Indications and Usage
Fluphenazine hydrochloride tablets are indicated in the management of manifestations of psychotic disorders.
Fluphenazine hydrochloride has not been shown effective in the management of behavioral complications in patients with mental retardation.
Dosage and Administration
Depending on the 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 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 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 loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage.
In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion.
Metabolic and Endocrine
Weight change, peripheral edema, abnormal lactation, gynecomastia, 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.
Allergic Reactions
Skin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and even exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions occurring in some patients should be borne in mind.
Hematologic
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 count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.
Hepatic
Liver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs. An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, has been reported in patients receiving fluphenazine hydrochloride who have had no clinical evidence of liver damage.
Others
Sudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines. Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents, or intramyocardial lesions.
Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol) may occur.
The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus-like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered electrocardiographic and electroencephalographic tracings, altered cerebrospinal fluid proteins, cerebral edema, asthma, laryngeal edema, and angioneurotic edema; with long-term use–skin pigmentation, and lenticular and corneal opacities.
To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Abuse and Dependence
In general, phenothiazines do not produce psychic dependence; however, gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt cessation of high dose therapy.
Reports suggest that these symptoms can be reduced if concomitant antiparkinsonian agents are continued for several weeks after the phenothiazine is withdrawn.
Facilities should be available for periodic checking of hepatic function, renal function and the blood picture. Renal function of patients on long-term therapy should be monitored; if BUN (blood urea nitrogen) becomes abnormal, treatment should be discontinued.
As with any phenothiazine, the physician should be alert to the possible development of “silent pneumonias” in patients under treatment with fluphenazine hydrochloride.
Description
Fluphenazine hydrochloride is a trifluoromethyl phenothiazine derivative intended for the management of schizophrenia. Chemically it is 4-[3-[2-(Trifluoromethyl) phenothiazin-10-yl]propyl]-1-piperazineethanol dihydrochloride which may be represented by the following structural formula:
Molecular Formula: C22H26 F3N3OS.2HCl
Molecular Weight: 510.44 g/mol.
Fluphenazine hydrochloride, USP is a white or nearly white, crystalline powder. It is soluble in water, and practically insoluble in acetone, methylene chloride and in chloroform.
Each tablet, for oral administration, contains 1 mg, 2.5 mg, 5 mg, or 10 mg of fluphenazine hydrochloride, USP per tablet. Inactive ingredients are: anhydrous lactose granulated, hydroxypropyl cellulose, hypromellose, magnesium stearate, polyethylene glycol, sodium lauryl sulphate and titanium dioxide.
The following coloring agents are employed:
2.5 mg – iron oxide yellow
5 mg – FD&C blue No. 1, iron oxide yellow
10 mg – iron oxide red, iron oxide yellow.
Meets USP Dissolution Test 2.
qwertyClinical Pharmacology
Fluphenazine hydrochloride has activity at all levels of the central nervous system as well as on multiple organ systems. The mechanism whereby its therapeutic action is exerted is unknown.
How Supplied / Storage and Handling
Fluphenazine Hydrochloride Tablets, USP are available containing either 1 mg, 2.5 mg, 5 mg or 10 mg of fluphenazine hydrochloride, USP.
Fluphenazine Hydrochloride Tablets USP, 1 mg are supplied as white to off-white colored, round shaped, film-coated tablets debossed with "D5" on one side and plain on other side.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 69238-1678-1
Fluphenazine Hydrochloride Tablets USP, 2.5 mg are supplied as yellow colored, round shaped, film-coated tablets debossed with "E4" on one side and plain on other side.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 69238-1679-1
Fluphenazine Hydrochloride Tablets USP, 5 mg are supplied as green colored, round shaped, film-coated tablets debossed with "E1" on one side and plain on other side.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 69238-1680-1
Fluphenazine Hydrochloride Tablets USP, 10 mg are supplied as orange to light orange colored, round shaped, film-coated tablets debossed with "E2" on one side and plain on other side.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 69238-1681-1
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Protect from light.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Manufactured by:
Amneal Pharmaceuticals Pvt. Ltd.
Oral Solid Dosage Unit
Ahmedabad 382213, INDIA
Distributed by:
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807
Rev. 11-2024-04
Patient Counseling Information
Given the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.