Doxorubicin is an active pharmaceutical ingredient in the Anthracyclines and Related Substances group (L01DB). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised April 11, 2025[1]
Doxorubicin is a cytotoxic medicinal product that is indicated in the following neoplastic conditions: • Small-cell lung cancer (SCLC) • Breast cancer • Recurrent ovarian carcinoma • Systemic treatment of local advanced or metastasized bladder carcinoma • Intravesical prophylaxis of recurrences of superficial bladder carcinoma following transurethral resection • Neoadjuvant and adjuvant therapy of osteosarcoma • Advanced soft-tissue sarcoma in adults • Ewing’s sarcoma • Hodgkin’s disease • Non-Hodgkin’s lymphoma • Acute lymphatic leukaemia • Acute myeloblastic leukaemia • Advanced multiple myeloma • Advanced or recurrent endometrial carcinoma • Wilms’ tumour • Advanced papillary/follicular thyroid cancer • Anaplastic thyroid cancer • Advanced neuroblastoma Doxorubicin is frequently used in combination chemotherapy regimens with other cytostatic medicinal products.
CACanada· Health Canada
6 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
Doxorubicin Hydrochloride for Injection USP (doxorubicin hydrochloride) has been used successfully both as a single-agent and also in combination with other approved cancer chemotherapeutic agents to produce regression in neoplastic conditions such as acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastomas, soft tissue sarcomas, bone sarcomas, breast carcinoma, gynecologic carcinomas, testicular carcinomas, bronchogenic carcinoma, Hodgkin’s disease, non- Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinomas, squamous cell carcinoma of the head and neck, and gastric carcinoma.
Doxorubicin Hydrochloride for Injection USP has also been used by instillation into the bladder for the topical treatment of superficial bladder tumors. A number of other solid tumors have also shown some responsiveness to doxorubicin hydrochloride alone or in combination with other drugs (see 4 DOSAGE AND ADMINISTRATION).
Studies to date have shown malignant melanoma, kidney carcinoma, large bowel carcinomas, brain tumors and metastases to the central nervous system not to be significantly responsive to doxorubicin hydrochloride therapy. 3 Pediatrics).
USUnited States· FDA
4 products
Uses
USOfficial regulatory label· revised April 30, 2026[3]
1 Adjuvant Breast Cancer Doxorubicin Hydrochloride Injection is indicated as a component of multi-agent adjuvant chemotherapy for treatment of women with axillary lymph node involvement following resection of primary breast cancer .
2 Other Cancers Doxorubicin Hydrochloride Injection is indicated for the treatment of • acute lymphoblastic leukemia • acute myeloblastic leukemia • Hodgkin lymphoma • non-Hodgkin lymphoma (NHL) • metastatic breast cancer • metastatic Wilms' tumor • metastatic neuroblastoma • metastatic soft tissue sarcoma • metastatic bone sarcoma • metastatic ovarian carcinoma • metastatic transitional cell bladder carcinoma • metastatic thyroid carcinoma • metastatic gastric carcinoma • metastatic bronchogenic carcinoma
How to take
EUEuropean Union· EMA
3 products
Uses
EUOfficial regulatory label· revised April 24, 2026[4]
Caelyx pegylated liposomal is indicated: - 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 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 pegylated liposomal 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 other anthracycline).
Drug interactions
Known interactions involving Doxorubicin. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 600. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PL224720003 · revised April 11, 2025
[2]Health Canada (DPD) · 02194465 · revised March 22, 2025
[3]FDA DailyMed · 00634b2b-4e48-41… · revised April 30, 2026 [PDF]
[4]European Medicines Agency · EMEA/H/C/000089 · revised April 24, 2026
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
How to take
GBOfficial regulatory label· revised April 11, 2025[1]
Treatment with Doxorubicin should be started by or after consultation with a doctor with extensive experience from cytostatic treatment. Due to the risk of a lethal cardiomyopathy, the risks and benefits to the individual patient should be weighted before each application.
Doxorubicin must not be used orally, subcutaneously, intramuscularly or intrathecally.
Note:
The dosages of S-liposomal doxorubicin and (conventional) doxorubicin are different. The two formulations cannot be interchanged. Posology For intravenous use The dosage of doxorubicin depends on dosage regimen, general status and previous treatment of the patient.
In order to avoid cardiomyopathy, it is recommended that the cumulative total lifetime dose of doxorubicin (including related medicinal products such as daunorubicin) should not exceed 450 - 550 mg/m² body surface area. 4). Dosage is usually calculated on the basis of body surface area.
On this basis, a dose of 60 - 75 mg/m² body surface area is recommended every three weeks when doxorubicin is used alone. If it is used in combination with other antitumour agents the dosage of doxorubicin should be reduced to 30 - 40 mg/m² every three weeks.
g. in case of immunosuppression, old age), an alternative dosage is 15 - 20 mg/m² body surface area per week. Patients with prior radiotherapy Patients who have received prior radiotherapy to the mediastinal/pericardial area should not receive doxorubicin greater than a total cumulative dose of 400 mg/m².
Elderly patients Dosage may need to be reduced in the elderly. Paediatric population In view of the substantial risk of doxorubicin induced cardiotoxicity during childhood certain maximum cumulative dosages that depend on the youth of patients should be applied.
In children (under 12 years of age) the maximal cumulative dose is usually considered 300 mg/m², whereas in adolescents (over 12 years of age) the maximal cumulative dose is set to 450 mg/m². For infants the maximal cumulative dosages are still indecisive, but even lower tolerability is assumed.
Dosage for children should be reduced, since they have an increased risk for cardiac toxicity, especially late toxicity. Myelotoxicity should be anticipated, with nadirs at 10 to 14 days after start of treatment. 3). Renal impairment In cases of renal insufficiency with a GFR less than 10 ml/min, 75 % of the calculated dose should be administered.
4). R). The recommended dose for intravesical treatment of superficial cancer of the bladder is 30 - 50 mg in 25 - 50 ml of physiological saline per instillation. The optimal concentration is about 1 mg/ml. 9 % or dextrose 5 % into a large vein using a Butterfly needle, taking 2 to 3 minutes over the injection.
This technique minimises the risk of thrombosis or perivenous extravasation, which can lead to severe local cellulitis and necrosis. Intravesical administration The solution should remain in the bladder for 1 - 2 hours. During this period the patient should be turned 90° every 15 minutes.
