Prochlorperazine, Prochlorperazine edisylate, Prochlorperazine mesylate, Compzine®, Stemzine® , Buccastem®, Stemetil®, Phenotil®

• Compzine®
• Stemzine®
• Buccastem®
• Stemetil®
• Phenotil®

• First-generation anti-psychotics (Typical)
• Phenothiazines

• Tablets: 5 mg, 10 mg
• Suppository: 25 mg
• Injectable Solution: 5mg/mL

• Migraine
• Vertigo due to Meniere’s syndrome
• Labyrinthitis
• Others

Pharmacodynamics:

Mechanism of action:

• Anti-dopamine action
• Adrenoreceptor antagonism => 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.
• Has an effect on temperature control and blocks conditioned avoidance responses.

Pharmacokinetics:

•  Absorption: GI tract (Orally –Po)
• Distribution: widely distributed to tissues including the brain, fat, kidney, heart and skin and is stored in reticuloendothelial tissues.
• Metabolism: Enterohepatic circulation
• Excretion: Very small amount (0.1%) of prochlorperazine and its metabolites (N-desmethyl Prochlorperazine => active metabolite) are excreted in the first 24 hours in the urine and the drug may continue to be excreted in the urine for up to 3 weeks after cessation of long term therapy. half-life is approximately 24 hours.

1. Nausea and Vomiting (Adults):

• Acute attack: 20 mg at once, followed, if necessary by 10 mg two hours later Maintenance dose: 5 or 10 mg two or three times daily.

• Attention: If oral administration is not practical, a deep intramuscular injection of 1 mL (12.5 mg) or a 25 mg suppository should be used, followed if required, by normal oral medication six hours later.
• Do not use a darkened solution for injection (more than pale yellow).
• Adjust the dose to the lowest clinically effective possible.

2. Nausea and Vomiting (Children):

• Preferebly do not use prochlorperazine for children. However if it is considered unavoidable => the dosage is 250 micrograms/kg
• Bodyweight two or three times a day.
• After a cumulative dosage of 500 micrograms/kg=> Watch out for dystonic reactions has been associated with Prochlorperazine => It should therefore be used cautiously in children.
• Not recommended for children weighing less than 10 kg and should not be given to children by the rectal or intramuscular route.
• When treating children, it is recommended that the 5 mg tablets be used.

3. Vertigo and Meniere’s Disease:

Adults:

• Oral: 5 to 10 mg three or four times daily. Dosage may be reduced gradually after several weeks to a maintenance dosage of 5 to 10 mg daily.

Children:

• Oral: Dose, same as for nausea and vomiting.

Geriatric:

• Dosages in the lower range are sufficient for most elderly patients. Dosage should be increased more gradually in elderly patients.

4. Impaired Liver Function:

 Prochlorperazine is extensively metabolised by the liver. Thus, dosage reduction may be necessary.

• Class Ia antiarrhythmics: Quinidine and Disopyramide
• Class III antiarrhythmics: Amiodarone and Sotalol
• Bepridil
• Cisapride
• Sultopride
• Thioridazine
• Methadone
• Intravenous erythromycin
• Intravenous vincamine
• Halofantrine
• Pentamidine
• Sparfloxacin
• Medicines which induce bradycardia: 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.
• Alcohol (Ethanol)
• Desferrioxamine

More frequent:

• Gastrointestinal
• Constipation
• Dry mouth
• Nervous System
• Drowsiness
• Akathisia
• Parkinsonism (dyskinesia, tremor and rigidity)
• Blurred vision

Less frequent:

• Biochemical abnormalities: Elevated serum levels of bilirubin and hepatic enzymes may occur if the patient develops cholestatic jaundice.
• Hypotension
• Peripheral oedema
• Cardiac arrhythmias
• QT interval prolongation
• Sudden cardiac death
• Venous thromboembolism
• Pulmonary embolism
• Dermatitis or contact dermatitis
• Maculopapular eruptions
• Erythema multiforme
• Urticarial
• Photosensitivity
• Abnormal pigmentation
• Elevated prolactin levels
• hyperglycaemia
• Hypoglycemia
• Menstrual irregularities
• Galactorrhoea
• Gynaecomastia
• Paralytic ileus
• Agranulocytosis
• Atypical lymphocytes
• Thrombocytopenia
• Leucopenia
• Aplastic anaemia
• Acute dystonic reactions
• Seizures
• EEG changes
• Headache
• Insomnia
• Catatonia
• Hyperpyrexia
• Pigmentary rentinopathy
• Activation of psychotic symptoms
• Respiratory depression

• Circulatory collapse
• Central nervous system depression (coma or drug intoxication)
• Previous history of a hypersensitivity reaction
• Bone marrow depression
• Renal dysfunction
• Parkinson’s disease
• Hypothyroidism
• Pheochromocytoma
• Myasthenia gravis
• Prostate hypertrophy

• Pregnancy: Category C
• Lactation: Not recommended in nursing mothers

1. Should be avoided in patients with renal dysfunction, Parkinson’s disease, hypothyroidism, phaeochromocytoma, myasthenia gravis and prostate hypertrophy.

