Fluphenazine Decanoate Injection B.P.

F

1. Name Of The Medicinal Product

Fluphenazine Decanoate Injection B.P.

2. Qualitative And Quantitative Composition

Fluphenazine Decanoate Injection B.P. 50 mg in 0.5 ml

per unit doseper ml

Fluphenazine Decanoate 50 mg 100 mg

Fluphenazine Decanoate Injection B.P. 100 mg in 1 ml

per unit doseper ml

Fluphenazine Decanoate 100 mg 100 mg

3. Pharmaceutical Form

Oily injection solution.

4. Clinical Particulars 4.1 Therapeutic Indications

The management of schizophrenic patients and those with paranoid psychoses. Fluphenazine is also particularly useful in the managment of patients who are unreliable at taking oral medication and of those who do not absorb their oral phenothiazines in adequate amounts.

4.2 Posology And Method Of Administration

ADULTS:

Suitable where a reduced injection volume is desirable and therefore most suitable for patients on high dose maintenance therapy.

1. NOT PREVIOUSLY TREATED:

Initially 0.5 ml by deep intramuscular injection into the gluteal region given at 2-5 week intervals, depending on patient response. Most patients are maintained on dose range of 0.5 - 4 ml.

If doses in excess of 100 mg are needed, increments of 12.5 (0.125 ml) should be implemented.

2. PREVIOUSLY TREATED:

i) Oral: Dosage must be titrated as for new patients.

ii) Depot: Restart on same dose as previously, possibly required at shorter dose intervals in the early weeks of treatment.

CHILDREN:

Not recommended for patients under 12 years of age.

ELDERLY:

Reduced maintenance doses may be needed in patients showing extrapyramidal symptoms, following initial dosing as above.

Initial dose - 0.25 ml (25 mg).

Patients not previously treated to a depot fluphenazine formulation, and over sixty years of age, should receive a lower initial dose.

N.B. Dose should not be increased without close supervision. Patients will respond in varying degrees to the drug. The response may be delayed. Symptoms may not recur for several weeks after discontinuation of treatment.

4.3 Contraindications

Comatose patients, hepatic damage, jaundice, renal insufficiency, marked cerebral atherosclerosis, phaeochromocytoma, cardiac insufficiency and severely depressed states.

4.4 Special Warnings And Precautions For Use

Sudden, unexplained death has been reported in patients on phenothiazines, revealing at autopsy an acute, fulminating pneumonia with aspiration.

The drug should be administered under the direction of an experienced clinician. Renal and hepatic function should be monitored periodically during treatment.

Use with caution in patients with cardiovascular disease, known hypersensitivity to other phenothiazines, convulsive disorders. Patients undergoing surgery may be at risk to hypotension. Body temperature controls may become altered particularly at high doses. Atropinic effects may be potentiated.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

CNS DEPRESSANTS: (alcohol, barbiturates, hypnotics, sedatives, strong analgesics all may show increased depressant effects).

May impair: - Antiparkinson effect of levodopa

- effect of anticonvulsants

- metabolism of tricyclic antidepressants

- control of diabetes

- action of adrenalin and other sympathomimetics.

May interact with lithium.

May enhance: - cardiac depressant effect of quinidine

- absorption of corticosteroids

- absorption of digoxin

- absorption of neuromuscular blocking agents

- effect of anticoagulants.

4.6 Pregnancy And Lactation

Use in Pregnancy:

The safety of this drug during pregnancy has not been established. The possible hazards should be weighed against the benefits when administering the drug to pregnant patients.

Use in Lactation:

Fluphenazine Decanoate may possibly be excreted in breast milk, as other phenothiazines are. Breast feeding is therefore not recommended during treatment.

4.7 Effects On Ability To Drive And Use Machines

Use may impair mental and physical abilities to drive or operate heavy machinery.

4.8 Undesirable Effects

ADVERSE REACTIONS:

Acute dystonic reactions occur frequently, usually within 24-48 hours. In susceptible individuals they may occur after small doses. Reaction may include ocuogyric crises and opisthotonos. Rapidly relived by intravenous antiparkinsonian agent such as procyclidine.

Parkinsonian like state may occur particularly between second and fifth day after injection. Can be reduced by using smaller doses more frequently or concomitant use of benzhexol, benztropine or procyclidine. Antiparkinson drugs should not be prescribed routinely because of the risk of aggravating antiucholinergic side effects or precipitating toxic confusion states or impairing therapeutic response. Careful monitoring will minimise use of antiparkinsonian drugs.

