Daunorubicin or Daunomycin is a chemotherapeutic medicine used in the treatment of various blood cancers including acute lymphoblastic leukemia and acute myeloid leukemia.

Indications of Daunorubicin:

• Acute lymphocytic leukemia:
  • It is indicated for the treatment (remission induction) of acute lymphocytic leukemia (ALL) in children and adults concurrently with other chemotherapy.
• Acute myeloid leukemia:
  • It is effective for treatment (remission induction) of acute myeloid leukemia (AML) in adults concurrently with other chemotherapy.

Daunorubicin dose in adults:

Note:

• If adults take more than 550 mg/m of Daunorubicin (or more than 400 mg/m if they've had chest radiation), there's a higher chance it can hurt their heart.
• Also, Daunorubicin can make people feel like throwing up, so it's recommended to take medicines that prevent this feeling.

Daunorubicin dose in the treatment of Acute lymphocytic leukemia:

CALGB 8811 regimen:

• Younger than 60 years: 45 mg/m on days 1-3 every 4 weeks.
• 60 years or older: 30 mg/m on days 1-3 every 4 weeks.
• Given with other medicines like cyclophosphamide, prednisone, vincristine, and asparaginase.

CCG 1961:

• For adults 21 years or younger: 25 mg/m once a week for 4 weeks.
• Given with medicines like vincristine, prednisone, and asparaginase.

GRAALL-2003:

• For adults 60 years or younger:
  • Start phase: 50 mg/m on days 1-3 and 30 mg/m on days 15-16.
  • Later strong phase: 30 mg/m on days 1-3.
• Given with medicines like prednisone, vincristine, asparaginase, cyclophosphamide, and G-CSF.

MRC UKALLXII/ECOG E2993:

• For adults younger than 60 years: 60 mg/m on days 1, 8, 15, and 22.
• Given with vincristine, asparaginase, and prednisone.

PETHEMA ALL-96:

• For adults 30 years or younger:
  • Start phase: 30 mg/m on days 1, 8, 15, and 22.
  • Next strong phases: 30 mg/m on days 1, 2, 8, and 9.
• Given with medicines like vincristine, prednisone, asparaginase, and cyclophosphamide.

Protocol 8707:

• For adults 60 years or younger: 60 mg/m on days 1-3. If disease still present on day 14, an extra 60 mg/m dose is given on day 15.
• Given with vincristine, prednisone, and asparaginase.

From the drug maker:

• 45 mg/m on days 1-3.
• Given with vincristine, prednisone, and asparaginase.

Daunorubicin dose in the treatment of Acute myeloid leukemia: Induction:

Daunorubicin dose in the treatment of Acute promyelocytic leukemia (off-label dosing):

Induction:

• Adults can receive either:
  • 50 mg/m through IV on days 3-6, given with ATRA (a form of vitamin A used to treat APL) and cytarabine (Powell 2010).
  • OR 60 mg/m through IV on days 1-3, also with ATRA and cytarabine (Ades 2008).

Consolidation (this is the treatment phase after induction to further reduce the number of cancer cells):

• Adults can receive either:
  • 50 mg/m through IV on days 1-3, for 2 treatment cycles. Given with ATRA, and before this, they would have received arsenic trioxide for 2 cycles (Powell 2010).
  • OR during the first consolidation cycle, 60 mg/m through IV on days 1-3 (given with cytarabine). For the second consolidation cycle, they'd receive 45 mg/m on days 1-3 (also with cytarabine) (Ades 2008).

Daunorubicin dose in children:

Note:

• The exact dose, how often it's taken, the number of times it's taken, and when you start can change based on the treatment plan.
• This medicine can make you feel like throwing up. It's good to take other medicines to prevent this feeling.
• Be very careful with the dosing measurements. Sometimes it's in mg/m and sometimes in mg/kg.
• For very young patients (babies and toddlers under 2 years), taking more than 10 mg/kg total can harm the heart. For older children and teens (above 2 years), taking more than 300 mg/m total can do the same.

