Doxorubicin is an anthracycline bacterial infections. সহজ বাংলা: ব্যাকটেরিয়ার সংক্রমণের ওষুধ।" data-rx-term="antibiotic" data-rx-definition="An antibiotic is a medicine used to treat bacterial infections. সহজ বাংলা: ব্যাকটেরিয়ার সংক্রমণের ওষুধ।">antibiotic with antineoplastic activity. Doxorubicin, isolated from the bacterium Streptomyces peucetius var. caesius, is the hydroxylated congener of daunorubicin. Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis. Additionally, doxorubicin inhibits topoisomerase II which results in an increased and stabilized cleavable enzyme-DNA linked complex during DNA replication and subsequently prevents the ligation of the nucleotide strand after double-strand breakage. Doxorubicin also forms oxygen free radicals resulting in cytotoxicity secondary to lipid peroxidation of cell membrane lipids; the formation of oxygen free radicals also contributes to the toxicity of the anthracycline antibiotics, namely the cardiac and cutaneous vascular effects.
Mechanism of Action of Doxorubicin
Doxorubicin hydrochloride is an antineoplastic bacterial infections. সহজ বাংলা: ব্যাকটেরিয়ার সংক্রমণের ওষুধ।" data-rx-term="antibiotic" data-rx-definition="An antibiotic is a medicine used to treat bacterial infections. সহজ বাংলা: ব্যাকটেরিয়ার সংক্রমণের ওষুধ।">antibiotic with pharmacologic actions similar to those of daunorubicin. Although the drug has anti-infective properties, its cytotoxicity precludes its use as an anti-infective agent. The precise and/or principal mechanism(s) of the antineoplastic action of doxorubicin is not fully understood. It appears that the cytotoxic effect of the drug results from a complex system of multiple modes of action related to free radical formation secondary to metabolic activation of the doxorubicin by electron reduction, intercalation of the drug into DNA, induction of DNA breaks and chromosomal aberrations, and alterations in cell membranes induced by the drug. Evidence from in vitro studies in cells treated with doxorubicin suggests that apoptosis (programmed cell death) also may be involved in the drug’s mechanism of action. These and other mechanisms (chelation of metal ions to produce drug-metal complexes) also may contribute to the cardiotoxic effects of the drug.
or
Doxorubicin undergoes enzymatic 1- and 2-electron reduction to the corresponding semiquinone and hydroquinone. 7-Deoxyaglycones are formed enzymatically by 1-electron reduction, and the resulting semiquinone free radical reacts with oxygen to produce the hydroxyl radical in a cascade of reactions; this radical may lead to cell death by reacting with DNA, RNA, cell membranes, and proteins. The hydroquinone that results from 2-electron reduction of doxorubicin also can be formed by the reaction of 2 semiquinones. In the presence of oxygen, dihydroquinone reacts to form hydrogen peroxide, and in its absence, loses its sugar and gives rise to the quinone methide, a monofunctional alkylating agent with low affinity for DNA. The contribution of hydroquinone and the quinone methide to the cytotoxicity of doxorubicin is unclear. Experimental evidence indicates that doxorubicin forms a complex with DNA by intercalation between base pairs, causing inhibition of DNA synthesis and DNA-dependent RNA synthesis by the resulting template disordering and steric obstruction. Doxorubicin also inhibits protein synthesis. Doxorubicin is active throughout the cell cycle including the interphase.
Indications of Doxorubicin
- Doxorubicin is used to produce regression in disseminated neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin’s disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types.
- Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.
- First line treatment of metastatic breast cancer in women
- As monotherapy for patients with metastatic breast cancer, where there is an increased cardiac risk
- For treatment of advanced ovarian cancer in women who have failed a first-line platinum-based chemotherapy regimen.
- In combination with bortezomib for the treatment of progressive multiple myeloma in patients who have received at least one prior therapy and who have already undergone or are unsuitable for a bone marrow transplant.
