Lomustine (Monograph)

Brand name: Gleostine
Drug class: Antineoplastic Agents

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

Introduction

Antineoplastic agent; a nitrosourea-derivative alkylating agent.¹⁰⁰

Uses for Lomustine

Brain Tumors

Used for the treatment of patients with primary and metastatic brain tumors following appropriate surgical and/or radiotherapeutic procedures.¹⁰⁰

Used as an adjuvant to radiation therapy in combination with procarbazine and vincristine in adults with certain types of astrocytic and oligodendroglial tumors.^{117 118 119 120 121 300}

Used as an adjuvant to surgery in combination with thioguanine, procarbazine, and vincristine in pediatric low-grade glioma.^{122 301}

Used as an adjuvant to surgical resection and radiation therapy in combination with other chemotherapeutic agents for the treatment of pediatric medulloblastoma.^{111 112 123 302}

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.¹⁰⁰

Combination regimens containing other agents currently are preferred for treatment of this cancer.³⁰³

Lomustine Dosage and Administration

General

Pretreatment Screening

• Obtain baseline pulmonary function tests (PFTs).¹⁰⁰

• Verify pregnancy status before initiating treatment with lomustine.¹⁰⁰

Patient Monitoring

• Monitor CBC weekly for at least 6 weeks following each dose.¹⁰⁰

• Monitor PFTs frequently during therapy.¹⁰⁰

• Monitor liver function during therapy.¹⁰⁰

• Monitor renal function and electrolytes during therapy.¹⁰⁰

Dispensing and Administration Precautions

Handling and Disposal

• Because lomustine is a cytotoxic drug, applicable special handling and disposal procedures must be followed.¹⁰⁰ To minimize exposure to cytotoxic lomustine, only handle bottles of lomustine capsules while wearing impervious gloves.¹⁰⁰ Do not break lomustine capsules and avoid exposure to broken capsules.¹⁰⁰ If skin contact occurs, wash the exposed skin areas immediately and thoroughly.¹⁰⁰

• 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.¹²⁴

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.¹⁰⁰ Dispense enough capsules at a time for 1 dose of lomustine.¹⁰⁰ Do not dispense the entire container.¹⁰⁰

• Both the prescriber and pharmacist should emphasize to the patient that the medication is dosed once every 6 weeks.¹⁰⁰

Administration

Oral Administration

Administer orally as a single dose once per treatment cycle (no more frequently than once every 6 weeks).¹⁰⁰

Handle cautiously; use impervious gloves and wash hands if skin contact occurs.¹⁰⁰

Dosage

Round dosage to the closest 10 mg.¹⁰⁰

Pediatric Patients

Brain Tumors

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.¹⁰⁰

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

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.¹⁰⁰

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.¹⁰⁰

Hodgkin's Lymphoma

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.¹⁰⁰

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

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.¹⁰⁰

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.¹⁰⁰

Adults

Brain Tumors

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.¹⁰⁰

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

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.¹⁰⁰

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.¹⁰⁰

Hodgkin's Lymphoma

Oral

130 mg/m² as a single dose; administer at intervals of at least 6 weeks.¹⁰⁰

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

When used in conjunction with other myelosuppressive drugs, reduce dose accordingly.¹⁰⁰

Adjust subsequent dosages based on nadir blood counts from preceding dose according to the schedule in Table 1.¹⁰⁰

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/mm³.¹⁰⁰

Adjust subsequent dosages based on nadir blood counts from previous dose.¹⁰⁰

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.¹⁰⁰

Renal Impairment

Manufacturer makes no specific dosage recommendations.¹⁰⁰

Geriatric Patients

Manufacturer makes no specific dosage recommendations.¹⁰⁰ Since geriatric patients are more likely to have reduced renal function, careful dosage selection and monitoring of renal function recommended.¹⁰⁰

Cautions for Lomustine

Contraindications

• None.¹⁰⁰

Warnings/Precautions

Warnings

Delayed Myelosuppression

Risk of myelosuppression (e.g., thrombocytopenia, leukopenia); effects are delayed, dose-related, and cumulative.¹⁰⁰ (See Boxed Warning.) Thrombocytopenia generally more severe than leukopenia.¹⁰⁰ Cumulative myelosuppression can manifest as cytopenias of greater severity and longer duration.¹⁰⁰ Following oral administration, myelosuppression occurs after approximately 4–6 weeks and persists for 1–2 weeks.¹⁰⁰ Manufacturer recommends performing blood counts weekly during and for at least 6 weeks after discontinuance of lomustine.¹⁰⁰ Adjust the dosage of lomustine based on nadir blood counts from the previous dose.¹⁰⁰

Risk of Overdosage

Risk of overdosage and fatal toxicity.¹⁰⁰ (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.¹⁰⁰ Dispense enough capsules at a time for 1 dose of lomustine.¹⁰⁰ Emphasize to the patient that the medication is dosed once every 6 weeks.¹⁰⁰

Pulmonary Toxicity

Risk of pulmonary toxicity (characterized by pulmonary infiltrates and/or fibrosis) at 6 months or later.¹⁰⁰ Risk factors include prolonged therapy (with cumulative doses >1100 mg/m²).¹⁰⁰

Perform pulmonary function tests prior to initiation of and frequently during therapy.¹⁰⁰

Patients with baseline forced vital capacity (FVC) or pulmonary diffusion capacity for carbon monoxide (DL_CO) <70% of predicted value are particularly at risk.¹⁰⁰