Daunorubicin dose in Acute lymphocytic leukemia (ALL):

Manufacturer's Guidelines:

• Babies and Small Children (under 2 years or with a body size less than 0.5 m^2):
  • Given 1 mg for each kg of their weight once a week. This is done for up to 4 to 6 times, along with other drugs like vincristine and prednisone.
• Older Children (2 years or older with a body size of 0.5 m^2 or more):
  • Given 25 mg/m once a week, for 4 to 6 weeks. Also given with vincristine and prednisone.

Alternate Dosing:

• CCG 1961:
  • Kids and Teens: Given 25 mg/m once a week for 4 weeks, along with drugs like vincristine, prednisone, and asparaginase.
• GRAALL-2003:
  • Teens 15 years or older:
    • Start Phase: 50 mg/m on the first 3 days and then 30 mg/m on the 15th and 16th days. Given with several other drugs.
    • Next Strong Phase: 30 mg/m on the first 3 days, along with various other drugs.
• MRC UKALLXII/ECOG E2993:
  • Teens 15 years or older: Given 60 mg/m on days 1, 8, 15, and 22, with other drugs like vincristine, asparaginase, and prednisone.
• PETHEMA ALL-96:
  • Teens 15 years or older:
    • Start Phase: Given 30 mg/m on days 1, 8, 15, and 22, along with several other drugs.
    • Next Strong Phases: Given 30 mg/m on days 1, 2, 8, and 9, along with other drugs like vincristine, dexamethasone, asparaginase, and cyclophosphamide.

Daunorubicin dose in the treatment of acute myelogenous leukemia (AML):

MRC AML 10/12:

• For babies and kids up to 16 years:
  • They get 50 mg/m on days 1, 3, and 5.
  • This happens for two rounds and is given with other drugs like cytarabine and etoposide.

CCG 2891:

• For babies and little kids under 3 years:
  • They get a dose based on their weight - 0.67 mg for each kg they weigh.
  • This is given continuously from days 0-4 and then days 10-14.
  • It's combined with other drugs like dexamethasone, cytarabine, thioguanine, and etoposide.
• For older kids (3 years and above) and teens:
  • They get 20 mg/m continuously from days 0-4 and then days 10-14.
  • It's given with the same combination of other drugs.

Pregnancy Risk Factor D

• Daunorubicin can cause problems during animal pregnancies.
• It can also pass into a baby if a pregnant woman takes it.
• So, women who can get pregnant should make sure they don't become pregnant while using this drug.

Daunorubicin use during breastfeeding:

• We don't know if daunorubicin gets into breast milk.
• Because it might harm a breastfeeding baby, the company suggests either stopping the medicine or not breastfeeding.
• The choice should consider how important the treatment is for the mother.Top of Form

Daunorubicin Dose adjustment in renal disease:

• If someone's blood test result shows S >3 mg/dL: Give them only half of the usual dose.
• Another recommendation (Aronoff 2007) says that no change in dosage is needed.

Daunorubicin Dose adjustment in liver disease:

If someone's blood test for bilirubin (a liver function test) shows:

• Bilirubin is between 1.2 to 3 mg/dL:
  • Manufacturer: Give them 75% of the usual dose.
  • Floyd 2006: Give them 75% of the usual dose.
• Bilirubin is more than 3 mg/dL but up to 5 mg/dL:
  • Manufacturer: Give them 50% of the usual dose.
  • Floyd 2006: Give them 50% of the usual dose.
• Bilirubin is more than 5 mg/dL:
  • Floyd 2006: It's better not to use the drug.

