Drugs List

Therapeutic Indications

Uses

Hodgkin's disease
Lymphoma
Malignant neoplasms

Contraindications

Children under 2 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 10ml/minute
Severe hepatic impairment
Severe leucopenia
Thrombocytopenia

Precautions and Warnings

Elderly
Cardiovascular disorder
Cerebrovascular disorder
Epileptic disorder
Hepatic impairment
Phaeochromocytoma
Renal impairment

Live virus vaccine should not be given for 6 months after treatment
Wear protective clothing if handling urine passed up to 48hrs after therapy
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment should be initiated in hospital
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Perform regular white blood cell and platelet counts
Interrupt treatment if allergic skin reactions occur
Suspend treatment if platelet count falls below 80,000 per cubic mm
Suspend treatment if white blood cell count falls below 3,000 per cubic mm
Advise patient that alcohol ingestion may cause a disulfiram-like reaction
Advise patient to avoid foods or beverages with a high tyramine content
Male & female: May cause infertility
Male & female: Ensure adequate contraception during treatment

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Isolated human foetal malformations have been reported following therapy during 1st trimester. The molecular weight indicates that transmission across the placenta should be expected.

Procarbazine has been shown to be mutagenic, carcinogenic and teratogenic in animals.

In combination therapy, the impact of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

The molecular weight is low enough that excretion into breast milk is likely and because of the potential for tumorigenesis, breastfeeding should be discontinued during treatment.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Allergic skin reactions
Altered liver function tests
Azoospermia
Decreased appetite
Increased risk of neoplasms
Jaundice
Leucopenia
Nausea
Ovarian failure
Thrombocytopenia
Vomiting

Presentation

Oral formulations of procarbazine hydrochloride

Drugs List

Therapeutic Indications

Uses

Hodgkin's disease
Lymphoma
Malignant neoplasms

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Elderly

Children

Contraindications

Children under 2 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 10ml/minute
Severe hepatic impairment
Severe leucopenia
Thrombocytopenia

Precautions and Warnings

Elderly
Cardiovascular disorder
Cerebrovascular disorder
Epileptic disorder
Hepatic impairment
Phaeochromocytoma
Renal impairment

Live virus vaccine should not be given for 6 months after treatment
Wear protective clothing if handling urine passed up to 48hrs after therapy
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment should be initiated in hospital
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Perform regular white blood cell and platelet counts
Interrupt treatment if allergic skin reactions occur
Suspend treatment if platelet count falls below 80,000 per cubic mm
Suspend treatment if white blood cell count falls below 3,000 per cubic mm
Advise patient that alcohol ingestion may cause a disulfiram-like reaction
Advise patient to avoid foods or beverages with a high tyramine content
Male & female: May cause infertility
Male & female: Ensure adequate contraception during treatment

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Isolated human foetal malformations have been reported following therapy during 1st trimester. The molecular weight indicates that transmission across the placenta should be expected.

Procarbazine has been shown to be mutagenic, carcinogenic and teratogenic in animals.

In combination therapy, the impact of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

The molecular weight is low enough that excretion into breast milk is likely and because of the potential for tumorigenesis, breastfeeding should be discontinued during treatment.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Allergic skin reactions
Altered liver function tests
Azoospermia
Decreased appetite
Increased risk of neoplasms
Jaundice
Leucopenia
Nausea
Ovarian failure
Thrombocytopenia
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: February 2013

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

BNF for Children (2012-2013) Pharmaceutical Press, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Procarbazine Capsules 50 mg. Alliance Pharmaceuticals. Revised March 2014.