2. Patients with hypotension: 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.

3. Epileptic patients: Piperazine derivatives are also less epileptogenic than other phenothiazines, but care should still be exercised in epileptic patients.

• Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary

4. Anticholinergic side- effects: 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.

5. Hypocalcaemia: Patients with hypoparathyroidism => prone to acute dystonic reactions with prochlorperazine.

6. Sedative effect: Prochlorperazine may impair mental and physical activity especially during the first few days of therapy:

• Avoid driving while taking prochlorperazine.
• Avoid working with dangerous machineries need concentration and full alertness.

7. Antiemetic effects: The antiemetic effects of prochlorperazine may mask signs of over dosage of toxic drugs or obscure the diagnosis of conditions such as intestinal obstruction, brain tumour. Caution along with close follow ups is advised!

8. Reye’s Syndrome and hepatic-encephalopatic patients: The use of prochlorperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye’s Syndrome and hepatic-encephalopathy.

9. Hypothermia: Severe hypothermia may occur during swimming in cold water or in patients receiving antipyretic therapy concomitantly with Prochlorperazine.

10. Liver disease: Caution should be used in patients with existing liver disease due to the extensive hepatic metabolism of prochlorperazine.

11. Tardive dyskinesia: repetitive involuntary movements of the tongue, face, mouth or jaw => protrusion of the tongue, puffing the cheeks, puckering of the mouth, chewing movements. The trunk and limbs are less frequently involved. Risk is greater in elderly patients, especially females:

• Relatively irreversible
• Caused by cumulative dose of the drug increases
• In case of Tardive dyskinesia : Discontinue the medication
• There is no known effective treatment for tardive dyskinesia. Start Clozapin if indicated! (Has moderatet effect in relieving sympotoms)

12. Neuroleptic Malignant Syndrome: potentially fatal syndrome in association with antipsychotic drugs => Symptoms: Muscular rigidity, fever, hyperthermia, altered consciousness and autonomic:

• Management: immediate discontinuation of anti-psychotic drugs, intensive monitoring + treatment of symptoms, and treatment of any associated medical problems

 13. QT Interval: QT interval prolongation => 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.

14. Cerebrovascular Events: Increase the risk of cerebrovascular events especially in elderly patients. Caution is advised!

15. Thromboembolism: Increased the risk of venous thromboembolism. Caution is advised!

16. Elderly Patients with Dementia: Elderly patients with dementia-related psychosis =>increased risk of death.

17. Hyperglycaemia: 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.

18. Prochlorperazine is not recommended for use in children under 10 kg in weight or less than 2 years of age => acute extrapyramidal reactions may occur.

• Attention: Prochlorperazine should not be given to children by the rectal or intramuscular route.

19. Do not consume Alcohol while taking Prochlorperazine: May enhance the CNS depressant effects of alcohol and other depressant drugs + potentiate the anticholinergic effects of atropinic agents + tricyclic antidepressants.

20. In patients taking Desferrioxamine: Simultaneous administration may cause transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours.

21. Patients taking Thiazide diuretics: May accentuate the orthostatic hypotension that may occur with phenothiazines.

22. Caution in patients on anti-coagulants: Phenothiazines can decrease the effect of oral anticoagulants.

23. Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.

24. Over-dosage:

• Symptoms: CNS depression progressing from drowsiness to coma with areflexia. Restlessness, confusion and excitement. Hypotension, tachycardia, hypothermia, pupillary constriction, restlessness, tremor, muscle twitching, spasm or rigidity, convulsions, muscular hypotonia, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, possibly with sudden
• Treatment: Emesis should not be induce, Generally is supportive therapy
• In case of Acute dystonic reactions: Intramuscular benztropine (or another antiparkinsonian agent- [Dopamin agonist / Anticholinergics]) should be given immediately (adults: 1 to 2 mg i.m., children: 0.2 mg i.m. initially with increments if necessary).