BRAND NAMES
- International: Stemetil
 MECHANISM OF ACTION
Prochlorperazine is a propylpiperazine derivative of phenothiazine. Like other phenothiazines, it exerts an antiemetic effect through a depressant action on the chemoreceptor trigger zone.
Prochlorperazine possesses also an antipsychotic activity, with less sedative action than chlorpromazine.
As with other phenothiazines, prochlorperazine has actions on several neurotransmitter systems:
- Antidopamine action, which probably contributes to both the therapeutic effect and unwanted effects including extrapyramidal disorders and endocrine disturbances
- alpha-Adrenoreceptor antagonism, which contributes to cardiovascular side effects such as
- orthostatic hypotension and reflex tachycardia.
- Potentiation of noradrenaline by blocking its reuptake into nerve terminals.
- Weak anticholinergic action.
- Weak antihistamine action.
- Weak serotonin antagonism.
- Nausea and vomiting due to various causes including migraine
- Vertigo due to Meniere's syndrome, labyrinthitis and other causes.
- Rectal Dosage: 25 mg twice daily.
- Oral Dosage: 5 or 10 mg two or three times daily. Acute: 20 mg at once, followed, if necessary by 10 mg two hours later.
- Circulatory collapse
- Central nervous system depression (coma or drug intoxication),
- Previous history of a hypersensitivity reaction (e.g. jaundice or blood dyscrasia) to phenothiazines especially to prochlorperazine
- Bone marrow depression.
 WARNINGS AND PRECAUTIONS
Prochlorperazine should be avoided in patients with renal dysfunction, Parkinson's disease, hypothyroidism, phaeochromocytoma, myasthenia gravis and prostate hypertrophy.
The autonomic side effects of the piperazine derivatives are less troublesome than those of other phenothiazines, however care should be taken if prochlorperazine is used in the elderly or in patients undergoing surgery with spinal anaesthesia.
Piperazine derivatives are also less epileptogenic than other phenothiazines, but care should still be exercised in epileptic patients.
Prochlorperazine can cause problems due to anticholinergic effects, especially in the elderly (urinary difficulties, constipation and precipitation of acute narrow angle glaucoma), but to a lesser extent than with other phenothiazines.
It appears from a study of 5 hypocalcaemic patients with hypoparathyroidism that such patients are prone to acute dystonic reactions with prochlorperazine.
Prochlorperazine may impair mental and physical activity especially during the first few days of therapy. Patients should be warned about activities requiring alertness.
The antiemetic effects of prochlorperazine may mask signs of overdosage of toxic drugs or obscure the diagnosis of conditions such as intestinal obstruction, brain tumour.
The extrapyramidal symptoms which can occur secondary to prochlorperazine may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g. Reye's Syndrome or other encephalopathy. The use of prochlorperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye's Syndrome.
Severe hypothermia may occur during swimming in cold water or in patients receiving antipyretic therapy.
Caution should be used in patients with existing liver disease due to the extensive hepatic metabolism of prochlorperazine. A past history of jaundice resulting from phenothiazine therapy indicates a hypersensitivity reaction and there is a likelihood of cross sensitivity to other phenothiazines.
Tardive dyskinesia may develop in patients on antipsychotic drugs. The disorder consists of repetitive involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of the tongue, puffing the cheeks, puckering of the mouth, chewing movements). The trunk and limbs are less frequently involved. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome. 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 the drug increases. Less commonly, the syndrome can develop after relatively brief treatment periods at low doses. The risk seems to be greater in elderly patients, especially females. The syndrome may become clinically recognisable either during treatment, upon dosage reduction, or upon withdrawal of treatment. The dosage of antipsychotic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder, since the syndrome may be masked by a higher dose. In patients requiring long-term treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. There is no known effective treatment for tardive dyskinesia. Antiparkinsonian agents usually do not alleviate symptoms. It is suggested that antipsychotic agents be discontinued if symptoms of tardive dyskinesia appear.
Neuroleptic Malignant Syndrome
A potentially fatal syndrome called neuroleptic malignant syndrome has been reported in association with antipsychotic drugs. The syndrome is characterised by muscular rigidity, fever, hyperthermia, altered consciousness and autonomic instability (e.g. tachycardia, labile blood pressure, profuse sweating, dyspnoea). The management of neuroleptic malignant syndrome should include immediate discontinuation of anti-psychotic drugs, intensive monitoring and treatment of symptoms, and treatment of any associated medical problems.
Very rare cases of QT interval prolongation have been reported with prochlorperazine. Neuroleptic phenothiazines may potentiate QT interval prolongation which increases the risk of onset of serious ventricular arrhythmias of the torsade de pointes type, which is potentially fatal (sudden death). QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalemia, and congenital or acquired (i.e., drug induced) QT prolongation. If the clinical situation permits, medical and laboratory evaluations should be performed to rule out possible risk factors before initiating treatment with a neuroleptic agent and as deemed necessary during treatment (see ADVERSE EFFECTS).
