ADRIAMYCIN PFS
Clinical safety rating
cautionComprehensive clinical and safety monograph for ADRIAMYCIN PFS (ADRIAMYCIN PFS).
Comprehensive clinical and safety monograph for ADRIAMYCIN PFS (ADRIAMYCIN PFS).
Acute lymphoblastic leukemiaAcute myeloblastic leukemiaWilms tumorNeuroblastomaSoft tissue and bone sarcomasBreast cancerOvarian cancerTransitional cell bladder cancerThyroid cancerGastric cancerHodgkin lymphomaNon-Hodgkin lymphomaMultiple myelomaSmall cell lung cancer
Intercalation between DNA base pairs, inhibition of topoisomerase II, and generation of free radicals leading to DNA damage and apoptosis.
| Metabolism | Primarily hepatic metabolism via aldo-keto reductases to doxorubicinol; also undergoes 4-O-demethylation and glucuronidation. CYP450 minimally involved. |
| Excretion | Primarily hepatobiliary (∼50% as unchanged drug and metabolites in bile); renal excretion accounts for ∼5-12% over 72 hours; fecal elimination ~40%. |
| Half-life | Triphasic: initial α half-life 30 min (distribution), intermediate β half-life 3-4 hours (metabolism), terminal γ half-life 20-48 hours (prolonged due to extensive tissue binding and slow efflux from tissues). |
| Protein binding | ∼70% bound to plasma proteins, primarily albumin; binding is concentration-dependent and saturable at high doses. |
| Volume of Distribution | Extensive: 20-30 L/kg (total body water far exceeded, indicating deep tissue compartment binding, especially in liver, spleen, heart, and bone marrow). |
| Bioavailability | Not bioavailable orally (0%, due to extensive first-pass metabolism and instability in GI tract); administered only intravenously. |
| Onset of Action | Intravenous: 2-5 minutes (rapid cellular uptake and DNA intercalation). |
| Duration of Action | Duration of pharmacodynamic effect (inhibition of DNA/RNA synthesis) persists for 1-2 weeks after a single dose due to slow release from tissue binding; clinical effects (e.g., myelosuppression) peak at 10-14 days. |
| Molecular Weight | 543.52 |
60-75 mg/m² IV every 21 days as a single agent; 40-60 mg/m² IV every 21-28 days in combination regimens. Cumulative lifetime dose not to exceed 450-550 mg/m² (or 400 mg/m² with prior chest irradiation).
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended for renal impairment; however, monitor for toxicity. GFR < 10 mL/min: consider dose reduction by 50% due to potential accumulation of active metabolites. |
| Liver impairment | Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated or reduce by 75% with extreme caution. |
| Pediatric use | 30-75 mg/m² IV every 21-28 days; cumulative dose limit 400-550 mg/m². Dose based on body surface area; for infants < 1 year or BSA < 0.5 m², use weight-based dosing: 1-2 mg/kg IV every 21 days. |
| Geriatric use | No specific dose adjustment based on age alone; use with caution due to increased risk of cardiotoxicity and myelosuppression. Consider starting at lower end of dosing range (e.g., 45-60 mg/m² every 21 days) and monitor cardiac function. |
| 1st trimester | Contraindicated due to teratogenicity; risk of fetal malformations and spontaneous abortion. |
| 2nd trimester | Contraindicated; may cause fetal harm including growth retardation and oligohydramnios. |
| 3rd trimester | Contraindicated; risk of neonatal myelosuppression and cardiac toxicity. |
Clinical note
Comprehensive clinical and safety monograph for ADRIAMYCIN PFS (ADRIAMYCIN PFS).
| Placental transfer | Doxorubicin crosses the placenta; detected in fetal tissues. Human data confirm transfer with fetal plasma levels approximately 10-20% of maternal levels. |
| Breastfeeding | Doxorubicin is excreted in breast milk; potential for serious adverse reactions in nursing infants, including myelosuppression and cardiotoxicity. Discontinue breastfeeding during therapy and for at least 10 days after last dose. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: high risk of major congenital malformations (e.g., CNS, cardiovascular) and spontaneous abortion. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and neonatal myelosuppression. Avoid use unless maternal benefit outweighs fetal risk. |
| Fetal Monitoring | Maternal: CBC with differential prior to each cycle, cardiac function (LVEF via MUGA or echocardiogram) at baseline and repeat at cumulative doses of 300-400 mg/m2; LFTs, renal function, urinalysis. Fetal: growth ultrasound every 4-6 weeks after 20 weeks, nonstress test or biophysical profile weekly after 32 weeks if maternal or fetal complications. |
| Fertility Effects | Doxorubicin causes severe gonadal toxicity. In females: dose-dependent ovarian failure, premature menopause, reduced fertility. In males: azoospermia or oligospermia, elevated FSH/LH, potential permanent infertility. Pre-treatment fertility preservation options should be offered. |
■ FDA Black Box Warning
Myocardial toxicity (including delayed congestive heart failure) may occur with cumulative doses >550 mg/m²; less if prior mediastinal irradiation. Extravasation causes severe tissue necrosis. Secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) reported. Hepatic impairment requires dose adjustment. Use during pregnancy only if benefit outweighs risk.
| Serious Effects |
Hypersensitivity to doxorubicin or any componentSevere hepatic impairment (Child-Pugh class C)Severe myelosuppression (absolute neutrophil count <1500/mm3)Baseline left ventricular ejection fraction below institutional lower limit of normalRecent myocardial infarction or severe arrhythmiaConcurrent use of live vaccines
| Precautions | Cardiotoxicity (cumulative dose-dependent, enhanced by prior chest irradiation, age >70, pre-existing cardiac disease); myelosuppression; extravasation injury; secondary malignancies; tumor lysis syndrome; hepatic impairment; radiation recall; mutagenic and carcinogenic potential; impairment of fertility. |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they may inhibit CYP3A4 metabolism and increase doxorubicin toxicity. No other significant food interactions; maintain adequate hydration and nutrition. |
| Clinical Pearls | Pre-medicate with antiemetics (e.g., 5-HT3 antagonist) prior to administration. Monitor left ventricular ejection fraction (LVEF) at baseline and periodically due to cumulative dose-related cardiotoxicity (lifetime max 450-550 mg/m2, lower with prior chest radiation). Extravasation causes severe tissue necrosis; administer through a free-flowing IV line. Reduce dose in hepatic impairment (bilirubin >1.2 mg/dL). Observe for urine discoloration (red) for 1-2 days post-infusion. Avoid concurrent use with trastuzumab or other cardiotoxic agents. |
| Patient Advice | Doxorubicin may cause temporary reddish discoloration of urine for 1-2 days after treatment; this is harmless. · Report any signs of infection (fever, sore throat), unusual bleeding or bruising, mouth sores, or shortness of breath. · Your heart function will be checked before and during treatment; report any chest pain, palpitations, or swelling of ankles/feet. · This drug can cause nausea and vomiting; you will receive medications to prevent these symptoms. · Avoid pregnancy during treatment; use effective contraception. Doxorubicin can harm a fetus and may cause infertility. · Do not receive live vaccines during chemotherapy. Avoid contact with people who have recently received oral polio vaccine. · Take oral care measures (soft toothbrush, bland rinses) to prevent mouth sores. · Limit intake of grapefruit and grapefruit juice as they may affect the drug's metabolism. |
Loading safety data…