PERPHENAN Film coated tablet Ref.[8267] Active ingredients: Perphenazine

The possibility of suicide in depressed patient’s remains during treatment and until significant remission occurs. Perphenazine should not be used alone when depression is predominant.

Perphenazine should be used with caution in patients with liver disease; severe respiratory disease; renal failure; epilepsy and conditions predisposing to epilepsy such as alcohol withdrawal or brain damage; Parkinson’s disease; patients who have shown sensitivity to other phenothiazines; personal or family history of narrow angle glaucoma; hypothyroidism, myasthenia gravis; phaeochromocytoma; or prostatic hypertrophy.

Perphenazine should be used with caution in patient with cardiovascular disease, such as cardiac arrhythmias, congestive heart failure, and a personal or family history of QT prolongation.

The concomitant use of other neuroleptics should be avoided because of possible potentiation of effects.

Since temperature regulation may be impaired, care should be taken in extremely hot and in cold weather, especially in the elderly and frail because of risk of hypothermia.

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 akathesia, dystonia and dyskinesia) has been reported. Therefore gradual withdrawal is advisable.

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 perphenazine 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.

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

Drug interactions affecting Perphenazine

Plasma concentrations of antipsychotics may increase when given with ritonavir or tricyclic antidepressants. Metabolism of perphenazine is inhibited when taken with paroxetine.

Kaolin or antacids may decrease the absorption of perphenazine. Memantine may reduce the effects of perphenazine

Interactions affecting other drugs

Perphenazine may enhance the hypotensive effect of other antihypertensive medication.

Risk of sedation and/or toxicity when perphenazine is administered with CNS depressants such as alcohol, antipsychotics, opioids, sedatives, and antihistamines.

Tramadol when given with perphenazine may increase the risk of convulsions.

Risk of extrapyramidal reactions/anticholinergic effects when perphenazine is administered with Lithium, metoclopramide, fluoxetine.

Perphenazine may antagonise the therapeutic effects of anticonvulsants.

Perphenazine may antagonise the therapeutic effects of drugs used for Parkinson’s disease and other movement disorders.

Perphenazine antagonises the hypoglycaemic effect of sulphonylureas. Phenothiazines may enhance the absorption of corticosteroids and digoxin. May affect action of anticoagulants and increase the bleeding time.

Increased risk of toxicity when perphenazine is given with myelosupressive drugs.

Use with concomitant QT prolonging drugs, drugs inhibiting the metabolism of perphenazine, and with drugs causing electrolyte imbalance is not recommended. If the benefit is considered to outweigh the risk in the individual patient, co-administration should be undertaken with caution and ECG monitoring should be considered (see section 4.4).

The safety of perphenazine in pregnancy has not yet been established.

Neonates exposed to antipsychotics (including perphenazine) 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 breast milk; breast feeding should be suspended during treatment.

Perphenazine may impair alertness, particularly when treatment is started. This may be potentiated by alcohol. Perphenazine may cause sedation and patients should be advised not to drive or operate machinery.

Not all the following side-effects have been reported with this specific drug. However pharmacological similarities with other phenothiazine derivatives require that each be considered. Many of the side effects may be prevented by a reduction in dosage. With the piperazine group (of which perphenazine is an example), the extrapyramidal symptoms like Opisthotonus, trismus, torticollis, retrocollis, aching and numbness of the limbs, motor restlessness, oculogyric crisis, hyperreflexia, dystonia, including protrusion, discoloration, aching and rounding of the tongue, tonic spasm of the masticatory muscles, tight feeling in the throat, slurred speech, dysphagia, akathisia, dyskinesia, parkinsonism and ataxia are more common, and others (e.g. sedation, jaundice, blood dyscrasias) are less frequent.

Frequencies of the ADRs is not defined, however the below mentioned ADRs have been reported.

Disorders of the Blood and the Lymphatic system: Agranulocytosis; Transient leucopenia.

Cardiac disorders: Tachycardia, Ventricular arrhythmias VF ,VT. Sudden unexplained death, cardiac arrest and Torsades de pointes, QT prolongation.

Endocrine disorders: Hyperprolactemia.

Disorders of the eye: Oculogyric crisis; Visual disorders including blurring of vision Corneal and lens deposits; Pigmented retinopathy.

Gastrointestinal disorders: Nausea; Oral dryness and saliva altered. Gastrointestinal atonic and hypomotility disorders including constipation, adynamic ileus

General disorders: Fatigue; Oedema, weight gain

Hepato-biliary disorders: Cholestasis and jaundice, Obstructive jaundice.

Disorders of the immune system: Antinuclear antibodies; Systemic lupus erythematous (SLE).

Investigations: Hyperglycemia, false positive pregnancy tests; Raised serum cholesterol

Neurological disorder: Headaches; Choreiform movements of the extremities; Dyskinesias and movement disorders including akathisia, orofacial dyskinesia, extrapyramidal disorder and tardive dyskinesias; Dystonia; Hyperreflexia; Disturbances in consciousness including somnolence, stupor; Dizziness. Parkinsonism; Tremors; Epileptic fits; CSF protein abnormalities; Impaired regulation of body temperature. Neuroleptic malignant syndrome has been reported in patients treated with neuroleptic drugs. It is a relatively uncommon, potentially lethal syndrome, characterized by severe extrapyramidal dysfunction, with rigidity and eventual stupor or coma, hyperthermia and autonomic disturbances, including cardiovascular effects

Psychiatric disorders: Confusional state, Agitation; Excitement; Insomnia.

Renal and urinary disorders: Urinary hesitancy or urinary retention

Disorders of the Reproductive system and breast: Menstruation with decreased bleeding Amenorrhea; Erectile dysfunction; impaired ejaculation. Gynaecomastia; Galactorrhoea.

Respiratory, thoracic and mediastinal disorders: Nasal stuffiness.

Skin and subcutaneous tissue disorders: Photosensitivity; Rashes; Hyperhidrosis.

Pregnancy, puerperium and perinatal conditions: Drug withdrawal syndrome neonatal (see 4.6) – Frequency not known.

Vascular disorders: Hypotension.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs – Frequency unknown.

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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@mo h.gov.il.

None known.