Common Side Effects of Daunorubicin:

• Cardiovascular:
  • Cardiac failure
  • ECG abnormality
• Dermatologic:
  • Alopecia (reversible)
• Gastrointestinal:
  • Nausea (mild)
  • Stomatitis
  • Vomiting (mild)
• Genitourinary:
  • Red urine discoloration
• Hematologic & oncologic:
  • Bone marrow depression
• Miscellaneous:
  • Radiation recall phenomenon

Rare Side Effects of Daunorubicin:

• Dermatologic:
  • Discoloration of sweat
• Endocrine & metabolic:
  • Hyperuricemia
• Gastrointestinal:
  • Abdominal pain
  • Diarrhea
  • Discoloration of saliva
  • Gastrointestinal ulcer
• Local:
  • Post-injection flare
• Ophthalmic:
  • Discoloration of tears

Contraindications to Daunorubicin:

• People allergic to daunorubicin or anything in the drug shouldn't use it.
• In Canada, the drug isn't recommended for people with heart issues or those 75 years and older.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

• This drug can seriously weaken the bone marrow, which can lead to infections or bleeding
• Be extra careful using it on people who already have weakened bone marrow because of other drugs, unless the benefits are really worth the risks
• Always check blood counts before starting and keep checking regularly during treatment.

Extravasation: [US Boxed Warning]

• This drug can cause serious skin and tissue damage if it leaks out of the vein
• It can lead to painful sores and dead tissue
• It should ONLY be given directly into a vein and NOT into a muscle or under the skin
• Make sure the needle is in the right place before and while giving the drug
• Always watch out for any leaks.

Gastrointestinal toxicities:

• This drug can upset your stomach. It can make you feel like throwing up.
• To prevent this, it's good to take other medicines that stop nausea and vomiting.

[US Boxed Warning] Cardiomyopathy

• The drug can cause heart damage. This can lead to heart failure.
• Damage can happen during treatment or even months to years after stopping the drug.
• There's a higher risk of heart damage when reaching certain total doses of the drug in one's lifetime.
  • Adults: 550 mg/m
  • Adults with chest radiation: 400 mg/m
  • Kids over 2 years: 300 mg/m
  • Kids under 2 years: 10 mg/kg
• Some factors increase the risk: existing heart disease, other cancer drugs, radiation to the chest, older age, and in very young patients.
• Check the heart's function regularly using tests like ECHO or MUGA scans and ECG.

Guidelines from ASCO on Heart Monitoring:

• There's a higher risk of heart damage in:
  • High doses of similar drugs or high-dose radiation where the heart is involved.
  • Medium doses of these drugs or medium-dose radiation with the heart in focus.
  • Lower doses of these drugs and some factors: having multiple heart risks (like smoking, high blood pressure), being 60 years or older when treated, or having a weak heart function.
• Before starting treatment, it's crucial to:
  • Check for heart disease risks.
  • Use tests like echocardiograms to see the heart's health.
  • Manage risks like smoking, high blood pressure.
  • Consider using protective medicines or specific ways of giving the drug if high doses are needed.
• If someone shows signs of heart problems during treatment, they should get heart tests, check heart-related proteins in the blood, and possibly see a heart doctor.

Secondary malignancy

• Using daunorubicin with other cancer treatments or radiation can sometimes lead to a second type of leukemia (a new cancer).

Tumor lysis syndrome

• Daunorubicin can lead to tumor lysis syndrome, where cancer cells break down quickly and release their contents into the bloodstream
• This can cause high uric acid levels
• To help prevent this, making the urine less acidic and taking medicine to reduce uric acid might be needed
• It's essential to keep track of body salts, kidney health, and make sure the patient is well-hydrated.

Hepatic impairment: [US-Boxed Warning]

• If someone has liver problems, they should take a lower dose of this drug.
• Serious liver issues can lead to more side effects from the medicine.

Renal impairment: [US-Boxed Warning]

• If someone has kidney problems, they should take a lower dose of this drug.
• Serious kidney issues can lead to more harmful effects from the medicine.

Daunorubicin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Blood Tests:

• Complete Blood Count (CBC) - to check all blood cells.
• Liver Function Test - to see how the liver is working.
• Renal Function Test - to check the kidneys.