To avoid undesired dilution with urine the patient should be informed not to drink anything for a period of 12 hours before the instillation (this should reduce the production of urine to about 50 ml/h). The instillation may be repeated with an interval of 1 week to 1 month, dependent on whether the treatment is therapeutic or prophylactic.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised April 11, 2025[1]
Treatment with doxorubicin often causes undesirable effects, and some of these effects are serious enough to entail careful monitoring of the patient. The frequency and kind of undesirable effects are influenced by the speed of administration and the dosage.
Bone-marrow suppression is an acute dose limiting adverse effect, but is mostly transient. Clinical consequences of doxorubicin bone marrow/haematological toxicity may be fever, infections, sepsis/septicaemia, haemorrhages, tissue hypoxia or death.
Nausea and vomiting as well as alopecia are seen in almost all patients. Within each system organ class, the adverse events have been ranked under the headings of frequency, most frequent reactions first. For the evaluation of adverse effects the following frequency specification will be used: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Not known (cannot be estimated from the available data) Infections and infestations Very common: Common: Uncommon: Infection Sepsis, septicaemia Septic shock Neoplasms benign, malignant and unspecified (incl.
e. g. e. 4) Investigations Very common: Asymptomatic decrease in LVEF, abnormal ECG, abnormal transaminase levels, weight gaina Surgical and medical procedures Not known: Extravasation can lead to severe cellulitis, vesication and local tissue necrosis which may require surgical measures (including skin grafts) aIn patients with early breast cancer who received adjuvant therapy with doxorubicin (NSABP B-15 study).
The described side effects of doxorubicin therapy are mostly reversible. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised April 11, 2025[1]
Like all chemotherapy, therapy with Doxorubicin hydrochloride should be carried out only under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Patients should recover from the acute toxicities of prior cytotoxic treatment (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) before beginning treatment with doxorubicin. g. ECG, UCG and MUGA scan) • daily inspection of the oral cavity and pharynx for mucosal changes • blood tests: haematocrit, platelets, differential white cell count, AST, ALT, LDH, bilirubin, uric acid.
e. e. delayed) events. e. acute) events: Early cardiotoxicity of doxorubicin consists mainly of sinus tachycardia and/or ECG abnormalities such as non-specific ST-T wave changes. Tachyarrhythmias, including premature ventricular contractions and ventricular tachycardia, bradycardia, as well as atrioventricular and bundle-branch block have also been reported.
These symptoms generally indicate acute transient toxicity. Flattening and widening of the QRS-complex beyond normal limits may indicate doxorubicin hydrochloride-induced cardiomyopathy. As a rule, in patients with a normal LVEF baseline value (= 50 %), a 10 % decrease of absolute value or dropping below the 50 % threshold indicates cardiac dysfunction and in such situation treatment with doxorubicin hydrochloride should be carefully considered.
e. delayed) events: Delayed cardiotoxicity usually develops late in the course of therapy with doxorubicin or within 2 to 3 months after treatment termination, but later events, several months to years after completion of treatment, have also been reported.
Delayed cardiomyopathy is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF) such as dyspnoea, pulmonary oedema, dependent oedema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion and gallop rhythm.
Subacute effects such as pericarditis/myocarditis have also been reported. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the medicinal product.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised April 11, 2025[1]
1, or to other anthracyclines or anthracenediones. g. urethral stenosis • haematuria • breast-feeding Dosage should not be repeated in the presence or development of bone marrow depression or buccal ulceration. The latter may be preceded by premonitory buccal burning sensations and repetition in the presence of this symptom is not advised.
This is not medical advice. Consult a qualified healthcare professional.
2 Geriatrics Geriatrics (≥ 60 years): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use.
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
). Studies to date have shown malignant melanoma, kidney carcinoma, large bowel carcinomas, brain tumors and metastases to the central nervous system not to be significantly responsive to doxorubicin hydrochloride therapy. 3 Pediatrics).
2 Geriatrics Geriatrics (≥ 60 years): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use. 2 CONTRAINDICATIONS • Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container.
For a complete listing, see the
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
). , delayed) events. , Acute) Events Early cardiotoxicity of doxorubicin consists mainly of sinus tachycardia and/ or ECG abnormalities such as non-specific ST-T wave changes. PrDoxorubicin Hydrochloride for Injection USP (doxorubicin hydrochloride) Page 11 of 30 Tachyarrhythmias, including premature ventricular contractions and ventricular tachycardia, bradycardia, and atrioventricular and bundle-branch block also have been reported.
Those effects usually do not predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance and generally do not necessitate discontinuation of doxorubicin treatment. , Delayed) Events Delayed cardiotoxicity usually develops late in the course of therapy with doxorubicin or within 2 to 3 months after treatment termination, but later events, several months to years after completion of treatment, have also been reported.
Delayed cardiomyopathy is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF) such as dyspnea, pulmonary edema, dependent edema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion and gallop rhythm.
Subacute effects such as pericarditis/myocarditis also have been reported. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and is the cumulative dose-limiting toxicity of anthracycline drugs. The probability of developing CHF is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m2 of doxorubicin HCl.
Thereafter, the risk of developing CHF increases steeply; 3 to 5% at a dose of 400 mg/m2, 5 to 8% at a dose of 450 mg/m2, and 6 to 20% at a dose of 500 mg/m2, when doxorubicin HCl is administered every 3 weeks. IT IS RECOMMENDED NOT TO EXCEED A MAXIMUM CUMULATIVE DOSE OF 550 MG/M2 OF DOXORUBICIN HYDROCHLORIDE FOR INJECTION USP.
The total dose of Doxorubicin Hydrochloride for Injection USP administered to a patient should take into account: prior therapy with related compounds such as epirubicin and daunorubicin or anthracene derivatives; and/or radiotherapy to the mediastinal area.
Risk factors for cardiac toxicity include active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones and concomitant use of drugs with the ability to suppress cardiac contractility or cardiotoxic drugs.
Anthracyclines including doxorubicin should not be administered in combination with other cardiotoxic agents unless the patient’s cardiac function is closely monitored. Patients receiving anthracyclines after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity.
The reported half-life of trastuzumab is approximately 28 - 38 days. Trastuzumab may persist in the circulation for up to 7 months. Therefore, physicians should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab when possible.
