Lomustine causes myelosuppression, including fatal myelosuppression. Myelosuppression is delayed, dose-related, and cumulative, occurring 4 to 6 weeks after drug administration and persisting for 1 to 2 weeks. Thrombocytopenia is generally more severe than leukopenia. Cumulative myelosuppression from lomustine is manifested by greater severity and longer duration of cytopenias. Monitor blood counts for at least 6 weeks after each dose. Do not give lomustine more frequently than every 6 weeks.
Prescribe, dispense, and administer only enough capsules for one dose. Fatal toxicity occurs with overdosage of lomustine. Both health care provider and pharmacist should emphasize to the patient that only one dose of lomustine is taken every 6 weeks.
Dosage guidance:
Safety: Do not administer courses of lomustine more frequently than every 6 weeks. Dispense only enough capsules for a single dose; do not dispense more than one dose at a time (Ref). Repeat courses should only be administered after adequate recovery of leukocytes to >4,000/mm3 and platelets to >100,000/mm3.
Dosing : Round doses to the nearest 10 mg.
Clinical considerations: Lomustine is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Brain tumors: Note: Doses should be rounded to the nearest 10 mg.
Astrocytomas:
Glioblastoma, adjuvant therapy, MGMT-methylated tumors (off-label combination): Adults ≤70 years: Oral: 100 mg/m2 on day 1 every 6 weeks for 6 cycles (in combination with temozolomide and concurrent radiation therapy) (Ref). Refer to protocol for dosage modification details.
Glioblastoma:
PCV regimen (off-label combination): Oral: 110 mg/m2 on day 1 every 6 weeks for 7 cycles (following radiation therapy and in combination with procarbazine and vincristine) (Ref).
Single-agent therapy, recurrent glioblastoma: Oral: 100 to 130 mg/m2 once every 6 weeks until disease progression or unacceptable toxicity (Ref) or 110 mg/m2 on day 1 every 6 weeks (maximum dose: 200 mg) for a maximum of 6 cycles (Ref).
Glioma, low grade, adjuvant therapy: PCV regimen (off-label combination): Note: Patients with grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma were included in these trials.
Oral: 110 mg/m2 on day 1 of each 8-week cycle for 6 cycles (following radiation therapy and in combination with procarbazine and vincristine) (Ref).
Medulloblastomas:
Medulloblastoma, newly-diagnosed, average risk, adjuvant therapy (off-label combination): Adults ≤21 years: Oral: 75 mg/m2 once every 6 weeks for 8 cycles (following radiation therapy and in combination with cisplatin and vincristine) (Ref).
Oligodendrogliomas:
Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted: PCV regimen (off-label combination):
Oral: 130 mg/m2 on day 1 every 6 weeks for up to 4 cycles prior to radiation therapy (in combination with procarbazine and vincristine) (Ref).
Oral: 110 mg/m2 on day 1 every 6 weeks for 6 cycles (following radiation therapy and in combination with procarbazine and vincristine) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling. The following adjustments have been recommended:
Kintzel 1995:
CrCl 46 to 60 mL/minute: Reduce dose to 75% of normal dose.
CrCl 31 to 45 mL/minute: Reduce dose to 70% of normal dose.
CrCl ≤30 mL/minute: Avoid use.
Krens 2019:
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 50 mL/minute: Reduce dose to 75% of normal dose.
CrCl <30 mL/minute: Use is not recommended.
Hemodialysis: Use is not recommended (Ref). Due to its lipophilic nature, lomustine is not dialyzable (Ref).
CAPD: Reduce dose to 25% to 50% of normal dose (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling. However, lomustine is hepatically metabolized and caution should be used in patients with hepatic dysfunction.
The following adjustments have been recommended (Ref):
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended.
American Society of Clinical Oncology guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Hematologic toxicity: Dosing adjustment for subsequent cycles:
Note: Dose adjustments should be based on nadir counts from prior dose.
Leukocytes ≥3,000/mm3, platelets ≥75,000/mm3: No dosage adjustment required.
Leukocytes 2,000 to 2,999/mm3, platelets 25,000 to 74,999/mm3: Reduce dose to 70% of prior dose.
Leukocytes <2,000/mm3, platelets <25,000/mm3: Reduce dose to 50% of prior dose.
Nonhematologic toxicity: Pulmonary fibrosis: Discontinue permanently.
Refer to adult dosing.
