Fluphenazine Hydrochloride 5 MG Oral Tablet

WARNINGS

Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

Fluphenazine hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING ).

Tardive Dyskinesia: Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (antipsychotic) drugs.

Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome.

Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown.

Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase.

However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn.

Neuroleptic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process.

The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia.

Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.

In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought.

The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered.

However, some patients may require treatment despite the presence of the syndrome.

(For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Tardive Dyskinesia .) Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs.

Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).

The diagnostic evaluation of patients with this syndrome is complicated.

In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS).

Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and, 3) treatment of any concomitant serious medical problems for which specific treatments are available.

There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered.

The patient should be carefully monitored, since recurrences of NMS have been reported.

The use of this drug may impair the mental and physical abilities required for driving a car or operating heavy machinery.

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.

Falls Fluphenazine hydrochloride tablets, USP may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

Usage in Pregnancy: The safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.

Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.

There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates.

These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Fluphenazine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 also contains corn starch, D&C Red No.

27 (2.5 mg and 5 mg tablet), D&C Red No.

30 (5 mg tablet), D&C Yellow No.

10 (5 mg tablet), dibasic calcium phosphate dihydrate, FD&C Blue No.

1 (5 mg tablet), FD&C Blue No.

2 (2.5 mg tablet), FD&C Red No.

40 (10 mg tablet), FD&C Yellow No.

6 (10 mg tablet), hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, pregelatinized starch, purified water, and titanium dioxide.

fluphenazine-molec-structure

HOW SUPPLIED

Fluphenazine Hydrochloride Tablets, USP are available as follows: 1 mg tablets are white, round, film-coated tablets debossed “LCI” on one side and “1788” on the other side.

They are supplied in bottles of 100 (NDC 0527-1788-01) and 500 (NDC 0527-1788-05).

2.5 mg tablets are blue, round, film-coated tablets debossed “LCI” on one side and “1789” on the other side.

They are supplied in bottles of 100 (NDC 0527-1789-01) and 500 (NDC 0527-1789-05).

5 mg tablets are dark pink, round, film-coated tablets debossed “LCI” on one side and “1790” on the other side.

They are supplied in bottles of 100 (NDC 0527-1790-01) and 500 (NDC 0527-1790-05).

10 mg tablets are orange, round, film-coated tablets debossed “LCI” on one side and “1791” on the other side.

They are supplied in bottles of 100 (NDC 0527-1791-01) and 500 (NDC 0527-1791-05).

Store at 20° to 25°C (68° to 77°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: Lannett Company, Inc.

Philadelphia, PA 19154 CIB70359C Rev.

08/17

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.

PREGNANCY

Usage in Pregnancy: The safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.

Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.

There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates.

These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Fluphenazine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

BOXED WARNING

WARNING Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.

Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.

Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.

Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality.

The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

Fluphenazine hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS ).

INFORMATION FOR PATIENTS

Information for Patients: 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.

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 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.