Drugs List

Therapeutic Indications

Uses

Neoplastic conditions

As palliative or supplementary treatment, usually in combination with radiotherapy and/or surgery or as part of multiple drug regimens in:
Brain tumours (primary or metastatic)
Lung tumours (especially oat-cell carcinoma)
Hodgkin's disease (resistant to conventional combination chemotherapy)
Metastatic malignant melanoma

May also be of value as second-line treatment in:
Non-Hodgkin's lymphoma
Myelomatosis
Gastrointestinal tumours
Carcinoma - kidney
Carcinoma - testis
Carcinoma - ovary
Carcinoma - cervix
Carcinoma - breast

Contraindications

Response failure to other nitrosoureas
Breastfeeding
Coeliac disease
Pregnancy
Severe myelosuppression
Severe renal impairment

Precautions and Warnings

Children under 18 years
Reduced respiratory reserve

Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Perform blood counts before and at weekly intervals during treatment
Bone marrow suppression is cumulative
Monitor hepatic function regularly
Monitor patients for development of second primary malignancies
Monitor pulmonary function regularly
Monitor renal function regularly
Restart therapy when platelets>100,000/cubic mm & leucocytes>4,000/cubic mm
Advise patient to report any symptoms of infections especially sore throats
Suspend therapy if platelet count falls below 75,000 per cubic mm
Suspend treatment if white blood cell count falls below 3,000 per cubic mm
Lifetime cumulative dose should be limited to 1000mg/m squared
Male: May cause infertility
Male & female: Contraception required during & for 6 months after treatment

Thrombocytopenia appears about four weeks after a dose of lomustine and lasts one or two weeks at a level around 80 - 100,000/cubic millimetre. Leucopenia appears after six weeks and persists for one or two weeks at about 4,000 - 5,000/cubic millimetre. The haematological toxicity of lomustine may be cumulative, leading to successively lower white cell and platelet counts with successive doses of the drug. Permanent bone marrow damage may occur with prolonged use.

Pulmonary function should be assessed prior to treatment and frequently during treatment. Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLco) are particularly at risk of pulmonary toxicity.

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Effects on human pregnancy are unknown however lomustine is embryotoxic and teratogenic in animals.

The effect 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.

Due to the lipophilic nature of lomustine, it is likely that it would be excreted in breast milk. There is therefore a potential risk to the nursing infant.

The effect of concurrent therapies must also be considered.

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

Acute leukaemia
Alopecia
Anaemia
Anorexia
Apathy
Azotaemia
Blindness after combined radiation therapy
Bone marrow depression
Cholestatic jaundice
Confusion
Diarrhoea
Disorientation
Dysarthria
Elevation of liver enzymes (transient)
Impaired co-ordination
Increase in alkaline phosphatase
Increase in serum transaminases
Interstitial pneumonia
Lethargy
Leucopenia
Myelodysplastic syndrome
Nausea
Pulmonary fibrosis
Pulmonary infiltration
Renal atrophy
Renal failure
Renal injury
Serum bilirubin increased
Sterility (male, permanent)
Stomatitis
Stuttering
Thrombocytopenia
Vomiting

Presentation

Oral formulations containing lomustine

Drugs List

Therapeutic Indications

Uses

Neoplastic conditions

As palliative or supplementary treatment, usually in combination with radiotherapy and/or surgery or as part of multiple drug regimens in:
Brain tumours (primary or metastatic)
Lung tumours (especially oat-cell carcinoma)
Hodgkin's disease (resistant to conventional combination chemotherapy)
Metastatic malignant melanoma

May also be of value as second-line treatment in:
Non-Hodgkin's lymphoma
Myelomatosis
Gastrointestinal tumours
Carcinoma - kidney
Carcinoma - testis
Carcinoma - ovary
Carcinoma - cervix
Carcinoma - breast

Dosage

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

Treatment and dosage is governed principally by haemoglobin, white cell count, platelet count and body surface area.

White blood cell counts below 3,000/cubic millimetre and platelets counts below 75,000/cubic millimetre should be allowed to recover to above 4,000/cubic millimetre and 100,000/cubic millimetre respectively before repeating dose. Bone marrow depression after lomustine is sustained longer than after nitrogen mustards and recovery of white cell and platelet counts may not occur for six weeks or more.

It is recommended not to exceed a maximum cumulative total lomustine dose of 1000 mg/square metre to avoid renal toxicity.

Adults

Elderly

Children

Additional Dosage Information

Contraindications

Response failure to other nitrosoureas
Breastfeeding
Coeliac disease
Pregnancy
Severe myelosuppression
Severe renal impairment

Precautions and Warnings

Children under 18 years
Reduced respiratory reserve

Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Perform blood counts before and at weekly intervals during treatment
Bone marrow suppression is cumulative
Monitor hepatic function regularly
Monitor patients for development of second primary malignancies
Monitor pulmonary function regularly
Monitor renal function regularly
Restart therapy when platelets>100,000/cubic mm & leucocytes>4,000/cubic mm
Advise patient to report any symptoms of infections especially sore throats
Suspend therapy if platelet count falls below 75,000 per cubic mm
Suspend treatment if white blood cell count falls below 3,000 per cubic mm
Lifetime cumulative dose should be limited to 1000mg/m squared
Male: May cause infertility
Male & female: Contraception required during & for 6 months after treatment

Thrombocytopenia appears about four weeks after a dose of lomustine and lasts one or two weeks at a level around 80 - 100,000/cubic millimetre. Leucopenia appears after six weeks and persists for one or two weeks at about 4,000 - 5,000/cubic millimetre. The haematological toxicity of lomustine may be cumulative, leading to successively lower white cell and platelet counts with successive doses of the drug. Permanent bone marrow damage may occur with prolonged use.

Pulmonary function should be assessed prior to treatment and frequently during treatment. Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLco) are particularly at risk of pulmonary toxicity.

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Effects on human pregnancy are unknown however lomustine is embryotoxic and teratogenic in animals.

The effect 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.

Due to the lipophilic nature of lomustine, it is likely that it would be excreted in breast milk. There is therefore a potential risk to the nursing infant.

The effect of concurrent therapies must also be considered.

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

Acute leukaemia
Alopecia
Anaemia
Anorexia
Apathy
Azotaemia
Blindness after combined radiation therapy
Bone marrow depression
Cholestatic jaundice
Confusion
Diarrhoea
Disorientation
Dysarthria
Elevation of liver enzymes (transient)
Impaired co-ordination
Increase in alkaline phosphatase
Increase in serum transaminases
Interstitial pneumonia
Lethargy
Leucopenia
Myelodysplastic syndrome
Nausea
Pulmonary fibrosis
Pulmonary infiltration
Renal atrophy
Renal failure
Renal injury
Serum bilirubin increased
Sterility (male, permanent)
Stomatitis
Stuttering
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: April 2013

Reference Sources

British National Formulary, 65th Edition (2013) Pharmaceutical Press, London.

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

Summary of Product Characteristics: Lomustine "medac" 40mg. medac GmbH. Revised February 2013

N.A.P.O.S - The Drug Database for Acute Porphyria
https://www.drugs-porphyria.com/languages/UnitedKingdom/index.php?l=gbr
Last Reviewed 9th July 2010
Last Accessed 22nd April 2013