Each ml of injection contains Fluphenazine Decanoate 25 mg.
Excipients/Inactive Ingredients: Also contains Benzyl Alcohol 1.5% v/v as preservative.
Pharmacology: Pharmacodynamics: Mode or Mechanisms of Action: Antipsychotic: Thought to improve psychotic conditions by blocking postsynaptic dopamine receptors in the brain. They also produce an alpha-adrenergic blocking effect and depress the release of hypothalamic, pituitary and hypophyseal hormones.
Pharmacokinetics: Protein Binding: very high; Biotransformation: Hepatic.
Onset of action: Gradual (up to several weeks) and variable between patients.
Time to peak effect: Approximately 4 to 7 days to achieve steady-state plasma concentration;
Peak therapeutic effects may take from 6 weeks to 6 months.
Elimination: Primarily renal, biliary.
Psychotic disorders including schizophrenia. It is not intended for use in non-psychotic disorders or for short term therapy.
Usual adult dose, initial: intramuscular or subcutaneous, 12.5 to 25 mg (0.5 ml to 1 ml), the dose being repeated or increased every one to three weeks as needed and tolerated.
Maintenance: intramuscular or subcutaneous, usually up to 50 mg every one to four weeks, as needed and tolerated. For dose more than 50 mg, increases should be made cautiously in increments of 12.5 mg. Maximum: 100mg / dose.
Symptoms: Difficulty in breathing due to spasm of the respiratory muscles and other severe extra pyramidal side effects.
Treatment is essentially symptomatic and supportive.
Do not attempt to induce emesis because a dystonic reaction of head and neck may develop that could result in aspiration of vomitus.
Early stomach lavage is often helpful.
Administering activated charcoal slurry and saline cathartic.
Maintaining respiratory functions and body temperature.
Monitoring cardiovascular function (monitor cardiac function for not less than 5 days).
Controlling cardiac arrhythmias with intravenous phenytoin, 9 to 11 mg / kg.
Digitalizing for cardiac failure.
Administering vasopressor such as norepinephrine for hypotension (do not use epinephrine, which may cause paradoxical hypotension).
Controlling convulsions with diazepam followed by phenytoin, 15 mg/kg, while monitoring ECG.
Benztropine or diphenhydramine may be administered to manage acute, parkinson-like symptoms may occur.
Severe CNS depression may require administration of a stimulant such as amphetamine, dextroamphetamine, or caffeine with sodium benzoate (picrotoxin or penthylene-tetrazol) should be avoided as they may induce convulsions.
Dialysis of phenothiazines has not been successful.
It is contra-indicated in patients with pre-existing CNS depression or coma, bone-marrow suppression, or phaeochromocytoma. It should not be used in patients with impaired liver, kidney, cardiovascular, cerebrovascular, and respiratory function and in those with closed-angle glaucoma, parkinsonism, diabetes mellitus, hypothyroidism, myasthenia gravis or prostatic hypertrophy. Because of its sedative effect, patients should not drive or operate machinery. Also contraindicated in patients with suspected or established subcortical damage. Hypersensitivity to fluphenazine: Caution should be observed in patients with a history of sensitivity to other phenothiazines, as cross sensitivity may occur.
As this preparation contains Benzyl Alcohol, its use should be avoided in children under 2 years of age. Not to be used in neonates.
Neuroleptic Malignant Syndrome: The neuroleptic malignant syndrome appears to be an idiosyncratic reaction to neuroleptic drug therapy. Clinical features usually include hyperthermia, severe extrapyramidal symptoms including muscular rigidity, autonomic dysfunction, and altered levels of consciousness. Skeletal muscle damage may occur. The incidence of the condition has been reported to vary from 0.02 to 3.2%; the mortality rate has been substantial although it has decreased over the years with improved diagnosis and management. Factors which possibly predispose to development of neuroleptic malignant syndrome include dehydration, pre-existing organic brain disease, and AIDS; infants and young males have also been reported to be particularly susceptible.