If anthracyclines are used before this time, careful monitoring of cardiac function is recommended. Cardiac function must be carefully monitored in patients receiving high cumulative doses and in those with risk factors. While cardiotoxicity with doxorubicin may occur at lower cumulative doses whether or not cardiac risk factors are present, it may be more likely to occur at lower cumulative doses in patients with these risk factors.
New studies show that children and adolescents are at an increased risk for developing delayed cardiotoxicity following doxorubicin administration (up to 15 years). Females may be at greater risk than males. Follow-up cardiac evaluations such as ECHO LVEF/MUGA are recommended periodically to monitor for this effect (see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests).
Vascular Effects Phlebosclerosis may result from an injection into a small vessel or from repeated injections into the same vein. Following the recommended administration procedures may minimize the risk of PrDoxorubicin Hydrochloride for Injection USP (doxorubicin hydrochloride) Page 12 of 30 phlebitis/thrombophlebitis at the injection site (see 4 DOSAGE AND ADMINISTRATION).
As with other cytotoxic agents, thrombophlebitis and thromboembolic phenomena, including pulmonary embolism (in some cases fatal), have been coincidentally reported with the use of doxorubicin. Contamination Toxicities With Co-Administration of Antineoplastic Agents Doxorubicin hydrochloride may potentiate the toxicity of other anticancer therapies.
Exacerbation of cyclophosphamide-induced hemorrhagic cystitis and enhancement of the hepatotoxicity of 6-mercaptopurine have been reported. Radiation-induced toxicity to the myocardium, mucosae, skin and liver has been reported to be increased by the administration of doxorubicin hydrochloride.
Patients should recover from acute toxicities of prior cytotoxic treatment (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) before beginning treatment with doxorubicin. Endocrine and Metabolism Tumor-Lysis Syndrome Doxorubicin may induce hyperuricemia as a consequence of the extensive purine catabolism that accompanies drug-induced rapid lysis of neoplastic cells (tumor-lysis syndrome).
Blood uric acid levels, potassium, calcium, phosphate and creatinine should be evaluated after initial treatment. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor-lysis syndrome.
Gastrointestinal Doxorubicin is emetogenic. Mucositis/stomatitis generally appears early after drug administration and, if severe, may progress over a few days to mucosal ulcerations. Most patients recover from this adverse event by the […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
1 Special Populations 03/2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed . RECENT MAJOR LABEL CHANGES............................................................................................
2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................
9 5 OVERDOSAGE ............................................................................................................. 9 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 9 7 WARNINGS AND PRECAUTIONS ................................................................................
1 Special Populations ........................................................................................ 1 Pregnant Women ....................................................................................... 2 Breast-feeding............................................................................................
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
• Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.
PrDoxorubicin Hydrochloride for Injection USP (doxorubicin hydrochloride) Page 5 of 30 • Hypersensitivity to doxorubicin or any other component of the product, other anthracyclines or anthracenediones such as PHARMORUBICIN (epirubicin hydrochloride), daunorubicin hydrochloride, mitoxantrone or mitomycin C.
• Marked persistent myelosuppression induced by prior treatment with other antitumor agents or by radiotherapy; • Severe hepatic impairment; • Severe myocardial insufficiency; • Recent myocardial infarction; • Severe arrhythmias; • History of severe cardiac disease; • Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin and/or other anthracyclines and anthracenediones (see 7 WARNINGS AND PRECAUTIONS).
Contraindication for intravesical use: • Hematuria; • Urinary tract infections; • Inflammation of the bladder.
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised April 30, 2026[3]
1 Recommended Dosage for Adjuvant Breast Cancer The recommended dosage of Doxorubicin Hydrochloride Injection is 60 mg/m 2 administered as an intravenous bolus on day 1 of each 21-day treatment cycle, in combination with cyclophosphamide, for a total of four cycles .
2 Recommended Dosage for Other Cancers • The recommended dosage of Doxorubicin Hydrochloride Injection when used as a single agent is 60 mg/m 2 to 75 mg/m 2 intravenously every 21 days. • The recommended dosage of Doxorubicin Hydrochloride Injection, when administered in combination with other chemotherapy drugs, is 40 mg/m 2 to 75 mg/m 2 intravenously every 21 to 28 days.
• Consider use of the lower Doxorubicin Hydrochloride Injection dose in the recommended dosage range or longer intervals between cycles for heavily pretreated patients, elderly patients, or obese patients. 1) ]. 1) ] . 4 Dosage Modifications for Hepatic Impairment Doxorubicin Hydrochloride Injection is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C or serum bilirubin greater than 5 mg/dL) [see Contraindications (4) ].
6) ] are provided in Table 1. Table 1. 5 Preparation and Administration Doxorubicin Hydrochloride Injection is a hazardous drug. Follow applicable special handling and disposal procedures. 9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.
• Protect from light following preparation until completion of infusion. • Use within 1 hour. If not used within 1 hour, discard the diluted product. Administration • Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit.
Discard if the solution is discolored, cloudy, or contains particulate matter. 45% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP. • Administer intravenously over 3 to 10 minutes. Decrease the rate of infusion if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur.
Administration by Continuous Intravenous Infusion • Administer diluted Doxorubicin Hydrochloride Injection solution only through a central intravenous line. Decrease the rate of infusion if erythematous streaking along the vein proximal to the site of infusion or facial flushing occur.
• Protect from light from preparation for infusion until completion of infusion. Management of Suspected Extravasation Immediately discontinue Doxorubicin Hydrochloride Injection for burning or stinging sensation or other evidence indicating peri-venous infiltration or extravasation.
Manage confirmed or suspected extravasation as follows: • Do not remove the needle until attempts are made to aspirate extravasated fluid. • Do not flush the line. • Avoid applying pressure to the site. • Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days.
• If the extravasation is in an extremity, elevate the extremity. 3) ] . Management of Contact with Skin or Eyes Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution.
Do not abrade the skin by using a scrub brush. Seek medical attention. Incompatibility with Other Drugs Do not admix Doxorubicin Hydrochloride Injection with other drugs. If Doxorubicin Hydrochloride Injection is mixed with heparin or fluorouracil, a precipitate may form.
Avoid contact with alkaline solutions which can lead to hydrolysis of doxorubicin hydrochloride.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised April 30, 2026[3]
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling. 7) ] The most common (>10%) adverse reactions are alopecia, nausea and vomiting. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc.
gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Breast Cancer The safety data below were collected from 1492 women who received doxorubicin hydrochloride at a dose of 60 mg/m 2 and cyclophosphamide at a dose of 600 mg/m 2 (AC) every 3 weeks for 4 cycles for the adjuvant treatment of axillary lymph node positive breast cancer.
