doxorubicin, liposomal

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Pre-existing cardiac disease or ↑ cumulative doses of anthracyclines;
Depressed bone marrow reserve;
Hepatic impairment (dose ↓ required if serum bilirubin >1.2 mg/dL);
Rep: Women of reproductive potential;
Geri: Children, older adults, prior mediastinal radiation, concurrent cyclophosphamide (↑ risk of cardiotoxicity).

Adv. Reactions/Side Effects ⬆ ⬇

CV: CARDIOMYOPATHY

Derm: hand-foot syndrome (HFS), alopecia

GI: nausea, diarrhea, ↑alkaline phosphatase, moniliasis, ORAL MALIGNANCY, stomatitis, vomiting

Hemat: anemia, leukopenia, thrombocytopenia

Local: injection site reactions

Neuro: weakness

Misc: INFUSION-RELATED REACTIONS, fever

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression with other antineoplastics or radiation therapy.
Pediatric patients who have received concurrent doxorubicin and dactinomycin have ↑ risk of recall pneumonitis following local radiation therapy.
May ↑ skin reactions at previous radiation therapy sites.
If paclitaxel is administered 1st, clearance of doxorubicin is ↓ and incidence and severity of neutropenia and stomatitis are ↑ (problem is less if doxorubicin is administered first).
Hematologic toxicity ↑ 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 ↓ levels and effectiveness.
May ↑ levels and risk of toxicity of phenytoin.
May ↑ risk of hemorrhagic cystitis from cyclophosphamide or hepatitis from mercaptopurine.
Cardiac toxicity may be ↑ by radiation therapy or cyclophosphamide.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Availability ⬆ ⬇

(Generic available)

Liposomal dispersion for injection: 2 mg/mL

Route/Dosage ⬆ ⬇

AIDS-Related Kaposi Sarcoma

IV (Adults ): 20 mg/m² every 3 wk until disease progression or unacceptable toxicity.

Ovarian Cancer

IV (Adults ): 50 mg/m² every 4 wk until disease progression or unacceptable toxicity.

Multiple Myeloma

IV (Adults ): 30 mg/m² on day 4 (after bortezomib) of each 21-day cycle for 8 cycles or until disease progression or unacceptable toxicity.

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.
Encapsulation in a liposome increases uptake by tumors, prolongs action, and may decrease some toxicity.

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; ↑concentrations delivered to Kaposi sarcoma lesions due to liposomal carrier.

Metabolism/Excretion: Mostly metabolized by the liver with conversion to an active compound. Excreted mostly in bile, 50% as unchanged drug. <5% eliminated unchanged in the urine.

Half-Life: 55 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 ⬆ ⬇

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; may precipitate GI 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; the 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.
Rep: May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during and for ≥6 mo after last dose of therapy. Inform patient before initiating therapy that this medication may cause irreversible gonadal suppression. In women, may cause infertility, amenorrhea, and premature menopause. In men, may result in oligospermia, azoospermia, and permanent loss of fertility. Some sperm counts have returned to normal several years after therapy ended. Advise women to avoid breastfeeding during therapy.
Emphasize the need for periodic lab tests to monitor for side effects.

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Indications ⬇

Contraind./Precautions ⬆ ⬇