Prochlorperazine maleate 3 mg Buccal Tablet (P)

For nausea and vomiting in previously diagnosed migraine, in adults aged 18 years and over.

To be placed in the buccal cavity, high up along the top gum under the upper lip, until dissolved. Do not chew or swallow the tablet.

Duration of treatment: Two days maximum.

Adults aged 18 years and over: One or two tablets twice a day.

Children and young adults under 18 years: Not recommended.

Elderly patients: There is no evidence that dosage need be modified for the elderly.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Impaired liver function

• Existing blood dyscrasias

• Epilepsy

• Parkinsons Disease

• Prostatic hypertrophy

• Narrow angle glaucoma

• Pregnancy.

Only use when migraine has previously been diagnosed by a doctor.

Prochlorperazine maleate Buccal Tablets should be avoided in patients with stroke risk factors and myasthenia gravis.

Agranulocytosis has been reported with phenothiazines. The occurrence of unexplained infections or fever may be evidence of blood dyscrasia (see section 4.8), and requires immediate haematological investigation.

It has been reported that patients with AIDS may be particularly susceptible to antipsychotic-induced extrapyramidal effects

Because of the risk of photosensitisation, patients should be advised to avoid exposure to direct sunlight and use sunscreen (see section 4.8).

Hypotension, usually postural, may occur, particularly in elderly or volume depleted patients.

Nausea and vomiting as a sign of organic disease may be masked by the anti-emetic action of Prochlorperazine maleate Buccal Tablets.

Neuroleptic malignant syndrome (NMS) is a potentially fatal symptom complex associated with antipsychotic medicinal products. Alteration in mental status and other neurological signs often precede systemic signs of NMS. It is imperative that treatment be discontinued in the event of NMS (characterised by unexplained fever, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity) (see section 4.8).

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 Prochlorperazine maleate Buccal Tablets and preventive measures undertaken (see section 4.8).

QT prolongation

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. Prochlorperazine maleate Buccal Tablets should be used with caution in patients with congenital or documented acquired QT prolongation and/or known risk factors for prolongation of the QT interval such as:

- cardiac disease e.g. heart failure, myocardial infarction

- proarrhythmic conditions e.g. bradycardia (< 50 bpm)

- a history of ventricular dysrhythmias

- uncorrected hypokalemia and/or hypomagnesemia

- and during concomitant administration with QT interval prolonging drugs (see section 4.5).

If signs of cardiac arrhythmia occur during treatment with Prochlorperazine maleate Buccal Tablets, treatment should be stopped and an ECG should be performed.

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.

Prochlorperazine maleate Buccal Tablets are not licensed for the treatment of dementia-related behavioural disturbances.

The tablet contains sucrose

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not use this medicine.

Alcohol and CNS depressants should be used with caution due to the possible additive CNS depressant effect. The mild anticholinergic effect of neuroleptics may be enhanced by other anticholinergic drugs.

Oral anticoagulants – may have diminished effect.

Anticonvulsants – efficacy may be diminished necessitating dosage adjustment, as prochlorperazine may lower the seizure threshold.

The hypotensive effect of antihypertensive drugs may be exaggerated.

The concomitant use of lithium may result in severe extrapyramidal side effects or severe neurotoxicity.

The concurrent use of desferrioxamine and prochlorperazine should be avoided.

There is an increased risk of arrhythmias when neuroleptics are used with concomitant QT prolonging drugs (including certain anti-arrhythmics, antidepressants, macrolide antibiotics and other antipsychotics) and drugs causing electrolyte imbalance (see section 4.4).

Prochlorperazine opposes the effects of levodopa.

Pregnancy

Prochlorperazine Maleate 3 mg Buccal Tablets is contraindicated during pregnancy (see section 4.3).

Neonates exposed to antipsychotics (including prochlorperazine) 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.

Breast-feeding

Since data from animal studies shows that prochlorperazine may be found in breast milk, Prochlorperazine Maleate 3 mg Buccal Tablets should not be used during breastfeeding.

Fertility

There are no data on the effects of prochlorperazine on fertility.

Patients who drive or operate machinery should be warned of the possibility of drowsiness.

Undesirable effects are listed by MedDRA System Organ Classes.

Assessment of undesirable effects is based on the following frequency groupings:

Very common: ≥ 1/10

Common: ≥ 1/100 to <1/10

Uncommon: ≥ 1/1,000 to <1/100

Rare: ≥ 1/10,000 to <1/1,000

Very rare: <1/10,000

Not known: cannot be estimated from the available data

Tabulated list of adverse reactions

* See 'Description of selected adverse reactions'

Description of selected adverse reactions

Impotence, ejaculation disorder, priapism, and agranulocytosis (see section 4.4) are class effects associated with phenothiazines.

Neuroleptic malignant syndrome may occur with any neuroleptic (see section 4.4).

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs- Frequency unknown (see section 4.4).

QT prolongation, cardiac arrhythmias, including ventricular arrhythmias which may result in ventricular fibrillation or cardiac arrest have been reported during neuroleptic phenothiazine therapy. Pre-existing cardiac disease, proarrhythmic conditions, hypokalaemia, hypomagnesemia, or concomitant administration with QT interval prolonging drugs may predispose.

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 Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

The signs and symptoms will be predominantly extrapyramidal and may be accompanied either by restlessness and agitation or central nervous depression. Hypotension may also occur. Treatment is essentially symptomatic and supportive. There is no specific antidote. Do not induce vomiting. Particular attention must be directed to maintaining a clear airway since this may be threatened by extrapyramidal muscle dystonias. Severe dystonic reactions usually respond to procyclidine or orphenadrine given i.m. or i.v. If convulsions occur, they should be treated using i.v. diazepam. If hypotension is present, strict attention to ventilation and posturing of the patient will often secure the desired effect, but failing this, consideration should be given to volume expansion by i.v. fluids. If this is insufficient, positive inotropic agents such as dopamine may be tried, but peripheral vasoconstrictor agents are not generally recommended. Adrenaline should NOT be used.

Pharmacotherapeutic group: Phenothiazines with piperazine structure

ATC code: N05AB04

Prochlorperazine is a member of the phenothiazine group of neuroleptics which, in doses lower than those used in psychiatry, is usually employed for its anti-emetic properties. The site of action is thought to be the chemoreceptor trigger zone.

Prochlorperazine maleate 3mg Buccal Tablets are placed in the buccal cavity where they form a gel from which the prochlorperazine is released and absorbed. The plasma levels achieved at steady-state on a dosage regimen of one 3 mg buccal tablet twice daily are similar to those observed with the standard oral dosage of one 5 mg tablet taken three times daily. The elimination half-life of prochlorperazine in this formulation is 9.0 hours, similar to that observed with the oral formulation.

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.

Compressible sugar

Povidone

Xanthan gum

Locust bean gum

Riboflavin 5-phosphate sodium

Talc

Magnesium stearate

None.

36 months

This medicinal product does not require any special storage conditions.

PVC/PVdC aluminium foil blisters.

Pack size: Blister packs of 2 or 8 buccal tablets.

Not all pack sizes may be marketed

Any unused medicinal product or waste material should be disposed of in accordance with local requirements