An increased risk of cerebrovascular events has been reported in elderly patients with dementia treated with atypical antipsychotic drugs. An increase in the risk of cerebrovascular events with other antipsychotic drugs or other populations of patients cannot be excluded. Prochlorperazine should therefore be used with caution in patients with stroke risk factors.
Cases of venous thromboembolism, sometimes fatal, have been reported with antipsychotic drugs. Therefore, prochlorperazine should be used with caution in patients with risk factors for thromboembolism.
Elderly Patients with Dementia Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Although the causes of death in clinical trials with atypical antipsychotics 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.
Hyperglycaemia Hyperglycaemia or intolerance to glucose has been reported in patients treated with prochlorperazine. Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes who are started on prochlorperazine, should get appropriate glycaemic monitoring during treatment .
Caution is required with the use of the following medicines due to the risk of QT prolongation:
- Class Ia antiarrhythmic agents such as quinidine and disopyramide.
- Class III antiarrhythmic agents such as amiodarone and sotalol.
- Other medications such as bepridil, cisapride, sultopride, thioridazine, methadone, intravenous erythromycin, intravenous vincamine, halofantrine, pentamidine, sparfloxacin.
- Medicines which induce bradycardia, such as bradycardia-inducing calcium channel blockers (diltiazem, verapamil), beta-blockers, clonidine, guanfacine, digitalis.
- Medicines which can cause hypokalaemia, such as diuretics, stimulant laxatives, intravenous amphotericin B, glucocorticoids, tetracosactides.
- Other antipsychotics .
Prochlorperazine may enhance the CNS depressant effects of alcohol and other depressant drugs, and potentiate the anticholinergic effects of atropinic agents and tricyclic antidepressants.
Simultaneous administration of desferrioxamine and prochlorperazine has been observed to induce a transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours.
Procarbazine has been reported to potentiate the extrapyramidal side effects encountered with the use of prochlorperazine. Phenothiazines have been reported both to impair and increase metabolism of phenytoin, with uncertain clinical significance. Patients on levodopa should not be given phenothiazines because the two drugs are physiologically antagonistic.
Thiazide diuretics may accentuate the orthostatic hypotension that may occur with phenothiazines.
Anithypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly.
Phenothiazines can diminish the effect of oral anticoagulants. Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs. Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary.
 PREGNANCY AND LACTATION
- Pregnancy Category C (US)
- Pregnancy Category C (Australia)
 SIDE EFFECTS
More common reactions: Constipation, dry mouth, drowsiness, akathisia, parkinsonism, (with dyskinesia, tremor and rigidity), blurred vision.
Less common reactions
- Biochemical abnormalities: Elevated serum levels of bilirubin and hepatic enzymes may occur if the patient develops cholestatic jaundice
- Cardiovascular: Hypotension, peripheral oedema, cardiac arrhythmias, ECG changes, QT interval prolongation. There have been isolated reports of sudden death, with possible causes of cardiac origin, as well as cases of unexplained sudden death, in patients receiving neuroleptic phenothiazines. Cases of venous thromboembolism, including cases of pulmonary embolism, sometimes fatal, and cases of deep vein thrombosis have been reported with antipsychotic drugs.
- Dermatological: Dermatitis or contact dermatitis, maculopapular eruptions, erythema multiforme, urticaria, photosensitivity, abnormal pigmentation.
- Endocrine: Endocrine disturbances including elevated prolactin levels, hyperglycaemia, hypoglycaemia, menstrual irregularities, galactorrhoea, gynaecomastia.
- Gastrointestinal: Paralytic ileus.
- Genitourinary: Urinary retention, inhibition of ejaculation.
- Haematological: Agranulocytosis, atypical lymphocytes, thrombocytopenia, leucopenia, aplastic anaemia.
- Hepatic: Cholestatic jaundice, liver damage.
- Nervous: System Acute dystonic reactions, seizures, EEG changes, headache, insomnia, catatonia, hyperpyrexia.
- Ocular: Pigmentary rentinopathy.
- Psychiatric: Activation of psychotic symptoms.
- Respiratory: Respiratory depression.
In post-marketing surveillance cases of hyperglycaemia or intolerance to glucose have been reported with antipsychotic phenothiazines.
Hypersensitivity reactions such as angioedema and urticaria have been reported.
Serious or Life Threatening Reactions
Prochlorperazine can cause very serious acute dystonic reactions in children leading to cyanosis from laryngospasm, apnoea requiring artificial ventilation, life-threatening tetanus like syndromes, coma and even death. These reactions can occur with a single therapeutic dose. Also, long-term phenothiazine therapy has been associated with ECG changes and life threatening cardiac arrhythmias.
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