Heart Tests:

• ECG - to record the heart's electrical activity.
• Left Ventricular Ejection Function - to measure how well the heart pumps. Can use:
  • Echocardiography (ECHO) or
  • Multigated Radionuclide Angiography (MUGA) scan.

Other:

• Look for signs/symptoms if the drug leaks out of the vein (extravasation).

Heart Monitoring Guidelines (ASCO [Armenian 2017])

• Before Treatment:
  • Detailed checkup and history.
  • Check for heart disease risks like high blood pressure, diabetes, high cholesterol, being overweight, and smoking.
  • Get an echocardiogram.

If Heart Issues Appear During Treatment:

• Get an echocardiogram. If that's not possible, go for:
  • Cardiac MRI (best option) or
  • MUGA scan.
• Test for heart-related proteins in the blood.

How to administer Daunorubicin?

Nausea and Vomiting:

• Daunorubicin can cause nausea and vomiting.
• Anti-nausea medicines are advised to prevent these side effects.

How to Administer:

• It should be given directly into the vein (IV) only.
• Don't give it into a muscle (IM) or under the skin (SubQ).
• It can be slowly pushed into a vein over 1 to 5 minutes, or mixed further and given over 15 to 30 minutes.

Important Warnings:

• It can damage skin and tissues if it leaks out of the vein. Make sure the needle or tube is correctly placed and avoid any leakage (extravasation).

If Leakage Happens (Extravasation Management):

• Stop the drug immediately but leave the needle in place.
• Try to gently pull out any leaked drug without flushing the line.
• Lift the affected limb.
• Use a specific antidote: either dexrazoxane or DMSO.
• Cold packs can help: place them for 20 mins, four times daily for 1-2 days. If using dexrazoxane, don't use cold packs 15 minutes before, during, and 15 minutes after the treatment.
• Don't use DMSO and dexrazoxane together; they can interfere with each other.

Specific Antidote Directions:

• Dexrazoxane: Given IV and the dosage depends on the patient's size and the timing since the leakage. The dose might need to be reduced if the patient has kidney issues.
• DMSO: Applied directly to the skin every 8 hours for a week. Start as soon as the leakage happens. Don't cover it.

Mechanism of action of Daunorubicin:

1. Interference with DNA and RNA:

• Daunorubicin slips in between the parts of DNA, blocking its normal function.
• This stops cells from making DNA and RNA, which they need to grow and divide.

2. DNA Structure Disruption:

• Daunorubicin finds places in DNA that are slightly open and fits itself there. Think of it like sticking a wedge in a partially open door.

3. DNA Damage and Repair Block:

• The exact process isn't fully understood, but daunorubicin not only binds to DNA but also prevents the repair of DNA.
• This leads to DNA being broken and not being able to fix itself.

In simple terms, Daunorubicin messes with the DNA in cells, stopping them from growing and causing damage they can't repair.

Where it Goes (Distribution):

• Daunorubicin spreads into many body parts, especially the liver, kidneys, lungs, spleen, and heart.
• It doesn't go into the brain and spinal cord area (CNS).

How it Changes (Metabolism):

• Mainly processed in the liver.
• First, it changes to daunorubicinol, which is active and works in the body.
• Later, it turns into inactive forms.

How Long it Stays (Half-life):

• At first, half of it is gone in 45 minutes.
• Finally, half of it is gone in 18.5 hours.
• The active form, daunorubicinol, takes about 27 hours for its levels to drop by half.

How it Leaves the Body (Excretion):

• About 40% goes out in the poop.
• Around 25% leaves in pee, both as the unchanged drug and its changed forms.

International Brands of Daunorubicin:

• Cerubidine
• Cerubidin
• Cerubidine
• Danocin
• Daunobin
• Daunoblastin
• Daunoblastina
• Daunocin
• Daunoplus
• Daunorrubicina
• Daunorubicin Injection
• Daunorubicina
• Daunotec
• DaunoXome
• Donobin
• Maxidauno
• Rubicin
• Rubilem

Daunorubicin Brand Names in Pakistan: