Fluphenazine Injection

• Tell all of your health care providers that you take fluphenazine injection. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• If you will be near phosphorus insecticides, talk with your doctor.
• Low white blood cell counts have happened with drugs like this one. This may lead to a higher chance of getting an infection. Deadly infections have rarely happened. Tell your doctor if you have ever had a low white blood cell count. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
• This medicine may raise the chance of very bad and sometimes deadly infections. Talk with the doctor.
• Do not stop taking fluphenazine injection all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this medicine, you will want to slowly stop it as ordered by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may cause the results of some pregnancy tests to be wrong. Talk with the doctor.
• If you are 65 or older, use fluphenazine injection with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Very bad dizziness or passing out.
• Very bad headache.
• Chest pain or pressure.
• Shortness of breath.
• Trouble swallowing or speaking.
• Twitching.
• Big change in balance.
• Drooling.
• Seizures.
• Swelling in the feet or hands.
• Change in eyesight.
• Not able to control eye movements.
• Any unexplained bruising or bleeding.
• Not able to pass urine or change in how much urine is passed.
• Feeling very tired or weak.
• Breast enlargement.
• Change in sex ability.
• For women, no period.
• Very loose stools (diarrhea).
• Very bad belly pain.
• A very bad and sometimes deadly health problem called neuroleptic malignant syndrome (NMS) may happen. Call your doctor right away if you have any fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, heartbeat that does not feel normal, or are sweating a lot.
• Some people who take this medicine may get a very bad muscle problem called tardive dyskinesia. This muscle problem may not go away even if fluphenazine injection is stopped. Sometimes, signs may lessen or go away over time after this medicine is stopped. The risk of tardive dyskinesia may be greater in people with diabetes and in older adults, especially older women. The risk is also greater the longer you take fluphenazine injection or with higher doses. Muscle problems may also occur after short-term use with low doses. Call your doctor right away if you have trouble controlling body movements or if you have muscle problems with your tongue, face, mouth, or jaw like tongue sticking out, puffing cheeks, mouth puckering, or chewing.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about fluphenazine injection, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about fluphenazine injection. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using fluphenazine injection.

Review Date: October 4, 2017

General

Because of the possibility of cross-sensitivity, fluphenazine decanoate should be used cautiously in patients who have developed cholestatic jaundice, dermatoses, or other allergic reactions to phenothiazine derivatives.

Psychotic patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena.  Moreover, it should be remembered that reduced amounts of anesthetics or CNS depressants may be necessary.

The effects of atropine may be potentiated in some patients receiving fluphenazine because of added anticholinergic effects.

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

The preparation should be used with caution in patients with a history of convulsive disorders, since grand mal convulsions have been known to occur.

Use with caution in patients with special medical disorders such as mitral insufficiency or other cardiovascular disease and pheochromocytoma.

The possibility of liver damage, pigmentary retinopathy, lenticular and corneal deposits, and development of irreversible dyskinesia should be remembered when patients are on prolonged therapy.

Outside state hospitals or other psychiatric institutions, fluphenazine decanoate should be administered under the direction of a physician experienced in the clinical use of psychotropic drugs, particularly phenothiazine derivatives.  Furthermore, 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 blood urea nitrogen (BUN) 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 decanoate.

Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer.  Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients.  An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs.  Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.

Pregnancy

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

Leukopenia, Neutropenia and Agranulocytosis

In clinical trial and postmarketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents.

Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia.  Patients with a pre-existing 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 Decanoate Injection, USP 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 <1,000/mm3) should discontinue Fluphenazine Decanoate Injection, USP and have their WBC followed until recovery.

Information for Patients

Given the likelihood that a substantial proportion of 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.

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.  Muscle rigidity sometimes accompanied by hyperthermia has been reported following use of fluphenazine decanoate.  Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below).  The frequency of such reactions is related in part to chemical structure: one can expect a higher incidence with fluphenazine decanoate than with less potent piperazine derivatives or with straight-chain phenothiazines such as chlorpromazine.  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.

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 the 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.

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 the enanthate ester of fluphenazine (a closely related compound) 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 CNS 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.

Injections of fluphenazine decanoate are extremely well tolerated, local tissue reactions occurring only rarely.

Consult your pharmacist.