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

Logo FLUVOXAMINE-HEXAL™ 100 mg film coated tablets

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

FLUVOXAMINE-HEXAL™ 100 mg film coated tablets

COMPOSITION
Each 100 mg tablet contains fluvoxamine maleate (5-methoxy-4’-(trifluoromethyl)valerophenone(E)-O-(2-aminoethyl)-oxime maleate (1:1)) 100 mg

PHARMACOLOGICAL CLASSIFICATION
A.1.2 Psychoanaleptics (antidepressants)

PHARMACOLOGICAL ACTION
The mechanism of action of fluvoxamine is presumably linked to its serotonin re-uptake inhibition in brain neurons.
Pharmacokinetics:
Fluvoxamine is variably absorbed after oral administration. Bioavailability is about 50%. Fluvoxamine is extensively metabolised in the liver. The metabolites are pharmacologically inactive and are renally excreted. The elimination half-life is 15 to 20 hours. Steady state plasma levels are reached within 2 weeks of treatment with a constant dose.

INDICATIONS
• Fluvoxamine-HEXAL is indicated for the treatment of major depressive disorders and for short-term treatment of severe, disabling obsessive-compulsive disorders, where the obsessions or compulsions significantly interfere with social or occupational functioning, cause severe distress or are time-consuming.

CONTRA-INDICATIONS
• Hypersensitivity to fluvoxamine or any of the ingredients of Fluvoxamine-HEXAL
• MAO Inhibitors: Fluvoxamine-HEXAL 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 Fluvoxamine-HEXAL.
• Children under the age of 18 years
• Pregnancy and Lactation
• Safety in liver impairment, moderate to severe renal impairment and epilepsy have not been established.

WARNINGS
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 Fluvoxamine-HEXAL 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 Fluvoxamine-HEXAL, 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, Fluvoxamine-HEXAL should be tapered (See PRECAUTIONS and DOSAGE AND DIRECTIONS FOR USE).
Fluvoxamine-HEXAL should be used with caution in:
• Patients with a history of seizures –There is an increased risk of seizures. Fluvoxamine-HEXAL should be discontinued in any patient who develops a seizure. Fluvoxamine-HEXAL should be used with caution in patients with controlled epilepsy and should be avoided in those with unstable epilepsy.
• Mania or history of mania - Reactivation of hypomania or mania may occur.
• Concomitant use of Fluvoxamine-HEXAL and alcohol is not advised.

INTERACTIONS
• Tricyclic antidepressants - Increased plasma concentrations of the tricyclic antidepressant has been reported.
• Monoamine oxidase inhibitors (MAOI) - Concurrent use is contra-indicated. (See CONTRA-INDICATIONS)
• Other serotonergic medicines or medicines with serotonergic activity, including tryptophan - Increased risk of developing the serotonin syndrome.
• Lithium -The combination has resulted in seizures and the serotonin syndrome.
• Warfarin - Concurrent use may result in an increase in warfarin plasma levels. Monitoring is required.
Fluvoxamine-HEXAL is a potent inhibitor of cytochrome P450 1A2 (CYP1A2) and has also been shown to inhibit CYP3A4 and CYP2C9 and to weakly inhibit CYP2D6. Fluvoxamine-HEXAL can therefore cause an increase in the plasma levels of co-administered medicines that are metabolised by these enzymes such as: some benzodiazepines (e.g. alprazolam, bromazepam and diazepam), propranolol, theophylline, carbamazepine, clozapine, phenytoin and methadone. It is advisable to lower the dose of these medicines when Fluvoxamine-HEXAL is administered concurrently.

PREGNANCY AND LACTATION
Safety and efficacy in pregnancy and lactation have not been established. Fluvoxamine-HEXAL is excreted into the breast milk.

DOSAGE AND DIRECTIONS FOR USE
Major depressive episodes
100 mg as a single dose in the evening.
The dose may be increased as needed and tolerated in increments of 50 mg a day up to a maximum of 300 mg a day. The effective daily dose usually varies between 100 mg to 200 mg a day.
Obsessive-compulsive disorder
50 mg as a single dose in the evening for 3 to 4 days.
The dose may be increased as needed and tolerated in increments of 50 mg a day up to a maximum of 300 mg a day. The effective daily dose usually varies between 100 mg to 200 mg a day with a maximum of 300 mg a day.
If the total daily dose is greater than 150 mg then it should be given in 2 or 3 divided doses. If patients being treated for obsessive-compulsive disorder have not improved within 10 weeks of therapy, Fluvoxamine-HEXAL therapy should be reconsidered. The patient should be maintained at the lowest effective dose and the need for treatment reassessed periodically.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects:
Central nervous system:
• Commonly occurring side-effects:
  Somnolence, agitation, tremor, headache, insomnia, drowsiness, dizziness, nervousness, dyskinesia, anxiety
Gastrointestinal:
• Most frequently occurring side-effects:
  Nausea, vomiting
• Commonly occurring side-effects:
  Constipation, anorexia, dry mouth, dyspepsia, diarrhoea
Kidney/Genitourinary:
• Commonly occurring side-effects:
  Decreased libido, abnormal (delayed) ejaculation
Musculoskeletal:
• Commonly occurring side-effect:
  Asthenia
Ocular:
• Commonly occurring side-effect:
  Vision disturbances
Skin:
• Commonly occurring side-effects:
  Sweating, rash
Other:
• Commonly occurring side-effects:
  Mass gain
Special Precautions:
• Patients with mild hepatic/renal impairment should start on a low dose of Fluvoxamine-HEXAL and liver/renal function should be regularly monitored. Fluvoxamine-HEXAL may increase liver enzymes. It is recommended that treatment should be withdrawn in these patients.
• Fluvoxamine-HEXAL may cause sedation. Patients are advised not to drive or operate machinery if they are affected.
• Extrapyramidal effects and exacerbation of Parkinson's disease have been reported with the use of selective serotonin re-uptake inhibitors. Fluvoxamine-HEXAL should be avoided in such patients.
• If therapy with Fluvoxamine-HEXAL is to be discontinued, it is recommended that the dose is decreased gradually in order to prevent the possibility of a withdrawal syndrome.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
(See SIDE-EFFECTS AND SPECIAL PRECAUTIONS)
There is no specific antidote to Fluvoxamine-HEXAL.
The stomach should be emptied as soon as possible in the event of overdosage. Treatment is symptomatic and supportive.

IDENTIFICATION
Round, biconvex, white film-coated tablets with score on one side;
Diameter: 11.8 –12.2 mm; Height: 4.5 –4.9 mm

PRESENTATION
White, opaque PVC/Aluminium blisters consisting of blister strips of 10 tablets packed in cartons of 30’s

STORAGE INSTRUCTIONS
Store in a well closed container below 25°C.
Protect from moisture and light.
KEEP OUT OF THE REACH OF CHILDREN.

REGISTRATION NUMBER
37/1.2/0102

NAME AND BUSINESS ADDRESS OF APPLICANT
HEXAL Pharma (SA) (Pty) Ltd
46 Mahogany Road
Mahogany Ridge
Pinetown
3610

DATE OF PUBLICATION OF PACKAGE INSERT
July 2003

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

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