PROCARBAZINE Capsule Ref.[8648] Active ingredients: Ibenzmethyzine

Procarbazine should be given only under the supervision of a physician who is experienced in cancer chemotherapy and having facilities for regular monitoring of clinical and haematological effects during and after administration.

Introduction of therapy should only be effected under hospital conditions.

Caution is advisable in patients with hepatic or renal dysfunction and Procarbazine should be avoided in patients with severe hepatic or renal disease. Its use should be avoided if creatinine clearance is less than 10mL/min. Caution is also advised in cardiovascular or cerebrovascular disease, phaeochromocytoma, or epilepsy.

Regular blood counts are of great importance due to the possibility of bone-marrow suppression. If during the initial treatment the total white cell count falls to 3,000 per mm³ or the platelet count to 80,000 per mm³, treatment should be suspended temporarily until the leucocyte and/or platelet levels recover, when therapy with the maintenance dose may be resumed.

Treatment should be interrupted on the appearance of allergic skin reactions.

Live vaccines should not be given during or within at least 6 months of treatment with immunosuppressive chemotherapy or radiotherapy for malignant disease.

Procarbazine is a weak MAO inhibitor and therefore interactions with certain foodstuffs and drugs, although very rare, must be borne in mind. Thus, owing to possible potentiation of the effect of barbiturates, narcotic analgesics (especially Pethidine), drugs with anticholinergic effects (including phenothiazine derivatives and tricyclic antidepressants), other central nervous system depressants (including anaesthetic agents) and anti-hypertensive agents, these drugs should be given concurrently with caution and in low doses.

Cytotoxics may reduce the absorption of phenytoin and cardiac glycosides.

Concomitant use of clozapine may increase the risk of agranulocytosis. Use with enzyme-inducing antiepileptics is associated with an increased risk of hypersensitivity reactions to procarbazine.

Intolerance to alcohol (Disulfiram-like reaction) may occur.

Pregnancy

Use of Procarbazine is contraindicated during the first trimester of pregnancy, and should be avoided throughout the remainder of the gestational period.

Studies in animals have shown reproductive toxicity (see 5.3). The potential risk for humans is unknown. There are no adequate data from the use of Procarbazine in pregnant women, however isolated human foetal malformations have been reported following MOPP combination therapy.

Breast-feeding

Procarbazine is contraindicated during breast-feeding.

Fertility

Procarbazine has been reported to cause azoospermia and ovarian failure, which may be irreversible. It is extremely important that the patient is provided with appropriate information and advice, particularly as men may wish to have semen saved for use after Procarbazine treatment (see section 4.8).

Patients should be warned of the possibility of lethargy (see section 4.8 Undesirable effects).

Tabulated list of adverse reactions

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.

Infections and infestations

Not known: Infections (see section 4.4)

Blood and lymphatic systems disorders

Not known: Leucopenia, Thrombocytopenia, Neutropenia

Immune system disorders

Not known: Severe hypersensitivity reactions with angioedema, urticaria and a precipitous drop in serum complement

Psychiatric disorders

Not known: Lethargy

Respiratory, thoracic and mediastinal disorders

Not known: Pneumonitis

Gastrointestinal disorders

Very common: Loss of appetite, Nausea, Vomiting

Hepatobiliary disorders

Not known: Hepatic complications including jaundice and abnormal liver function tests

Skin and subcutaneous tissue disorders

Not known: Allergic skin reactions

Reproductive system and breast disorders

Not known: Azoospermia, Ovarian failure

Description of selected adverse reactions

Leucopenia and thrombocytopenia are almost always reversible and seldom require complete cessation of therapy.

Loss of appetite, nausea and vomiting are usually confined to the first few days of treatment and then tend to disappear.

Azoospermia and ovarian failure may be irreversible. It is extremely important that the patient is provided with appropriate information and advice, particularly as men may wish to have semen saved for use after Procarbazine treatment.

Procarbazine is carcinogenic and an increased incidence of acute myelogenous leukaemia has been reported in patients receiving MOPP chemotherapy for Hodgkins disease.

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, Website: www.mhra.gov.uk/yellowcard.

Not applicable.