Tardive dyskinesia may appear on long term therapy or after drug has been discontinued. Elderly female patients on high doses seem to be most at risk. Symptoms are persistent and in some cases irreversible. The syndrome is characterised by rhythmical, involuntary movement of the tongue, face, mouth or jaw. Sometimes accompanied by involuntary movements of limbs. There is no known effective treatment. Antiparkinson drugs do not usually alleviate symptoms. It is suggested that antipsychotic agents be discontinued if such symptoms occur. It is reported that fine vermicular movements of the tongue may be an early sign of the syndrome, and cessation of treatment at this stage may prevent development of the full syndrome.

Drowsiness, lethargy, blurred vision, dryness of the mouth, constipation, urinary hesitancy or incontinence, mild hypotension, impairment of judgement and mental skills, epileptic form attacks are all occasionally seen.

Blood dyscrasia are rarely reported. Blood counts should be performed if persistent infection develops. Transient leucopenia and thrombocytopenia have been reported. Antinuclear antibodies and SLE are very rarely reported.

Jaundice and transient abnormalities of liver function are rarely reported.

Long term high dose phenothiazine use may result occasionally in abnormal skin pigmentation and lens opacity.

Skin rashes have been rarely reported.

Elderly patients may be more susceptible to sedative or hypertensive effects.

Cardiovascular effects of phenothiazines are dose related. ECG changes, including prolongation of QT interval and T wave changes have been reported commonly in patients treated with moderate to high dose therapy. The effects are reversible on reducing the dose. Rarely the effects may precipitate arrhythmias including ventricular tachycardia and fibrillation. These effects may also occur on overdosage.

Sudden, unexplained death has also been reported in hospitalised psychotic patients receiving phenothiazines.

Phenothiazines may impair body temperature regulation. Severe hypothermia or hyperpyrexia have been reported in association with moderate or high doses. Elderly patients may be particularly susceptible to hypothermia. Hyperpyrexia may be increased by hot or humid weather or by antiparkinsonian drugs which impair sweating.

Neuroleptic malignant syndrome (NMS) is rarely reported. The syndrome is characterised by hyperthermia, together with some or all of the following: muscular rigidity, autonomic instability, akinesia, altered consciousness, sometimes progressing to coma or stupor. Leucocytoses, elevated CPK, liver function abnormalities and acute renal failure. Neuroleptic drug therapy should be discontinued immediately. The syndrome is potentially fatal, and must be treated with vigorous symptomatic treatment.

Hormonal effects of phenothiazines include hyperprolactinaemia, which may cause galactorrhoea, gynacomastia and oligo or ammenorrhoea. Sexual function may be impaired.

4.9 Overdose

Supportive measures and symptomatic treatment. Extrapyramidal symptoms can be controlled with procyclidine or benztropine. Hypotension can be treated with vasoconstrictors and fluid replacement - but avoid using adrenalin.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Fluphenazine is a piperazine phenothiazine used widely in the treatment of schizophrenia. The action is thought to be through dopamine receptor blockade in the mesolimbic system. Fluphenazine has weak anticholinergic effects, sedative effects, antiadrenal effects and neuroendocrine effects. Side effects from extrapyramidal symptoms are common.

In an oil vehicle as the decanoate, fluphenazine ester slowly diffuses into the circulation. After hydrolysis, the drug passes the blood brain barrier as free drug.

5.2 Pharmacokinetic Properties

Esterification of fluphenazine slows the rate of release from fat and thus prolongs the duration of action. Further delay is achieved by formulation in an oily solvent. Onset of action is within 48-72 hours, duration may be 1-6 weeks with an average of 2 weeks.

Distribution and metabolism are not fully described. Plasma half life has been shown to be 6-9 days following intramuscular administration of the decanoate.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Fluphenazine Decanoate Injection B.P. 50 mg in 0.5 ml

per unit doseper ml

Sesame Oil BP to 0.5 ml to 1 ml

Fluphenazine Decanoate Injection B.P. 100 mg in 1 ml

per unit doseper ml

Sesame Oil to 1 ml to 1 ml

6.2 Incompatibilities

Not applicable. An oily injection for intramuscular use only.

6.3 Shelf Life

The medicinal product as packaged for sale has an 24 month shelf life.

6.4 Special Precautions For Storage

Store between 15°C - 25°C. Protect from light.

6.5 Nature And Contents Of Container

50 mg in 0.5 ml - Type I clear glass ampoules of 0.5 ml x 5 pack.

100 mg in 1 ml - Type I clear glass ampoules of 1 ml x 5 pack.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Faulding Pharmaceuticals Plc

Queensway

Royal Leamington Spa

Warwickshire

CV31 3RW

8. Marketing Authorisation Number(S)

PL 04515/0056

9. Date Of First Authorisation/Renewal Of The Authorisation

14th March 2002

10. Date Of Revision Of The Text

14th March 2002

11. Legal Category

POM

Fluphenazine Decanoate Injection B.P.

.