Largazin Syrup

Largazin is indicated in the following conditions:

• Schizophrenia and other psychoses (especially paranoid), mania and hypomania.
• In anxiety psychomotor agitation excitement, violent or dangerously impulsive behaviour. Largazin is used as an adjunct in the short-term management of these conditions.
• Intractable hiccup.
• Nausea and vomiting of terminal illness (where other medicines have failed or are not available).
• Childhood schizophrenia and autism.

Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use).

Adults: In general medicine and psychiatry-

• Oral route: average daily dose of 30 to 75 mg (mild cases) or 75 to 100 mg (more severe cases) in divided doses. It is occasionally necessary to give a higher dosage which, when increased gradually, can reach 900 mg or more per day in some psychiatric patients.
• Once the optimum dosage has been reached, it is maintained as long as necessary for the control of symptoms during the critical phase of the illness. Eventually, however, it should be gradually reduced so that the patient can be maintained on the lowest effective dosage.

Adults: In surgery and anesthesia-

• To potentiate hypnotics, analgesics and anesthetics and as an antiemetic.
• Oral route: doses of 25 to 50 mg are administered 2 to 3 hours before anesthesia and every 4 to 6 hours after surgery.

Children:

• Usual single dose: 1/4 mg per pound (1/2 mg/kg) by oral route. This dose can be repeated every 4 to 6 hours as necessary. The normal daily dose is 40 mg for a child of 5 years (40 pounds), 75 mg for children of 5 to 12 years (50 to 100 pounds) except in psychiatric patients where dosages can be progressively elevated above these levels.
• In surgery and anesthesia, doses of 1/4 mg per pound, by the same method recommended for adults.

Interactions resulting in decreased chlorpromazine levels: Food, alcohol and benztropine can reduce the absorption of chlorpromazine. Antacids can slow the absorption of chlorpromazine. Lithium and chronic administration of barbiturates can lead to increased clearance of chlorpromazine.

Interactions resulting in increased chlorpromazine levels: Tricyclic antidepressants decrease the clearance of chlorpromazine and may lead to increased serum levels. Administration of chlorpromazine with CYP1A2 inhibitors, in particular strong (such as ciprofloxacin and fluvoxamine) or moderate (such as oral contraceptives and vemurafenib) inhibitors leads to an increase in chlorpromazine plasma concentrations. Therefore, patients may experience any chlorpromazine dose-dependent adverse drug reaction.

Severe CNS depression or comatose states due to alcohol, barbiturates, analgesics or other CNS depressants. In patients with blood dyscrasias, severe liver disease or a sensitivity to phenothiazines.

Drowsiness frequently occurs at the beginning of treatment but gradually disappears or subsides with a downward adjustment of the dosage - also at the beginning of treatment, there are rare cases of orthostatic hypotension, particularly when high doses are used - dystonic and extrapyramidal reactions may appear during prolonged treatment with elevated dosages, but can be eliminated by lowering the doses or administering an antiparkinsonian agent.

Other side effects which are observed less frequently include: nasal congestion, blurred vision, xerostomy, sedation, nausea, constipation, changes in libido, gynecomastia, weight gain, skin and corneal pigmentation, photosensitivity, blood dyscrasias, leukopenia, eosinophilia and EEG changes.

Very rare cases of QT interval prolongation have been reported. 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.

Cholestatic jaundice and liver injury, mainly of cholestatic or mixed type, are rarely reported in patients treated with Largazin.

Systemic lupus erythematosis has been very rarely reported in patients treated with Largazin. In some cases, positive anti-nuclear antibodies may be seen without evidence of clinical disease.

Priapism has been very rarely reported in patients treated with Largazin.

Pregnancy category C. Studies in animals by oral route have shown reproductive toxicity (dose-related embryo fetotoxicity: increased resorptions and dead foetuses). Increased incidence of malformations was observed in mice but only at doses inducing maternal mortality. There is inadequate animal data regarding reproductive toxicity with chlorpromazine by parenteral route. In humans, the teratogenic risk of chlorpromazine has not been evaluated. Different prospective epidemiological studies conducted with other phenothiazines have yielded contradictory results regarding teratogenic risk. Chlorpromazine has been found to be excreted in breast milk in variable amounts, therefore it is not recommended for nursing mothers unless the expected benefits outweigh any potential risk.

Largazin can potentiate the effects of other phenothiazines and CNS depressants. When treatment is initiated, the usual doses of barbiturates, analgesics, narcotics or antihistamines should be reduced by half. Patients should be warned against consuming alcoholic beverages while on Largazin therapy.

Neuroleptic phenothiazines may potentiate QT interval prolongation. QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalemia, and congenital or acquired (i.e., drug induced) QT prolongation.

Largazin should be used cautiously in patients suffering from arteriosclerosis, cardiovascular disease or other conditions where it is necessary to avoid a sudden drop in blood pressure. If hypotension does occur and it is necessary to use a hypertensive agent, norepinephrine should be used, not epinephrine, as the latter agent can aggravate hypotension.

Because of its anticholinergic properties, Largazin must be used with caution in patients with glaucoma or prostatic hypertrophy.

During protracted therapy and especially if high dosages are administered, it is recommended that blood counts and liver function tests be performed at regular intervals.

Drowsiness may occur at the beginning of treatment; patients should therefore be warned against operating motor vehicles or participating in activities requiring mental alertness until this effect has subsided.

Phenothiazines can provoke epileptic seizures by lowering the seizure threshold; therefore, during Largazin therapy, the patient's usual anticonvulsant medication should be continued at the same dosage.

Because of its antiemetic effect, Largazin can obscure symptoms of intracranial hypertension or intestinal obstruction.

False positive or negative pregnancy tests have occurred in patients receiving phenothiazine therapy.

Elderly: The elderly are relatively more susceptible to the adverse effects of chlorpromazine. The starting dose should be about half the usual adult dose and dosage increments should be gradual and reviewed regularly.

Anti-emetic drugs, Phenothiazine drugs, Phenothiazine related drugs

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.