Lomustine (Monograph)

Brand name: Gleostine
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Warning

Lomustine causes myelosuppression (e.g., thrombocytopenia, leukopenia), including fatal myelosuppression. Myelosuppression is delayed, dose-related, and cumulative. Thrombocytopenia is generally more severe than leukopenia. Monitor blood counts and do not give lomustine more frequently than every 6 weeks.
Prescribe, dispense, and administer enough capsules of lomustine for 1 dose. Fatal toxicity occurs with overdosage of lomustine. Both physician and pharmacist should emphasize to the patient that only 1 dose of lomustine is taken every 6 weeks.

Introduction

Antineoplastic agent; a nitrosourea-derivative alkylating agent.

Uses for Lomustine

Brain Tumors

Used for the treatment of patients with primary and metastatic brain tumors following appropriate surgical and/or radiotherapeutic procedures.

Used as an adjuvant to radiation therapy in combination with procarbazine and vincristine in adults with certain types of astrocytic and oligodendroglial tumors.

Used as an adjuvant to surgery in combination with thioguanine, procarbazine, and vincristine in pediatric low-grade glioma.

Used as an adjuvant to surgical resection and radiation therapy in combination with other chemotherapeutic agents for the treatment of pediatric medulloblastoma.

Hodgkin’s Lymphoma

Used in combination with other agents for the treatment of Hodgkin's lymphoma in patients whose disease has progressed following initial chemotherapy.

Combination regimens containing other agents currently are preferred for treatment of this cancer.

Lomustine Dosage and Administration

General

Pretreatment Screening

Obtain baseline pulmonary function tests (PFTs).
Verify pregnancy status before initiating treatment with lomustine.

Patient Monitoring

Monitor CBC weekly for at least 6 weeks following each dose.
Monitor PFTs frequently during therapy.
Monitor liver function during therapy.
Monitor renal function and electrolytes during therapy.

Dispensing and Administration Precautions

Because lomustine is a cytotoxic drug, applicable special handling and disposal procedures must be followed. To minimize exposure to cytotoxic lomustine, only handle bottles of lomustine capsules while wearing impervious gloves. Do not break lomustine capsules and avoid exposure to broken capsules. If skin contact occurs, wash the exposed skin areas immediately and thoroughly.
Based on the Institute for Safe Medication Practices (ISMP), lomustine is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.

Other General Considerations

The manufacturer recommends prescribing and dispensing only 1 dose of lomustine per treatment cycle, because dispensing or administering >1 dose per treatment cycle may lead to fatal toxicity. Dispense enough capsules at a time for 1 dose of lomustine. Do not dispense the entire container.
Both the prescriber and pharmacist should emphasize to the patient that the medication is dosed once every 6 weeks.

Administration

Oral Administration

Administer orally as a single dose once per treatment cycle (no more frequently than once every 6 weeks).

Handle cautiously; use impervious gloves and wash hands if skin contact occurs.

Dosage

Round dosage to the closest 10 mg.

Pediatric Patients

Brain Tumors

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.

100 mg/m² as a single dose is recommended in patients with compromised bone marrow function.

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.

Hodgkin's Lymphoma

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.

100 mg/m² as a single dose is recommended in patients with compromised bone marrow function.

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.

Adults

Brain Tumors

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.

100 mg/m² as a single dose is recommended in patients with compromised bone marrow function.

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.

Hodgkin's Lymphoma

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.

100 mg/m² as a single dose is recommended in patients with compromised bone marrow function.

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.

Dosage Modification for Toxicity

Do not administer repeat courses until leukocyte count returns to at least 4000/mm³ and platelet count returns to at least 100,000/mm³.

Adjust subsequent dosages based on nadir blood counts from previous dose.

Table 1. Dosage Adjustments for Hematologic Toxicities Based on Nadir After Prior Dose.100
Nadir After Prior Dose - Leukocytes (cells/mm³)	Nadir After Prior Dose - Platelets (cells/mm³)	Percentage of Prior Dose to be Given
≥4000	≥100,000	100%
3000–3999	75,000–99,999	100%
2000–2999	25,000–74,999	70%
<2000	<25,000	50%

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Manufacturer makes no specific dosage recommendations. Since geriatric patients are more likely to have reduced renal function, careful dosage selection and monitoring of renal function recommended.

Cautions for Lomustine

Contraindications

None.

Warnings/Precautions

Warnings

Delayed Myelosuppression

Risk of myelosuppression (e.g., thrombocytopenia, leukopenia); effects are delayed, dose-related, and cumulative. (See Boxed Warning.) Thrombocytopenia generally more severe than leukopenia. Cumulative myelosuppression can manifest as cytopenias of greater severity and longer duration. Following oral administration, myelosuppression occurs after approximately 4–6 weeks and persists for 1–2 weeks. Manufacturer recommends performing blood counts weekly during and for at least 6 weeks after discontinuance of lomustine. Adjust the dosage of lomustine based on nadir blood counts from the previous dose.

