Stemetil

Stemetil 5 mg tablets

Prochlorperazine maleate 5 mg tablets

Tablet

Stemetil tablets 5 mg and prochlorperazine tablets BP 5mg (1000 tablet pack): Off-white to pale cream coloured circular tablets for oral use. The tablets are marked on one face 'STEMETIL' around a centrally impressed '5', reverse face plain.

Prochlorperazine tablets BP 5mg ('own label' supplier for 84 and 1000 tablets): Off-white to pale cream coloured circular tablets for oral use. The tablets are marked on one face '4L1”, reverse face plain.

Vertigo due to Meniere's Syndrome, labyrinthis and other causes, and for nausea and vomiting from whatever cause including that associated with migraine. It may also be used for schizophrenia (particularly in the chronic stage), acute mania and as an adjunct to the short-term management of anxiety.

Adults

Children

Elderly

A lower dose is recommended. Please see Special Warnings and Special Precautions for Use.

Known hypersensitivity to prochlorperazine or to any of the other ingredients.

Stemetil should be avoided in patients with liver or renal dysfunction, Parkinson's disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostate hypertrophy. It should be avoided in patients known to be hypersensitive to phenothiazines or with a history of narrow angle glaucoma or agranulocytosis.

Close monitoring is required in patients with epilepsy or a history of seizures, as phenothiazines may lower the seizure threshold.

As agranulocytosis has been reported, regular monitoring of the complete blood count is recommended. The occurrence of unexplained infections or fever may be evidence of blood dyscrasia , and requires immediate haematological investigation.

It is imperative that treatment be discontinued in the event of unexplained fever, as this may be a sign of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity). Signs of autonomic dysfunction, such as sweating and arterial instability, may precede the onset of hyperthermia and serve as early warning signs. Although neuroleptic malignant syndrome may be idiosyncratic in origin, dehydration and organic brain disease are predisposing factors.

Acute withdrawal symptoms, including nausea, vomiting and insomnia, have very rarely been reported following the abrupt cessation of high doses of neuroleptics. Relapse may also occur, and the emergence of extrapyramidal reactions has been reported. Therefore, gradual withdrawal is advisable.

In schizophrenia, the response to neuroleptic treatment may be delayed. If treatment is withdrawn, the recurrence of symptoms may not become apparent for some time.

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).8).

Avoid concomitant treatment with other neuroleptics.

Stroke: In randomised clinical trials versus placebo performed in a population of elderly patients with dementia and treated with certain atypical antipsychotic drugs, a 3-fold increase of the risk of cerebrovascular events has been observed. The mechanism of such risk increase is not known. An increase in the risk with other antipsychotic drugs or other populations of patients cannot be excluded. Stemetil should be used with caution in patients with stroke risk factors.

As with all antipsychotic drugs, Stemetil should not be used alone where depression is predominant. However, it may be combined with antidepressant therapy to treat those conditions in which depression and psychosis coexist.

Because of the risk of photosensitisation, patients should be advised to avoid exposure to direct sunlight.

To prevent skin sensitisation in those frequently handling preparations of phenothiazines, the greatest care must be taken to avoid contact of the drug with the skin.

It should be used with caution in the elderly, particularly during very hot or very cold weather (risk of hyper-, hypothermia).

The elderly are particularly susceptible to postural hypotension.

Stemetil should be used cautiously in the elderly owing to their susceptibility to drugs acting on the central nervous system and a lower initial dosage is recommended. There is an increased risk of drug-induced Parkinsonism in the elderly particularly after prolonged use. Care should also be taken not to confuse the adverse effects of Stemetil, e.g. orthostatic hypotension, with the effects due to the underlying disorder.

Children: Stemetil has been associated with dystonic reactions particularly after a cumulative dosage of 0.5 mg/kg. It should therefore be used cautiously in children

Increased Mortality in Elderly people with Dementia

Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.

Stemetil is not licensed for the treatment of dementia-related behavioural disturbances.

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Stemetil and preventative measures undertaken.

Hyperglycaemia or intolerance to glucose has been reported in patients treated with antipsychotic phenothiazines. Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes who are started on Stemetil, should get appropriate glycaemic monitoring during treatment.

