Lomustine

Lomustine
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

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Black Box Warning

WARNINGS See full prescribing information for complete Boxed Warning. * Gleostine (lomustine) should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Bone marrow suppression, notably thrombocytopenia and leukopenia, which may contribute to bleeding and overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of Gleostine. Since the major toxicity is delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose. At the recommended dosage, courses of Gleostine should not be given more frequently than every 6 weeks. The bone marrow toxicity of Gleostine is cumulative and therefore dosage adjustment must be considered on the basis of nadir blood counts from prior dose.

Overview

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Gleostine has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following:

• Brain tumors—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures.

• Hodgkin's disease—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.

Dosage

• The recommended dose of Gleostine in adult and pediatric patients as a single agent in previously untreated patients is 130 mg/m2 as a single oral dose every 6 weeks . In individuals with compromised bone marrow function, the dose should be reduced to 100 mg/m2 every 6 weeks. When Gleostine is used in combination with other myelosuppressive drugs, the doses should be adjusted accordingly. All doses of Gleostine must be rounded to the nearest 10 mg by the prescriber .

• Doses subsequent to the initial dose should be adjusted according to the hematologic response of the patient to the preceding dose. The following schedule is suggested as a guide to dosage adjustment:

This image is provided by the National Library of Medicine.

• A repeat course of Gleostine should not be given until circulating blood elements have returned to acceptable levels (platelets above 100,000/mm3; leukocytes above 4000/mm3), and this is usually in 6 weeks. Adequate number of neutrophils should be present on a peripheral blood smear. Blood counts should be monitored weekly and repeat courses should not be given before 6 weeks because the hematologic toxicity is delayed and cumulative.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition1

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Condition2

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Condition3

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Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

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Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Lomustine in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

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Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lomustine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding FDA-Labeled Use of Lomustine in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Lomustine in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lomustine in pediatric patients.

Contraindications

• Condition1

Warnings

WARNINGS See full prescribing information for complete Boxed Warning. * Gleostine (lomustine) should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Bone marrow suppression, notably thrombocytopenia and leukopenia, which may contribute to bleeding and overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of Gleostine. Since the major toxicity is delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose. At the recommended dosage, courses of Gleostine should not be given more frequently than every 6 weeks. The bone marrow toxicity of Gleostine is cumulative and therefore dosage adjustment must be considered on the basis of nadir blood counts from prior dose.

• Description

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

Hematologic Toxicity

• The most frequent and most serious toxicity of Gleostine is delayed myelosuppression. It usually occurs 4 to 6 weeks after drug administration and is dose related. Thrombocytopenia occurs at about 4 weeks post administration and persists for 1 to 2 weeks. Leukopenia occurs at 5 to 6 weeks after a dose of Gleostine and persists for 1 to 2 weeks. Approximately 65% of patients receiving 130 mg/m2 develop white blood counts below 5000 wbc/mm3. Thirty-six percent developed white blood counts below 3000 wbc/mm3. Thrombocytopenia is generally more severe than leukopenia. However, both may be dose-limiting toxicities.

• Gleostine may produce cumulative myelosuppression, manifested by more depressed indices or longer duration of suppression after repeated doses.

• The occurrence of acute leukemia and bone marrow dysplasias have been reported in patients following long-term nitrosourea therapy.

• Anemia also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia.

Pulmonary Toxicity

• Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis has been reported rarely with Gleostine. Onset of toxicity has occurred after an interval of 6 months or longer from the start of therapy with cumulative doses of Gleostine usually greater than 1100 mg/m2. There is 1 report of pulmonary toxicity at a cumulative dose of only 600 mg.

• Delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in patients who received related nitrosoureas in childhood and early adolescence (1–16 years) combined with cranial radiotherapy for intracranial tumors. There appeared to be some late reduction of pulmonary function of all long-term survivors. This form of lung fibrosis may be slowly progressive and has resulted in death in some cases. In this long-term study of carmustine, all those initially treated at less than 5 years of age died of delayed pulmonary fibrosis.

Gastrointestinal Toxicity

• Nausea and vomiting may occur 3 to 6 hours after an oral dose and usually last less than 24 hours. Prior administration of antiemetics is effective in diminishing and sometimes preventing this side effect. Nausea and vomiting can also be reduced if Gleostine is administered to fasting patients.

Hepatotoxicity

A reversible type of hepatic toxicity, manifested by increased transaminase, alkaline phosphatase, and bilirubin levels, has been reported in a small percentage of patients receiving Gleostine.

Nephrotoxicity

• Renal abnormalities consisting of progressive azotemia, decrease in kidney size, and renal failure have been reported in patients who received large cumulative doses after prolonged therapy with Gleostine. Kidney damage has also been reported occasionally in patients receiving lower total doses.

Other Toxicities

• Stomatitis, alopecia, optic atrophy, and visual disturbances, such as blindness, have been reported infrequently.

• Neurological reactions, such as disorientation, lethargy, ataxia, and dysarthria have been noted in some patients receiving Gleostine. However, the relationship to medication in these patients is unclear.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Lomustine in the drug label.

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lomustine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lomustine during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Lomustine with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Lomustine with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Lomustine with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Lomustine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lomustine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Lomustine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Lomustine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lomustine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Lomustine in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

There is limited information regarding Monitoring of Lomustine in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Lomustine in the drug label.

Overdosage

• Accidental overdose with lomustine has been reported, including fatal cases. Accidental overdose has been associated with bone marrow suppression, abdominal pain, diarrhea, vomiting, anorexia, lethargy, dizziness, abnormal hepatic function, cough, and shortness of breath.

• No proven antidotes have been established for Gleostine overdosage. In case of overdose, appropriate supportive measures should be taken.

Pharmacology

There is limited information regarding Lomustine Pharmacology in the drug label.

Mechanism of Action

Structure

• GleostineTM (lomustine) (CCNU) is one of the nitrosoureas used in the treatment of certain neoplastic diseases. It is 1-(2-chloro-ethyl)-3-cyclohexyl-1-nitrosourea. It is a yellow powder with the empirical formula of C9H16ClN3O2 and a molecular weight of 233.71. Gleostine is soluble in 10% ethanol (0.05 mg per mL) and in absolute alcohol (70 mg per mL). Gleostine is relatively insoluble in water (<0.05 mg per mL).

It is relatively un-ionized at a physiological pH.

Inactive ingredients in Gleostine Capsules are magnesium stearate and mannitol.

The structural formula is:

This image is provided by the National Library of Medicine.

• Gleostine is available in 10 mg, 40 mg, and 100 mg capsules for oral administration.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Lomustine in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Lomustine in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Lomustine in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Lomustine in the drug label.

How Supplied

Storage

There is limited information regarding Lomustine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Lomustine in the drug label.

Precautions with Alcohol

• Alcohol-Lomustine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• GLEOSTINE

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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