The median number of cycles received was 4. Selected adverse reactions reported in this study are provided in Table 2. No treatment-related deaths were reported in patients on either arm of the study. Table 2. 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of Doxorubicin Hydrochloride Injection.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac – Cardiogenic shock Cutaneous – Skin and nail hyperpigmentation, oncolysis, rash, itching, photosensitivity, urticaria, acral erythema, palmar plantar erythrodysesthesia Gastrointestinal – Nausea, mucositis, stomatitis, necrotizing colitis, typhlitis, gastric erosions, gastrointestinal tract bleeding, hematochezia, esophagitis, anorexia, abdominal pain, dehydration, diarrhea, hyperpigmentation of the oral mucosa Hypersensitivity – Anaphylaxis Laboratory Abnormalities – Increased ALT, increased AST Neurological – Peripheral sensory and motor neuropathy, seizures, coma Ocular – Conjunctivitis, keratitis, lacrimation Vascular – Phlebosclerosis, phlebitis/thrombophlebitis, hot flashes, thromboembolism Other – Malaise/asthenia, fever, chills, weight gain
USOfficial regulatory label· Warnings and precautions· revised April 30, 2026[3]
5 WARNINGS AND PRECAUTIONS • Radiation-Induced Toxicity : Can be increased by the administration of Doxorubicin Hydrochloride Injection. Radiation recall can occur in patients who receive Doxorubicin Hydrochloride Injection after prior radiation therapy.
7 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and on the use of effective contraception. Advise males with female partners of reproductive potential to use effective contraception.
Advise males with pregnant partners to use condoms. 1 Cardiomyopathy and Arrhythmias Cardiomyopathy Doxorubicin hydrochloride can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy is generally proportional to the cumulative exposure.
Include prior doses of other anthracyclines or anthracenediones in calculations of total cumulative dosage for doxorubicin hydrochloride. Cardiomyopathy may develop during treatment or up to several years after completion of treatment and can include decrease in LVEF and signs and symptoms of congestive heart failure (CHF).
The probability of developing cardiomyopathy is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m 2 of doxorubicin hydrochloride, 3 to 5% at a dose of 400 mg/m 2 , 5 to 8% at a dose of 450 mg/m 2 , and 6 to 20% at a dose of 500 mg/m 2 , when doxorubicin hydrochloride is administered every 3 weeks.
There is an additive or potentially synergistic increase in the risk of cardiomyopathy in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents, such as cyclophosphamide and trastuzumab.
Pericarditis and myocarditis have also been reported during or following doxorubicin hydrochloride treatment. , MUGA or echocardiogram) prior to initiation of Doxorubicin Hydrochloride Injection, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity.
Increase the frequency of assessments as the cumulative dose exceeds 300 mg/m 2 . 4) ] . 3) ] . Consider the use of dexrazoxane to reduce the incidence and severity of cardiomyopathy due to doxorubicin hydrochloride administration in patients who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m 2 and who will continue to receive doxorubicin hydrochloride.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised April 30, 2026[3]
2) ] • Severe myocardial insufficiency ( 4 ) • Recent myocardial infarction ( 4 ) • Severe persistent drug-induced myelosuppression ( 4 ) • Severe hepatic impairment ( 4 ) • Severe hypersensitivity to doxorubicin hydrochloride ( 4 )
This is not medical advice. Consult a qualified healthcare professional.
How to take
EUOfficial regulatory label· revised April 24, 2026[4]
Caelyx pegylated liposomal should only be administered under the supervision of a qualified oncologist specialised in the administration of cytotoxic agents. Caelyx pegylated liposomal exhibits unique pharmacokinetic properties and must not be used interchangeably with other formulations of doxorubicin hydrochloride.
3 Posology Breast cancer/Ovarian cancer Caelyx pegylated liposomal is administered intravenously at a dose of 50 mg/m2 once every 4 weeks for as long as the disease does not progress and the patient continues to tolerate treatment.
Multiple myeloma Caelyx pegylated liposomal is administered at 30 mg/m² on day 4 of the bortezomib 3 week regimen as a 1 hour infusion administered immediately after the bortezomib infusion. 3 mg/m² on days 1, 4, 8, and 11 every 3 weeks.
The dose should be repeated as long as patients respond satisfactorily and tolerate treatment. Day 4 dosing of both medicinal products may be delayed up to 48 hours as medically necessary. Doses of bortezomib should be at least 72 hours apart.
AIDS-related KS Caelyx pegylated liposomal is administered intravenously at 20 mg/m2 every two-to-three weeks. Avoid intervals shorter than 10 days as medicinal product accumulation and increased toxicity cannot be ruled out. Treatment of patients for two-to-three months is recommended to achieve a therapeutic response.
Continue treatment as needed to maintain a therapeutic response. 8), immediately discontinue the infusion, give appropriate premedications (antihistamine and/or short acting corticosteroid) and restart at a slower rate. Guidelines for Caelyx pegylated liposomal dose modification To manage adverse events such as palmar-plantar erythrodysesthesia (PPE), stomatitis or haematological toxicity, the dose may be reduced or delayed.
Guidelines for Caelyx pegylated liposomal dose modification secondary to these adverse effects are provided in the tables below. The toxicity grading in these tables is based on the National Cancer Institute Common Toxicity Criteria (NCI-CTC).
The tables for PPE (Table 1) and stomatitis (Table 2) provide the schedule followed for dose modification in clinical trials in the treatment of breast or ovarian cancer (modification of the recommended 4 week treatment cycle): if these toxicities occur in patients with AIDS-related KS, the recommended 2 to 3 week treatment cycle can be modified in a similar manner.
The table for haematological toxicity (Table 3) provides the schedule followed for dose modification in clinical trials in the treatment of patients with breast or ovarian cancer only. Dose modification in patients with AIDS-KS is provided following Table 4.