Adrenaline must not be used in patients overdosed with Stemetil.

The CNS depressant actions of neuroleptic agents may be intensified (additively) by alcohol, barbiturates and other sedatives. Respiratory depression may occur.

Anticholinergic agents may reduce the antipsychotic effect of neuroleptics and the mild anticholinergic effect of neuroleptics may be enhanced by other anticholinergic drugs, possibly leading to constipation, heat stroke, etc.

Some drugs interfere with absorption of neuroleptic agents: antacids, anti-Parkinson drugs and lithium.

Where treatment for neuroleptic-induced extrapyramidal symptoms is required, anticholinergic antiparkinsonian agents should be used in preference to levodopa, since neuroleptics antagonise the antiparkinsonian action of dopaminergics.

High doses of neuroleptics reduce the response to hypoglycaemic agents, the dosage of which might have to be raised.

The hypotensive effect of most antihypertensive drugs especially alpha adrenoceptor blocking agents may be exaggerated by neuroleptics.

The action of some drugs may be opposed by phenothiazine neuroleptics; these include amfetamine, levodopa, clonidine, guanethidine, adrenaline.

Increases or decreases in the plasma concentrations of a number of drugs, e.g. propranolol, phenobarbital have been observed but were not of clinical significance.

Simultaneous administration of desferrioxamine and prochlorperazine has been observed to induce transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours.

There is an increased risk of arrhythmias when neuroleptics are used with concomitant QT prolonging drugs (including certain antiarrhythmics, antidepressants and other antipsychotics) and drugs causing electrolyte imbalance.

There is an increased risk of agranulocytosis when neuroleptics are used concurrently with drugs with myelosuppressive potential, such as carbamazepine or certain antibiotics and cytotoxics.

In patients treated concurrently with neuroleptics and lithium, there have been rare reports of neurotoxicity.

There is inadequate evidence of safety in pregnancy. There is evidence of harmful effects in animals. Stemetil should be avoided in pregnancy unless the physician considers it essential. Neuroleptics may occasionally prolong labour and at such time should be withheld until the cervix is dilated 3-4 cm. Possible adverse effects on the neonate include lethargy or paradoxical hyperexcitability, tremor and low apgar score.

Neonates exposed to antipsychotics (including Stemetil) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Phenothiazines may be excreted in milk, therefore breast feeding should be suspended during treatment.

Patients should be warned about drowsiness during the early days of treatment and advised not to drive or operate machinery.

Generally, adverse reactions occur at a low frequency; the most common reported adverse reactions are nervous system disorders.

Adverse effects:

Immune System Disorders:

Type I hypersensitivity reactions such as angioedema and urticaria.

Blood and lymphatic system disorders: A mild leukopenia occurs in up to 30% of patients on prolonged high dosage. Agranulocytosis may occur rarely: it is not dose related.

Endocrine: Hyperprolactinaemia which may result in galactorrhoea, gynaecomastia, amenorrhoea; impotence.

Nervous system disorders: Acute dystonia or dyskinesias, including oculogyric crisis, usually transitory are commoner in children and young adults, and usually occur within the first 4 days of treatment or after dosage increases.

Akathisia characteristically occurs after large initial doses.

Parkinsonism is more common in adults and the elderly. It usually develops after weeks or months of treatment. One or more of the following may be seen: tremor, rigidity, akinesia or other features of Parkinsonism. Commonly just tremor.

Tardive dyskinesia: If this occurs it is usually, but not necessarily, after prolonged or high dosage. It can even occur after treatment has been stopped. Dosage should therefore be kept low whenever possible.

Insomnia and agitation may occur.

Convulsions.

Eye disorders: Ocular changes and the development of metallic greyish-mauve coloration of exposed skin have been noted in some individuals mainly females, who have received chlorpromazine continuously for long periods (four to eight years). This could possibly happen with Stemetil.

