FLUPHENAZINE HYDROCHLORIDE

INDICATIONS AND USAGE Fluphenazine hydrochloride tablets, USP are indicated in the management of manifestations of psychotic disorders. Fluphenazine hydrochloride USP has not been shown effective in the management of behavioral complications in patients with mental retardation.

DOSAGE AND ADMINISTRATION Depending on severity and duration of symptoms, total daily dosage for adult psychotic patients may range initially from 2.5 mg to 10 mg and should be divided and given at 6 hour to 8 hour intervals. The smallest amount that will produce the desired results must be carefully determined for each individual, since optimal dosage levels of this potent drug vary from patient to patient. In general, the oral dose has been found to be approximately 2 to 3 times the parenteral dose of fluphenazine. Treatment is best instituted with a low initial dosage, which may be increased, if necessary, until the desired clinical effects are achieved. Therapeutic effect is often achieved with doses under 20 mg daily. Patients remaining severely disturbed or inadequately controlled may require upward titration of dosage. Daily doses up to 40 mg may be necessary; controlled clinical studies have not been performed to demonstrate safety of prolonged administration of such doses. When symptoms are controlled, dosage can generally be reduced gradually to daily maintenance doses of 1 mg to 5 mg, often given as a single daily dose. Continued treatment is needed to achieve maximum therapeutic benefits; further adjustments in dosage may be necessary during the course of therapy to meet the patient’s requirements. For psychotic patients who have been stabilized on a fixed daily dosage of orally administered fluphenazine hydrochloride dosage forms, conversion to the long-acting fluphenazine decanoate may be indicated (see package insert for fluphenazine decanoate for conversion information). For geriatric patients, the suggested starting dose is 1 mg to 2.5 mg daily, adjusted according to the response of the patient.

CONTRAINDICATIONS Phenothiazines are contraindicated in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. The presence of blood dyscrasia or liver damage precludes the use of fluphenazine hydrochloride. Fluphenazine hydrochloride tablets are contraindicated in patients who have shown hypersensitivity to fluphenazine; cross-sensitivity to phenothiazine derivatives may occur.

ADVERSE REACTIONS Central Nervous System: The side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants. Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as benztropine mesylate or intravenous caffeine and sodium benzoate injection, and by subsequent reduction in dosage. Extrapyramidal Symptoms: Dystonia: Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups. Tardive Dyskinesia: See WARNINGS. The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusion of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk and extremities. The severity of the syndrome and the degree of impairment produced vary widely. The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome. Other CNS Effects: Occurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy (see WARNINGS , Neuroleptic Malignant Syndrome ); leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS. Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered. Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams. Autonomic Nervous System: Hypertension and fluctuations in blood pressure have been reported with fluphenazine hydrochloride. Hypotension has rarely presented a problem with fluphenazine. However, patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency such as mitral insufficiency appear to be particularly prone to hypotensive reactions with phenothiazine compounds, and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of intravenous vasopressor drugs should be instituted immediately. Norepinephrine Bitartrate Injection is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives have been found to reverse its action, resulting in a further lowering of blood pressure. Autonomic reactions including nausea and lo …

Leukopenia, Neutropenia and Agranulocytosis: In clinical trial and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including fluphenazine hydrochloride. Agranulocytosis (including fatal cases) has also been reported. Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue fluphenazine hydrochloride at the first sign of a decline in WBC in the absence of other causative factors. Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm 3 ) should discontinue fluphenazine hydrochloride and have their WBC followed until recovery.

DESCRIPTION Fluphenazine hydrochloride is a trifluoromethyl phenothiazine derivative intended for the management of schizophrenia. The chemical designation is 4-[3-[2-(Trifluoromethyl) phenothiazin-10-yl] propyl]-1-piperazineethanol dihydrochloride. The structural formula is represented below: Fluphenazine Hydrochloride Tablets, USP, for oral administration, contain 1 mg, 2.5 mg, 5 mg, or 10 mg fluphenazine hydrochloride, USP per tablet. Each tablet contains hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch (maize), starlac (which contains lactose monohydrate and maize starch) and titanium dioxide. In addition, 1 mg tablet contains talc, 2.5 mg tablet contains D&C Yellow # 10 Aluminium Lake and FD& C Yellow # 6/sunset yellow Aluminum Lake, 5 mg tablet contains D&C Yellow # 10 Aluminium Lake, FD & C Blue # 1/Brilliant Blue FCF Aluminum Lake and FD& C Yellow # 6/sunset yellow Aluminum Lake, 10 mg tablet contains FD& C Yellow # 6/sunset yellow Aluminum Lake. Meets USP Dissolution Test 2. str

HOW SUPPLIED Fluphenazine Hydrochloride Tablets, USP are available as follows: 1 mg tablets are white in color, biconvex round shaped film-coated tablet debossed with ‘FL’ on one side and ‘1’ on the other side. They are supplied as follows: Bottles of 100 NDC 59651-686-01 2.5 mg tablets are yellow in color, biconvex round shaped film-coated tablet debossed with ‘FL’ on one side and ‘2.5’ on the other side. They are supplied as follows: Bottles of 100 NDC 59651-687-01 5 mg tablets are green in color, biconvex round shaped film-coated tablet debossed with ‘FL’ on one side and ‘5’ on the other side. They are supplied as follows: Bottles of 100 NDC 59651-688-01 Bottles of 500 NDC 59651-688-05 10 mg tablets are orange in color, biconvex round shaped film-coated tablet debossed with ‘FL’ on one side and ‘10’ on the other side. They are supplied as follows: Bottles of 100 NDC 59651-689-01 Bottles of 500 NDC 59651-689-05 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Avoid excessive heat. Protect from light. Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad–500 032, India Revised: 11/2024