Idarubicin is an anthracycline antibiotic chemotherapy agent. It's used primarily in the treatment of acute myeloid leukemia (AML). Like other anthracyclines, idarubicin interferes with DNA synthesis by inhibiting topoisomerase II and by creating free radicals that can damage DNA.

Idamycin (Idarubicin) is an anthracycline antileukemic medicine that has potent bone marrow suppressant properties. It is used in conjunction with other drugs to treat acute leukemia.

Idamycin (Idarubicin) Uses:

• Acute myeloid leukemia:
  • Used for treatment of acute myeloid leukemia (AML) in adults (in combination with other approved chemotherapy agents).

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Idamycin (Idarubicin) Dose in Adults:

• Idarubicin can make you feel sick and cause vomiting. It's advised to take medicines that help prevent this feeling.

Idamycin (Idarubicin) Dose in the treatment of Acute myeloid leukemia (AML): 

For treating Acute Myeloid Leukemia (AML) with Idarubicin:

According to the manufacturer's guidelines:

• For the initial treatment, Idarubicin is given through an IV at a dose of 12 mg for each square meter of your body's surface area, for 3 days.
• This is done alongside another medicine called cytarabine.
• If the first round doesn't work as hoped, they might do a second round of this treatment.

For specific cases where AML comes back or doesn't respond to the first treatments:

• They use a treatment plan called FLAG-IDA. Here, Idarubicin is given at a dose of 10 mg for each square meter of your body's surface area, for 3 days.
• This is combined with three other medicines: fludarabine, cytarabine, and filgrastim.
• After the patient recovers from this treatment, they might do a second round for better results.

Idamycin (Idarubicin) Dose in the treatment of Acute promyelocytic leukemia (APL):

for treating Acute Promyelocytic Leukemia (APL) with Idarubicin:

According to the LPA 2005 guidelines for high-risk patients:

• Starting Treatment (for all ages):
  • They get 12 mg of Idarubicin for each square meter of their body's surface area on days 2, 4, 6, and 8.
  • But, older patients (above 70 years old) don't get the dose on day 8.
  • This treatment is given with another medicine called ATRA (or tretinoin).
• Follow-up Treatment (for people 60 years old or younger):
  • They get 5 mg of Idarubicin for each square meter of their body's surface area for 4 days during the first follow-up cycle.
  • During the third follow-up cycle, they get 12 mg just for 1 day.
  • This treatment is combined with ATRA (or tretinoin) and another medicine called cytarabine.

For the APML4 treatment plan:

• Starting Treatment for different age groups:
  • Younger than 60 years: They get 12 mg of Idarubicin for each square meter of their body's surface area on days 2, 4, 6, and 8. This is combined with ATRA (or tretinoin) and a medicine called arsenic trioxide.
  • Ages 61 to 70 years: They get 9 mg of Idarubicin on days 2, 4, 6, and 8. Given with the same other medicines as above.
  • Older than 70 years: They get 6 mg of Idarubicin on days 2, 4, 6, and 8. Given with the same other medicines as above.

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Idamycin (Idarubicin) Dose in Childrens:

Note:

• The amount of Idarubicin given, how often it's given, and when it starts can change based on the treatment plan.
• Make sure to check the exact plan being used.
• Idarubicin can make you feel like throwing up, so it's suggested to take medicines to help prevent feeling sick.

Idamycin (Idarubicin) Dose in the treatment of Acute myeloid leukemia (AML):

For treating Acute Myeloid Leukemia (AML) in infants, children, and teenagers using Idarubicin:

• At the start of treatment (based on the CCG-2961 plan):
  • Induction: They get 5 mg of Idarubicin (per square meter of body surface) through a drip (IV) every day for 4 days (days 0 to 3). This is given with other medicines: cytarabine, etoposide, thioguanine, and dexamethasone.
• For strengthening the treatment:
  • They can get one of two treatments:
    • 5 mg of Idarubicin every day for 4 days (days 0 to 3), with the same combination of medicines as before.
    • OR, a higher dose of 12 mg of Idarubicin every day but only for 3 days (days 0 to 2). This is given with two other medicines: fludarabine and cytarabine.

