Treosulfan

Treosulfan is a prescription medication indicated in:

• Combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation in adult and pediatric patients aged 1 year and older with acute myeloid leukemia (AML)
• Combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation in adult and pediatric patients aged 1 year and older with myelodysplastic syndrome (MDS) 

Treosulfan is available under the following different brand names: Grafapex.

Common side effects of Treosulfan include:

• musculoskeletal pain
• stomatitis
• pyrexia
• nausea 
• edema 
• infection 
• vomiting
• increased GGT 
• increased bilirubin
• increased ALT
• increased AST 
• increased creatinine

Serious side effects of Treosulfan include:

• not available

Rare side effects of Treosulfan include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to the FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injection

• 1 g/vial and 5 g/vial treosulfan as a lyophilized powder in a single-dose vial
• Preparative regimen for allogeneic transplant

Adult and pediatric dosage

Recommended dosage

• 10 g/m²body surface area (BSA) per day as a two-hour intravenous infusion, given on three consecutive days (day -4, -3, -2) in conjunction with fludarabine before hematopoietic stem cell infusion (day 0)

Dosage Considerations – Should be Given as Follows: 

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Treosulfan has no noted severe interactions with any other drugs
• Treosulfan has no noted serious interactions with any other drugs
• Treosulfan has no noted moderate interactions with any other drugs
• Treosulfan has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Treosulfan is contraindicated in patients with hypersensitivity to any component of the drug product

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Treosulfan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Treosulfan?”

Cautions

• Myelosuppression 
  • Profound myelosuppression with pancytopenia is the desired therapeutic effect of treosulfan-based preparative regimens, occurring in all patients
  • Do not begin the preparative regimen if the stem cell donor is not available. 
  • Monitor blood cell counts daily until hematopoetic recovery. Provide standard supportive care for infections, anemia, and thrombocytopenia until there is adequate hematopoietic recovery.
• Seizures
  • There have been reports of seizures in patients following treatment with treosulfan 
  • Monitor patients for signs of neurological adverse reactions. 
  • Clonazepam prophylaxis may be considered for patients at higher risk for seizures, including infants. 
• Skin disorders
  • Increase  skin disorders (e.g. rash, dermatitis) observed when patients received sodium bicarbonate-containing hydration in the course of treosulfan infusion, potentially because of:
    • acceleration of the pH-dependent formation of alkylating epoxides
  • Keep skin clean and dry on days of treosulfan infusion and change occlusive dressings after infusion. 
  • Change diapers frequently during the 12 hours after each injection of treosulfan
  • Dermatitis may occur under occlusive dressings; change occlusive dressings after each infusion of treosulfan
• Injection site reactions and tissue necrosis
  • May cause local tissue necrosis and injection site reactions, including erythema, pain, and swelling, in case of extravasation
  • Assure venous access patency before starting treosulfan infusion, and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of treosulfan
  • If extravasation occurs, stop the infusion immediately and manage medically as required
• Secondary malignancies
  • There is an increased risk of a secondary malignancy with the use of treosulfan
    • The risk of secondary malignancy is increased in patients with Fanconi anemia and other DNA
• Breakage disorders
  • Safety and efficacy of treosulfan have not been established for patients with these disorders
  • Increased early morbidity and mortality at dosages higher than recommended
  • Avoid exceeding the recommended dosage of 10 g/m2 daily for three consecutive days
• Embryo-fetal toxicity
  • Can cause fetal harm
  • Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception

Pregnancy and Lactation

Based on its mechanism of action, treosulfan can cause fetal harm when administered to a pregnant woman because it is genotoxic and affects dividing cells.

There is no available human clinical data on the use of treosulfan in pregnant women to support the estimation of a drug-associated risk 

Specific embryo-fetal developmental toxicity studies with treosulfan in animals were not conducted 

Advise pregnant women of the potential risk to a fetus

• Females and Males of Reproductive Potential
  • Based on its mechanism of action, treosulfan causes fetal harm when administered to a pregnant woman 
• Pregnancy testing
  • Conduct pregnancy testing in females of reproductive potential within 7 days before initiating therapy with treosulfan
• Contraception
• Females
  • Advise females of reproductive potential to use effective contraception during and up to 6 months after treatment with treosulfan
• Males
  • Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with Treosulfan and for 3 months after the last dose
• Infertility
  • Based on findings in animal studies, treosulfan can impair fertility in females and males and may cause temporary or permanent infertility
• Lactation
  • There is no data on the presence of treosulfan or its metabolites in human milk, the effects on the breastfed child, or milk production
  • Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with treosulfan and for 1 week after the last dose