Gleostine 40mg Capsules
WARNING: This drug may lower the ability of the bone marrow to make blood cells that the body needs. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. Some infections have been severe and even deadly. If you have questions, talk with the doctor.Most of the time, this drug is to be taken as 1 dose every 6 weeks. Taking more often than you are told may raise your chance of very bad and sometimes deadly side effects. Do not take a dose of this drug more than 1 time within a 6 week period without talking with your doctor.Have your blood work checked often for at least 6 weeks after a dose. Talk with your doctor. @ COMMON USES: It is used to treat a type of brain tumor.It is used to treat a type of lymphoma.
Drug Class
Antineoplastic agent
Pharmacologic Class
Alkylating agent (Nitrosourea)
Pregnancy Category
D
FDA Approved
May 1976
DEA Schedule
Not Controlled
Overview
What is this medicine?
Lomustine is a chemotherapy medicine used to treat certain types of cancer, like brain tumors and Hodgkin's lymphoma. It works by damaging the cancer cells' genetic material, which stops them from growing and multiplying. It's taken as a capsule, usually once every six weeks.
How to Use This Medicine
To take this medication correctly, follow your doctor's instructions and read all accompanying information carefully. Your prescribed dose may consist of two or more different strengths and colors of capsules.
To minimize the risk of stomach upset or nausea, consider taking this medication on an empty stomach. However, consult with your doctor before doing so.
When handling this medication, it's essential to take special precautions. Consult your doctor or pharmacist for guidance on proper handling procedures. Wear gloves when touching the capsules to avoid exposure. If you come into contact with a broken capsule or the medication inside, immediately wash the affected area with soap and water.
To store this medication, keep it at room temperature in a dry location, avoiding bathrooms. If you miss a dose, contact your doctor for advice on the best course of action.
To minimize the risk of stomach upset or nausea, consider taking this medication on an empty stomach. However, consult with your doctor before doing so.
When handling this medication, it's essential to take special precautions. Consult your doctor or pharmacist for guidance on proper handling procedures. Wear gloves when touching the capsules to avoid exposure. If you come into contact with a broken capsule or the medication inside, immediately wash the affected area with soap and water.
To store this medication, keep it at room temperature in a dry location, avoiding bathrooms. If you miss a dose, contact your doctor for advice on the best course of action.
Lifestyle & Tips
- Avoid contact with people who are sick or have infections, as your immune system will be weakened.
- Report any signs of infection (fever, chills, sore throat) immediately.
- Avoid activities that could cause cuts or bruises due to increased bleeding risk.
- Maintain good oral hygiene to prevent mouth sores.
- Stay well-hydrated.
- Avoid live vaccines during treatment and for a period after.
- Use effective contraception during treatment and for several months after, as this drug can harm a fetus.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
130 mg/m² orally as a single dose every 6 weeks
Dose Range:
100 - 130 mg
Condition-Specific Dosing:
brainTumors:
130 mg/m² orally as a single dose every 6 weeks
hodgkinsDisease:
130 mg/m² orally as a single dose every 6 weeks (often in combination with other agents, dose may be reduced to 100 mg/m²)
myelosuppression:
Dose reduction based on nadir blood counts (e.g., if WBC < 3000/mm³ or platelets < 75,000/mm³, reduce dose by 25-50%)
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
130 mg/m² orally as a single dose every 6 weeks (similar to adult dosing, but use with extreme caution and only when benefits outweigh risks)
Adolescent:
130 mg/m² orally as a single dose every 6 weeks
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor renal function closely.
Moderate:
Use with caution; consider dose reduction and close monitoring of renal function and hematologic parameters.
Severe:
Not recommended due to increased risk of toxicity; if used, significant dose reduction and close monitoring are required.
Dialysis:
Not available (Lomustine is highly lipophilic and rapidly metabolized, unlikely to be significantly removed by dialysis. Use with extreme caution, if at all, and monitor closely).
Hepatic Impairment:
Mild:
Use with caution; monitor liver function tests and hematologic parameters.
Moderate:
Use with caution; consider dose reduction and close monitoring of liver function and hematologic parameters.
Severe:
Not recommended due to increased risk of toxicity; if used, significant dose reduction and close monitoring are required.
Pharmacology
Mechanism of Action
Lomustine is a nitrosourea alkylating agent. It acts by alkylating DNA and RNA, leading to cross-linking of DNA strands and inhibition of DNA synthesis, RNA synthesis, and protein synthesis. This results in cell cycle arrest and ultimately cell death. It is cell cycle non-specific.