(For additional information see "Lomustine: Pediatric drug information")
Note: At FDA approved dosages, lomustine should only be dispensed and administered as a single dose once every 6 weeks due to delayed myelotoxicity; serious errors have occurred when lomustine was inadvertently administered daily. Repeat courses should only be administered after adequate recovery of leukocytes to >4,000/mm3 and platelets to >100,000/mm3. Details concerning dosage in combination regimens should also be consulted; dose, frequency, number of doses, and start date may vary by protocol and treatment phase.
Note: Round doses to the nearest 10 mg. Lomustine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Brain tumors:
General dosing: Manufacturer's labeling: Infants, Children, and Adolescents: Oral: Initial: 130 mg/m2 as a single dose every 6 weeks (dosage reductions may be recommended for combination chemotherapy regimens).
Compromised marrow function: Reduce initial dose to 100 mg/m2 as a single dose once every 6 weeks; Note: Subsequent doses may require adjustment after initial treatment according to platelet and leukocyte counts.
Medulloblastoma: Children ≥3 years and Adolescents: Limited data available: Oral: 75 mg/m2 on day 0 of each chemotherapy cycle in combination with cisplatin, vincristine, and radiotherapy (Ref).
Gliomas: Limited data available:
Low grade: Infants, Children, and Adolescents: Oral: 110 mg/m2 on day 3 of a 6-week cycle in combination with thioguanine, vincristine, and procarbazine for up to 8 cycles for low grade, nonoperable (usually) gliomas (including astrocytomas) (Ref).
High grade: Jakacki 2016: Astrocytoma, glioblastoma: Children ≥3 years and Adolescents: Oral: 90 mg/m2 on day 1 every 42 days (or repeated when counts recovered) in combination with temozolomide and following radiotherapy for a total of 6 cycles (Ref).
Hodgkin lymphoma: Note: Although FDA approved (Gleostine prescribing information), other contemporary therapies have replaced the use of lomustine in the treatment of progressive Hodgkin lymphoma. Hodgkin lymphoma guidelines do not include lomustine as a treatment component for Hodgkin lymphoma management (Ref).
Infants, Children, and Adolescents: Oral: Initial: 130 mg/m2 as a single dose every 6 weeks (dosage reductions may be recommended for combination chemotherapy regimens) (Ref): Note: Subsequent doses may require adjustment after initial treatment according to platelet and leukocyte counts.
Compromised marrow function: Reduce initial dose to 100 mg/m2 as a single dose once every 6 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment based on toxicity: Infants, Children, and Adolescents:
Hematologic toxicity (nadir for subsequent cycles):
Leukocytes ≥3,000/mm3, platelets ≥75,000/mm3: No adjustment required.
Leukocytes 2,000 to 2,999/mm3, platelets 25,000 to 74,999/mm3: Administer 70% of prior dose.
Leukocytes <2,000/mm3, platelets <25,000/mm3: Administer 50% of prior dose.
Nonhematologic toxicity: Pulmonary fibrosis: Discontinue permanently.
There are no dosage adjustments provided in manufacturer's labeling; based on experience in adult patients, dosing adjustment suggested.
There are no dosage adjustments provided in manufacturer's labeling; however, lomustine is hepatically metabolized and caution should be used in patients with hepatic dysfunction.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Frequency not defined:
Dermatologic: Alopecia
Gastrointestinal: Nausea, stomatitis, vomiting
Hematologic & oncologic: Bone marrow depression, leukopenia, second primary malignant neoplasm (including acute leukemia and myelodysplastic syndrome), thrombocytopenia
Hepatic: Hepatotoxicity, increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases
Nervous system: Ataxia, disorientation, dysarthria, lethargy
Ophthalmic: Blindness, optic atrophy, visual disturbance
Renal: Nephron atrophy, renal failure syndrome
Respiratory: Pulmonary infiltrates
Postmarketing: Respiratory: Pulmonary fibrosis (Dent 1982)
US labeling: There are no contraindications listed in the manufacturer’s labeling.
Canadian labeling: Hypersensitivity to lomustine or any component of the formulation; severe leukopenia and/or thrombocytopenia.