The pathogenesis of the neuroleptic malignant syndrome is still unclear. It may be the result of central dopamine-receptor blockade although peripheral mechanisms such as sustained muscular contraction and vasomotor paralysis may be partly responsible for the hyperthermia. Symptoms develop rapidly over 24 to 72 hours and may occur days to months after initiation of neuroleptic medication or increase in dosage. There appears, however, to be no consistent correlation with dosage or duration of therapy. Symptoms may last for up to 14 days after cessation of oral neuroleptics, or for up to 4 weeks after cessation of depot preparations. Deport preparation may be associated with prolonged recovery from the syndrome if it develops, and hence a higher mortality rate.
Concomitant administrations of other drugs such as lithium carbonate or antimuscarinic agents may increase the likelihood of developing the syndrome.
On diagnosis of neuroleptic malignant syndrome neuroleptics should be immediately withdrawn and symptomatic and supportive therapy indicated. Specific pharmacological therapy is less well established and is based mainly on case reports. Dantrolene was first used because of its effectiveness in malignant hyperthermia. It has a direct action on skeletal muscle and may be particularly effective for the reversal of hyperthermia of muscle origin. In contrast, dopaminergic agonists may resolve hyperthermia of central origin, restoring dopaminergic transmission and hence alleviating extrapyramidal symptoms. The presynaptic agonists amantadine and levodopa have been used with some success, but the postsynaptic agonist bromocriptine is generally preferred. Any underlying psychosis may, however, be aggravated by dopaminergic drugs. There is as yet no consensus over the choice between bromocriptine and dantrolene as first line agent for the treatment of neuroleptic malignant syndrome. In view of their differing modes of action a combination of the two may prove to be the optimum therapy. Isolated success in the management of neuroleptic malignant syndrome has also been reported with diazepam, sodium nitroprusside, pancuronium bromide, nifedipine, and electroconvulsive therapy. A suggestion that the neuroleptic malignant syndrome is a form of acute phase reaction controllable by salicylates and paracetamol, also requires confirmation. Re-introduction of neuroleptic therapy may be possible after resolution of neuroleptic malignant syndrome but is not always successful; extreme caution is advised.
The use of fluphenazine decanoate may impair the mental and physical abilities required for driving a car or operating heavy machinery. Physicians should be alert to the possibility that severe adverse reactions may occur which require immediate medical attention. Potentiation of the effects of alcohol may occur with the use of this drug. Since there is no adequate experience in children who have received this drug, safety and efficacy in children have not been established.
Care is required in epileptic patients receiving anticonvulsant therapy as it may lower the seizure threshold; and should be avoided in untreated epileptics. Elderly and debilitated patients may be more prone to its adverse effects. Administration at extremes of temperature may be hazardous since body temperature regulation is impaired by these agents. Regular eye examination are advisable for patients receiving long-term Fluphenazine therapy and avoidance of undue exposure to direct sunlight is recommended. Patients should remain supine for at least 30 minutes after parental administration, and blood pressure should be monitored.
Use in Pregnancy: Risk-benefit must be considered since jaundice and prolonged extra pyramidal effects have been reported in the neonates of mothers who receive some fluphenazine near terms. It is not recommended for use during pregnancy.
Use in Lactation: Risk-benefit must be considered since small amounts of some phenothiazine have been found in breast milk, possibly causing drowsiness and an increased risk of dystonias and tardive dyskinesia in the baby. Most phenothiazines increase prolactin secretion in the mother.
Pregnancy: Risk-benefit must be considered since jaundice and prolonged extra pyramidal effects have been reported in the neonates of mothers who receive some fluphenazine near terms. It is not recommended for use during pregnancy.
Breast-feeding: Risk-benefit must be considered since small amounts of some phenothiazine have been found in breast milk, possibly causing drowsiness and an increased risk of dystonias and tardive dyskinesia in the baby. Most phenothiazines increase prolactin secretion in the mother.