Table 1. Palmar–Plantar erythrodysesthesia Week after prior Caelyx pegylated liposomal dose Toxicity grade at current assessment Week 4 Week 5 Week 6 Grade 1 (mild erythema, swelling, or desquamation not interfering with daily activities) Redose unless patient has experienced a previous grade 3 or 4 skin toxicity, in which case wait an additional week Redose unless patient has experienced a previous grade 3 or 4 skin toxicity, in which case wait an additional week Decrease dose by 25%; return to 4 week interval 4 Grade 2 (erythema, desquamation, or swelling interfering with, but not precluding normal physical activities; small blisters or ulcerations less than 2 cm in diameter) Wait an additional week Wait an additional week Decrease dose by 25%; return to 4 week interval Grade 3 (blistering, ulceration, or swelling interfering with walking or normal daily activities; cannot wear regular clothing) Wait an additional week Wait an additional week Withdraw patient Grade 4 (diffuse or local process causing infectious complications, or a bedridden state or hospitalisation) Wait an additional week Wait an additional week Withdraw patient Table 2.
Stomatitis Week after prior Caelyx pegylated liposomal dose Toxicity grade at current assessment Week 4 Week 5 Week 6 Grade 1 (painless ulcers, erythema, or mild soreness) Redose unless patient has experienced a previous grade 3 or 4 stomatitis in which case wait an additional week Redose unless patient has experienced a previous grade 3 or 4 stomatitis in which case wait an additional week Decrease dose by 25%; return to 4 week interval or withdraw patient per physician’s assessment Grade 2 (painful erythema, oedema, or ulcers, but can eat) Wait an additional week Wait an additional week Decrease dose by 25%; return to 4 week interval or withdraw patient per physician’s assessment Grade 3 (painful erythema, edema, or ulcers, but cannot eat) Wait an additional week Wait an additional week Withdraw patient Grade 4 (requires parenteral or enteral support) Wait an additional week Wait an additional week Withdraw patient Table 3.
Haematological toxicity (ANC or platelets) – Management of patients with breast or ovarian cancer GRADE ANC PLATELETS MODIFICATION Grade 1 1,500 – 1,900 75,000 – 150,000 Resume treatment with no dose reduction. Grade 2 1,000 – < 1,500 50,000 – < 75,000 Wait until ANC ≥ 1,500 and platelets ≥ 75,000; redose with no dose reduction.
Grade 3 500 – < 1,000 25,000 – < 50,000 Wait until ANC ≥ 1,500 and platelets ≥ 75,000; redose with no dose reduction. 5 Grade 4 < 500 < 25,000 Wait until ANC ≥ 1,500 and platelets ≥ 75,000; decrease dose by 25% or continue full dose with growth factor support.
For multiple myeloma patients treated with Caelyx pegylated liposomal in combination with bortezomib who experience PPE or stomatitis, the Caelyx pegylated liposomal dose should be modified as described in Table 1 and 2 above respectively.
Table 4, below provides the schedule followed for other dose modifications in the clinical trial in the treatment of patients with multiple myeloma receiving Caelyx pegylated liposomal and bortezomib combination therapy. For more detailed information on […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised April 24, 2026[4]
Summary of the safety profile The most frequent adverse reactions (≥ 20%) were neutropaenia, nausea, leukopaenia, anaemia, and fatigue. Severe adverse reactions (Grade 3/4 adverse reactions occurring in ≥ 2% of patients) were neutropaenia, PPE, leukopaenia, lymphopaenia, anaemia, thrombocytopaenia, stomatitis, fatigue, diarrhoea, vomiting, nausea, pyrexia, dyspnoea, and pneumonia.
Less frequently reported severe adverse reactions included Pneumocystis jirovecii pneumonia, abdominal pain, cytomegalovirus infection including cytomegalovirus chorioretinitis, asthenia, cardiac arrest, cardiac failure, cardiac failure congestive, pulmonary embolism, thrombophlebitis, venous thrombosis, anaphylactic reaction, anaphylactoid reaction, toxic epidermal necrolysis, and Stevens-Johnson syndrome.
Tabulated list of adverse reactions Table 5 summarises the adverse drug reactions that occurred in patients receiving Caelyx pegylated liposomal in 4,231 patients for the treatment of breast cancer, ovarian cancer, multiple myeloma, and AIDS-related KS.
Post-marketing adverse reactions are also included, as indicated by “b”. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (frequency cannot be estimated from the available data).
Within each frequency grouping, where relevant, adverse reactions are presented in order of decreasing seriousness.
Table 5:
Adverse reactions in patients treated with Caelyx pegylated liposomal System Organ Class Frequency All Grades Adverse Drug Reaction Infections and infestations Common Sepsis Pneumonia Pneumocystis jirovecii pneumonia Cytomegalovirus infection including cytomegalovirus chorioretinitis Mycobacterium avium complex infection Candidiasis Herpes zoster Urinary tract infection Infection Upper respiratory tract infection Oral candidiasis Folliculitis Pharyngitis Nasopharyngitis Uncommon Herpes simplex Fungal infection Rare Opportunistic infection (including Aspergillus, Histoplasma, Isospora, 11 Legionella, Microsporidium, Salmonella, Staphylococcus, Toxoplasma, Tuberculosis)a Neoplasms benign, malignant and unspecified (including cysts and polyps) Not known Acute myeloid leukaemiab Myelodysplastic syndromeb Oral neoplasmb Blood and lymphatic system disorders Very common Leukopaenia Neutropaenia Lymphopaenia Anaemia (including hypochromic) Common Thrombocytopaenia Febrile neutropaenia Uncommon Pancytopaenia Thrombocytosis Rare Bone marrow failure Immune system disorders Uncommon Hypersensitivity Anaphylactic reaction Rare Anaphylactoid reaction Metabolism and nutrition disorders Very common Decreased appetite Common Cachexia Dehydration Hypokalaemia Hyponatraemia Hypocalcaemia Uncommon Hyperkalaemia Hypomagnesaemia Psychiatric disorders Common Confusional state Anxiety Depression Insomnia Nervous system disorders Common Neuropathy peripheral Peripheral sensory neuropathy Neuralgia Paraesthesia Hypoaesthesia Dysgeusia Headache Lethargy Dizziness Uncommon Polyneuropathy Convulsion Syncope Dysaesthesia Somnolence Eye disorders Common Conjunctivitis Uncommon Vision blurred Lacrimation increased Rare Retinitis Cardiac disordersa Common Tachycardia Uncommon Palpitations Cardiac arrest Cardiac failure Cardiac failure congestive Cardiomyopathy 12 Cardiotoxicity Rare Ventricular arrhythmia Bundle branch block right Conduction disorder Atrioventricular block Cyanosis Vascular disorders Common Hypertension Hypotension Flushing Uncommon Pulmonary embolism Infusion site necrosis (including soft