Anquil Tablets

For the control of deviant anti-social sexual behaviour.

Posology

Adults

0.25-1.5 mg/day in divided doses. Dosage is best initiated and adjusted under close clinical supervision as individual response to neuroleptic drugs is variable.

In determining dosage, consideration should be given to the patient's age, severity of symptoms and previous response to other neuroleptic drugs.

Patients who are debilitated, or those with previously reported adverse reactions to neuroleptic drugs, may require less Anquil, and half the normal starting dose may be sufficient for therapeutic response.

In adolescents, a lower dose may be advisable.

Elderly

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

Paediatric population

Not recommended.

As with all medications the lowest effective dose should be used.

Method of administration

Oral.

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

Hypersensitivity to other butyrophenones.

Comatose states.

Patients with extrapyramidal symptoms, CNS depression, depressive disorders or Parkinson's disease.

Rare cases of sudden and unexplained death have been reported in psychiatric patients receiving antipsychotic drugs. However, Anquil has not been clearly implicated in any case.

Acute withdrawal symptoms, including nausea, vomiting and insomnia, have very rarely been described after abrupt cessation of high doses of antipsychotic drugs. Relapse may also occur and gradual withdrawal is advisable.

Where prolonged treatment with Anquil is envisaged, it would be a reasonable precaution to carry out regular blood counts and tests of liver function.

Caution is advised in patients with liver disease, renal failure, cardiovascular disease, epilepsy, and conditions predisposing to epilepsy and convulsions.

As with other neuroleptics, cases of QT interval prolongation may occur. Consequently, and if the clinical situation permits, absence of the following risk factors for onset of this type of arrhythmia should be verified prior to administration:

• Cardiac disease.

• A family history of sudden death and/or QT prolongation.

• Uncorrected electrolyte disturbances.

• A history of QT interval prolongation, ventricular arrhythmias or Torsades de Pointes.

Prior to initiation of treatment with Anquil, it may be appropriate to consider an ECG with measurement of serum calcium, magnesium and potassium levels. This is especially important in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination. During therapy, periodic serum electrolyte levels may be monitored and corrected if necessary, especially during long-term usage; if concomitant diuretics are taken; or during inter-current illness. Concomitant neuroleptics should be avoided.

An ECG may be appropriate to assess the QT interval whenever dose escalation is proposed and when the maximum therapeutic dose is reached. The dose of Anquil should be reduced if the QT interval is prolonged and discontinued if the QTc interval is greater than 500ms.

An approximately 3-fold increased risk of cerebrovascular adverse events has been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Benperidol should be used with caution in patients with risk factors for stroke.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicine as it contains lactose.

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 Anquil and preventive measures undertaken.

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.

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

In common with all neuroleptics, Anquil can increase the CNS depression produced by other CNS- depressant drugs, including alcohol, hypnotics, sedatives, strong analgesics or sedating antihistamines and may antagonise the action of adrenaline (epinephrine) and other sympathomimetic agents.

Certain agents (e.g. phenobarbital, carbamazepine, phenytoin, rifampicin, primidone), as well as smoking and alcohol consumption, which stimulate metabolising enzymes in the liver, may theoretically enhance the metabolic breakdown of neuroleptics, necessitating an increased dose. Fluoxetine, buspirone and ritonavir may cause an increase in the plasma concentration of Anquil necessitating a dose modification.

The effect of Anquil may be reduced by concomitant antimuscarinic medications.

Anquil may impair the anti-Parkinson effects of levodopa and other dopamine agonists. The dosage of anti-convulsants may need to be increased to take account of the lowered seizure threshold.

The use of Anquil with anticonvulsants such as barbiturates, carbamazepine, ethosuximide, oxcarbazepine, phenytoin, primidone and valproate may lower the seizure threshold, thereby necessitating a review of the anticonvulsant dose requirement.

The risk of hypotension with antihypertensive drugs, anaesthetics and opioid analgesics may be increased when Anquil is given concomitantly.

Enhanced CNS effects when combined with methyldopa have been reported for some butyrophenones.

Medicines that can prolong the QT interval should be avoided, as should any medicines that can cause electrolyte imbalance. In particular amiodarone and moxifloxacin should be avoided.

It is advised that Anquil should be avoided if artemether/lumefantrine is administered. Concomitant use of pramipexole or ropinirole with Anquil should be avoided as there may be antagonism of their effect.

The risk of extrapyramidal side effects is increased if amantadine, metoclopramide or tetrabenazine are used concomitantly with Anquil.

Concomitant treatment with lithium increases the risk of extrapyramidal side effects, and may cause neurotoxicity.

The effects of antipsychotics may be reduced by concomitant treatment with memantine.

The effect of sodium benzoate or sodium phenylbutyrate may be reduced by concomitant butyrophenones.

The safety of Anquil in pregnancy has not been established, although studies in animals have not demonstrated teratogenic effects. As with other drugs, it is not advisable to administer Anquil in pregnancy.

Neonates exposed to antipsychotics (including Anquil) 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.

Butyrophenones are excreted in breast milk and are not recommended during lactation. If the use of Anquil is considered essential, breast feeding should be discontinued.

Anquil may interfere with activities requiring mental alertness. Therefore, patients should be advised not to drive or operate machinery until their individual susceptibility is known.

The undesirable effects reported with Anquil during clinical trials and post-marketing surveillance are shown in the table below. They are listed by System-Organ Class (SOC) and in order of frequency, using the following convention: 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).

Table 1 Frequency of adverse events

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

Symptoms

In general, the manifestations of Anquil overdosage are an extension of its pharmacological action. In patients who have received daily doses of 160 mg, the most prominent side effects were extrapyramidal symptoms such as oculogyric crisis, salivation, muscle rigidity, akinesia and akathisia. Drowsiness or paradoxical excitement may occur.

Treatment

There is no specific antidote to Anquil. Treatment consists of supportive and symptomatic measures combined with standard measures to remove any unabsorbed drug. Extrapyramidal symptoms should be treated with anti-Parkinson drugs as required.

Pharmacotherapeutic group: Antipsychotics, butyrophenone derivatives, ATC code: N05AD07

Benperidol is a potent neuroleptic of the butyrophenone series with general properties similar to those of haloperidol.

After administration of benperidol (2 mg tablets PO) to volunteers, the following values have been reported:

C_max 4.1 ± 1.7 µg/l , T_max 2.9 ± 1.8 h, AUC(0-24) 39.8 ± 9.4 µg.h/l.

After repeated administration of 3 and 12 mg benperidol to patients, plasma levels of 10 and 30 μg/l respectively have been reported.

No relevant information additional to that contained elsewhere in the Summary of Product Characteristics.

Lactose

Starch

Magnesium stearate

Not applicable.

60 months.

Protect from light.

The tablets are supplied in PVC/PVdC/Aluminium blister packs, containing 100 or 112 tablets.

Not all pack sizes may be marketed.

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