Central Nervous System:
Fluphenazine produces in general a lesser degree of central depression than the barbiturates or benzodiazepines, and tolerance to its sedative effects develops fairly quickly in most patients. It produces extrapyramidal dysfunction probably as a result of its effect on central dopaminergic transmission. Resultant disorders include acute dystonia, a parkinsonism-like syndrome, and akathisia; late effects include tardive dyskinesia and perioral tremor.
Autonomic Nervous System:
It has antimuscarinic properties and may cause adverse effects such as dry mouth, constipation, difficulty with micturition, blurred vision, and mydriasis. Tachycardia, electrocardiographic changes and rarely cardiac arrhythmias may occur and hypotension is common.
Metabolism and Endocrine System:
Weight change, peripheral edema, abnormal lactation, gynaecomastia, menstrual irregularities, false results on pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy.
Hypersensitivity reactions include urticaria, exfoliative dermatitis, erythema multiforme and contact sensitivity.
Routine blood counts are advisable during therapy since blood dyscrasias including leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia and pancytopenia have been observed with phenothiazine derivatives. Furthermore, if any soreness of the mouth, gums or throat or any symptoms of upper respiratory infection occur and confirmatory leukocyte indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.
Liver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occur.
Pain and irritation at the injection site have been reported.
The possibility should be borne in mind that phenothiazines may: Increase the central nervous system depression produced by drugs such as alcohol, hypnotics, sedatives and strong analgesics.
Antagonise the action of adrenaline and other sympathomimetic agents and reverse the blood-pressure-lowering effects of adrenergic blocking agents such as guanethidine and clonidine.
lmpair: The antiparkinsonian effects of L-dopa; The effects of anticonvulsants; Metabolism of tricyclic antidepressants; The control of diabetes.
Increase the effect of anticoagulants.
Interact with lithium.
Anti-parkinsonian drugs may enhance anticholinergic effects. Phenothiazines may enhance the cardiac-depressant effects of quinidine, the absorption of corticosteroids and digoxin and neuromuscular blocking agents.
ACE lnhibitors, hypotension-producing medications, other: concurrent use with phenothiazines may produce severe hypotension with postural syncope.
Beta-adrenergic blocking agents: concurrent use of beta-blockers, possibly including ophthalmics, with phenothiazines may result in an increased plasma concentration of each medication because of inhibition of metabolism; this may result in additive hypotensive effects, irreversible retinopathy, cardiac arrhythmias, and tardive dyskinesia.
Anticholinergics or other medications with anticholinergic action: concurrent use with phenothiazines may intensify anticholinergic side effects, especially confusion, hallucinations, and nightmares, because of the phenothiazines' secondary anticholinergic effects; medications with anticholinergic effects may potentiate the hyperpyretic effect of phenothiazines, especially when environmental temperatures are high, by preventing sweating as a cooling mechanism; this effect could lead to heat stroke; also, patients should be advised to report occurrence of gastrointestinal problems since paralytic ileus may occur with concurrent therapy.
Antacids, aluminum- or magnesium-containing or Antidiarrheals, adsorbent: Concurrent use of these medications with phenothiazines may inhibit the absorption of orally administered phenothiazines; simultaneous use should be avoided.
Amphetamines: Stimulant effects may be decreased when amphetamines are used concurrently with phenothiazines since phenothiazines produce alpha-adrenergic blockade; also, the antipsychotic effectiveness of phenothiazines may be reduced.
The injection may be given IM or SC. A dry syringe or needle of at least 21G should be used. Use of wet needle/syringe may cause the solution to become cloudy.
Store below 30°C. Protect from light and freezing.
Shelf-Life: 3 years.
N05AB02 - fluphenazine ; Belongs to the class of phenothiazine antipsychotics with piperazine structure.
Inj 25 mg/mL (a yellowish, clear, viscous, oily sterile solution in amp) x 1 mL x 5's.