If the leukemia comes back or doesn't respond to the initial treatment:

• Children and teenagers get 12 mg of Idarubicin (per square meter of body surface) once a day for 3 days. This is combined with the medicines fludarabine and cytarabine.

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Idamycin (Idarubicin) Pregnancy Risk Category: D

• Problems were seen in animals when given idarubicin during pregnancy.
• There's a report of a baby not surviving when a pregnant woman took it in the second trimester.
• Doctors' guidelines suggest using a different similar medicine for treating leukemia in pregnant women during the later parts of pregnancy and getting help from a team of experts.
• It's also advised that women who could get pregnant avoid getting pregnant while taking this medicine.

Use of Idarubicin while breastfeeding

• We don't know if idarubicin gets into breast milk.
• But because there's a risk it could harm a breastfeeding baby, the company that makes it says mothers shouldn't breastfeed while taking it.

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Idamycin (Idarubicin) Dose in Kidney Disease:

The company that makes the medicine doesn't give clear instructions on how to adjust the dose, but they do say that changes might be needed. In many tests, people with high levels of S didn't get the medicine.

However, based on other recommendations:

• If your kidneys work really well (CrCl >50), take the regular dose.
• If your kidneys work somewhat slower (CrCl 10 to 50), take three-quarters of the regular dose.
• If your kidneys work quite slowly (CrCl <10), take half the regular dose.
• If you're on hemodialysis or a specific type of dialysis called CAPD, you don't need an extra dose.

Idamycin (Idarubicin) Dose in Liver Disease:

• If your bilirubin level is between 2.6 and 5, take half the regular dose of the medicine.
• If your bilirubin level is above 5, you shouldn't use the medicine at all.

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• The relative cardiotoxicity of idarubicin as compared to doxorubicin is not clear.
• Some investigators have reported no increase in cardiac toxicity for adults at cumulative oral idarubicin doses up to 540 mg/m²
• Other reports have suggested a maximum cumulative intravenous dose of 150 mg/m².

Common Side Effects of Idamycin (Idarubicin):

• Cardiovascular:
  • Cardiac Failure
  • ECG Abnormalities
• Central Nervous System:
  • Headache
• Dermatologic:
  • Alopecia
  • Skin Rash
  • Urticaria
• Gastrointestinal:
  • Vomiting
  • Gastrointestinal Hemorrhage
  • Diarrhea
  • Stomatitis
  • Nausea
• Genitourinary:
  • Urine Discoloration
• Hematologic & Oncologic:
  • Anemia
  • Bone Marrow Suppression
  • Thrombocytopenia
• Hepatic:
  • Increased Serum Bilirubin
  • Increased Serum Transaminases
• Miscellaneous:
  • Radiation Recall Phenomenon

Less Common Side Effects of Idamycin (Idarubicin):

• Central nervous system:
  • Peripheral neuropathy
  • Seizure

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Contraindications to Idamycin (Idarubicin):

The company that makes the medicine doesn't mention any reasons why someone shouldn't take it.

But, in Canada, they say don't take it if:

• You're allergic to idarubicin or similar medicines.
• You have an infection that isn't under control.
• You've had severe heart problems or recent heart attacks.
• You've already taken a lot of idarubicin or similar medicines in the past.
• Your bone marrow doesn't work well because of a drug.
• You have really bad liver or kidney problems.

Also, since medicines in this group are similar, if you're allergic to one, you might be allergic to others too. But, it's not entirely certain.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

• Using idarubicin can severely lower the activity of your bone marrow, which helps make blood cells.
• This means you might get infections easier because you'll have fewer white blood cells (neutropenia) and could bleed more because you'll have fewer platelets (thrombocytopenia).
• These issues can be life-threatening.
• Make sure to check your blood counts often.
• If your bone marrow is already weak, don't take this medicine unless it's really necessary.

