Gleostine 10mg (ten Mg) 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
Category D
FDA Approved
Aug 2012
DEA Schedule
Not Controlled
Overview
What is this medicine?
Lomustine is a chemotherapy medicine used to treat certain types of cancer, especially brain tumors and Hodgkin's lymphoma. It works by damaging the cancer cells' DNA, which prevents them from growing and spreading. Because it affects rapidly growing cells, it can also affect healthy cells, leading to side effects.
How to Use This Medicine
To use 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 vomiting, consider taking this medication on an empty stomach. However, consult with your doctor before doing so.
When handling this medication, exercise caution and follow the guidance provided by your doctor or pharmacist. It is recommended to wear gloves when touching the capsules. If you come into contact with a broken capsule or the medication inside, wash the affected area with soap and water immediately.
To maintain the medication's potency, store 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 take.
To minimize the risk of stomach upset or vomiting, consider taking this medication on an empty stomach. However, consult with your doctor before doing so.
When handling this medication, exercise caution and follow the guidance provided by your doctor or pharmacist. It is recommended to wear gloves when touching the capsules. If you come into contact with a broken capsule or the medication inside, wash the affected area with soap and water immediately.
To maintain the medication's potency, store 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 take.
Lifestyle & Tips
- Take the capsules whole with water on an empty stomach (at least 1 hour before or 2 hours after a meal).
- Do not open, crush, or chew the capsules.
- Follow the dosing schedule exactly; doses are typically given only once every 6 weeks.
- 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.
- Use effective contraception during treatment and for a period after (men: at least 3 months, women: at least 6 months) due to potential harm to a fetus.
- Avoid live vaccines during treatment.
- Stay well-hydrated.
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)
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
130 mg/m² orally as a single dose every 6 weeks (for brain tumors, similar to adult dosing, but careful monitoring is crucial)
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 extended dosing interval based on hematologic toxicity.
Severe:
Use with extreme caution; significant dose reduction likely required, or avoid use. Monitor closely.
Dialysis:
Not available; Lomustine is highly protein-bound and extensively metabolized, so dialysis is unlikely to be effective for removal. Use with extreme caution.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended, but monitor liver function closely.
Moderate:
Use with caution; consider dose reduction based on hematologic toxicity and liver function. Monitor closely.
Severe:
Use with extreme caution; significant dose reduction likely required, or avoid use. Monitor closely.
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. It also carbamoylates proteins, which may contribute to its cytotoxic effects. It is cell cycle non-specific.
Pharmacokinetics
Absorption:
Bioavailability:
Not precisely quantified, but well absorbed orally.
Tmax:
Approximately 3-4 hours for parent drug; active metabolites peak later (6 hours).
FoodEffect:
Food may delay absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
Not available (extensively distributed)
ProteinBinding:
High (approximately 50% for parent drug, metabolites also highly bound)
CnssPenetration:
Yes (readily crosses the blood-brain barrier, which is important for its use in brain tumors)
Elimination:
HalfLife:
Parent drug: 16-72 hours (variable); Active metabolites: 1.5-6.5 days.
Clearance:
Not available (highly variable due to extensive metabolism)
ExcretionRoute:
Primarily renal (approximately 60% within 48 hours), with some fecal excretion.
Unchanged:
Less than 1% (parent drug)
Pharmacodynamics
OnsetOfAction:
Delayed (due to mechanism of action and myelosuppression onset)
PeakEffect:
Myelosuppression peak typically occurs 4-6 weeks after a dose.
DurationOfAction:
Single dose effect lasts for 6 weeks (due to prolonged myelosuppression and slow elimination of active metabolites).
Safety & Warnings
BLACK BOX WARNING
Myelosuppression: Lomustine causes delayed and cumulative myelosuppression. Thrombocytopenia and leukopenia are common and may be severe. Platelet and leukocyte counts should be monitored weekly for at least 6 weeks after each dose. Doses should not be repeated more frequently than every 6 weeks. Pulmonary Toxicity: Pulmonary toxicity, including pulmonary fibrosis, has been reported with lomustine. The risk is dose-related and increases with cumulative doses. Baseline and periodic pulmonary function tests are recommended.
