Daunorubicin Hydrochloride – Uses, Dosage, Side Effects, Interaction

Daunorubicin Hydrochloride is the hydrochloride salt of an anthracycline antineoplastic antibiotic with therapeutic effects similar to those of doxorubicin. Daunorubicin exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein synthesis.

Daunorubicin is an anthracycline antibiotic and antineoplastic agent. It acts by inhibiting cellular reproduction through interference with DNA replication although it may contribute to the induction of cell death by increasing oxidative stress through the generation of reactive oxygen species and free radicals. As an antineoplastic agent, daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin also exhibits cardiotoxicity in proportion with the cumulative dose received over time.

Use in Cancer

Daunorubicin hydrochloride is approved to be used with other drugs as remission induction therapy to treat:

• Acute lymphoblastic leukemia in adults and children.
• Acute myeloid leukemia in adults.

It is also being studied in the treatment of other types of cancer.

Contraindications

• are allergic to daunorubicin or any ingredients of this medication
• are breast-feeding
• have already been treated with the maximum allowable lifetime dose of any anthracycline drug (daunorubicin, doxorubicin, epirubicin, idarubicin) or mitoxantrone
• have heart failure?
• have low blood cell counts caused by previous cancer drug treatment or radiation therapy?
• are over the age of 75
• a bacterial infection?
• opportunistic fungal infection?
• an infection? due to a protozoa organism
• decreased function of bone marrow?
• low levels of granulocytes, a type of white blood cell
• low levels of a type of white blood cell called neutrophils
• inflammation? of the covering of the heart or pericardium?
• cardiomyopathy?, a disease of the heart muscle?
• rapid ventricular heartbeat
• abnormal heart rhythm
• chronic heart failure
• inflammation of the middle tissue heart muscle
• liver problems
• seizures
• high amount of uric acid in the blood
• pregnancy
• a patient who is producing milk and breastfeeding
• kidney? disease with likely reduction in kidney function
• an increased risk of developing an uncommon viral infection? called an opportunistic infection

Dosage

Strengths: 20 mg; 5 mg/mL; 50 mg

Acute Nonlymphocytic Leukemia

Remission Induction in Combination:
Under 60 years:

• 45 mg/m2 IV once daily on days 1, 2, and 3 of the first course and on days 1 and 2 of subsequent courses AND cytosine arabinoside (ara-C) 100 mg/m2 IV once daily for 7 days for the first course and 5 days for subsequent courses
• The attainment of a normal-appearing bone marrow may require up to 3 courses of induction.
• The doses presented here are manufacturer suggested; consult local and institutional protocol for further guidance.
• For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) in adults

Acute Lymphocytic Leukemia

Remission Induction in Combination:

• 45 mg/m2/day IV on days 1, 2, and 3 AND vincristine 2 mg IV on days 1, 8, and 15; prednisone 40 mg/m2/day orally on days 1 through 22, then tapered between days 22 to 29; L-asparaginase 500 IU/kg/day IV on days 22 through 32
• The doses presented here are manufacturer suggested; consult local and institutional protocol for further guidance.

Acute Nonlymphocytic Leukemia

Remission Induction in Combination:
60 years and older:

• 30 mg/m2 IV once daily on days 1, 2, and 3 of the first course and on days 1 and 2 of subsequent courses AND cytosine arabinoside (ara-C) 100 mg/m2 IV once daily for 7 days for the first course and 5 days for subsequent courses
• Duration of therapy: The attainment of a normal-appearing bone marrow may require up to 3 courses of induction.
• The doses presented here are manufacturer suggested; consult local and institutional protocol for further guidance.
• This daunorubicin dose-reduction is based on a single study and may not be appropriate if optimal supportive care is availabl
• For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) in adults

Pediatric Dose

Acute Lymphocytic Leukemia

Remission Induction in Pediatric Acute Lymphocytic Leukemia:
In Combination:
LESS THAN 2 YEARS OR LESS THAN 0.5 M2:

• 1 mg/kg IV on day 1 every week, vincristine 1.5 mg/m2 IV on day 1 every week, prednisone 40 mg/m2 orally daily; complete remission will usually be obtained within 4 courses of therapy; however, if after 4 courses the patient is in partial remission, an additional 1 or 2 courses may be given to obtain complete remission

GREATER THAN 2 YEARS OR GREATER THAN 0.5 M2:

• 25 mg/m2 IV on day 1 every week, vincristine 1.5 mg/m2 IV on day 1 every week, prednisone 40 mg/m2 orally daily; complete remission will usually be obtained within 4 courses of therapy; however, if after 4 courses the patient is in partial remission, an additional 1 or 2 courses may be given to obtain complete remission
• The doses presented here are manufacturer suggested; consult local and institutional protocol for further guidance.

Administration advice:

• This drug is for IV use only and should not be administered by intramuscular or subcutaneous routes, as severe tissue necrosis will result.
• This drug should be given into a rapidly flowing IV infusion of 0.9% sodium chloride or 5% dextrose injection.
• The tubing should be connected to a butterfly needle, inserted preferably into a large vein. The dose and the size of the vein will determine the rate of administration, which should not be less than 3 to 5 minutes. Erythematous streaking and facial flushing are indications of too rapid administration.
• A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration.

Side Effects

The Most Common

• abdominal pain
• constipation
• darkening of soles, palms, or nails
• nausea
• vomiting
• sores in the mouth and throat
• diarrhea
• stomach pain
• hair loss
• red urine
• redness, pain, swelling, or burning at the site where the injection was given
• rash
• hives
• itching
• difficulty breathing or swallowing

More Common

• diarrhea
• hot flashes
• nausea and vomiting
• reddish-coloured urine (not blood) – this is normal, and lasts 1 to 2 days after each dose
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• chest pain,
• shortness of breath,
• sores in your mouth and throat,
• easy bruising,
• unusual bleeding (nose, mouth, vagina, or rectum),
• nausea,
• upper stomach pain,
• itching,
• loss of appetite,
• dark urine,
• clay-colored stools,
• yellowing of the skin or eyes (jaundice), and
• pain, burning, irritation, or skin changes where the injection was given

Rare

• reduction in number of menstrual periods
• temporary total loss of hair (returns after treatments end)
• skin rash or itching
• sores in mouth and on lips
• black, tarry stools
• blood in urine
• cough or hoarseness with fever or chills
• fever or chills
• irregular heartbeat or palpitations in the chest
• lower back or side pain with fever or chills
• pain at injection site
• painful or difficult urination with fever or chills
• pinpoint red spots on skin
• shortness of breath or swelling of the lips, tongue, or face
• swelling of feet and lower legs
• unusual bleeding or bruising

Interaction

Pregnancy and Lactation

Pregnancy Category D

Pregnancy

There is a possibility of birth defect if either the man or woman is using daunorubicin at the time of conception, or if it is taken during pregnancy. Effective birth control should be practiced while using this medication. This medication may harm the baby if used during pregnancy. Tell your doctor immediately if you become pregnant while using this medication.

Lactation

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Cerubidine (daunorubicin) , mothers should be advised to discontinue nursing during Cerubidine therapy.

References