Cardiomyopathy [US Boxed Warning]

• Idarubicin can harm the heart and lead to heart failure.
• This heart risk is higher for people who have previously taken similar medicines (anthracyclines) or who have heart problems.
• The risk is also higher if someone had radiation to the chest area, has anemia, bone marrow issues, infections, or certain heart-related conditions.
• People with active or past heart problems, taking heart-harming drugs (like trastuzumab or cyclophosphamide), or who had similar medicines before are also at greater risk.
• Dangerous heart failure, serious heart rhythm issues, or other heart problems can happen.
• It's important to regularly check how well the heart pumps (called left ventricular ejection fraction or LVEF), especially if someone has heart risks or heart issues.
• Be careful with timing: After stopping other heart-harming medicines, avoid using idarubicin for several months (up to 7 months after stopping trastuzumab, for example).
• Monitor the heart during treatment.
• Risk Factors for Heart Problems:
  • High doses of anthracycline drugs (like doxorubicin or epirubicin) or high-dose radiotherapy to the chest can raise the risk.
  • Even lower doses of anthracyclines with lower-dose radiotherapy to the chest can increase risk.
  • Lower-dose anthracyclines or trastuzumab alone along with multiple heart risk factors, older age (60 or older) during cancer treatment, or heart issues before or during treatment also increase risk.
• Steps for Safety According to ASCO Guidelines:
  • Check patients' heart health before starting treatment, including physical exams and heart checks.
  • Control modifiable risk factors (like smoking, high blood pressure, diabetes) before treatment.
  • Think about using protective drugs like dexrazoxane or continuous infusions for people getting high doses of anthracyclines.
  • If patients show signs of heart problems during treatment, do tests like echocardiograms or cardiac MRIs to understand what's happening.
  • Check blood markers for heart health and consult a heart specialist if needed.

Extravasation: [US Boxed Warning]

• Idarubicin can hurt the tissue if it leaks outside the vein (extravasation).
• It's given through a drip into a vein, not as a shot under the skin or into the muscle.
• Make sure the IV line is working well before and during the drip.
• Be careful to prevent the medicine from leaking into the surrounding tissue.

Gastrointestinal toxicities:

• Idarubicin can make you feel sick and want to throw up. Taking anti-sickness medicines can help prevent this.
• Some people also experience stomach pain, diarrhea, or painful mouth sores.
• In rare cases, it can cause a severe gut issue that can lead to a hole in the gut.

Hyperuricemia

• Quick destruction of certain blood cells by the drug can cause high levels of uric acid in the blood.
• Make sure to drink enough fluids and think about using medicines to control the uric acid levels.

Hepatic impairment: [US-Boxed Warning]

• People with liver issues should take a lower dose of Idarubicin.
• If someone has a very high bilirubin level (more than 5 mg/dL), they shouldn't use this medicine.

Infections

• Treat any body-wide infections before starting the medicine.

Renal impairment: [US-Boxed Warning]

• People with kidney issues should take a lower dose of the medicine.

Idarubicin: Drug Interaction

Risk Factor C (Monitor therapy)
Cardiac Glycosides	May diminish the cardiotoxic effect of Anthracyclines. Anthracyclines may decrease the serum concentration of Cardiac Glycosides. The effects of liposomal formulations may be unique from those of the free drug, as liposomal formulation have unique drug disposition and toxicity profiles, and liposomes themselves may alter digoxin absorption/distribution.
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Cyclophosphamide	May enhance the cardiotoxic effect of Anthracyclines.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Lumacaftor	May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
P-glycoprotein/ABCB1 Inducers	May decrease the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Smallpox and Monkeypox Vaccine (Live)	Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live).
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Risk Factor D (Consider therapy modification)
Ado-Trastuzumab Emtansine	May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination.
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect 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.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fam-Trastuzumab Deruxtecan	May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Lenograstim	Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Lipegfilgrastim	Antineoplastic Agents may diminish the therapeutic effect 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.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Palifermin	May enhance the adverse/toxic effect 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.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Taxane Derivatives	May enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Trastuzumab	May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Bevacizumab	May enhance the cardiotoxic effect of Anthracyclines.
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Lasmiditan	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Upadacitinib	Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live).

Monitoring parameters:

Regular Checks Needed:

• Blood Tests:
  • Complete blood count (CBC) with details often.
  • Check liver function with tests like ALT, AST, and bilirubin before and during treatment.
  • Look at kidney health with serum creatinine tests before and during treatment.
  • Measure uric acid levels.
• Heart Health:
  • Check how well the heart pumps (LVEF) before and while on the medicine.
• Other:
  • Keep an eye on where the medicine is given for any leaks.
  • Watch out for stomach issues and infections.

Heart Checks (Based on ASCO Guidelines):

• Before Treatment:
  • Full health check-up, including looking at risks like high blood pressure, diabetes, high cholesterol, being overweight, and smoking.
  • Heart scan (echocardiogram).
• If Heart Problems Appear:
  • Recommended to get another heart scan (echocardiogram).
  • If you can't get that, then a cardiac MRI is the next best thing, or a MUGA scan.
  • Check blood markers related to heart health.

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How to administer Idarubicin?

Nausea and Vomiting:

• Idarubicin can make you feel like throwing up.
• It's recommended to take medicines that help prevent this feeling.

How to Give Idarubicin:

• It should only be given into a vein (IV).
• Do not give it as a shot into the muscle (IM) or under the skin (SubQ).
• It should be given slowly over 10-15 minutes into a flowing IV solution.

Be Careful about Leaks (Extravasation):

• Idarubicin can damage tissues if it leaks out of the vein.
• Make sure the needle or tube is properly placed before and during the treatment to avoid this.

If the Medicine Leaks:

• Stop giving the medicine and remove the tube, but leave the needle in place.
• Try to pull out any leaked medicine gently, but don't push any fluids in.
• Raise the arm or leg where it was given.
• Use a specific medicine (dexrazoxane or DMSO) to treat the area.
• Apply a cold pack for 20 minutes, 4 times a day for 1-2 days. If you're using dexrazoxane, don't use cold packs 15 minutes before, during, or 15 minutes after its treatment.

Specific Treatments for Leaks:

• Dexrazoxane: Given into a vein, but not the one where the leak happened. It's given on days 1, 2, and 3. The dose depends on your body size and should start within 6 hours of the leak. For people with poor kidney function, the dose should be halved.
• DMSO: Put this on the skin covering twice the affected area. Start within 10 minutes of the leak and apply it every 8 hours for 7 days. Don't cover the area with a bandage.

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Mechanism of action of Idamycin (Idarubicin):

• Idarubicin gets in between the building blocks of DNA, which is like the instruction manual of our cells.
• This action is called "intercalation" and it blocks the cell from reading its DNA correctly.
• Idarubicin also stops the cell from repairing its DNA by targeting a helper protein called topoisomerase II.
• Because of these actions, the DNA gets broken, and the cell can't make its essential molecules like RNA.
• The exact way all of this works is still not fully understood, but these effects stop the cells from growing and dividing.

Spread in the Body:

• Volume of Distribution (V): Idarubicin spreads widely in the body, roughly equal to 1,500 liters for every square meter of a person's body surface.
• It binds a lot to body tissues and a small amount can also reach the fluid around the brain, known as CSF.

Binding in the Blood:

• Idarubicin mostly attaches to proteins in the blood. About 94% to 97% of it is bound, which means it's not floating freely.

How the Body Processes It:

• The liver changes idarubicin into another form called idarubicinol, which is still active in the body.

How Long It Stays in the Body:

• Children over 1 year and Teenagers: On average, it takes about 17.6 hours for half of the idarubicin to leave the body. But this can range from around 8.3 to 29.6 hours.
• Adults: For adults, it's about 22 hours, but this can vary a lot (from 4 to 48 hours). For idarubicinol, the changed form, it can take more than 45 hours for half of it to leave the body.

How It Leaves the Body:

• Most of it goes out with the bile, a digestive fluid made by the liver.
• A small part, about 8% to 10% as idarubicinol and 2% to 5% as unchanged idarubicin, leaves through urine.

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International Brands of Idarubicin:

• Idamycin PFS
• Idamycin
• Idaralem
• Ondarubin
• Zavedos
• Zavedos CS
• Zavel
• Zaverucin

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Idarubicin Brand Names in Pakistan:

Idarubicin Injection 5 mg
Zavedos	Pfizer Laboratories Ltd.

Idarubicin Injection 10 mg
Zavedos	Pfizer Laboratories Ltd.

Idarubicin Injection 10 mg/ml
Idarubicin Hydrochloride Ahp	Al-Habib Pharmaceuticals.