Side Effects
Serious Side Effects: Seek Medical Help Right Away
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 immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever
Chest pain
Confusion
Extreme fatigue or weakness
Balance problems
Speech difficulties
Mouth irritation or sores
Changes in vision
Loss of vision
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Stomach upset 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 immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever
Chest pain
Confusion
Extreme fatigue or weakness
Balance problems
Speech difficulties
Mouth irritation or sores
Changes in vision
Loss of vision
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Stomach upset 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
- Sore throat, cough, or other signs of infection
- Unusual bleeding or bruising
- Extreme tiredness or weakness
- Shortness of breath or new/worsening cough
- Yellowing of skin or eyes (jaundice)
- Dark urine or pale stools
- Severe nausea, vomiting, or diarrhea
- Mouth sores or pain when eating/drinking
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 medications, natural products, and vitamins.
Discuss any health problems you have, as they may affect the safety and efficacy of this medication.
* Before starting, stopping, or changing the dose of any medication, consult with your doctor to confirm it is safe to do so in conjunction with this medication.
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 medications, natural products, and vitamins.
Discuss any health problems you have, as they may affect the safety and efficacy of this medication.
* Before starting, stopping, or changing the dose of any medication, consult with your doctor to confirm it is safe to do so in conjunction with this medication.
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.
Be aware that you may experience easier bleeding, so it is vital to be cautious and avoid injuries. To minimize the risk of bleeding, use a soft toothbrush and an electric razor. Additionally, long-term use of this medication may increase the risk of developing other types of cancer, so it is essential to discuss any concerns with your doctor.
If you experience stomach upset, vomiting, diarrhea, or a decrease in appetite, consult your doctor, as they may be able to suggest ways to alleviate these side effects.
Before receiving any vaccinations, consult your doctor, as some 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 parents or guardians should discuss the potential risks and benefits with their doctor.
It is also important to note that this medication may affect fertility, potentially making it difficult to become pregnant or father a child. If you plan to conceive, discuss your plans with your doctor before starting this medication.
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. Your doctor will advise you on the duration of birth control use. If you or your partner becomes pregnant, 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.
Be aware that you may experience easier bleeding, so it is vital to be cautious and avoid injuries. To minimize the risk of bleeding, use a soft toothbrush and an electric razor. Additionally, long-term use of this medication may increase the risk of developing other types of cancer, so it is essential to discuss any concerns with your doctor.
If you experience stomach upset, vomiting, diarrhea, or a decrease in appetite, consult your doctor, as they may be able to suggest ways to alleviate these side effects.
Before receiving any vaccinations, consult your doctor, as some 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 parents or guardians should discuss the potential risks and benefits with their doctor.
It is also important to note that this medication may affect fertility, potentially making it difficult to become pregnant or father a child. If you plan to conceive, discuss your plans with your doctor before starting this medication.
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. Your doctor will advise you on the duration of birth control use. If you or your partner becomes pregnant, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (very low blood counts)
- Severe nausea and vomiting
- Liver toxicity
- Kidney toxicity
- Neurological symptoms (e.g., confusion, seizures)
What to Do:
Seek immediate medical attention. There is no specific antidote. Treatment is supportive, focusing on managing symptoms and complications (e.g., transfusions for myelosuppression, antiemetics). Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live or live-attenuated vaccines (due to immunosuppression)
Major Interactions
- Other myelosuppressive agents (e.g., other chemotherapy, radiation therapy) - increased risk of severe myelosuppression.
- Phenytoin (decreased phenytoin levels, increased risk of seizures).
- 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., ketoconazole, ritonavir) - potential for increased lomustine exposure and toxicity.
- CYP3A4 inducers (e.g., rifampin, carbamazepine) - potential for decreased lomustine exposure and efficacy.
- Nephrotoxic agents (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 a major 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 (RFTs) - BUN, 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) including DLCO
Rationale: To establish baseline pulmonary status, especially in patients with pre-existing lung disease or those receiving other pulmonary toxic agents, due to risk of pulmonary fibrosis.
