Rosemont Pharmaceuticals Limited


Rosemont House
Yorkdale Industrial Park
Braithwaite Street
Leeds
Yorkshire
LS11 9XE

Telephone: +44 (0)113 244 1400
Facsimile: +44 (0)113 246 0738
WWW: http://www.rosemontpharma.com
Customer Care direct line: +44 (0)800 919 312
Document last updated on the eMC: Fri 23 May 2003

Promazine Syrup 25mg/5ml


1. NAME OF THE MEDICINAL PRODUCT

Promazine Syrup 25mg/5ml


2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Promazine Hydrochloride 25mg/5ml


3. PHARMACEUTICAL FORM

Oral Syrup


4. CLINICAL PARTICULARS


4.1 Therapeutic indications

1. As an adjunct to short-term management of moderate to severe psychomotor agitation

2. Agitation and restlessness in the elderly



4.2 Posology and method of administration

For oral administration only.

Dosage varies with the individual and the purpose for which the drug is used, so the following dosages are only for general guidance with regard to possible effectiveness and good tolerance.

Initial dosages should be low, with increments at frequent, regular intervals until the desired response is obtained. Dosage intervals are usually six to eight hours, but in some patients the 24 hour requirement may be conveniently administered in a single bedtime dose.

The commencement and increase of dosage should be performed under close supervision.

Psychomotor Agitation

Adults: 100mg to 200mg, four times daily.

Elderly: Half the normal starting dose may be sufficient for a therapeutic response.

Agitation and Restlessness

Elderly: 25mg initially, increasing, if necessary, up to 50mg, four times a day.

Children: Promazine is not recommended for children



4.3 Contraindications

Use in patients hypersensitive to the active ingredient or other phenothiazines.



4.4 Special warnings and precautions for use

1. Acute withdrawal symptoms, including nausea, vomiting, sweating and insomnia have been described after abrupt cessation of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported.

2. Phenothiazine should only be used with great caution in patients with a history of jaundice or with existent liver dysfunction, or blood dyscrasias, coronary insufficiency or cardiac disease.

3. Respiratory depression may occur in patients with severe respiratory disease.

4. Promazine should be used with caution in patients with renal failure.

5. Patients receiving phenothiazines over a prolonged period require regular and careful surveillance with particular attention to potential for inducing eye changes (corneal and lens opacities and purplish pigmentation of the skin, cornea, conjunctiva and retina), effects on haemopoiesis, liver dysfunction, myocardial conduction effects, particularly if other concurrently administered drugs also have potential effects on these systems.

6. Use of phenothiazines at high (relative or absolute) doses may induce extrapyramidal side effects, dyskinesia, akathisia, dystonia. These are likely to be particularly severe in children. Caution should be exercised in patients with Parkinson's disease. Anti-parkinson agents should not be prescribed routinely because of the risk of aggravating anticholinergic side effects of Promazine, of precipitating toxic-confusional states or of impairing its therapeutic efficacy. They should be given only as required.

7. Prolonged administration of phenothiazines may result in persistent or tardive dyskinesias particularly in the elderly. The risk of tardive dyskinesia and the likelihood of irreversibility are believed to increase as the duration of therapy and total cumulative dose increase. Neuroleptic therapy should be withdrawn if dyskinesia develops.

8. Care should be exercised if Promazine is used for the treatment of patients with cerebral arteriosclerosis, coronary heart disease or other conditions in which a fall in blood pressure might be undesirable.

9. Caution should be observed with patients suffering from epilepsy or conditions predisposing to epilepsy.

10. Personal or family history of narrow angle glaucoma.

11. Phenothiazines may impair body temperature regulation. Caution should be observed in very hot weather.

12. Hypothyroidism.

13. Myasthenia gravis.

14. Phaeochromocytoma.

15. Prostatic hypertrophy.

16. Antipsychotic drugs may increase prolactin secretion.

Excipients in the Formulation

This product contains hydroxybenzoate esters. These are known to cause urticaria, delayed type reactions such as contact dermatitis and rarely an immediate reaction with urticaria and bronchospasm.



4.5 Interaction with other medicinal products and other forms of interaction

The concomitant administration of this product with other medication such as central nervous system depressants (including alcohol and anaesthetics) or antihypertensives, anticholinergic or dopaminergic drugs will result in accentuation of their effects, while potentiation of action will also occur with monoamine oxidase inhibitors, antidepressants and analgesics. Promazine may impair the effects of anticonvulsants. Promazine may affect the control of diabetes. Undesirable anticholinergic effects can be enhanced by anti-parkinson or other anticholinergic drugs.

The concomitant administration of this product with myelosuppressive drugs (carbamazepine, co-trimoxazole, chloramphenicol, sulphonamides, pyralizone analgesics (e.g. azapropazone), penicillamine and cytotoxics) will result in increased toxicity.

Lithium administration will result in an increased risk of extrapyramidal effects and the possibility of neurotoxicity.

Sotalol administration will result in an increased risk of ventricular arrhythmia.