Pharmacokinetics
Absorption:
Bioavailability:
Rapid and nearly complete oral absorption (approximately 30-50% of administered dose is absorbed)
Tmax:
Approximately 3-4 hours for parent drug; active metabolites peak later (e.g., 6 hours)
FoodEffect:
Food may delay absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
Not precisely quantified, but widely distributed throughout the body, including high penetration into the cerebrospinal fluid (CSF) due to its lipophilicity.
ProteinBinding:
Approximately 50% (parent drug); metabolites are also protein-bound.
CnssPenetration:
Yes (high penetration across the blood-brain barrier)
Elimination:
HalfLife:
Parent drug: 16-72 hours (highly variable); Active metabolites: 1.8-6.5 days (due to enterohepatic recirculation)
Clearance:
Not precisely quantified due to extensive metabolism and variable half-life.
ExcretionRoute:
Primarily renal (approximately 60% within 48 hours, 75% within 96 hours); small amount excreted in feces.
Unchanged:
< 1% (parent drug)
Pharmacodynamics
OnsetOfAction:
Not directly applicable for cytotoxic effect; myelosuppression is delayed.
PeakEffect:
Myelosuppression nadir typically occurs 4-6 weeks after a dose.
DurationOfAction:
Single dose effect lasts for 6 weeks (due to delayed and prolonged myelosuppression).
Safety & Warnings
BLACK BOX WARNING
Myelosuppression: Lomustine causes delayed and cumulative myelosuppression, affecting both white blood cells and platelets. Nadirs typically occur 4-6 weeks after a dose and recovery may take 1-2 weeks. Thrombocytopenia and leukopenia are common and can be severe. Complete blood counts must be monitored weekly for at least 6 weeks after each dose. Subsequent doses should not be given until blood counts have recovered. Pulmonary Toxicity: Fatal pulmonary toxicity has been reported with lomustine, particularly with cumulative doses greater than 1100 mg/m². Patients should be monitored for signs of pulmonary toxicity, and pulmonary function tests should be performed periodically.
Side Effects
Serious Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of infection, including:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or changed sputum production
+ Pain while urinating
+ Mouth sores
+ Wounds that won't heal
Signs of bleeding, such as:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that get bigger
+ Uncontrollable bleeding
Signs of liver problems, including:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine production
+ Blood in the urine
+ Sudden weight gain
Signs of lung or breathing problems, including:
+ Shortness of breath or other breathing difficulties
+ Cough
+ Fever
Chest pain
Confusion
Extreme tiredness or weakness
Balance changes
Speech difficulties
Mouth irritation or mouth sores
Changes in vision
Loss of vision
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they don't go away, contact your doctor or seek medical help:
Upset stomach or vomiting
Hair loss
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of infection, including:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or changed sputum production
+ Pain while urinating
+ Mouth sores
+ Wounds that won't heal
Signs of bleeding, such as:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that get bigger
+ Uncontrollable bleeding
Signs of liver problems, including:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine production
+ Blood in the urine
+ Sudden weight gain
Signs of lung or breathing problems, including:
+ Shortness of breath or other breathing difficulties
+ Cough
+ Fever
Chest pain
Confusion
Extreme tiredness or weakness
Balance changes
Speech difficulties
Mouth irritation or mouth sores
Changes in vision
Loss of vision
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they don't go away, contact your doctor or seek medical help:
Upset stomach or vomiting
Hair loss
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever (100.4°F or higher) or chills
- Unusual bleeding or bruising
- Extreme tiredness or weakness
- Shortness of breath or persistent cough
- Yellowing of skin or eyes
- Severe nausea, vomiting, or diarrhea
- Sores in mouth or throat
- Signs of kidney problems (e.g., changes in urination, swelling)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are breastfeeding or plan to breastfeed. You should not breastfeed while taking this medication and for 2 weeks after your last dose.
Potential Interactions with Other Medications or Health Conditions
This medication may interact with other medications or worsen certain health conditions. To ensure your safety, it is crucial to:
Inform your doctor and pharmacist about all medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Disclose any health problems you have, as they may affect the safety and efficacy of this medication.
Verify with your doctor that it is safe to take this medication with all your other medications and health conditions.
Do not start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are breastfeeding or plan to breastfeed. You should not breastfeed while taking this medication and for 2 weeks after your last dose.
