DOXOrubicin, liposomal (dox-oh-roo-bi-sin lye-poe-sohmal) Doxil

 Indications

AIDS-related Kaposi’s sarcoma (KS) in patients who

cannot tolerate or fail conventional therapy. Ovarian

cancer that has progressed or recurred after platinumbased

chemotherapy. Multiple myeloma with bortezomib

in patients who have not previously received bortezomib

and have received at least one prior therapy.

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.

Pharmacokinetics

Absorption: Administered IV only, resulting in complete

bioavailability.

Distribution: Widely distributed; does not cross the

blood-brain barrier; extensively bound to tissues (q

concentrations delivered to KS lesions due to liposomal

carrier).

Metabolism and 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.

TIME/ACTION PROFILE (effect on blood

counts)

ROUTE ONSET PEAK DURATION

IV 10 days 14 days 21–24 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB, Lactation:

Fetal harm may occur.

Use Cautiously in: Pre-existing cardiac disease or

qcumulative doses of anthracyclines; Depressed bone

marrow reserve; Liver impairment (doseprequired if

serum bilirubin 1.2 m g/dL); Geri, Pedi: Children,

geriatric patients, prior mediastinal radiation, concurrent

cyclophosphamide (qrisk of cardiotoxicity); OB:

Patients with child-bearing potential.

Adverse Reactions/Side Effects

CNS: weakness. CV: CARDIOMYOPATHY. GI: nausea, diarrhea,

qalkaline phosphatase, moniliasis, ORAL MALIGNANCY,

stomatitis, vomiting. Derm: hand-foot syndrome,

alopecia. Hemat: anemia, leukopenia,

thrombocytopenia. Local: injection site reactions.

Misc: ANAPHYLACTOID ALLERGIC REACTIONS, acute infusion-

related reactions, fever.

Interactions

Drug-Drug:qbone marrow depression with other

antineoplastics or radiation therapy. Pediatric patients

who have received concurrent doxorubicin and

dactinomycin haveqrisk of recall pneumonitis following

local radiation therapy. Mayqskin reactions at

previous radiation therapy sites. If paclitaxel is administered

first, clearance of doxorubicin ispand incidence

and severity of neutropenia and stomatitis areq

(problem is less if doxorubicin is administered first).

Hematologic toxicity isqby concurrent use of cyclosporine;

risk of coma and seizures is alsoq. Incidence

and severity of neutropenia and thrombocytopenia are

qby concurrent progesterone. Phenobarbital may

qclearance andpeffects of doxorubicin. Doxorubicin

maypmetabolism andqeffects of phenytoin. Streptozocin

mayqthe half-life of doxorubicin (dose reduction

of doxorubicin recommended). Mayqrisk of

hemorrhagic cystitis from cyclophosphamide or hepatitis

from mercaptopurine. Cardiac toxicity may be

qby radiation therapy or cyclophosphamide. May

pantibody response to live-virus vaccines andqrisk

of adverse reactions.

Route/Dosage

AIDS-Related KS

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.

Availability (generic available)

Liposomal dispersion for injection: 2 mg/mL.