4.6 Pregnancy and lactation

Do not use during pregnancy, especially during the first three months, unless there are compelling reasons. There is insufficient evidence of the safety of Promazine in human pregnancy nor is there evidence from animal studies that it is free from hazard.

Promazine should not be used during lactation.



4.7 Effects on ability to drive and use machines

Phenothiazines may impair alertness and induce drowsiness especially at the start of treatment. Persons taking these drugs should not drive or operate machinery unless the drug has been shown not to interfere with physical or mental ability.



4.8 Undesirable effects

Promazine is a member of the phenothiazine group of drugs and the side effects associated with that group have been noted. These include drowsiness, sedation, dry mouth, nasal stuffiness. Other possible anticholinergic side effects are blurred vision, tachycardia, constipation and urinary hesitancy or retention when due to enlarged prostate.

Confusional states or epileptic fits can occur. Sexual function may be impaired. Agranulocytosis and transient leucopenia have rarely been reported. Allergic skin reactions have also been reported.

Promazine rarely causes obstructive jaundice associated with stasis in biliary canaliculi. Promazine treatment should then be withdrawn and not given again. Transient abnormalities of liver function tests may occur without jaundice.

Some individuals may be susceptible to the drug in low dosage and show paradoxical effects of excitement, agitation or insomnia and other minor side effects. The elderly are particularly susceptible to side effects of Promazine, especially to the sedative, hypotensive and temperature regulation effects. These effects may be dose related.

Withdrawal symptoms, including nausea, vomiting, sweating, insomnia, recurrence of psychotic symptoms and involuntary movement disorders have been noted (see Section 4.4).



4.9 Overdose

Ingestion of large amounts of Promazine is followed by deep sleep, with or without a pronounced fall in blood pressure and without particular change in respiration rate, other than the slowing attendant upon sedation. Occasionally an initial period of excitement may precede coma, followed by grand mal seizures.

In the absence of any specific antidote, treatment should be based on ordinary therapeutic principles with special emphasis on the following measures:

a. Gastric lavage;

b. Treat convulsions if present;

c. Correction of acute hypotension if necessary;

d. Counteraction of the effects of an excess of Promazine on the central nervous system;

e. Control and natural recovery of hypothermia.


5. PHARMACOLOGICAL PROPERTIES


5.1 Pharmacodynamic properties

Promazine has a wide range of activity arising from its depressant actions on the central nervous system and its alpha-adrenergic blocking and weaker anticholinergic activities. It is a dopamine inhibitor; it inhibits prolactin release-inhibitory factor, considered to be dopamine, thus stimulating the release of prolactin. The turnover of dopamine in the brain is also increased.



5.2 Pharmacokinetic properties

Promazine is readily absorbed from the gastro-intestinal tract but is subject to considerable first-pass metabolism in the gut wall. It is also extensively metabolised in the liver and is excreted in the urine and faeces in the form of numerous active and inactive metabolites; there is evidence of enterohepatic recycling. Owing to the first-pass effect, plasma concentrations following oral administration are much lower than those following intramuscular administration.

Moreover, there is very wide intersubject variation in plasma concentrations of Promazine; no simple correlation has been found between plasma concentrations of Promazine and its metabolites, and their therapeutic effect. Paths of metabolism of Promazine include hydroxylation and conjugation with glucuronic acid, N-oxidation, oxidation of a sulphur atom, and dealkylation. Its duration of therapeutic effect can range from a few days to several weeks or possibly longer.

Promazine is very extensively bound to plasma proteins. It is widely distributed in the body and crosses the blood-brain barrier to achieve higher concentrations in the brain than in the plasma. Promazine and its metabolites also cross the placental barrier and are excreted in milk.



5.3 Preclinical safety data

None stated


6. PHARMACEUTICAL PARTICULARS


6.1 List of excipients

Propylene glycol (E1520), methyl hydroxybenzoate (E218), ethyl hydroxybenzoate (E214), propyl hydroxybenzoate (E216), sucrose, liquid glucose, ascorbic acid (E300), green lemon flavour 545489E and purified water.



6.2 Incompatibilities

None known



6.3 Shelf life

36 months



6.4 Special precautions for storage

Store below 25°C. Protect from light.



6.5 Nature and contents of container

Amber (type III) glass bottle with capacities of 150ml, 200ml and 500ml

1. Aluminium, wadded, roll-on, pilfer proof closure.

2. HDPE, child resistant, tamper evident, EPE wadded closure.

3. HDPE, tamper evident, EPE wadded closure.



6.6 Instructions for use, handling and disposal

Dispense in amber glass bottles. If a dose of under 5ml is required, the oral syrup should be administered using an oral dosing device.


7. MARKETING AUTHORISATION HOLDER

Rosemont Pharmaceuticals Ltd, Rosemont House, Yorkdale Industrial Park, Braithwaite Street, Leeds, LS11 9XE


8. MARKETING AUTHORISATION NUMBER(S)

PL 0427/0054


9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

5.2.82 / 24.3.95/5.4.02


10. DATE OF REVISION OF THE TEXT

October 2002