Drugs List

Therapeutic Indications

Uses

Hodgkin's disease
Leukaemia - chronic lymphocytic
Lymphoma - non-Hodgkin's
Waldenstrom's macroglobulinaemia

Unlicensed Uses

Nephrotic syndrome - steroid sensitive

Contraindications

Recent radiotherapy
Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

Bone marrow infiltrated with malignant cells
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of seizures
Lactose intolerance
Myelosuppression
Nephrotic syndrome
Renal impairment

Give pre-treatment counselling and consideration of sperm cryopreservation
May reduce seizure threshold
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor blood counts regularly
Monitor serum biochemistry regularly
Neutrophil count may decrease for up to 10 days after last the dose
Immunosuppressive drugs may increase risk of malignancy
May affect immune response to live vaccines
Potentially leukaemogenic
Consider dose reduction in severe hepatic impairment
May cause impaired fertility
Male & female: Ensure adequate contraception during treatment

Chlorambucil administration should be avoided if possible or given with great care for at least 4 weeks after radiotherapy or other chemotherapy (unless low doses of radiation have been used on areas remote from the bone marrow and neutrophil and platelet counts are not depressed).

Children with nephrotic syndrome, patients prescribed high pulse dosing regimens and patients with a history of seizure disorder should be closely monitored as they may have an increased risk of seizures.

Chlorambucil is classed as probably not porphyrinogenic by the drug database for acute porphyria (NAPOS).

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Chlorambucil is potentially teratogenic and has demonstrated in vitro and in vivo mutagenicity.

There is evidence of human foetal risk in a small number of exposed pregnancies particularly those exposed during the first trimester.
The use of chlorambucil should be avoided whenever possible during pregnancy, however the benefits to the mother may be acceptable despite the risks.

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 at https://www.toxbase.org/

Lactation

Chlorambucil is contraindicated in breastfeeding.

There is a lack of data on the concentrations which appear in human breast milk but considering the potential for serious adverse effects, women should not breastfeed whilst on chlorambucil treatment.

Hale (2006) recommends withholding breastfeeding for at least 24 hours after the last dose.

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 reaction
Anaemia
Angioneurotic oedema
Bone marrow damage (irreversible)
Bone marrow depression
Cystitis
Diarrhoea
Hepatotoxicity
Impaired fertility
Interstitial pneumonia
Jaundice
Leucopenia
Leukaemia
Mouth ulcers
Myelodysplastic syndrome
Myoclonus
Nausea
Neutropenia
Pancytopenia
Peripheral neuropathy
Pulmonary fibrosis
Pyrexia
Rash
Seizures
Stevens-Johnson syndrome
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Twitching
Urticaria
Vomiting

Presentation

Chlorambucil oral formulations.

Drugs List

Therapeutic Indications

Uses

Hodgkin's disease
Leukaemia - chronic lymphocytic
Lymphoma - non-Hodgkin's
Waldenstrom's macroglobulinaemia

Unlicensed Uses

Nephrotic syndrome - steroid sensitive

Dosage

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

The daily dose should not exceed 100 microgram/kg when lymphocytic infiltration of the bone marrow is present or the bone marrow is hypoplastic.

Adults

Elderly

Children

Patients with Renal Impairment

Contraindications

Recent radiotherapy
Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

Bone marrow infiltrated with malignant cells
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of seizures
Lactose intolerance
Myelosuppression
Nephrotic syndrome
Renal impairment

Give pre-treatment counselling and consideration of sperm cryopreservation
May reduce seizure threshold
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor blood counts regularly
Monitor serum biochemistry regularly
Neutrophil count may decrease for up to 10 days after last the dose
Immunosuppressive drugs may increase risk of malignancy
May affect immune response to live vaccines
Potentially leukaemogenic
Consider dose reduction in severe hepatic impairment
May cause impaired fertility
Male & female: Ensure adequate contraception during treatment

Chlorambucil administration should be avoided if possible or given with great care for at least 4 weeks after radiotherapy or other chemotherapy (unless low doses of radiation have been used on areas remote from the bone marrow and neutrophil and platelet counts are not depressed).

Children with nephrotic syndrome, patients prescribed high pulse dosing regimens and patients with a history of seizure disorder should be closely monitored as they may have an increased risk of seizures.

Chlorambucil is classed as probably not porphyrinogenic by the drug database for acute porphyria (NAPOS).

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Chlorambucil is potentially teratogenic and has demonstrated in vitro and in vivo mutagenicity.

There is evidence of human foetal risk in a small number of exposed pregnancies particularly those exposed during the first trimester.
The use of chlorambucil should be avoided whenever possible during pregnancy, however the benefits to the mother may be acceptable despite the risks.

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 at https://www.toxbase.org/

Lactation

Chlorambucil is contraindicated in breastfeeding.

There is a lack of data on the concentrations which appear in human breast milk but considering the potential for serious adverse effects, women should not breastfeed whilst on chlorambucil treatment.

Hale (2006) recommends withholding breastfeeding for at least 24 hours after the last dose.

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 reaction
Anaemia
Angioneurotic oedema
Bone marrow damage (irreversible)
Bone marrow depression
Cystitis
Diarrhoea
Hepatotoxicity
Impaired fertility
Interstitial pneumonia
Jaundice
Leucopenia
Leukaemia
Mouth ulcers
Myelodysplastic syndrome
Myoclonus
Nausea
Neutropenia
Pancytopenia
Peripheral neuropathy
Pulmonary fibrosis
Pyrexia
Rash
Seizures
Stevens-Johnson syndrome
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Twitching
Urticaria
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: May 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007). Ed. Schaefer C, Peters P, Miller R. Elsevier, 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.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Chlorambucil tablets. Aspen. Revised November 2012

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 August 2017

The Drug Database for Acute Porphyria (NAPOS).
Available at: https://www.drugs-porphyria.org/
Chlorambucil Last revised: September 25, 2009
Last accessed: May 31, 2013