Timing: Prior to first dose (if indicated)
Routine Monitoring
Complete Blood Count (CBC) with differential and platelet count
Frequency: Weekly for at least 6 weeks after each dose
Target: WBC > 4,000/mm³, Platelets > 100,000/mm³ (general guideline for next dose)
Action Threshold: If WBC < 3,000/mm³ or platelets < 75,000/mm³, delay next dose or reduce dose. If nadir is severe, consider dose reduction for subsequent cycles.
Liver Function Tests (LFTs)
Frequency: Prior to each subsequent dose (every 6 weeks)
Target: Within normal limits or stable baseline
Action Threshold: Significant elevations may require dose modification or discontinuation.
Renal Function Tests (RFTs)
Frequency: Prior to each subsequent dose (every 6 weeks)
Target: Within normal limits or stable baseline
Action Threshold: Significant elevations may require dose modification or discontinuation.
Pulmonary Function Tests (PFTs)
Frequency: Periodically, especially with cumulative doses or symptoms
Target: Stable
Action Threshold: Significant decline in DLCO or onset of respiratory symptoms may indicate pulmonary toxicity and require discontinuation.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising
- Fatigue, weakness, pallor (signs of anemia)
- Nausea, vomiting, loss of appetite
- Stomatitis or mouth sores
- Shortness of breath, cough, difficulty breathing (signs of pulmonary toxicity)
- Yellowing of skin or eyes, dark urine (signs of liver problems)
- Changes in urination (signs of kidney problems)
- Neurological changes (e.g., confusion, seizures, ataxia)
Special Patient Groups
Pregnancy
Lomustine can cause fetal harm when administered to a pregnant woman. It is teratogenic and embryotoxic. Advise pregnant women of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.
Trimester-Specific Risks:
First Trimester:
High risk of major birth defects and fetal death due to organogenesis.
Second Trimester:
Risk of fetal growth restriction, myelosuppression, and other adverse effects.
Third Trimester:
Risk of fetal myelosuppression and other adverse effects.
Lactation
It is not known whether lomustine is excreted in human milk. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with lomustine and for 1 week after the last dose.
Infant Risk:
High risk of serious adverse effects including myelosuppression and carcinogenicity.
Pediatric Use
Safety and effectiveness have been established in pediatric patients with brain tumors. Dosing is based on body surface area, similar to adults. Pediatric patients may be more susceptible to the long-term effects of chemotherapy, including secondary malignancies and organ toxicity (e.g., pulmonary fibrosis, renal failure). Close monitoring is essential.
Geriatric Use
Clinical studies of lomustine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients may have reduced renal or hepatic function, which could increase toxicity. Dose selection for an elderly patient should be cautious, generally starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Close monitoring for myelosuppression and other toxicities is crucial.
Clinical Information
Clinical Pearls
- Lomustine is a highly lipophilic drug that readily crosses the blood-brain barrier, making it effective for brain tumors.
- The delayed and cumulative myelosuppression is the dose-limiting toxicity. It is crucial to monitor blood counts weekly for at least 6 weeks after each dose and to adhere strictly to the 6-week dosing interval.
- Nadir for platelets typically occurs at 4 weeks, and for leukocytes at 5-6 weeks, after a dose.
- Pulmonary toxicity (fibrosis) is a serious, dose-related, and potentially fatal complication. Cumulative doses over 1000 mg/m² significantly increase this risk.
- Administer on an empty stomach to minimize nausea and vomiting, although antiemetics are often necessary.
- Capsules must be swallowed whole; do not open or crush them due to the hazardous nature of the drug.
- Ensure patients understand the importance of infection prevention and reporting any signs of infection immediately.
Alternative Therapies
- Temozolomide (for glioblastoma)
- Carmustine (BCNU, another nitrosourea)
- Procarbazine (for Hodgkin's lymphoma)
- Dacarbazine (for Hodgkin's lymphoma)
- Other alkylating agents (e.g., cyclophosphamide, ifosfamide)
- Radiation therapy (for brain tumors)
- Surgery (for brain tumors)
Cost & Coverage
Average Cost:
Varies widely, typically several thousand dollars per 30 capsules (e.g., 10mg, 40mg, 100mg)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization, often covered under medical benefit for oncology)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to 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 details about the medication taken, the amount, and the time it happened.