Daunorubicin (Conventional)

• It is used to treat leukemia.
• It may be given to you for other reasons. Talk with the doctor.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about daunorubicin (conventional), please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about daunorubicin. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using daunorubicin.

Review Date: October 4, 2017

• Cerubidine
• Conventional Daunomycin
• Daunomycin
• DAUNOrubicin Hydrochloride
• Rubidomycin Hydrochloride

Inhibits DNA and RNA synthesis by intercalation between DNA base pairs and by steric obstruction. Daunomycin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA.

Distribution

Distributes widely into tissues, particularly the liver, kidneys, lung, spleen, and heart; does not distribute into the CNS

Metabolism

Primarily hepatic to daunorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides

Excretion

Feces (40%); urine (~25% as unchanged drug and metabolites)

Half-Life Elimination

Initial: 45 minutes; Terminal: 18.5 hours; Daunorubicinol plasma half-life: ~27 hours

Hypersensitivity to daunorubicin or any component of the formulation

Daunorubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Basch, 2011; Roila, 2010).

Manufacturer’s labeling: Note: Cumulative doses above 550 mg/m2 in adults without risk factors for cardiotoxicity and above 400 mg/m2 in adults receiving chest irradiation are associated with an increased risk of cardiomyopathy.

Acute lymphocytic leukemia (ALL):

IV: 45 mg/m2 on days 1, 2, and 3 (in combination with vincristine, prednisone, and asparaginase)

Acute myeloid leukemia (AML):

Adults <60 years: Induction: IV: 45 mg/m2 on days 1, 2, and 3 of the first course of induction therapy; subsequent courses: 45 mg/m2 on days 1 and 2 (in combination with cytarabine)

Adults ≥60 years: Induction: IV: 30 mg/m2 on days 1, 2, and 3 of the first course of induction therapy; subsequent courses: 30 mg/m2 on days 1 and 2 (in combination with cytarabine)

Indication-specific dosing (off-label dosing):

ALL:

CALGB 8811 regimen: IV: 45 mg/m2 (in patients <60 years) or 30 mg/m2 (in patients ≥60 years) on days 1, 2, and 3 of induction (Course I; 4 week cycle), in combination with cyclophosphamide, prednisone, vincristine, and asparaginase (Larson, 1995)

CCG 1961: Adults ≤21 years: IV: Induction: 25 mg/m2 once weekly for 4 weeks (in combination with vincristine, prednisone, and asparaginase) (Nachman, 2009)

GRAALL-2003: Adults ≤60 years: IV:

Induction: 50 mg/m2 on days 1, 2, and 3 and 30 mg/m2 on days 15 and 16 (in combination with prednisone, vincristine, asparaginase, cyclophosphamide, and G-CSF support) (Huguet, 2009)

Late intensification: 30 mg/m2 on days 1, 2, and 3 (in combination with prednisone, vincristine, asparaginase, cyclophosphamide, and G-CSF support) (Huguet, 2009)

MRC UKALLXII/ECOG E2993: Adults <60 years: IV: Induction (Phase I): 60 mg/m2 on days 1, 8, 15, and 22 (in combination with vincristine, asparaginase, and prednisone) (Rowe, 2005)

PETHEMA ALL-96: Adults ≤30 years: IV:

Induction: 30 mg/m2 on days 1, 8, 15, and 22 (in combination with vincristine, prednisone, asparaginase, and cyclophosphamide) (Ribera, 2008)

Consolidation-2/Reinduction: 30 mg/m2 on days 1, 2, 8, and 9 (in combination with vincristine, dexamethasone, asparaginase, and cyclophosphamide) (Ribera, 2008)

Protocol 8707: Adults ≤60 years: IV: Induction and Consolidation 2A cycles: 60 mg/m2 on days 1, 2, and 3 (in combination with vincristine, prednisone, and asparaginase). An additional 60 mg/m2 daunorubicin dose may be administered on day 15 of induction if bone marrow biopsy on day 14 shows residual disease (Linker, 2002).

AML: Induction:

CCG 2891: Adults <21 years: IV: 20 mg/m2/day continuous infusion on days 0 to 4 and 10 to 14 (in combination with dexamethasone, cytarabine, thioguanine, and etoposide) (Woods, 1996)

Adults <60 years: IV: 90 mg/m2 on days 1, 2, and 3 (in combination with cytarabine). If residual disease was observed on day 12 to day 14 bone marrow biopsy, 45 mg/m2 for 3 days was administered (in combination with cytarabine) (Fernandez, 2009).

Adults <60 years: IV: 60 mg/m2 on days 1, 2, and 3 (in combination with cytarabine and cladribine); may repeat if partial remission occurs (Holowiecki, 2012).

Adults ≥60 years: IV: 45 or 90 mg/m2 on days 1, 2, and 3 (in combination with cytarabine); the escalated 90 mg/m2 dose was associated with increased remission rates and overall survival in the subgroup of patients 60 to 65 years of age as compared to patients >65 years (Lowenberg, 2009)

Acute promyelocytic leukemia (APL):

Induction: Adults: IV: 50 mg/m2 on days 3, 4, 5, and 6 (in combination with ATRA and cytarabine) (Powell, 2010) or 60 mg/m2 on days 1, 2, and 3 (in combination with ATRA and cytarabine) (Ades, 2008)

Consolidation: Adults: IV: 50 mg/m2 on days 1, 2, and 3 for 2 cycles (in combination with ATRA; arsenic trioxide was administered for 2 cycles prior to daunorubicin and ATRA) (Powell, 2010) or 60 mg/m2 on days 1, 2, and 3 during cycle 1 of consolidation (in combination with cytarabine), followed by 45 mg/m2 on days 1, 2, and 3 during cycle 2 of consolidation (in combination with cytarabine) (Ades, 2008)

Solution: Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light. Retain in carton until time of use. Solution prepared for infusion in D5W or NS may be stored at 20°C to 25°C (68°F to 77°F) for up to 24 hours. Discard unused portion.

Lyophilized powder [Canadian product]: Store intact vials of powder at 15°C to 30°C (59°F to 86°F). Protect from light. Retain in carton until time of use. Reconstituted daunorubicin is stable for 24 hours at room temperature or 48 hours when refrigerated at 2°C to 8°C (36°F to 46°F). Protect reconstituted solution from light.

Daunorubicin must be given into a rapidly flowing intravenous infusion. It must never be given by the intramuscular or subcutaneous route. Severe local tissue necrosis will occur if there is extravasation during administration.

It is recommended that daunorubicin be administered only by physicians who are experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity.The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection.

Severe myelosuppression occurs when used in therapeutic doses; this may lead to infection or hemorrhage.

Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The incidence of myocardial toxicity increases after a total cumulative dose exceeding 400 to 550 mg/m2 in adults, 300 mg/m2 in children older than 2 years of age, or 10 mg/kg in children younger than 2 years of age.

Dosage should be reduced in patients with impaired hepatic function.

Dosage should be reduced in patients with impaired renal function.