Fluphenazine decanoate, Fluphenazine hydrochloride, Prolixin®, Fluphenazine Omega®

• Prolixin®
• Fluphenazine Omega®

• First-generation anti-psychotics (Typical)
• Phenothiazines

• Fluphenazine hydrochloride => orally or IM
• Fluphenazine decanoate => Slow Release => IV Injection form

1. Shizophrenia: Fluphenazine decanoate injections is a long-acting parenteral preparation

2. Maintenance treatment of non-agitated, chronic schizophrenia.

3. Not indicated for:

• Severely agitated psychotic patients, psychoneurotic patients or geriatric patients with confusion and/or agitation
• Children under 12 years of age.

Pharmacodynmics:

• Mechanism Of Action: Blocking dopamine and other catecholamine receptor sites.

Pharmacokinetics:

Absorption:

• Onset of action => 24 to 72 hours. Initial effects= > within 48 to 96 hours
• Onset of action: 24 and 72 hours after injection

Distribution:

Not fully elucidated; reportedly crosses blood-brain barrier.  Phenothiazines cross the placenta and are distributed into milk.

Metabolism:

• Highly protein-bound (greater than 90%) in plasma. Peak plasma concentration : 24-hours after intramuscular injection

Excretion:

• Serum half-life=> 7-10 days. Feces and Urine.

1. Adults Patients:

• Initial dose: 5 mg to 12.5 mg of fluphenazine decanoate (12.5 mg is usually well tolerated)/ 10 mg daily of fluphenazine hydrochlorid.
• Use fluphenazine hydrochloride dosages more than10 mg daily with caution! Safety of prolonged administration of dosages up to 40 mg daily not
• In particularly sensitive patients, a second dose of 12.5 mg or 25 mg can be given 4 to 10 days after the initial injection.
• Controlled with 25 mg or less, every two to three weeks.
• Max dose: 100mg only in some patients!
• Response to a single injection lasts usually two to three weeks; it may last for four weeks or more.
• Fluphenazine Omega 100 mg/mL may be administered in preference to Fluphenazine Omega 25 mg/mL in patients who complain of discomfort with a large injection volume or when a smaller injection volume is wanted.

2. Elderlies:

• The suggested initial test dose is 2.5 mg, gradually adjusted according to the response of the patient. Maintenance doses in the lower range (1/4 to 1/3 of those in younger adults) may be sufficient for most elderly patients.

• Fluphenazine Omega (fluphenazine decanoate injection) is usually given as an intramuscular injection gluteus Maximus and sometimes subcutaneously. Fluphenazine Omega is not for intravenous.

• CNS Depressants
• Alcohol
• Analgesics
• Tricyclic Antidepressants
• Lithium
• ACE inhibitors
• Thiazide Diuretics
• Guanethidine, clonidine and other adrenegic-blocking antihypertensive agents may be blocked. Clonidine may decrease the antipsychotic activity of phenothiazines.
• Beta Blockers: Plasma levels of both drugs may be increased.
• Metrizamide: Phenothiazines may predispose patients to metrizamide-induces seizures => Discontinue for 48 hours prior to (at least 24 hours ) myelography.
• Epinephrine and other sympathomimetics: Phenothiazines may antagonize the action of adrenaline and other sympathomimetics and may cause severe hypotension.
• Levodopa: Phenothiazines may impair the anti-Parkinson effect of L-Dopa
• Anticholinergics / Antimuscarinics: Cholinergic r muscarinergic blockade may be exaggerated when Fluphenazine is administered with anticholinergic agents, especially in older patients/ Atropine
• Anticonvulsants: Anticonvulsant action may be impaired by Fluphenazine.
• Anticoagulants: Phenothiazines may alter the effects of anticoagulants.

• Cimetidine: Cimetidine may reduce plasma concentrations (Enzyme inducer effect) of phenothiazines.
• Antacids / Antidiarrheal Agents: Concurrent administration may interfere with absorption. Administration of antacids should be spaced at least 1 hour before or 2-3 hours after fluphenazine dose.
• Amphetamine / Anorectic Agents: Concurrent administration may produce antagonistic pharmacologic effects.