- For treatment of AIDS-related Kaposi’s sarcoma (KS) in patients with low CD4 counts (<200 CD4 lymphocytes/mm3) and extensive mucocutaneous or visceral disease.
- Caelyx may be used as first-line systemic chemotherapy, or as second-line chemotherapy in AIDS-KS patients with disease that has progressed with, or in patients intolerant to, prior combination systemic chemotherapy comprising at least two of the following agents: a vinca alkaloid, bleomycin and standard doxorubicin (or another anthracycline).
- Treatment of hepatoblastoma
- Bladder Cancer
- Breast Cancer
- Acute Lymphoblastic Leukemia
- Acute Myeloblastic Leukemia
- Bronchogenic Carcinoma
- Diffuse Large B-Cell Lymphoma
- Hodgkin’s Lymphoma
- Lymphoma
- Mantle Cell Lymphoma
- Multiple Myeloma
- Neuroblastoma
- Osteosarcoma
- Ovarian Cancer
- Soft Tissue Sarcoma
- Stomach Cancer
- Thyroid Cancer
Therapeutic Uses
- Antibiotics; Antineoplastic Agents
- Doxorubicin has been used successfully to produce regression in disseminated neoplastic conditions such as acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin’s disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types.
- Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer. /Included in US product label/
- DOXIL (doxorubicin hydrochloride, liposomal) is an anthracycline topoisomerase inhibitor indicated for ovarian cancer after failure of platinum-based chemotherapy.
- DOXIL (doxorubicin hydrochloride, liposomal) is an anthracycline topoisomerase inhibitor indicated for AIDS-related Kaposi’s Sarcoma after the failure of prior combination chemotherapy or intolerance to such therapy. Results are based on objective response rate; no results are available from controlled trials that demonstrate clinical benefit.
- DOXIL (doxorubicin hydrochloride, liposomal) is an anthracycline topoisomerase inhibitor indicated for multiple myeloma in combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy.
- Doxorubicin is indicated for the treatment of/ Ewing’s sarcoma.
Contra-Indications of Doxorubicin
- Severe infection
- Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- Decreased function of bone marrow
- Anemia
- Decreased Blood Platelets
- Decreased Neutrophils a Type of White Blood Cell
- heart attack within the last 30 days
- Disease of the Muscle of the Heart with Enlargement
- Atrioventricular Heart Block
- Bundle Branch Block
- Abnormal heart rhythm
- Heart Failure
- infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">Inflammation of the Middle Tissue Heart Muscle
- liver problems
- High Amount of jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।" data-rx-term="bilirubin" data-rx-definition="Bilirubin is a yellow pigment that can build up in jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।">Bilirubin in the Blood
- Tingling
- Pain
- Redness and Edema of Hands and Feet
- Pregnancy
- A mother who is producing milk and breastfeeding
- Dysfunction of Left Ventricle of Heart Without Symptoms
- Anemia from Pyruvate Kinase and G6PD Deficiencies
- Allergies to Anthracyclines
Dosage of Doxorubicin
Strengths: 10 mg; 20 mg; 50 mg; 150 mg; 2 mg/mL; 75 mg; 100 mg
NOTE: Several dosage regimens exist for this drug. The information presented here is manufacturer recommended dosing. Some cancers are more responsive to this drug than others. Always consult institutional protocol.
