Dosing & Uses
Dosage Forms & Strengths
capsule
- 5mg
- 10mg
- 40mg
- 100mg
Brain Tumors
Round dose to nearest 5 mg
Compromised bone marrow: 100 mg/m² PO once q6week
Hodgkin Lymphoma
Round dose to nearest 5 mg
Compromised bone marrow: 100 mg/m² PO once q6week
Dosage Modifications
For SI Units, convert full U.S. value by x 10^6/L
Do not repeat course until platelets >100000/mm³ and leukocytes >4000/mm³/
Give full dose if
- Leukocytes >3000/mm³
- Platelets >75000/mm³
Give 70% if
- Leukocytes: 2000-2999/mm³
- Platelets: 25000-74999/mm³
Give 50% if
- Leukocytes <1999/mm³
- Platelets <24999/mm³
Renal impairment
- CrCl >50 mL/min: Administer full dose
- CrCl 10-50 mL/min: Administer 75% of regular dose
- CrCl <10 mL/min: Administer 25-50% of regular dose
Hepatic impairment
- Use caution, not studied
Monitor
CBC, pulmonary function, LFTs, renal function
Adjust dose based on WBC counts; do not repeat dose until WBC >4000/mm³ & Plts >100000/mm³
Other Indications & Uses
Malignant gliomas
Off-label: pancreatic, liver, gastric, colorectal cancer; multiple myeloma; mycosis fungoides, psoriasis (topical)
Dosage Forms & Strengths
capsule
- 5mg
- 10mg
- 40mg
- 100mg
Brain Tumors
Round dose to nearest 5 mg
Compromised bone marrow: 100 mg/m² PO once q6week
Hodgkin Lymphoma
Round dose to nearest 5 mg
Compromised bone marrow: 100 mg/m² PO once q6week
Dosing Considerations
Pediatric use, including dose, is not based on adequate and well-controlled clinical studies, although it has approved indications for brain tumors and Hodgkin lymphoma
Dosage Modifications
For SI Units, convert full U.S. value by x 10^6/L
Do not repeat course until platelets >100000/mm³ and leukocytes >4000/mm³/
Give full dose if
- Leukocytes >3000/mm³
- Platelets >75000/mm³
Give 70% if
- Leukocytes: 2000-2999/mm³
- Platelets: 25000-74999/mm³
Give 50% if
- Leukocytes <1999/mm³
- Platelets <24999/mm³
Renal impairment
- CrCl >50 mL/min: Administer full dose
- CrCl 10-50 mL/min: Administer 75% of regular dose
- CrCl <10 mL/min: Administer 50% of regular dose
Hepatic impairment
- Use caution, not studied
Monitor
CBC, pulmonary function, LFTs, renal function
Adjust dose based on WBC counts; do not repeat dose until WBC >4000/mm³ & Plts >100000/mm³
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Nausea (54%)
Vomiting (54%)
1-10%
Neurotoxicity
Myelosuppression (delayed 4-5 weeks)
Frequency Not Defined
Ataxia
Lethargy
Disorientation
Stomatitis
Mucositis
Pulmonary fibrosis (rare)
Pulmonary toxicity
Elevated LFTs
Leukemia
Renal toxicity
Hepatic toxicity
Infertility
Alopecia
Optic atrophy (rare)
Warnings
Black Box Warnings
Myelosuppression is delayed, dose-related, and cumulative; thrombocytopenia is generally more severe than leukopenia; may occur 4-6 weeks after drug administration and persist for 1- 2 weeks; thrombocytopenia and leucopenia may contribute to bleeding and overwhelming infections in an already compromised patient; monitor blood counts weekly for 6 or more weeks after a dose; do not give therapy more frequently than every 6 weeks; bone marrow toxicity is cumulative; adjust dose based on nadir blood counts from prior dosage
Therapy should be administered by experienced cancer physician; prescribe, dispense, and administer enough capsules for one dose; fatal toxicity occurs with overdosage; prescribe, dispense, and administer only enough capsules for one dose; both physician and pharmacist should emphasize to patient that only one dose of the drug is taken every 6 weeks
Contraindications
Hypersensitivity
Cautions
Causes myelosuppression that can result in fatal infections and bleeding; monitor blood counts for at least 6 weeks after each dose; do not give more frequently than q6wk due to delayed myelosuppression
Avoid pregnancy; can cause fetal harm; advise males and females of reproductive potential of potential risk to fetus and to use effective contraception; advise males with female partners of reproductive potential to use effective contraception during treatment and for 3.5 months after the final dose; therapy may result in reduced fertility in males and females of reproductive potential
Hepatotoxicity reported; increased levels of transaminases, alkaline phosphatase and bilirubin can occur; monitor liver function
Can cause renal failure; monitor renal function
Delayed pulmonary toxicity may occur; pulmonary infiltrates and/or fibrosis may occur; perform pulmonary function tests prior to treatment and repeat frequently; permanently discontinue therapy in patients diagnosed with pulmonary fibrosis
Secondary malignancies reported; acute leukemia and myelodysplasia can occur with long-term use
Pregnancy & Lactation
Pregnancy Category: D
Lactation: Unknown if metabolites present in breast milk; avoid nursing during treatment and for 2 weeks after final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Not completely understood
Inhibition of DNA & RNA synthesis resulting from carbamylation of DNA polymerase, alkylation of DNA, and alteration of RNA proteins
Pharmacokinetics
Half-Life Elimination (biphasic): 16-24 hr (parent drug); 16-48 hr (active metabolite)
Peak plasma time: ~3 hr
Metabolism: Liver
Duration: 5-6 weeks (bone marrow recovery)
Excretion: Urine (50%); feces (<5%)
Administration
Oral Administration
Images
Patient Handout
Formulary
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Adding plans allows you to:
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- Compare formulary status to other drugs in the same class.
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