Perphenazine

The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g. fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.

Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.

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. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Consequently, newborns should be monitored carefully.

Perphenazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Safe use of perphenazine during pregnancy has not been established; therefore, in administering the drug to pregnant patients, the possible benefits must be weighed against the possible hazards to mother and child.

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 – 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.