"Feb. 22, 2011 -- The FDA has issued a safety announcement notifying health care professionals that it has updated the pregnancy section of drug labels for the entire class of antipsychotic medications.
Antipsychotic drugs are used to "...
Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with 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 antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic 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 antipsychotic 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cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic 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, antipsychotics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that 1) is known to respond to antipsychotic 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 antipsychotics, 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 and ADVERSE REACTIONS.
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.
An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) has occurred in a few patients treated with lithium plus an antipsychotic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of lithium and antipsychotics, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS).
Patients who have demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) with a phenothiazine should not be re-exposed to any phenothiazine, including Stelazine (trifluoperazine HCl), unless in the judgment of the physician the potential benefits of treatment outweigh the possible hazard.
Stelazine (trifluoperazine) Concentrate contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.
Stelazine (trifluoperazine HCl) may impair mental and/or physical abilities, especially during the first few days of therapy. Therefore, caution patients about activities requiring alertness (e.g., operating vehicles or machinery).
If agents such as sedatives, narcotics, anesthetics, tranquilizers or alcohol are used either simultaneously or successively with the drug, the possibility of an undesirable additive depressant effect should be considered.
Usage in Pregnancy
Safety for the use of Stelazine (trifluoperazine) during pregnancy has not been established. Therefore, it is not recommended that the drug be given to pregnant patients except when, in the judgment of the physician, it is essential. The potential benefits should clearly outweigh possible hazards. There are reported instances of prolonged jaundice, extrapyramidal signs, hyperreflexia or hyporeflexia in newborn infants whose mothers received phenothiazines.
Reproductive studies in rats given over 600 times the human dose showed an increased incidence of malformations above controls and reduced litter size and weight linked to maternal toxicity. These effects were not observed at half this dosage. No adverse effect on fetal development was observed in rabbits given 700 times the human dose nor in monkeys given 25 times the human dose.
There is evidence that phenothiazines are excreted in the breast milk of nursing mothers. Because of the potential for serious adverse reactions in nursing infants from trifluoperazine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Given the likelihood that some patients exposed chronically to antipsychotics 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.
Thrombocytopenia and anemia have been reported in patients receiving the drug. Agranulocytosis and pancytopenia have also been reported—warn patients to report the sudden appearance of sore throat or other signs of infection. If white blood cell and differential counts indicate cellular depression, stop treatment and start antibiotic and other suitable therapy.
Jaundice of the cholestatic type of hepatitis or liver damage has been reported. If fever with grippe-like symptoms occurs, appropriate liver studies should be conducted. If tests indicate an abnormality, stop treatment.
One result of therapy may be an increase in mental and physical activity. For example, a few patients with angina pectoris have complained of increased pain while taking the drug. Therefore, angina patients should be observed carefully and, if an unfavorable response is noted, the drug should be withdrawn.
Because hypotension has occurred, large doses and parenteral administration should be avoided in patients with impaired cardiovascular systems. To minimize the occurrence of hypotension after injection, keep patient lying down and observe for at least V2 hour. If hypotension occurs from parenteral or oral dosing, place patient in head-low position with legs raised. If a vasoconstrictor is required, Levophed® * and Neo-Synephrine®† are suitable. Other pressor agents, including epinephrine, should not be used as they may cause a paradoxical further lowering of blood pressure.
An antiemetic action of Stelazine (trifluoperazine HCl) may mask the signs and symptoms of toxicity or overdosage of other drugs and may obscure the diagnosis and treatment of other conditions such as intestinal obstruction, brain tumor and Reye's syndrome.
With prolonged administration at high dosages, the possibility of cumulative effects, with sudden onset of severe central nervous system or vasomotor symptoms, should be kept in mind.
Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately 1/3 of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescribing 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 antipsychotic drugs. Neither clinical 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.
Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents treated with certain antipsychotics.
Because phenothiazines may interfere with thermoregulatory mechanisms, use with caution in persons who will be exposed to extreme heat.
As with all drugs which exert an anticholinergic effect, and/or cause mydriasis, trifluoperazine should be used with caution in patients with glaucoma.
Phenothiazines may diminish the effect of oral anticoagulants.
Phenothiazines can produce alpha-adrenergic blockade.
Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.
Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concurrently.
Thiazide diuretics may accentuate the orthostatic hypotension that may occur with phenothiazines.
Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Potentiation of anticonvulsant effects does not occur. However, it has been reported that phenothiazines may interfere with the metabolism of Dilantin®* and thus precipitate Dilantin toxicity.
Drugs which lower the seizure threshold, including phenothiazine derivatives, should not be used with Amipaque®§. As with other phenothiazine derivatives, Stelazine (trifluoperazine) should be discontinued at least 48 hours before myelography, should not be resumed for at least 24 hours postprocedure and should not be used for the control of nausea and vomiting occurring either prior to myelography or postprocedure with Amipaque.
The presence of phenothiazines may produce false-positive phenylketonuria (PKU) test results.
To lessen the likelihood of adverse reactions related to cumulative drug effect, patients with a history of long-term therapy with Stelazine (trifluoperazine HCl) and/or other antipsychotics should be evaluated periodically to decide whether the maintenance dosage could be lowered or drug therapy discontinued.
Last reviewed on RxList: 4/10/2009
This monograph has been modified to include the generic and brand name in many instances.
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