Version July 2025
Treosulfan causes severe and prolonged myelosuppression at the recommended dosage. Hematopoietic stem cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression. Monitor hematologic laboratory parameters.
Dosage guidance:
Safety: Do not begin the conditioning regimen for hematopoietic cell transplantation (including treosulfan) until hematopoietic donor cells are available. Consider clonazepam prophylaxis in patients at higher risk of seizures.
Dosing: Avoid exceeding 10 g/m2/day for 3 consecutive days.
Clinical considerations: Nausea and vomiting may commonly occur; premedicate with antiemetics prior to the first dose of treosulfan and continue antiemetics through completion of treosulfan administration to prevent nausea and vomiting. Provide standard supportive care (for infections, anemia, and thrombocytopenia) until adequate hematopoietic recovery has occurred.
Hematopoietic cell transplantation conditioning regimen: IV: 10 g/m2/day for 3 days on days −4, −3, and −2 prior to hematopoietic cell infusion (total dose/course is 30 g/m2) (in combination with fludarabine), followed by hematopoietic cell infusion on day 0 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to treatment initiation :
CrCl ≥60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in treosulfan pharmacokinetics were observed.
CrCl <60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effect on treosulfan pharmacokinetics is unknown).
Liver impairment prior to treatment initiation:
Mild (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 × ULN with any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in treosulfan pharmacokinetics were observed.
Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (effect on treosulfan pharmacokinetics is unknown).
Refer to adult dosing.
(For additional information see "Treosulfan: Pediatric drug information")
Dosage guidance:
Dosing: Dosing presented as g/m2; use caution. Nausea and vomiting may commonly occur; consider prophylactic antiemetics to prevent nausea and vomiting. Dose, frequency, number of doses, and/or start date may vary by protocol. Refer to individual protocols.
Hematopoietic stem cell transplantation (allogeneic) conditioning regimen, hematologic malignancies:
Note: Other conditioning regimens (ie, total body irradiation-based regimens) are preferred over chemoconditioning for children ≥4 years and adolescents with acute lymphoblastic leukemia receiving allogeneic stem cell transplantation (Ref).
Acute myeloid leukemia, myelodysplastic syndrome:
BSA-directed dosing: Children and Adolescents: IV: 10 g/m2/dose once daily for 3 days on days −4, −3, and −2 prior to stem cell infusion (in combination with fludarabine).
BSA-banded dosing: Limited data available (Ref):
Infants, Children, and Adolescents:
BSA ≤0.5 m2: IV: 10 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
BSA >0.5 to ≤1 m2: IV: 12 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
BSA >1 m2: IV: 14 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
Other hematologic malignancies: Limited data available (Ref):
Infants, Children, and Adolescents:
BSA ≤0.5 m2: IV: 10 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
BSA >0.5 to ≤1 m2: IV: 12 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
BSA >1 m2: IV:14 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
Hematopoietic stem cell transplantation (allogeneic) conditioning regimen, nonmalignant diseases (eg, primary immune deficiency): Limited data available: Various regimens have been described (Ref):
Age-directed dosing:
Infants ≤3 months: IV: 10 g/m2/dose once daily for 3 days on days −7, −6, and −5 prior to stem cell infusion (in combination with fludarabine and either alemtuzumab or anti-thymocyte globulin) (Ref).
Infants >3 to 12 months: IV: 12 g/m2/dose once daily for 3 doses administered on 3 consecutive days (in combination with fludarabine and either alemtuzumab or anti-thymocyte globulin); reported days of treosulfan doses prior to stem cell infusion varied; one trial reported administration on days −7, −6, and −5 (Ref) and a retrospective report described administration on days −6, −5, and −4 in patients with chronic granulomatous disease (Ref).
Children and Adolescents: IV: 14 g/m2/dose once daily for 3 doses administered on 3 consecutive days (in combination with fludarabine and either alemtuzumab or anti-thymocyte globulin); reported days of treosulfan doses prior to stem cell infusion varied; one trial reported administration on days −7, −6, and −5 (Ref) and a retrospective report described administration on days −6, −5, and −4 in patients with chronic granulomatous disease (Ref).
BSA-banded dosing (Ref):
Infants, Children, and Adolescents:
BSA ≤0.5 m2: IV: 10 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
BSA >0.5 to ≤1 m2: IV: 12 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
BSA >1 m2: IV: 14 g/m2/dose once daily for 3 days on days −6, −5, and −4 prior to stem cell infusion (in combination with fludarabine ± thiotepa).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents:
Mild or moderate impairment: No dosage adjustments necessary.
Severe impairment: Use is contraindicated.
Infants, Children, and Adolescents:
Mild or moderate impairment: No dosage adjustments necessary.
Severe impairment: Use is contraindicated.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported for combination therapy in adults.
