Drugs and medications - Lartil Injection

Colourless or almost colourless solution.

ACTIONS & MODE OR MECHANISMS OF ACTIONS:
Prochloperazine is a phenothiazine with a piperazine moiety in the side chain. It processes strong antiemetic and antipsychotic activity with less sedative action than chlorpromazine. As with other phenothiazines, prochloperazine has actions on several neurotransmitter systems:
1. Antidopamine action, which probably contributes to both the therapeutic effect and unwanted effects including extrapyramidal disorders and endocrine disturbances.
2. Alpha-adrenoceptors antagonism, which contributes to cardiovascular side effects such as orthostatic hypotension and reflex tachycardia.

3. Potentiation of noradrenaline by blocking its reuptake into nerve terminals.
4. Weak antiacetylcholinre action.
5. Weak antihistanminic action.
6. Weak serotonin antagonism.
Prochlorperazine also has an effect on temperature control and blocks conditioned avoidance responses.

PHARMACOLOGY
Pharmacokinetics
There are few published data on prochlorperazine pharmacokinetics in humans. Most studies have been done in rats and dose levels do not correspond to those used clinically and metabolic pathway may differ. Similar overall pharmacokinetic patterns however would occur in humans. Prochlorperazine is well absorbed from the gastrointestinal tract in rats but absorption is slowed in repeatedly treated animal. The drug is widely distributed to tissues including the brain, fat, kidney, heart and skin and is stored in reticuloendothelial tissues. Phenothiazines are metabolized primarily in the liver and are subject to enterohepatic circulation. Excretion is mainly in the faeces. Only a very small amount (approx. 0.1%) of prochlorperazine and its metabolites 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. The elimination half-life is approximately 24 hours, presumably due to its enterohepatic circulation.

INDICATIONS
Nausea and vomiting due to various causes including migraine; vertigo due to Meniere's syndrome, labyrinthitis and other causes; minor mental and emotional disturbances.

CONTRAINDICATIONS
Circulatory collapse, central nervous system depression (coma or drug intoxication), previous history of a hypersensitivity reaction (eg. jaundice or blood dyscrasia) to phenothiazines especially to prochlorperazine, bone marrow depression).

SIDE EFFECTS/ADVERSE REACTIONS
The following reactions have been reported for prochloperazine or phenothiazines in general.

More common reactions
Gastrointestinal: constipation, dry mouth.
Nervous System: Drowsiness, akathisia, parkinsonism (with dyskinesia, tremor and rigidity).
Ocular: Blurred vision.

Less common reaction
Biochemical abnormalities: elevated serum level of bilirubin and hepatic enzymes may occur if the patient develops cholestatic jaundice. Cardiovascular: hypotension, propheral oedema, cardiac arrhytmias, ECG changes.
Dermatological: dermatitis, maculopopular eruption, erythema, multiform, urticaria, photosensitivity, abnormal pigmentation.
Gastrointestinal: paralytic ileus.
Genito-urinary: 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.
Psychiatric: Activation of psychotic symptoms.
Serious or life threatening reactions:
Prochloperazine can cause very serious acute dystonic reactions in children leading cyanosis from laryngospasm, apnoea requiring artificial ventilation, life threatening tetanus like syndromes, coma and even death. These reaction can occur with a single therapeutic dose. For treatment, see Overdosage. Also, long term phenothiazine therapy has been associated with ECG changes and life threatening cardiac arrhythmias.

PRECAUTIONS/WARNINGS

WARNING
This preparation contains sulphite that may cause allergic type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible individuals. Sulphite sensitivity is seen more frequently in asthmatic patients.

Prochlorperazine should be avoided in patients with renal dysfunction, Parkinson's disease, hypothyroidism, phaeochromocytoma, myasthenia gravis, prostate hypertrophy

Hypotension
The autonomic side effects of the piperazine derivatives are less troublesome than those of other phenothiazines, however care should be taken if prochloperazine injection is used in the elderly or in patients undergoing surgery with spinal anaesthesia.

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

Anticholinergic 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.

Hypocalcaemia
It appears from a study of 5 hypocalcaemic patients with hypoparathyroidism that such patients are particularly prone to acute severe 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 prochloperazine may mask signs of overdosage of toxic drugs or obscure the diagnosis of conditions such as intestinal obstruction and brain tumour.

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 consist repetitive involuntary movements of the tongue, face, mouth or jaw (eg. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). The trunk and limbs are less frequently involved. It has been reported that form vermicular movement 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 greater in elderly patients, especially females. The syndrome may become clinically recognizable either drug treatment, or 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 the sign 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. Antiparkinson agents usually do not alleviate the symptoms of this syndrome, if theses symptoms appear, it is suggested that the antipsychotic be discontinued if symptoms of tardive dyskinesia appear.