More Frequent:

• Orthostatic Hypotension
• Fluctuations in blood pressure
• Extra Pyramid Side effects => Especially in Fluphenazine Omega (fluphenazine decanoate injection) = > Acute Dystonia, Akatasia, Parkinsonism, Rigidity, Tremor, tardive Dyskinasia
• Drowsiness or lethargy
• Neuroleptic malignant syndrome (NMS)

Less Frequent:

• Loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation.
• Blurred vision
• Glaucoma,
• Bladder paralysis
• Fecal impaction
• Paralytic ileus
• Tachycardia
• Nasal congestion
• Weight change,
• Peripheral edema
• Hyponatremia
• Syndrome of inappropriate antidiuretic hormone secretion
• Abnormal lactation
• Gynecomastia
• Menstrual irregularities
• False results on pregnancy tests
• Impotency in men and libido changes in women have all been known to occur in some patients on phenothiazine therapy
• Allergic Reactions
• Leukopenia,
• Agranulocytosis,
• Thrombocytopenic or non-thrombocytopenic purpura
• Eosinophilia and pancytopenia
• Cholestatic jaundice

• Known hypersensitivity to Fluphenazine and other Phenothiazines.
• Marked cerebral athero-sclerosis
• Suspected or established subcortical brain damage, +/- hypothalamic damage, since a hyperthermic reaction with temperatures above 40C may occur, sometimes not until 14-16 hours after drug administration.
• Patients receiving large doses of CNS depressants => Alcohol, barbiturates, narcotics, hypnotics, etc => possibility of potentiation.
• Comatose or severity depressed states
• Blood dyscrasias
• Liver damage
• Renal insufficiency
• Pheochromocytoma
• Severe cardiovascular disorders

• Pregnancy: Category C
• Lactation: Not recommended in nursing mother

1. Fluphenazine exerts activity at various levels of the central nervous system as well as on peripheral organ systems:

• Less potentiating effect on central nervous system depressants and anesthetics than do some of the phenothiazines and appears to be less sedating => Be cautious for side effects!

2. Fluphenazine (Phenothiazines) cross the blood-brain barrier, placenta easily => cannot be removed by dialysis

3. Severe adverse reactions requiring immediate medical attention may occur and are difficult to predict => Monitor the patient closely!

4. Caution for sedative effect of Fluphenazine! Avoid driving or using dangerous machineries need full alertness.

5. The safety and efficacy of fluphenazine decanoate in children have not been established.

6. Neuroleptic Malignant Syndrome: potentially fatal syndrome in association with antipsychotic drugs => Symptoms: Muscular rigidity, fever, hyperthermia, altered consciousness and autonomic:

• Management: Immediate discontinuation of anti-psychotic drugs, intensive monitoring + treatment of symptoms, and treatment of any associated medical problems

7. Tardive dyskinesia: repetitive involuntary movements of the tongue, face, mouth or jaw => protrusion of the tongue, puffing the cheeks, puckering of the mouth, chewing movements. The trunk and limbs are less frequently involved. Risk is greater in elderly patients, especially females:

• Relatively irreversible
• Caused by cumulative dose of the drug increases
• In case of Tardive dyskinesia: Discontinue the medication
• There is no known effective treatment for tardive dyskinesia. Start Clozapin if indicated! (Has moderated effect in relieving symptoms)

8. Cerebrovascular Events: Increase the risk of cerebrovascular events especially in elderly patients. Caution is advised!

9. Possibility of cross-sensitivity => Fluphenazine decanoate injection should be used with caution in patients with cholestatic jaundice, and dermatoses, or other allergic reactions to phenothiazine derivatives.

10. Hypotensive phenomena may develop in phenothiazine-treated patients who are undergoing surgery => Careful observation is necessary

11. Caution for Anticholinergics effects of Fluphenazine => Paralytic ileus, even resulting in death, may occur especially in the elderly.

12. Fluphenazine decanoate should be used cautiously in patients exposed to extreme heat or phosphorus insecticides.

13. Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration.

14. Test for phenylketonuria (PKU): False Positive test may occur.

15. Tests for pregnancy: False Positive test may occur.

16. Tests for urobilinogen, amylase, uroporphyrins, porphobilinogens, 5-hydroxyindolacetic acid: Urinary metabolites of phenothiazines may cause urine to darken and result in false-positive test results

17. Abrupt Withdrawl: Generally phenothiazines do not produce psychic dependence; however:

• Symptoms: gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt discontinuation of high-dose therapy => concomitant antiparkinson agents therapy can diminish the withdrawal symptoms if administrated several weeks after phenothiazine is withdrawn.

18. Use in the Elderly:

• Used with care in elderly patients (>60 years old)
• Doses 1/4 to 1/3 of those in younger adults

19. Caution in patients with: pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency => prone to hypotensive reactions with phenothiazine compounds.

20. Over-dosage:

• Symptoms: CNS depression progressing from drowsiness to coma with areflexia. Restlessness, confusion and excitement. Hypotension, tachycardia, hypothermia, pupillary constriction, restlessness, tremor, muscle twitching, spasm or rigidity, convulsions, muscular hypotonia, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, possibly with sudden
• Treatment: Emesis should not be induce, Generally is supportive therapy
• In case of acute dystonic reactions: Intramuscular benztropine (or another antiparkinsonian agent- Dopamin agonist or Anticholinergics) should be given immediately (adults: 1 to 2 mg i.m, children: 0.2 mg i.m. initially with increments if necessary).