>10%:
Cardiovascular: Edema (29%), hypertension (14%)
Dermatologic: Skin rash (17%)
Gastrointestinal: Abdominal pain (15%), constipation (12%), diarrhea (17%; grades 3/4: 1%), nausea (33%; grades 3/4: 3%), stomatitis (38%; grades 3/4: 6%), vomiting (22%; grades 3/4: 1%)
Hematologic & oncologic: Anemia (100%), febrile neutropenia (15%; grades 3/4: 15%), hemorrhage (14%; grades 3/4: 1%), neutropenia (100%), thrombocytopenia (100%)
Hepatic: Increased gamma-glutamyl transferase (16%)
Infection: Infection (23%)
Nervous system: Fatigue (13%), headache (16%)
Neuromuscular & skeletal: Musculoskeletal pain (39%)
Miscellaneous: Fever (34%)
1% to 10%:
Cardiovascular: Embolism (<10%), flushing (<10%), heart failure (<10%), hypotension (<10%), pericardial effusion (<10%), tachycardia (10%)
Dermatologic: Dermatitis (<10%), erythema of skin (<10%), palmar-plantar erythrodysesthesia (<10%), pruritus (<10%), skin hyperpigmentation (<10%), xeroderma (<10%)
Endocrine & metabolic: Impaired glucose tolerance (<10%), weight gain (<10%), weight loss (<10%)
Gastrointestinal: Abdominal distention (<10%), decreased appetite (<10%), dyspepsia (<10%), dysphagia (<10%), gastritis (<10%), hiccups (<10%), mouth pain (<10%), xerostomia (<10%)
Genitourinary: Dysuria (<10%), hematuria (<10%)
Hematologic & oncologic: C-reactive protein increased (<10%), second primary malignant neoplasm (<10%)
Hepatic: Hepatotoxicity (10%), increased serum alanine aminotransferase (6%), increased serum aspartate aminotransferase (4%), increased serum bilirubin (6%)
Nervous system: Agitation (<10%), chills (<10%), confusion (<10%), dizziness (<10%), insomnia (<10%), pain (<10%), paresthesia (<10%), vertigo (<10%), voice disorder (<10%)
Renal: Acute kidney injury (<10%), increased serum creatinine (3%)
Respiratory: Cough (<10%), dyspnea (<10%), oropharyngeal pain (<10%), pleural effusion (<10%), pneumonitis (<10%)
Miscellaneous: Inflammation (pharyngeal or laryngeal: <10%)
Frequency not defined: Hematologic & oncologic: Bone marrow depression
Postmarketing:
Endocrine & metabolic: Acidosis
Hypersensitivity: Hypersensitivity reaction
Nervous system: Peripheral sensory neuropathy, seizure
Renal: Kidney failure
Hypersensitivity to treosulfan or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Active non-controlled infectious disease; severe concomitant cardiac, lung, liver, or renal impairment; Fanconi anemia and other DNA breakage repair disorders; pregnancy; administration of live vaccine.
Concerns related to adverse effects:
• Bone marrow suppression: Treosulfan causes profound myelosuppression with pancytopenia in all treated patients. Profound myelosuppression with pancytopenia is the desired effect of treosulfan-based conditioning treatment. Hematopoietic cell transplantation (HCT) is required to prevent potentially fatal complications of the prolonged myelosuppression. The time to ANC >500/mm3 following allogeneic HCT in adult patients treated with treosulfan (in combination with fludarabine) as conditioning chemotherapy was 18 days (range: 7 to 42 days).
• Dermatologic toxicity: An increased incidence of skin disorders (eg, rash, dermatitis) was observed when patients received sodium bicarbonate-containing hydration in the course of treosulfan infusion, which may accelerate the pH-dependent formation of alkylating epoxides. Keep skin clean and dry on treosulfan infusion days; change occlusive dressings after each treosulfan infusion (dermatitis may occur under occlusive dressings). Diaper dermatitis may occur secondary to urinary excretion of treosulfan; change diapers frequently for the first 12 hours following each infusion.
• Early morbidity and mortality: A higher incidence of early and/or fatal serious adverse reactions was observed in patients treated with treosulfan at a dose of 14 g/m2/day for 3 consecutive days (in combination with fludarabine) as conditioning chemotherapy prior to allogeneic HCT in the initial clinical trial. Avoid exceeding the recommended dosage of treosulfan.
• Extravasation: Irritant; extravasation may result in local tissue necrosis and injection-site reactions, including erythema, pain, and swelling. If extravasation occurs, immediately terminate the infusion and medically manage as required. For IV administration only; do not administer by IM or SUBQ routes. Ensure venous access patency prior to and during infusion. Avoid extravasation.
• Neurologic toxicity: Seizures have been reported in patients following treatment with treosulfan.
• Secondary malignancy: The use of treosulfan is associated with an increased risk of secondary malignancy. The risk of secondary malignancy is increased in patients with Fanconi anemia and other DNA breakage disorders (safety and efficacy of treosulfan has not been established in patients with these disorders).
Duration of neutropenia following therapy may be longer in pediatric as compared to adult patients; median duration of neutropenic period was 21 to 24 days in pediatric patients as compared to 14 to 17.5 days in adults. Consider prophylactic or empiric anti-infective treatment (eg, bacterial, viral, fungal).