tissue necrosis and skin necrosis) Phlebitis Orthostatic hypotension Rare Thrombophlebitis Venous thrombosis Vasodilatation Respiratory, thoracic and mediastinal disorders Common Dyspnoea Dyspnoea exertional Epistaxis Cough Uncommon Asthma Chest discomfort Rare Throat tightness Not Known Interstitial lung disease Gastrointestinal disorders Very common Stomatitis Nausea Vomiting Diarrhoea Constipation Common Gastritis Aphthous stomatitis Mouth ulceration Dyspepsia Dysphagia Oesophagitis Abdominal pain Abdominal pain upper Oral pain Dry mouth Uncommon Flatulence Gingivitis Rare Glossitis Lip ulceration Skin and subcutaneous tissue disorders Very common Palmar plantar erythrodysaesthesia syndromea Rash (including erythematous, maculo-papular, and papular) Alopecia Common Skin exfoliation Blister Dry skin Erythema Pruritus 13 Hyperhidrosis Skin hyperpigmentation Uncommon Dermatitis Dermatitis exfoliative Acne Skin ulcer Dermatitis allergic Urticaria Skin discolouration Petechiae Pigmentation disorder Nail disorder Rare Toxic epidermal necrolysis Erythema multiforme Dermatitis bullous Lichenoid keratosis Not known Stevens-Johnson syndromeb Musculoskeletal and connective tissue disorders Very common Musculoskeletal pain (including musculoskeletal chest pain, back pain, pain in extremity) Common Muscle spasms Myalgia Arthralgia Bone pain Uncommon Muscular weakness Renal and urinary disorders Common Dysuria Not Known Renal-limited thrombotic microangiopathy Reproductive disorders Uncommon Breast pain Rare Vaginal infection Scrotal erythema General disorders and administration site conditions Very common Pyrexia Fatigue Common Infusion-related reaction Pain Chest pain Influenza-like illness Chills Mucosal inflammation Asthenia Malaise Oedema Oedema peripheral Uncommon Administration site extravasation Injection site reaction Face oedema Hyperthermia Rare Mucous membrane disorder Investigations Common Weight decreased Uncommon Ejection fraction decreased Rare Liver function test abnormal (including Blood bilirubin increased, Alanine aminotransferase increased and Aspartate aminotransferase increased) 14 Blood creatinine increased Injury, poisoning and procedural complications Uncommon Radiation recall phenomenona a See Description of selected adverse reactions b Post-marketing adverse reaction Description of selected adverse reactions Palmar plantar erythrodysaesthesia The […]
EUOfficial regulatory label· Warnings and precautions· revised April 24, 2026[4]
Given the difference in pharmacokinetic profiles and dosing schedules, Caelyx pegylated liposomal should not be used interchangeably with other formulations of doxorubicin hydrochloride. Cardiac toxicity It is recommended that all patients receiving Caelyx pegylated liposomal routinely undergo frequent ECG monitoring.
Transient ECG changes such as T-wave flattening, S-T segment depression and benign arrhythmias are not considered mandatory indications for the suspension of Caelyx pegylated liposomal therapy. However, reduction of the QRS complex is considered more indicative of cardiac toxicity.
, endomyocardial biopsy, must be considered. More specific methods for the evaluation and monitoring of cardiac functions as compared to ECG are a measurement of left ventricular ejection fraction by echocardiography or preferably by Multigated Angiography (MUGA).
These methods must be applied routinely before the initiation of Caelyx pegylated liposomal therapy and repeated periodically during treatment. The evaluation of left ventricular function is considered to be mandatory before each additional administration of Caelyx pegylated liposomal that exceeds a lifetime cumulative anthracycline dose of 450 mg/m2.
The evaluation tests and methods mentioned above concerning the monitoring of cardiac performance during anthracycline therapy are to be employed in the following order: ECG monitoring, measurement of left ventricular ejection fraction, endomyocardial biopsy.
If a test result indicates possible cardiac injury associated with Caelyx pegylated liposomal therapy, the benefit of continued therapy must be carefully weighed against the risk of myocardial injury. In patients with cardiac disease requiring treatment, administer Caelyx pegylated liposomal only when the benefit outweighs the risk to the patient.
Exercise caution in patients with impaired cardiac function who receive Caelyx pegylated liposomal. , < 45%), endomyocardial biopsy may be considered and the benefit of continued therapy must be carefully evaluated against the risk of developing irreversible cardiac damage.
Congestive heart failure due to cardiomyopathy may occur suddenly, without prior ECG changes and may also be encountered several weeks after discontinuation of therapy. Caution must be observed in patients who have received other anthracyclines.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised April 24, 2026[4]
3. 1. 3. PHARMACEUTICAL FORM Concentrate for solution for infusion (sterile concentrate) The dispersion is sterile, translucent and red. 4. 1 Therapeutic indications Caelyx pegylated liposomal is indicated: - 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 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 pegylated liposomal 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 other anthracycline).
2 Posology and method of administration Caelyx pegylated liposomal should only be administered under the supervision of a qualified oncologist specialised in the administration of cytotoxic agents. Caelyx pegylated liposomal exhibits unique pharmacokinetic properties and must not be used interchangeably with other formulations of doxorubicin hydrochloride.
3 Posology Breast cancer/Ovarian cancer Caelyx pegylated liposomal is administered intravenously at a dose of 50 mg/m2 once every 4 weeks for as long as the disease does not progress and the patient continues to tolerate treatment.
Multiple myeloma Caelyx pegylated liposomal is administered at 30 mg/m² on day 4 of the bortezomib 3 week regimen as a 1 hour infusion administered immediately after the bortezomib infusion. 3 mg/m² on days 1, 4, 8, and 11 every 3 weeks.
The dose should be repeated as long as patients respond satisfactorily and tolerate treatment. Day 4 dosing of both medicinal products may be delayed up to 48 hours as medically necessary. Doses of bortezomib should be at least 72 hours apart.
AIDS-related KS Caelyx pegylated liposomal is administered intravenously at 20 mg/m2 every two-to-three weeks. Avoid intervals shorter than 10 days as medicinal product accumulation and increased toxicity cannot be ruled out. Treatment of patients for two-to-three months is recommended to achieve a therapeutic response.
