Doxorubin
Doxorubin Uses, Dosage, Side Effects, Food Interaction and all others data.
Doxorubin is a cytotoxic anthracycline antibiotic. The cytotoxic action results from its binding to DNA and inhibition of nucleic acid synthesis. Doxorubin has been shown to produce regression in a variety of disseminated malignancies.
Doxorubin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.
| Trade Name | Doxorubin |
| Availability | Prescription only |
| Generic | Doxorubicin |
| Doxorubicin Other Names | 14-hydroxydaunomycin, 14-hydroxydaunorubicine, Doxorubicin, Doxorubicina, Doxorubicine, Doxorubicinum, Hydroxydaunorubicin |
| Related Drugs | prednisone, methotrexate, dexamethasone, Keytruda, Armour Thyroid, Arimidex, rituximab, carboplatin, pembrolizumab, fluorouracil |
| Type | Injection |
| Formula | C27H29NO11 |
| Weight | Average: 543.5193 Monoisotopic: 543.174060775 |
| Protein binding | Doxorubicin and its major metabolite, doxorubicinol, is 74-76% bound to plasma protein. The extent to binding is independent of plasma concentration up to 1.1 mcg/mL. Doxorubicin does not cross the blood brain barrier. |
| Groups | Approved, Investigational |
| Therapeutic Class | Cytotoxic Chemotherapy |
| Manufacturer | Khandelwal Laboratories Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Doxorubin is an anthracycline topoisomerase II inhibitor used for:
- Ovarian cancer: After failure of platinum-based chemotherapy.
- AIDS-related Kaposi’s Sarcoma: After failure of prior systemic chemotherapy or intolerance to such therapy.
- Multiple Myeloma: In combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy.
Doxorubin is also used to associated treatment for these conditions: Acute Lymphoblastic Leukaemias (ALL), Acute Myeloblastic Leukemia, Advanced Endometrial Cancer, Advanced Soft Tissue Sarcoma, Bladder transitional cell carcinoma, Carcinoma, Bronchogenic, Gastric Carcinoma, Kaposi's Sarcoma AIDS Related, Lymphoma, Hodgkins, Malignant Lymphomas, Metastatic Breast Cancer, Multiple Myeloma (MM), Mycosis Fungoides (MF), Neuroblastomas, Ovarian Cancer Metastatic, Ovarian Carcinoma, Sarcoma, Bone, Sezary Syndrome, Soft Tissue Sarcoma (STS), Thyroid Carcinoma, Waldenström's Macroglobulinemia (WM), Wilms' tumor, Advanced Thymoma, Advanced uterine sarcoma
How Doxorubin works
Doxorubin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.
Dosage
Doxorubin dosage
Administer Doxorubin at an initial rate of 1 mg/min to minimize the risk of infusion reactions. If no infusion related reactions occur, increase rate of infusion to complete administration over 1 hour. Do not administer as bolus injection or undiluted solution.
- Ovarian cancer: 50 mg/m2 IV every 4 weeks
- AIDS-related Kaposi’s Sarcoma: 20 mg/m2 IV every 3 weeks
- Multiple Myeloma: 30 mg/m2 IV on day 4 following bortezomib
Side Effects
Leucopenia, thrombocytopenia, nausea, vomiting, diarrhoea. Rarely facial flushing, rash, alopecia. Blurred vision, headache, seizures, paraesthesia, confusion, malaise, lethargy, skin pigmentation.
Toxicity
LD50=21800 ug/kg (rat, subcutaneous)
Precaution
Elderly, children, hepatic impairment. Monitor blood counts and ECG.
Interaction
Doxorubin interacts with a number of other drugs e.g. antibiotics (aminoglycosides), steroids, aminophylline and propranolol.
Food Interaction
- Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of doxorubicin.
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of doxorubicin.
Doxorubin Drug Interaction
Moderate: aprepitant, aprepitant, pegfilgrastim, pegfilgrastim, ondansetron, ondansetronMinor: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, cyclophosphamide, cyclophosphamideUnknown: lorazepam, lorazepam, diphenhydramine, diphenhydramine, loratadine, loratadine, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol
Doxorubin Disease Interaction
Major: infections, cardiomyopathy, hepatic dysfunction, myelosuppression
Volume of Distribution
The distributive half-life is 5 minutes, which suggests that doxorubicin is rapidly taken up by tissue. Steady state volume of distribution = 809 to 1214 L/m2
Half Life
Terminal half life = 20 - 48 hours.
Clearance
- 324-809 mL/min/m2 [by metabolism and biliary excretion]
- 1088 mL/min/m2 [Men]
- 433 mL/min/m2 [Women]
- 1540 mL/min/m2 [children greater than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
- 813 mL/min/m2 [infants younger than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
Elimination Route
40% of the dose appears in bile in 5 days. 5-12% of the drug and its metabolites appears in urine during the same time period. <3% of the dose recovered in urine was doxorubicinol.