Seizures have been reported in pediatric patients; one trial reported seizures in 3 patients ≤4 months of age with primary immunodeficiencies following conditioning with treosulfan (Slatter 2017); another trial reported idiopathic epilepsy in a patient 47 months of age (Morillo-Gutierrez 2020). Monitor for signs of neurological adverse reactions, including seizures; consider seizure prophylaxis.
Respiratory toxicity (grade 3/4) is more common in infants than older patients (Trecondi European Medicines Agency 2024). Hepatotoxicity is commonly observed in all age groups; associated disorientation/confusion may be more common in children and adolescents (Trecondyv Canadian product labeling 2021).
Diaper dermatitis may occur in infants and young children due to treosulfan excretion in the urine. Frequent diaper changes are required in the 6 to 8 hours following treosulfan infusion (Trecondi European Medicines Agency 2024; Trecondyv Canadian product labeling 2021).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Grafapex: 1 g (1 ea); 5 g (1 ea)
No
Solution (reconstituted) (Grafapex Intravenous)
1 g (per each): $732.00
5 g (per each): $3,660.00
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.
Solution Reconstituted, Intravenous:
Trecondyv: 5 g (1 ea)
IV: Infuse over 2 hours (Ref). Administer treosulfan prior to fludarabine on the days when both medications are administered [Canadian product monograph].
Irritant. Ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion and implement general extravasation management measures.
Nausea and vomiting may commonly occur; premedicate with antiemetics prior to the first dose of treosulfan and continue antiemetics through completion of treosulfan administration to prevent nausea and vomiting. If occlusive dressing are being utilized, change dressings after each infusion (dermatitis may occur under occlusive dressings).
Note: Nausea and vomiting may commonly occur; consider prophylactic antiemetics to prevent nausea and vomiting.
Parenteral: IV: Infuse over 2 hours. Administer prior to fludarabine on days when both medications are administered. On days treosulfan administered, use of topical creams should be avoided and diapers should be changed frequently during the 6 to 8 hours following each infusion.
Irritant: Ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, implement general extravasation management measures.
This medication is not on the NIOSH (2024) list; however, it meets the criteria for a hazardous drug. Treosulfan contains manufacturer's special handling information (MSHI) and is a hazardous drug (per the product labeling).
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 2023; NIOSH 2024; USP-NF 2020).
Hematopoietic cell transplantation conditioning regimen: Conditioning regimen (in combination with fludarabine) prior to allogeneic hematopoietic cell transplantation in adults and pediatric patients ≥1 year of age with acute myeloid leukemia or myelodysplastic syndrome.
Treosulfan may be confused with busulfan.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (chemotherapeutic agent, parenteral and oral; contraindicated in pregnancy) 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).
None known.
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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. 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 (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP2C19 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Treosulfan may increase serum concentration of CYP2C19 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Treosulfan may increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects 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 decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects 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 increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 increase immunosuppressive effects 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 decrease therapeutic effects 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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects 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 decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects 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 decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of 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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects 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 increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects 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
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Evaluate pregnancy status prior to use; a pregnancy test is recommended within 7 days prior to initiating treosulfan in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during treosulfan treatment and for 6 months after the last treosulfan dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 3 months after the last dose of treosulfan.
Adverse effects to male fertility were observed in animal toxicology studies; data are lacking on possible fertility effects in humans.
A long-term study followed patients for up to 12 years who received treosulfan as part of the conditioning treatment prior to allogeneic hematopoietic stem cell transplantation. Successful pregnancies and fatherhood were reported (Lazzari 2021).
Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to treosulfan may cause fetal harm.
It is not known if treosulfan is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 week after the last dose of treosulfan.
CBC with differential and platelets (daily until hematopoietic recovery); hepatic and kidney function (as clinically indicated). Verify pregnancy status within 7 days prior to treosulfan initiation (in patients who could become pregnant). Monitor infusion site during infusion for signs/symptoms of extravasation (eg, redness, swelling, pain, necrosis). Monitor for signs/symptoms of infection, dermatologic toxicity, and neurologic toxicity (eg, seizure). Monitor for secondary malignancy.
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.
Treosulfan is a bifunctional alkylating agent prodrug with cytotoxic activity in hematopoietic stem cells. Treosulfan undergoes spontaneous, pH-dependent conversion into a monoepoxide intermediate and L-diepoxibutane; the epoxides alkylate and cross-link DNA, and are considered responsible for the stem cell depleting, immunosuppressive, and antitumor effects in leukemia animal models.
Distribution: Vd: ~41 L.
Metabolism: Converted spontaneously (non-enzymatically) into the active monoepoxide intermediate and finally to active L-diepoxibutane.
Half-life elimination: Adults: 1.7 ± 0.4 hours.
Excretion: Median: Urine: 42%, as unchanged drug (89% of unchanged fraction excreted within the first 8 hours following administration).