Continue treatment as needed to maintain a therapeutic response. 8), immediately discontinue the infusion, give appropriate premedications (antihistamine and/or short acting corticosteroid) and restart at a slower rate. Guidelines for Caelyx pegylated liposomal dose modification To manage adverse events such as palmar-plantar erythrodysesthesia (PPE), stomatitis or haematological toxicity, the dose may be reduced or delayed.
Guidelines for Caelyx pegylated liposomal dose modification secondary to these adverse effects are provided in the tables below. The toxicity grading in these tables is based on the National Cancer Institute Common Toxicity Criteria (NCI-CTC).
The tables for PPE (Table 1) and stomatitis (Table 2) provide the schedule followed for dose modification in clinical trials in the treatment of breast or ovarian cancer (modification of the recommended 4 week treatment cycle): if these toxicities occur in patients with AIDS-related KS, the recommended 2 to 3 week treatment cycle can be modified in a similar manner.
The table for haematological toxicity (Table 3) provides the schedule followed for dose modification in clinical trials in the treatment of patients with breast or ovarian cancer only. Dose modification in patients with AIDS-KS is provided following Table 4.
Table 1. Palmar–Plantar erythrodysesthesia Week after prior Caelyx pegylated liposomal dose Toxicity grade at current assessment Week 4 Week 5 Week 6 Grade 1 (mild erythema, swelling, or desquamation not interfering with daily activities) Redose unless patient has experienced a previous grade 3 or 4 skin toxicity, in which case wait an additional week Redose unless patient has experienced a previous grade 3 or 4 skin toxicity, in which case wait an additional week Decrease dose by 25%; return to 4 week interval 4 Grade 2 (erythema, desquamation, or swelling interfering with, but not precluding normal physical activities; small blisters or ulcerations less than 2 cm in diameter) Wait an additional week Wait an additional week Decrease dose by 25%; return to 4 week interval Grade 3 (blistering, ulceration, or swelling interfering with walking or normal daily activities; cannot wear regular clothing) Wait an additional week Wait an additional week Withdraw patient Grade 4 (diffuse or local process causing infectious complications, or a bedridden state or hospitalisation) Wait an additional week Wait an additional week Withdraw patient Table 2.
Stomatitis Week after prior Caelyx pegylated liposomal dose Toxicity grade at current assessment Week 4 Week 5 Week 6 Grade 1 (painless ulcers, erythema, or mild soreness) Redose unless patient has experienced a previous grade 3 or 4 stomatitis in which case wait an additional week Redose unless patient has experienced a previous grade 3 or 4 stomatitis in which case wait an additional week Decrease dose by 25%; return to 4 week interval or withdraw patient per physician’s assessment Grade 2 (painful erythema, oedema, or ulcers, but can eat) Wait an additional week Wait an additional week Decrease dose by 25%; return to 4 week interval or withdraw patient per physician’s assessment Grade 3 (painful erythema, edema, or ulcers, but cannot […]
This is not medical advice. Consult a qualified healthcare professional.
Cardiac function should be assessed before patients undergo treatment with doxorubicin and must be monitored throughout therapy to minimize the risk of incurring severe cardiac impairment. The risk may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of doxorubicin at the first sign of impaired function.
The appropriate quantitative method for repeated assessment of cardiac function (evaluation of LVEF) includes multi-gated radionuclide angiography (MUGA) or echocardiography (ECHO). A baseline cardiac evaluation with an ECG and either a MUGA scan or an ECHO is recommended, especially in patients with risk factors for increased cardiotoxicity.
Repeated MUGA or ECHO determinations of LVEF should be performed, particularly with higher, cumulative anthracycline doses. The technique used for assessment should be consistent throughout follow-up. The probability of developing CHF, estimated around 1 % to 2 % at a cumulative dose of 300 mg/m² slowly increases up to the total cumulative dose of 450 - 550 mg/m².
Thereafter, the risk of developing CHF increases steeply and it is recommended not to exceed a maximum cumulative dose of 550 mg/m². If the patient has other potential risk factors of cardiotoxicity (history of cardiovascular disease, previous therapy with other anthracyclines or anthracenediones, prior or concomitant radiotherapy to the mediastinal/pericardial area, and concomitant use of medicinal products with the ability to suppress cardiac contractility, including cyclophosphamide and 5-fluoruracil), cardiotoxicity with doxorubicin may occur at lower cumulative doses and cardiac function should be carefully monitored.
Children and adolescents are at an increased risk for developing delayed cardiotoxicity following doxorubicin administration. There may be a greater risk for females than males for cardiotoxicity. Follow-up cardiac evaluations are recommended periodically to monitor the effect.
It is probable that the toxicity of doxorubicin and other anthracyclines or anthracenediones is additive. Pre-treatment with digoxin (250 μg daily starting 7 days before doxorubicin) showed a protective effect against cardiotoxicity.
Myelosuppression There is a high incidence of bone marrow depression, primarily of leucocytes, requiring careful haematological monitoring. With the recommended dosage schedule, leukopenia is usually transient, reaching its nadir at 10 - 14 days after treatment, with recovery usually occurring by the 21st day.
White blood cell counts as low as 1,000/mm³ are to be expected during treatment with appropriate doses of doxorubicin. Red blood cell and platelet levels should also be monitored, since they may also be depressed. Clinical consequences of severe myelosuppression include fever, infections, sepsis/septicaemia, septic shock, haemorrhage, tissue hypoxia or death.
Myelosuppression is more common in patients who have had extensive radiotherapy, bone infiltration by tumour, impaired liver function (when appropriate dosage reduction has not been adopted) and simultaneous treatment with other myelosuppressive agents.
Haematological toxicity may require dose reduction or […]
1 Mechanism of Action ..................................................................................... 2 Pharmacodynamics ........................................................................................ 3 Pharmacokinetics...........................................................................................
18 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 18 12 SPECIAL HANDLING INSTRUCTIONS........................................................................... 18 PART II: SCIENTIFIC INFORMATION ......................................................................................
21 17 SUPPORTING PRODUCT MONOGRAPHS.................................................................... 21 PATIENT MEDICATION INFORMATION ................................................................................. 22 PrDoxorubicin Hydrochloride for Injection USP (doxorubicin hydrochloride) Page 4 of 30 PART I: HEALTH PROFESSIONAL INFORMATION CAUTION: DOXORUBICIN HYDROCHLORIDE FOR INJECTION USP (DOXORUBICIN HYDROCHLORIDE) IS A POTENT DRUG AND SHOULD BE USED ONLY BY PHYSICIANS EXPERIENCED WITH CANCER CHEMOTHERAPY DRUGS (SEE 7 WARNINGS AND PRECAUTIONS).
