May 2005
Source: Pharmaceutical Industry

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