Potential Interactions with Other Medications or Health Conditions
This medication may interact with other medications or worsen certain health conditions. To ensure your safety, it is crucial to:
Inform your doctor and pharmacist about all medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Disclose any health problems you have, as they may affect the safety and efficacy of this medication.
Verify with your doctor that it is safe to take this medication with all your other medications and health conditions.
Do not start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regularly check your lung function as directed by your doctor and discuss any concerns with them.
As this medication may increase your risk of developing infections, it is crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
You may experience an increased risk of bleeding due to this medication. To minimize this risk, be cautious and avoid injuries. Additionally, use a soft toothbrush and an electric razor to reduce the risk of bleeding.
Long-term use of this medication may increase the risk of developing other types of cancer. If you have any questions or concerns, discuss them with your doctor.
If you experience gastrointestinal side effects such as stomach upset, vomiting, diarrhea, or decreased appetite, consult your doctor, as they may be able to suggest ways to alleviate these symptoms.
Before receiving any vaccinations, consult your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication.
This medication should be used with caution in children, and your doctor should be consulted to discuss the potential risks and benefits.
It is also important to note that this medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss this with your doctor before starting treatment.
Women who are pregnant or may become pregnant should be aware that this medication may harm the unborn baby. If you or your partner may become pregnant, it is essential to use birth control while taking this medication and for a specified period after the last dose, as advised by your doctor. If pregnancy occurs, notify your doctor immediately.
As this medication may increase your risk of developing infections, it is crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
You may experience an increased risk of bleeding due to this medication. To minimize this risk, be cautious and avoid injuries. Additionally, use a soft toothbrush and an electric razor to reduce the risk of bleeding.
Long-term use of this medication may increase the risk of developing other types of cancer. If you have any questions or concerns, discuss them with your doctor.
If you experience gastrointestinal side effects such as stomach upset, vomiting, diarrhea, or decreased appetite, consult your doctor, as they may be able to suggest ways to alleviate these symptoms.
Before receiving any vaccinations, consult your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication.
This medication should be used with caution in children, and your doctor should be consulted to discuss the potential risks and benefits.
It is also important to note that this medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss this with your doctor before starting treatment.
Women who are pregnant or may become pregnant should be aware that this medication may harm the unborn baby. If you or your partner may become pregnant, it is essential to use birth control while taking this medication and for a specified period after the last dose, as advised by your doctor. If pregnancy occurs, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (profound leukopenia, thrombocytopenia, anemia)
- Severe gastrointestinal toxicity (nausea, vomiting, diarrhea, stomatitis)
- Neurotoxicity (ataxia, disorientation, seizures)
- Hepatotoxicity
- Nephrotoxicity
What to Do:
There is no specific antidote for lomustine overdose. Management is supportive, including aggressive supportive care for myelosuppression (e.g., transfusions, growth factors, antibiotics for infection), antiemetics for GI symptoms, and monitoring of vital organ function. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live or live-attenuated vaccines (risk of severe or fatal infection in immunocompromised patients)
Major Interactions
- Other myelosuppressive agents (e.g., other chemotherapies, radiation therapy) - increased risk of severe myelosuppression
- Phenytoin (reduced phenytoin levels due to enzyme induction by lomustine metabolites)
- Cimetidine (may inhibit lomustine metabolism, increasing toxicity)
- Drugs causing pulmonary toxicity (e.g., Bleomycin, Busulfan) - increased risk of pulmonary fibrosis
Moderate Interactions
- CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics, grapefruit juice) - potential for increased lomustine exposure and toxicity
- CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's Wort) - potential for decreased lomustine exposure and efficacy
- Nephrotoxic drugs (e.g., aminoglycosides, NSAIDs) - increased risk of renal toxicity
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelet count
Rationale: To establish baseline hematologic status before initiating therapy, as myelosuppression is the dose-limiting toxicity.
Timing: Prior to first dose
Liver Function Tests (LFTs) - AST, ALT, bilirubin, alkaline phosphatase
Rationale: To assess baseline hepatic function, as lomustine is hepatically metabolized and can cause hepatotoxicity.
Timing: Prior to first dose
Renal Function Tests - BUN, serum creatinine
Rationale: To assess baseline renal function, as lomustine and its metabolites are primarily renally excreted and can cause nephrotoxicity.
Timing: Prior to first dose
Pulmonary Function Tests (PFTs) - FVC, DLCO
Rationale: To establish baseline pulmonary function, especially in patients with pre-existing lung disease or prior exposure to pulmonary toxic agents, due to risk of pulmonary fibrosis.