Risk of Overdosage

Risk of overdosage and fatal toxicity. (See Boxed Warning.) Manufacturer recommends prescribing and dispensing only 1 dose of lomustine per treatment cycle; dispensing or administering >1 dose per treatment cycle can lead to fatal toxicity. Dispense enough capsules at a time for 1 dose of lomustine. Emphasize to the patient that the medication is dosed once every 6 weeks.

Pulmonary Toxicity

Risk of pulmonary toxicity (characterized by pulmonary infiltrates and/or fibrosis) at 6 months or later. Risk factors include prolonged therapy (with cumulative doses >1100 mg/m²).

Perform pulmonary function tests prior to initiation of and frequently during therapy.

Patients with baseline forced vital capacity (FVC) or pulmonary diffusion capacity for carbon monoxide (DL_CO) <70% of predicted value are particularly at risk.

Permanently discontinue lomustine in patients who develop pulmonary fibrosis.

Secondary Malignancies

Risk of secondary malignancies (e.g., acute leukemia, myelodysplasia) following long-term use.

Hepatotoxicity

Hepatic toxicity, manifested by increases in serum transaminase, alkaline phosphatase, and bilirubin concentrations reported. Monitor hepatic function.

Nephrotoxicity

Decrease in kidney size and renal failure reported. Monitor renal function.

Fetal/Neonatal Morbidity and Mortality

Possible fetal harm; teratogenicity and embryotoxicity demonstrated in animals. Avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Verify pregnancy status before initiation. Advise females of reproductive potential to use effective contraception during lomustine therapy and for at least 2 weeks following the final dose.

Advise males with female partners of reproductive potential to use condoms during treatment with lomustine and for 3.5 months following the final dose.

Specific Populations

Pregnancy

No data in pregnant women. May cause fetal harm. Verify pregnancy status before initiating lomustine. Inform pregnant women of the potential fetal risk.

Lactation

Not known whether lomustine is distributed into human milk. Discontinue breastfeeding during therapy and for 2 weeks following the last dose because of potential risk to nursing infants.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraception during lomustine therapy and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use condoms during treatment with lomustine and for 3.5 months following the final dose.

May adversely affect fertility in males and females of reproductive potential.

Pediatric Use

Use of lomustine (including dosage) not well-established in pediatric patients.

Geriatric Use

No data available in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Other reported clinical experience has not identified differences in response.

Substantially eliminated by kidneys; monitor renal function periodically since geriatric patients are more likely to have decreased renal function.

Hepatic Impairment

Impact of hepatic impairment on pharmacokinetics of lomustine not known.

Renal Impairment

Impact of renal impairment on pharmacokinetics of lomustine not known. Risk of toxic reactions may be increased in those with renal impairment because lomustine and its metabolites undergo substantial renal excretion.

Common Adverse Effects

Common adverse effects include delayed myelosuppression, nausea, vomiting, stomatitis, alopecia.

Drug Interactions

Formal drug interaction studies not conducted.

Lomustine Pharmacokinetics

Absorption

Special Populations

Age, sex, race, renal impairment, hepatic impairment: effect on lomustine pharmacokinetics not known.

Distribution

Extent

Crosses the blood-brain barrier.

Not known whether lomustine is distributed into human milk.

Elimination

Metabolism

Metabolic pathways involved in elimination not fully characterized.

Elimination Route

Excreted principally in urine as metabolites.

Following oral administration, about 50% of radioactivity excreted within 24 hours.

Half-life

16-48 hours.

Stability

Storage

Oral

Capsules

Store at 25°C (excursions permitted to 15–30°C). Avoid temperatures >40°C.

Actions

Alkylates DNA and RNA.
May inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.

Advice to Patients

Advise patients that periodic blood count monitoring is necessary during lomustine therapy. Advise patients to contact their healthcare provider for new onset of bleeding, fever, or symptoms of infection.
Inform patients that toxicity, including fatal toxicity, has occurred with overdosage of lomustine.
Inform patients that lomustine must be taken as directed, and that each dose may consist of 2 or more different strengths or colors of capsules. Lomustine is taken as a single oral dose that will not be repeated for at least 6 weeks. Administration of lomustine at the recommended dose more frequently than every 6 weeks has resulted in toxicities, including fatal toxicities.
Advise patients to contact their healthcare provider if they experience a new or worsening cough, chest pain, or shortness of breath.
Inform patients that lomustine can cause hepatoxicity and that liver function must be monitored during treatment.
Inform patients that lomustine can cause nephrotoxicity and that renal function and electrolytes must be monitored during treatment.
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Stress importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Inform females of reproductive potential of the potential fetal risk with lomustine and to inform their healthcare providers of a known or suspected pregnancy. Inform females of reproductive potential to use effective contraception during lomustine therapy and for at least 2 weeks following the final dose. Inform males with female partners of reproductive potential to use condoms during treatment with lomustine and for 3.5 months following the final dose. Advise women to avoid breast-feeding during lomustine therapy and for 2 weeks following the final dose.
Inform females and males of reproductive potential of the potential for reduced fertility from lomustine therapy.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.