Concerns related to adverse effects:
• Bone marrow suppression: Lomustine causes myelosuppression, which may result in fatal infections or bleeding. Hematologic toxicity is dose-related, delayed (occurring 4 to 6 weeks after drug administration and persisting for 1 to 2 weeks), and cumulative. Thrombocytopenia is generally more severe than leukopenia. Cumulative myelosuppression from lomustine is manifested by greater severity and longer duration of cytopenias. Do not administer lomustine more frequently than once every 6 weeks.
• Hepatotoxicity: Hepatotoxicity (transaminase, alkaline phosphatase and bilirubin elevations) has been reported.
• Pulmonary toxicity: May cause pulmonary toxicity (infiltrates and/or fibrosis). Pulmonary toxicity is usually related to cumulative doses >1,100 mg/m2. May be delayed 6 months or longer after treatment initiation. Patients with baseline below 70% of predicted forced vital capacity or carbon monoxide diffusing capacity are at increased risk. Patients treated at a younger age may also be at increased risk for pulmonary toxicity.
• Renal toxicity: Progressive renal failure with a decrease in kidney size has been reported. Use with caution in patients with renal impairment.
• Secondary malignancies: Long-term use of nitrosoureas is associated with the development of secondary malignancies, including acute leukemia and myelodysplasia.
Other warnings/precautions:
• Medication error prevention: Lomustine should only be prescribed/dispensed as a single dose once every 6 weeks. Serious and fatal adverse events have occurred with overdosage (when lomustine was inadvertently administered daily). Health care providers should emphasize to the patient that only 1 dose of lomustine is taken every 6 weeks. The Institute for Safe Medication Practices (ISMP) recommends that prescribers only prescribe one dose at a time and pharmacies dispense only enough capsules for a single dose; in addition, patients should receive both verbal counseling and written instructions regarding proper dose and administration (ISMP 2014).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Gleostine: 10 mg, 40 mg, 100 mg
No
Capsules (Gleostine Oral)
10 mg (per each): $134.99
40 mg (per each): $539.94
100 mg (per each): $1,490.51
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
CeeNU: 10 mg, 40 mg
Lomustine is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Oral: Administering on an empty stomach may reduce the incidence of nausea and vomiting.
Varying strengths of capsules may be required to obtain necessary dose. Dispense only enough capsules for a single dose; do not dispense more than one dose at a time (ISMP 2014). Do not break capsules. If contact with skin occurs, immediately wash area (thoroughly). Avoid exposure to broken capsules.
Lomustine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Oral: Administering on an empty stomach may reduce the incidence of nausea and vomiting.
Varying strengths of capsules may be required to obtain necessary dose. Dispense only enough capsules for a single dose; do not dispense more than one dose at a time (Ref). Do not break capsules. If contact with skin occurs, immediately wash area thoroughly; avoid exposure to broken capsules.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Brain tumors: Treatment of primary and metastatic brain tumors (after appropriate surgical and/or radiotherapeutic procedures).
Lomustine may be confused with bendamustine, carmustine
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Lomustine should only be administered as a single dose once every 6 weeks; serious and fatal adverse events have occurred when lomustine was inadvertently administered daily. The manufacturer and the Institute for Safe Medication Practices (ISMP) recommend prescribing, dispensing, and administering only enough capsules for a single dose (ISMP 2014).
Substrate of CYP2D6 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Antithyroid Agents: Myelosuppressive Agents may enhance the neutropenic effect of Antithyroid Agents. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Linezolid: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients who could become pregnant should use effective contraception during treatment and for 2 weeks after the final lomustine dose. Patients with partners who may become pregnant should use effective contraception during treatment and for 3.5 months after the final lomustine dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to lomustine may cause fetal harm.
It is not known if lomustine is present in breast milk.
Due to the potential for serious adverse reactions in the nursing infant, the manufacturer does not recommend breastfeeding during treatment and for 2 weeks after the final lomustine dose.
CBC with differential and platelet count (weekly for at least 6 weeks after a dose), hepatic and renal function tests (periodic). Monitor pulmonary function tests (baseline and periodic). Monitor for secondary malignancies. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Lomustine inhibits DNA, RNA, and protein synthesis via alkylation and carbamylation of DNA and RNA; lomustine is cell cycle non-specific (Perry 2012).
Distribution: Crosses blood-brain barrier; CNS concentrations are high (Perry 2012)
Metabolism: Hepatic to active metabolites (Perry 2012)
Half-life elimination: Metabolites: 16 to 48 hours
Time to peak, serum: ~3 hours (Perry 2012)
Excretion: Urine (~50%, as metabolites)
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