BLOOD COUNTS AND HEPATIC FUNCTION TESTS SHOULD BE PERFORMED REGULARLY. BECAUSE OF THE EXPERIENCE WITH CARDIAC TOXICITY, IT IS NOT RECOMMENDED TO EXCEED A TOTAL DOSE OF DOXORUBICIN HYDROCHLORIDE 550 MG/M2 WITH THE 21-DAY REGIMEN AND 700 MG/M2 WITH THE WEEKLY REGIMEN.
CARDIAC MONITORING IS ADVISED IN THOSE PATIENTS WHO HAVE RECEIVED MEDIASTINAL RADIOTHERAPY, OTHER ANTHRACYCLINE OR ANTHRACENE THERAPY, WITH PRE-EXISTING CARDIAC DISEASE, OR WHO HAVE RECEIVED PRIOR DOXORUBICIN HYDROCHLORIDE CUMULATIVE DOSES […]
Arrhythmias Doxorubicin hydrochloride can result in arrhythmias, including life-threatening arrhythmias, during or within a few hours after doxorubicin hydrochloride administration and at any time point during treatment. Tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia, can occur.
Electrocardiographic changes, including non-specific ST-T wave changes, atrioventricular and bundle-branch block can also occur. These electrocardiographic changes may be transient and self-limited and may not require a dosage modification of doxorubicin hydrochloride.
2 Secondary Malignancies The risk of developing secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) is increased following treatment with doxorubicin hydrochloride. 5% at 10 years in two separate trials involving the adjuvant treatment of women with breast cancer.
These leukemias generally occur within 1 to 3 years of treatment. 3 Extravasation and Tissue Necrosis Extravasation of doxorubicin hydrochloride can cause severe local tissue injury manifesting as blistering, ulceration, and necrosis requiring wide excision of the affected area and skin grafting.
Extravasation should be considered if a patient experiences a burning or stinging sensation or shows other evidence indicating peri-venous infiltration or extravasation; however, extravasation may be present in patients who do not experience a stinging or burning sensation or when blood return is present on aspiration of the infusion needle.
When given via a peripheral venous line, infuse Doxorubicin Hydrochloride Injection over 10 minutes or less to minimize the risk of thrombosis or perivenous extravasation. 5) ] . Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days.
In adults, if appropriate, administer dexrazoxane at the site of extravasation as soon as possible and within the first 6 hours after extravasation. 4 Severe Myelosuppression Doxorubicin hydrochloride can cause myelosuppression. 1%).
A dose-dependent, reversible neutropenia is the predominant manifestation of myelosuppression from doxorubicin hydrochloride. When doxorubicin hydrochloride is administered every 21 days, the neutrophil count reaches its nadir 10 to 14 days after administration with recovery usually occurring by day 21.
Obtain complete blood counts prior to each treatment and carefully monitor patients during treatment for possible clinical complications due to myelosuppression. Delay next dose of Doxorubicin Hydrochloride Injection if severe myelosuppression has not improved.
Consider dose reduction for patients with prolonged myelosuppression based on severity of reaction. 3) ] . Doxorubicin Hydrochloride Injection is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see Contraindications (4) ].
4) ] . Obtain liver tests including ALT, AST, alkaline phosphatase, and bilirubin prior to and during therapy. 6 Tumor Lysis Syndrome Doxorubicin hydrochloride can induce tumor lysis syndrome in patients with rapidly growing tumors. Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment.
Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome. 7 Potentiation of Radiation Toxicity and Radiation Recall Doxorubicin hydrochloride can increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver.
Radiation recall, including but not limited to cutaneous and pulmonary toxicity, can occur in patients who receive doxorubicin hydrochloride after prior radiation therapy. 8 Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection during the 1 st trimester.
Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2 nd and 3 rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and rabbits at doses lower than the recommended human dose.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 6 months after treatment. Advise males with female partners of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 3 months after treatment.
1) ] .
, 5-fluorouracil. Cardiac toxicity also may occur at cumulative anthracycline doses lower than 450 mg/m2 in patients with prior mediastinal irradiation or in those receiving concurrent cyclophosphamide therapy. 8). Myelosuppression Many patients treated with Caelyx pegylated liposomal have baseline myelosuppression due to such factors as their pre-existing HIV disease or numerous concomitant or previous medications, or tumours involving bone marrow.
In the pivotal trial in patients with ovarian cancer treated at a dose of 50 mg/m2, myelosuppression was generally mild to moderate, reversible, and was not associated with episodes of neutropaenic infection or sepsis. Moreover, in a controlled clinical trial of Caelyx pegylated liposomal vs.
topotecan, the incidence of treatment related sepsis was substantially less in the Caelyx pegylated liposomal-treated ovarian cancer patients as compared to the topotecan treatment 8 group. A similar low incidence of myelosuppression was seen in patients with metastatic breast cancer receiving Caelyx pegylated liposomal in a first-line clinical trial.
8). Because of the potential for bone marrow suppression, periodic blood counts must be performed frequently during the course of Caelyx pegylated liposomal therapy, and at a minimum, prior to each dose of Caelyx pegylated liposomal.
Persistent severe myelosuppression, may result in superinfection or haemorrhage. In controlled clinical studies in patients with AIDS-KS against a bleomycin/vincristine regimen, opportunistic infections were apparently more frequent during treatment with Caelyx pegylated liposomal.
Patients and doctors must be aware of this higher incidence and take action as appropriate. Secondary haematological malignancies As with other DNA-damaging antineoplastic agents, secondary acute myeloid leukemias and myelodysplasias have been reported in patients having received combined treatment with doxorubicin.
Therefore, any patient treated with doxorubicin should be kept under haematological supervision. Secondary oral neoplasms Very rare cases of secondary oral cancer have been reported in patients with long-term (more than one year) exposure to Caelyx pegylated liposomal or those receiving a cumulative Caelyx pegylated liposomal dose greater than 720 mg/m2.
Cases of secondary oral cancer were diagnosed both, during treatment with Caelyx pegylated liposomal, and up to 6 years after the last dose. Patients should be examined at regular intervals for the presence of oral ulceration or any oral discomfort that may be indicative of secondary oral cancer.
Infusion-associated reactions Serious and sometimes life-threatening infusion reactions, which are characterised by allergic-like or anaphylactoid-like reactions, with […]