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, 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

Interactions

⬆ ⬇

Drug-drug:

CYP2D6 inhibitors, CYP3A4 inhibitors, and P-glycoprotein inhibitors may ↑ risk of toxicity; avoid concurrent use
CYP2D6 inducers, CYP3A4 inducers, and P-glycoprotein inducers may ↓ effectiveness; avoid concurrent use
↑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 first).
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.
Phenobarbital may ↑ clearance and ↓ effects of doxorubicin.
Doxorubicin may ↓ metabolism and ↑ effects of phenytoin.
Streptozocin may ↑ the half-life of doxorubicin (dosage ↓ 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. Less than 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 of doxorubicin to patient.
Instruct patient to notify health care professional promptly if fever; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased 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 professional 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 professional 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 professional.
Inform patient that medication may cause urine to appear red for 1–2 days.
Instruct patient to notify health care professional 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 at least 5 days post-treatment.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
Inform patient that doxorubicin may increase risk of developing secondary cancers.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 mo after last dose and to avoid breastfeeding during and for 10 days to 6 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during 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, or irreversible amenorrhea or early menopause.
Emphasize the need for periodic lab tests to monitor for side effects.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆

Indications

Contraind./Precautions