Timing: Prior to first dose (consider if risk factors present)
Routine Monitoring
Complete Blood Count (CBC) with differential and platelet count
Frequency: Weekly for at least 6 weeks after each dose, or until counts recover.
Target: WBC > 4000/mm³, Platelets > 100,000/mm³ before next dose.
Action Threshold: If WBC < 3000/mm³ or platelets < 75,000/mm³, consider dose reduction for subsequent cycles. If severe myelosuppression, delay next dose until recovery.
Liver Function Tests (LFTs)
Frequency: Before each subsequent dose (every 6 weeks) or as clinically indicated.
Target: Within normal limits or stable from baseline.
Action Threshold: Significant elevations may warrant dose adjustment or discontinuation.
Renal Function Tests
Frequency: Before each subsequent dose (every 6 weeks) or as clinically indicated.
Target: Within normal limits or stable from baseline.
Action Threshold: Significant elevations may warrant dose adjustment or discontinuation.
Pulmonary Function Tests (PFTs)
Frequency: Periodically, especially if cumulative dose is high or symptoms develop.
Target: Stable from baseline.
Action Threshold: Significant decline may indicate pulmonary toxicity and require discontinuation.
Symptom Monitoring
- Fever, chills, sore throat, unusual bleeding or bruising (signs of myelosuppression/infection)
- Fatigue, weakness (anemia)
- Nausea, vomiting, stomatitis, diarrhea (gastrointestinal toxicity)
- Shortness of breath, cough, dyspnea (pulmonary toxicity)
- Yellowing of skin/eyes, dark urine, abdominal pain (hepatotoxicity)
- Changes in urination, swelling (renal toxicity)
- Headache, dizziness, confusion (CNS effects)
Special Patient Groups
Pregnancy
Lomustine can cause fetal harm when administered to a pregnant woman. It is teratogenic and embryotoxic. Women of childbearing potential should be advised to avoid becoming pregnant during therapy and to use effective contraception. If used during pregnancy or if the patient becomes pregnant, the patient should be apprised of the potential hazard to the fetus.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations and spontaneous abortion due to organogenesis.
Second Trimester:
Risk of fetal growth restriction, myelosuppression, and other toxicities.
Third Trimester:
Risk of fetal myelosuppression and other toxicities; may affect neonatal blood counts.
Lactation
It is not known whether lomustine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from lomustine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Breastfeeding is generally contraindicated.
Infant Risk:
High risk of serious adverse effects including myelosuppression, immunosuppression, and potential carcinogenicity/mutagenicity.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established in controlled clinical trials. However, lomustine has been used in pediatric oncology for brain tumors. Dosing is typically based on body surface area, similar to adults. Pediatric patients may be more susceptible to long-term toxicities, including delayed myelosuppression, pulmonary fibrosis, and secondary malignancies. Close monitoring is essential.
Geriatric Use
No specific dose adjustments are generally recommended based solely on age. However, elderly patients may have reduced renal or hepatic function, or more comorbidities, which could increase the risk of toxicity. Close monitoring of hematologic, renal, and hepatic parameters is particularly important in this population.
Clinical Information
Clinical Pearls
- Lomustine's myelosuppression is delayed and cumulative; nadirs typically occur 4-6 weeks after a dose, necessitating a 6-week dosing interval.
- Ensure patients understand the importance of weekly blood counts for at least 6 weeks after each dose.
- Pulmonary toxicity, including fatal pulmonary fibrosis, is a significant risk, especially with cumulative doses > 1100 mg/m². Monitor for respiratory symptoms and consider PFTs.
- Administer on an empty stomach or at least 1 hour before or 2 hours after a meal to minimize nausea and vomiting, though food does not significantly affect absorption extent.
- Antiemetics should be prescribed routinely due to high emetogenic potential.
- Capsules should be swallowed whole; do not chew, crush, or open.
- Patients should be advised to avoid live vaccines during treatment and for a period afterward due to immunosuppression.
Alternative Therapies
- Temozolomide (for glioblastoma)
- Procarbazine, Dacarbazine (other alkylating agents)
- Other chemotherapy regimens for Hodgkin's lymphoma (e.g., ABVD, BEACOPP)
- Radiation therapy (for brain tumors)
- Surgical resection (for brain tumors)
Cost & Coverage
Average Cost:
Varies widely, typically several thousand USD per 5-count bottle (e.g., 40mg capsules)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide information about the medication taken, the amount, and the time it happened.