Permanently discontinue lomustine in patients who develop pulmonary fibrosis.¹⁰⁰

Secondary Malignancies

Risk of secondary malignancies (e.g., acute leukemia, myelodysplasia) following long-term use.¹⁰⁰

Hepatotoxicity

Hepatic toxicity, manifested by increases in serum transaminase, alkaline phosphatase, and bilirubin concentrations reported.¹⁰⁰ Monitor hepatic function.¹⁰⁰

Nephrotoxicity

Decrease in kidney size and renal failure reported.¹⁰⁰ Monitor renal function.¹⁰⁰

Fetal/Neonatal Morbidity and Mortality

Possible fetal harm; teratogenicity and embryotoxicity demonstrated in animals.¹⁰⁰ Avoid pregnancy during therapy.¹⁰⁰ If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹⁰⁰

Verify pregnancy status before initiation.¹⁰⁰ Advise females of reproductive potential to use effective contraception during lomustine therapy and for at least 2 weeks following the final dose.¹⁰⁰

Advise males with female partners of reproductive potential to use condoms during treatment with lomustine and for 3.5 months following the final dose.¹⁰⁰

Specific Populations

Pregnancy

No data in pregnant women.¹⁰⁰ May cause fetal harm.¹⁰⁰ Verify pregnancy status before initiating lomustine.¹⁰⁰ Inform pregnant women of the potential fetal risk.¹⁰⁰

Lactation

Not known whether lomustine is distributed into human milk.¹⁰⁰ Discontinue breastfeeding during therapy and for 2 weeks following the last dose because of potential risk to nursing infants.¹⁰⁰

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.¹⁰⁰ Advise males with female partners of reproductive potential to use condoms during treatment with lomustine and for 3.5 months following the final dose.¹⁰⁰

May adversely affect fertility in males and females of reproductive potential.¹⁰⁰

Pediatric Use

Use of lomustine (including dosage) not well-established in pediatric patients.¹⁰⁰

Geriatric Use

No data available in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹⁰⁰ Other reported clinical experience has not identified differences in response.¹⁰⁰

Substantially eliminated by kidneys; monitor renal function periodically since geriatric patients are more likely to have decreased renal function.¹⁰⁰

Hepatic Impairment

Impact of hepatic impairment on pharmacokinetics of lomustine not known.¹⁰⁰

Renal Impairment

Impact of renal impairment on pharmacokinetics of lomustine not known.¹⁰⁰ Risk of toxic reactions may be increased in those with renal impairment because lomustine and its metabolites undergo substantial renal excretion.¹⁰⁰

Common Adverse Effects

Common adverse effects include delayed myelosuppression, nausea, vomiting, stomatitis, alopecia.¹⁰⁰

Drug Interactions

Formal drug interaction studies not conducted.¹⁰⁰

Lomustine Pharmacokinetics

Absorption

Special Populations

Age, sex, race, renal impairment, hepatic impairment: effect on lomustine pharmacokinetics not known.¹⁰⁰

Distribution

Extent

Crosses the blood-brain barrier.¹⁰⁰

Not known whether lomustine is distributed into human milk.¹⁰⁰

Elimination

Metabolism

Metabolic pathways involved in elimination not fully characterized.¹⁰⁰

Elimination Route

Excreted principally in urine as metabolites.¹⁰⁰

Following oral administration, about 50% of radioactivity excreted within 24 hours.¹⁰⁰

Half-life

16-48 hours.¹⁰⁰

Stability

Storage

Oral

Capsules

Store at 25°C (excursions permitted to 15–30°C).¹⁰⁰ Avoid temperatures >40°C.¹⁰⁰

Actions

• Alkylates DNA and RNA.¹⁰⁰

• May inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.¹⁰⁰

Advice to Patients

• Advise patients that periodic blood count monitoring is necessary during lomustine therapy.¹⁰⁰ Advise patients to contact their healthcare provider for new onset of bleeding, fever, or symptoms of infection.¹⁰⁰

• Inform patients that toxicity, including fatal toxicity, has occurred with overdosage of lomustine.¹⁰⁰

• 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.¹⁰⁰ Lomustine is taken as a single oral dose that will not be repeated for at least 6 weeks.¹⁰⁰ Administration of lomustine at the recommended dose more frequently than every 6 weeks has resulted in toxicities, including fatal toxicities.¹⁰⁰

• Advise patients to contact their healthcare provider if they experience a new or worsening cough, chest pain, or shortness of breath.¹⁰⁰

• Inform patients that lomustine can cause hepatoxicity and that liver function must be monitored during treatment.¹⁰⁰

• Inform patients that lomustine can cause nephrotoxicity and that renal function and electrolytes must be monitored during treatment.¹⁰⁰

• 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.¹⁰⁰

• Stress importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰⁰ Inform females of reproductive potential of the potential fetal risk with lomustine and to inform their healthcare providers of a known or suspected pregnancy.¹⁰⁰ Inform females of reproductive potential to use effective contraception during lomustine therapy and for at least 2 weeks following the final dose.¹⁰⁰ Inform males with female partners of reproductive potential to use condoms during treatment with lomustine and for 3.5 months following the final dose.¹⁰⁰ Advise women to avoid breast-feeding during lomustine therapy and for 2 weeks following the final dose.¹⁰⁰

• Inform females and males of reproductive potential of the potential for reduced fertility from lomustine therapy.¹⁰⁰

• Inform patients of other important precautionary information.¹⁰⁰

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.

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