Pregnancy & Breastfeeding use
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Contraindication
Cardiac disease, neonates, pregnancy and lactation, prior irradiation to mediastinum. IM/SC admin. Severe myelosuppression due to previous treatment with antitumour agents or radiotherapy.
Special Warning
Hepatic Impairment-
serum-bilirubin: 12-30 mcg/ml: Half the normal dose;
serum-bilirubin: >30 mcg/ml: Quarter of the usual dose.
Acute Overdose
Acute overdosage may increase the toxic effects of mucositis, leukopenia and thrombocytopenia. Treatment includes hospitalisation of the severely myelosuppressed patient, antimicrobials, platelet transfusions and symptomatic treatment of mucositis. Use of haemopoietic growth factor (G-CSF, GM-CSF) may be considered. Cumulative dosage increases risk of cardiomyopathy and resultant congestive heart failure which may be managed with digitalis preparations, diuretics, and after load reducers such as ACE inhibitors.
Storage Condition
Powder for injection: Store at 15-30°C.
Solution for injection & liposomal formulations: Refrigerate at 2-8°C. Do not freeze.
Innovators Monograph
You find simplified version here Doxorubin
Doxorubin contains Doxorubicin see full prescribing information from innovator Doxorubin Monograph, Doxorubin MSDS, Doxorubin FDA label
FAQ
What is Doxorubin used for?
Doxorubin is used in combination with other medications to treat certain types of bladder, breast, lung, stomach, and ovarian cancer; Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's lymphoma (cancer that begins in the cells of the immune system); and certain types of leukemia (cancer of the white blood cells). It is often used together with other chemotherapy agents.
How safe is Doxorubin?
Doxorubin effects help patients achieve lengthy and good quality of life remission and survival times for many types of malignancies. Although Doxorubin poses significant risks in administration and toxicity, it is one of the most effective chemotherapeutic agents in veterinary medicine.
What is the mechanism of action of Doxorubin?
Doxorubin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.
What are the common side effects of Doxorubin?
Common side effects of Doxorubin are include:
- Atazanavir
- Boceprevir
- Cobicistat
- Lopinavir
- Measles Virus Vaccine, Live
- Mumps Virus Vaccine, Live
- Nelfinavir
- Rotavirus Vaccine, Live
- Rubella Virus Vaccine, Live
- Saquinavir
- Tasonermin
- Telaprevir
- Varicella Virus Vaccine, Live
- Zoster Vaccine, Live
Is Doxorubin safe during pregnancy?
Cyclophosphamide and Doxorubin are pregnancy category D agents; however, potential benefits may warrant treatment with these agents during pregnancy under special circumstances.
Is Doxorubin safe during breastfeeding?
Most sources consider breastfeeding to be contraindicated during maternal antineoplastic Doxorubin therapy, especially anthracyclines such as Doxorubin.
Can I drink alcohol with Doxorubin?
The drinking of alcohol does not appear to affect the safety or usefulness of pegylated liposomal Doxorubin.
How often do I take Doxorubin?
Doxorubin is usually given once every 21 to 28 days.
How long does Doxorubin take to work?
Doxorubin is a light red liquid that you have through a drip (infusion) into your bloodstream. It usually takes between 30 to 90 minutes each time you have it.
How long is Doxorubin treatment?
You usually have liposomal Doxorubin every 2 to 4 weeks. Your treatment plan will depend on the type of cancer you have.
What is the half life of Doxorubin?
The initial distribution half-life of approximately 5 minutes suggests rapid tissue uptake of doxorubicin, while its slow elimination from tissues is reflected by a terminal half-life of 20 to 48 hours.
What happens if I miss a dose?
Call your doctor for instructions if you miss an appointment for your Doxorubin injection.
What happens if I overdose?
Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.
Who should not take Doxorubin?
You should not use Doxorubin if you have severe liver disease, severe heart problems, very low blood cell counts caused by prior chemotherapy, or if you recently had a heart attack. You should not use this medicine if you are allergic to Doxorubin or similar medications or if you have:
very low blood cell counts caused by chemotherapy you received in the past; severe liver disease; severe heart problems; or if you have recently had a heart attack.
Will Doxorubin affect my fertility?
We know that certain chemotherapy medicines are more likely than others to cause infertility, including Doxorubin.
Can Doxorubin affects my heart?
Doxorubin is well recognized that Doxorubin may cause damage to the heart in some individuals.
Can Doxorubin affect my kidneys?
Researches have shown that Doxorubin chemotherapy could generate severe tissue injury in heart and kidney and the symptoms of renal damage like hematuresis and proteinuria are especially evident.
Can Doxorubin affects my liver?
While hepatotoxicity from Doxorubin, epirubicin or idarubicin may be rare, it is likely due to direct toxic injury to the liver. Doxorubin and its analogues are metabolized in the liver via microsomal enzymes, and production of a toxic or immunogenic intermediate may trigger liver injury.
What happen If I stop taking Doxorubin?
If you decide to stop chemotherapy, be sure you're still getting relief from symptoms such as pain, constipation, and nausea. This is called palliative care, and it's meant to improve your quality of life
