doxorubicin hydrochloride

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

History of cardiac disease or high cumulative doses of anthracyclines;
Depressed bone marrow reserve;
Hepatic impairment (↓ dose if serum bilirubin >1.2 mg/dL);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Children, older adults, mediastinal radiation, or concurrent cyclophosphamide (↑ risk of cardiotoxicity).

Adv. Reactions/Side Effects ⬆ ⬇

CV: CARDIOMYOPATHY, ECG changes

Derm: alopecia, photosensitivity

Endo: prepubertal growth failure with temporary gonadal impairment (children only)

GI: diarrhea, esophagitis, nausea, stomatitis, vomiting

GU: red urine, sterility

Hemat: ANEMIA, LEUKOPENIA, THROMBOCYTOPENIA

Local:

phlebitis at IV site

tissue necrosis

Metab: hyperuricemia

Resp: recall pneumonitis

Misc: hypersensitivity reactions, SECOND MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

CYP2D6 inhibitors, CYP3A4 inhibitors, and P-glycoprotein inhibitors may ↑ levels and risk of toxicity; avoid concurrent use.
CYP2D6 inducers, CYP3A4 inducers, and P-glycoprotein inducers may ↓ levels and effectiveness; avoid concurrent use.
↑risk of bone marrow depression with other antineoplastics or radiation therapy.
Pediatric patients who have received concurrent doxorubicin and dactinomycin have an ↑ risk of recall pneumonitis at variable times following local radiation therapy.
May ↑ skin reactions at previous radiation therapy sites.
If paclitaxel is administered first, clearance of doxorubicin is ↓ and the incidence and severity of neutropenia and stomatitis are ↑ (problem is diminished if doxorubicin is administered 1st).
Hematologic toxicity is ↑ and prolonged by concurrent use of cyclosporine; risk of coma and seizures is also ↑.
Incidence and severity of neutropenia and thrombocytopenia are ↑ by concurrent progesterone.
May ↑ levels and risk of toxicity of phenytoin.
Streptozocin may ↑ levels and risk of toxicity; ↓ dose of doxorubicin recommended.
May ↑ risk of hemorrhagic cystitis from cyclophosphamide.
May ↑ risk of hepatotoxicity from mercaptopurine.
Cardiac toxicity may be ↑ by radiation therapy or cyclophosphamide.
↑risk of cardiac toxicity with trastuzumab; avoid use of doxorubicin for up to 7 mo after discontinuing trastuzumab.
If dexrazoxane is administered at initiation of doxorubicin-containing regimens, may ↑ risk of therapeutic failure and tumor progression.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 10 mg/vial; 50 mg/vial; 150 mg/vial
Solution for injection: 2 mg/mL

Route/Dosage ⬆ ⬇

IV (Adults ): 60–75 mg/m² daily, repeat every 21 days; or 25–30 mg/m² daily for 2–3 days, repeat every 3–4 wk or 20 mg/m²/wk. Total cumulative dose should not exceed 550 mg/m² without monitoring of cardiac function or 400 mg/m² in patients with previous chest radiation or other cardiotoxic chemotherapy.
IV (Children ): 30 mg/m²/day for 3 days every 4 wk.

Hepatic Impairment

IV (Adults ): Serum bilirubin 1.2–3 mg/dL:↓ dose by 50%; Serum bilirubin 3.1–5 mg/dL:↓ dose by 75%.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits DNA and RNA synthesis by forming a complex with DNA; action is cell-cycle S-phase specific.
Also has immunosuppressive properties.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: anthracyclines

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues; does not cross the blood-brain barrier.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2D6 and CYP3A4 isoenzymes to an active metabolite. Excreted predominantly in the bile, 50% as unchanged drug. <5% eliminated unchanged in the urine.

Half-Life: 16.7 hr.

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

(effect on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	10 days	14 days	21–24 days

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other Rx, OTC, or herbal products.
Instruct patient to notify health care provider promptly if fever; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; ↑ fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
Instruct patient to report pain at injection site immediately.
Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush, rinse mouth with water after eating and drinking, and confer with health care provider if mouth pain interferes with eating. Pain may require treatment with opioid analgesics. The risk of developing stomatitis is greatest 5–10 days after a dose; usual duration is 3–7 days.
Instruct patient to notify health care provider immediately if irregular heartbeat, shortness of breath, swelling of lower extremities, or skin irritation (swelling, pain, or redness of feet or hands) occurs.
Discuss the possibility of hair loss with patient. Explore methods of coping. Regrowth usually occurs 2–3 mo after discontinuation of therapy.
Instruct patient not to receive any vaccinations without advice of health care provider.
Inform patient that medication may cause urine to appear red for 1–2 days.
Instruct patient to notify health care provider if skin irritation occurs at site of previous radiation therapy.
Advise family and/or caregivers to take precautions (i.e., latex gloves) in handling body fluids for >5 days post-treatment.
Inform patient that doxorubicin may ↑ risk of developing secondary cancers.
Emphasize the need for periodic lab tests to monitor for side effects.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 6 mo after last dose and to avoid breastfeeding during therapy and for 10 days–6 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during therapy and for 3–6 mo after last dose of doxorubicin. A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499). Inform patient before initiating therapy that this medication may cause irreversible gonadal suppression, irreversible amenorrhea, or early menopause.

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Indications ⬇

Contraind./Precautions ⬆ ⬇