Cardiac disorders: ECG changes include QT prolongation (as with other neuroleptics), ST depression, U-Wave and T-Wave changes. Cardiac arrhythmias, including ventricular arrhythmias and atrial arrhythmias, a-v block, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest have been reported during neuroleptic phenothiazine therapy, possibly related to dosage. Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic antidepressants may predispose.

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.

Vascular disorders: Hypotension, usually postural, commonly occurs. Elderly or volume depleted subjects are particularly susceptible; it is more likely to occur after intramuscular injection. Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs - Frequency unknown

Gastrointestinal disorders: dry mouth may occur.

Metabolism and nutrition disorders:

Hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion.

Respiratory, thoracic and mediastinal disorders: Respiratory depression is possible in susceptible patients. Nasal stuffiness may occur.

Hepato-biliary disorders: Jaundice, usually transient, occurs in a very small percentage of patients taking neuroleptics. A premonitory sign may be sudden onset of fever after one to three weeks of treatment followed by the development of jaundice. Neuroleptic jaundice has the biochemical and other characteristics of obstructive jaundice and is associated with obstruction of the canaliculi by bile thrombi; the frequent presence of an accompanying eosinphilia indicates the allergic nature of this phenomenon. Treatment should be withheld on the development of jaundice.

Skin and subcutaneous tissue disorders: Contact skin sensitisation may occur rarely in those frequently handling preparations of certain phenothiazines. Skin rashes of various kinds may also be seen in patients treated with the drug. Patients on high dosage should be warned that they may develop photosensitivity in sunny weather and should avoid exposure to direct sunlight.

General disorders and administration site conditions: Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic dysfunction and altered consciousness) may occur with any neuroleptic.

Intolerance to glucose, hyperglycaemia

Pregnancy, puerperium and perinatal conditions; drug withdrawal syndrome neonatal - Frequency not known.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Symptoms of phenothiazine overdosage include drowsiness or loss of consciousness, hypotension, tachycardia, ECG changes, ventricular arrhythmias and hypothermia. Severe extrapyramidal dyskinesias may occur.

If the patient is seen sufficiently soon (up to 6 hours) after ingestion of a toxic dose, gastric lavage may be attempted. Pharmacological induction of emesis is unlikely to be of any use. Activated charcoal should be given. There is no specific antidote. Treatment is supportive.

Generalised vasodilatation may result in circulatory collapse; raising the patient's legs may suffice. In severe cases, volume expansion by intravenous fluids may be needed; infusion fluids should be warmed before administration in order not to aggravate hypothermia.

Positive inotropic agents such as dopamine may be tried if fluid replacement is insufficient to correct the circulatory collapse. Peripheral vasoconstrictor agents are not generally recommended. Avoid the use of adrenaline.

Ventricular or supraventricular tachy-arrhythmias usually respond to restoration of normal body temperature and correction of circulatory or metabolic disturbances. If persistent or life threatening, appropriate anti-arrhythmic therapy may be considered. Avoid lidocaine and, as far as possible, long acting anti-arrhythmic drugs.

Pronounced central nervous system depression requires airway maintenance or, in extreme circumstances, assisted respiration. Severe dystonic reactions usually respond to procyclidine (5-10 mg) or orphenadrine (20-40 mg) administered intramuscularly or intravenously. Convulsions should be treated with intravenous diazepam.

Neuroleptic malignant syndrome should be treated with cooling. Dantrolene sodium may be tried.

Pharmacotherapeutic group: Antipsychotics, ATC code: N05AB04

Stemetil is a potent phenothiazine neuroleptic

There is little information about blood levels, distribution and excretion in humans. The rate of metabolism and excretion of phenothiazines decreases in old age.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Lactose

Maize starch

Aerosil (E551)

Magnesium stearate

None stated.

3 years

Store protected from light.

Stemetil tablets 5mg are available in “securitainers” or HDPE bottles in packs of 25, 250 and 1000 tablets and PVDC coated UPVC/aluminium foil blisters containing 28 or 84 tablets.

No special requirements

Aventis Pharma Limited also trading as

Aventis Pharma

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

Or trading as

Sanofi-aventis or Sanofi

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

PL 04425/0593

Date of first authorisation: 2 October 2006

10 February 2016