Breast Cancer
- As a single agent: 60 to 75 mg/m2 IV over 3 to 10 minutes every 21 days
- In combination with other chemotherapy drugs: 40 to 75 mg/m2 IV every 21 to 28 days
Neuroblastoma
- As a single agent: 60 to 75 mg/m2 IV over 3 to 10 minutes every 21 days
- In combination with other chemotherapy drugs: 40 to 75 mg/m2 IV every 21 to 28 days
Ovarian Cancer
- As a single agent: 60 to 75 mg/m2 IV over 3 to 10 minutes every 21 days
- In combination with other chemotherapy drugs: 40 to 75 mg/m2 IV every 21 to 28 days
Stomach Cancer
- As a single agent: 60 to 75 mg/m2 IV over 3 to 10 minutes every 21 days
- In combination with other chemotherapy drugs: 40 to 75 mg/m2 IV every 21 to 28 days
Acute Lymphoblastic Leukemia
- As a single agent: 60 to 75 mg/m2 IV over 3 to 10 minutes every 21 days
- In combination with other chemotherapy drugs: 40 to 75 mg/m2 IV every 21 to 28 days
Bladder Cancer
- As a single agent: 60 to 75 mg/m2 IV over 3 to 10 minutes every 21 days
- In combination with other chemotherapy drugs: 40 to 75 mg/m2 IV every 21 to 28 days
Thyroid Cancer
- As a single agent: 60 to 75 mg/m2 IV over 3 to 10 minutes every 21 days
- In combination with other chemotherapy drugs: 40 to 75 mg/m2 IV every 21 to 28 days
Side Effects of Doxorubicin
Most Common
- Pain, redness, swelling at the place of injection
- Painful swallowing
- Signs of anemia (e.g., feeling weak, dizzy, or short of breath)
- Signs of bleeding (e.g., bloody nose, blood in urine, coughing blood, cuts that don’t stop bleeding)
- Signs of a blood clot in blood vessels, such as sudden vision change or dizziness, chest pain, pain and swelling in one leg muscle
- Signs of an infection (e.g., fever over 38°C, chills or sweating, sore throat, coughing, redness or swelling around a cut, wound or catheter site, painful or difficult urination, unusual vaginal itching or discharge)
More Common
- Hair loss, thinning of hair
- Nausea and vomiting
- Sores in the mouth and on the lips
- Darkening of the soles, palms, or nails
- Diarrhea
- Fast or irregular heartbeat
- Shortness of breath
- Swelling of the feet and lower legs
Less Common
- Cough or hoarseness accompanied by fever or chills
- Darkening or redness of the skin (if you recently had radiation treatment)
- Fast or irregular heartbeat
- Fever or chills
- Joint pain
- Lower back or side pain accompanied by fever or chills
- Pain at the injection site
- Painful or difficult urination accompanied by fever or chills
- Red streaks along the injected vein
Drug Interactions of Doxorubicin
Doxorubicin may interact with following drugs, supplements & may change the efficacy of drugs
- antipsychotics (e.g., chlorpromazine, clozapine)
- atorvastatin
- “azole” antifungals (e.g., fluconazole, itraconazole, voriconazole)
- bevacizumab
- bupropion
- calcium channel blockers (e.g., diltiazem, verapamil)
- carbamazepine
- carvedilol
- celecoxib
- ciprofloxacin
- cyclosporine
- dasatinib
- desipramine
- dexamethasone
- hydrocortisone
- loperamide
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- mercaptopurine
- metronidazole
- non-drowsy” antihistamines (e.g., cetirizine, desloratadine, loratadine)
- norfloxacin
- other anthracyclinecancer medications (e.g., daunorubicin, idarubicin)
- other cancer medications (e.g., cyclophosphamide, doxetaxel, irinotecan, paclitaxel)
- oxcarbazepine
- pentobarbital
- phenobarbital
- phenytoin
- prazosin
- primidone
- progesterone
- propranolol
- protease inhibitors (e.g., lopinavir, ritonavir, stavudine)
- selegiline
- SSRI antidepressants (e.g., fluoxetine, paroxetine, sertraline)
- St. John’s wort
- tacrolimus
- tamoxifen
- tetracycline
Pregnancy Category
FDA Pregnancy Category: D
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
This medication passes into breast milk. If you are a breast-feeding mother and are taking doxorubicin, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. Children who receive doxorubicin are at an increased risk of developing leukemia. Children may also be more susceptible to effects of this medication on the heart.
References
