DOXOrubicin hydrochloride liposome

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
dox-oh-ROO-bi-sin hye-droe-KLOR-ide LYE-poe-sohm [Pronunciation]

Trade Name(s)

• Doxil

Pregnancy Category
Category D

Ther. class.
antineoplastics

Pharm. class.
anthracyclines

Indications

• AIDS-related Kaposi's sarcoma (KS) in patients who cannot tolerate conventional therapy

• Ovarian carcinoma

• 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 Effect(s):
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 (↑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

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity

• OB: Pregnancy or lactation

Use Cautiously in:

• Pre-existing cardiac disease or ↑ cumulative doses of anthracyclines

• Depressed bone marrow reserve

• Liver impairment (dose reduction required if serum bilirubin >1.2 mg/dl)

• Geri: Pedi: Children, geriatric patients, prior mediastinal radiation, concurrent cyclophosphamide (increased risk of cardiotoxicity)

• OB: Patients with childbearing potential

Adverse Reactions/Side Effects

CNS: weakness.

CV: CARDIOMYOPATHY.

GI: nausea, diarrhea, increased alkaline phosphatase, moniliasis, stomatitis, vomiting.

Derm: alopecia, palmar-plantar erythrodysesthesia.

Hemat: anemia, leukopenia, thrombocytopenia.

Local: injection site reactions.

Misc: ANAPHYLACTOID ALLERGIC REACTIONS, acute infusion-related reactions, fever.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

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 first, clearance of doxorubicin is ↓ and incidence and severity of neutropenia and stomatitis are ↑ (problem is less if doxorubicin is administered first)

• Hematologic toxicity is ↑ 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 (dose reduction of doxorubicin recommended)

• 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

Route/Dosage

• Other regimens are used

• IV (Adults):
AIDS-related KS—20 mg/m² every 3 wk;
metastatic ovarian cancer—40–50 mg/m² every 4 wk;
Multiple myeloma—30 mg/m²on day 4 after following borezomib for up to 8 cycles.

Availability

• Liposomal dispersion for injection: 20 mg/10 ml in 10-ml and 25 ml vials

Assessment

• Monitor blood pressure, pulse, respiratory rate, and temperature frequently during administration. Report significant changes

• Monitor for acute infusion-related reactions consisting of flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, chest or throat tightness, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, which may be accompanied by hypotension. Reactions usually resolve over 1 day and are usually limited to first dose. Slowing infusion rate may minimize this reaction. Reaction is thought to be due to liposome

• Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue doxorubicin and notify health care professional immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction

• Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension

• Monitor intake and output ratios, and report occurrence of significant discrepancies. Encourage fluid intake of 2000–3000 ml/day. Allopurinol and alkalinization of the urine may be used to decrease serum uric acid levels and to help prevent urate stone formation

• Severe and protracted nausea and vomiting may occur as early as 1 hr after therapy and may last 24 hr. Administer parenteral antiemetics 30–45 min prior to therapy and routinely around the clock for the next 24 hr as indicated. Monitor amount of emesis and notify health care professional if emesis exceeds guidelines to prevent dehydration

• Monitor for development of signs of cardiac toxicity, which may be either acute and transient (ST segment depression, flattened T wave, sinus tachycardia, and extrasystoles) or late onset (usually occurs 1–6 mo after initiation of therapy) and characterized by intractable CHF (peripheral edema, dyspnea, rales/crackles, weight gain); occurs more frequently in patients receiving a cumulative dose of ≥550 mg/m². Chest x-ray, echocardiography, ECGs, and radionuclide angiography may be ordered prior to and periodically during therapy. Cardiotoxicity is more prevalent in children younger than 2 yr and geriatric patients. Dexrazoxane may be used to prevent cardiotoxicity in patients receiving cumulative doses of >300 mg/m²

• Assess injection site frequently for redness, irritation, or inflammation. Doxorubicin is a vesicant but may infiltrate painlessly even if blood returns on aspiration of infusion needle. Severe tissue damage may occur if doxorubicin extravasates. If extravasation occurs, stop infusion immediately, restart, and complete dose in another vein. Local infiltration of antidote is not recommended. Apply ice packs and elevate and rest extremity for 24–48 hr to reduce swelling, then resume normal activity as tolerated. If swelling, redness, and/or pain persists beyond 48 hr, immediate consultation for possible debridement is indicated

• Assess oral mucosa frequently for development of stomatitis. Increased dosing interval and/or decreased dose is recommended if lesions are painful or interfere with nutrition

• Monitor for skin toxicity with prolonged use; palmar-plantar erythrodysesthesia usually occurs after 6 wk of treatment and consists of swelling, pain, and erythema of the hands and feet. This may progress to desquamation but usually regresses after 2 wk. In severe cases, modification and delay of future doses of doxorubicin liposome may be necessary

Lab Test Considerations

• Monitor CBC and differential prior to and periodically during therapy. The WBC nadir occurs 10–14 days after administration, and recovery usually occurs by the 21st day. Thrombocytopenia and anemia may also occur. ↑ dosing interval and/or ↓ dose is recommended if ANC is <1000 cells/mm³ and/or platelet count is <50,000 cells/mm³

» Monitor renal (BUN and creatinine) and hepatic (AST, ALT, LDH, and serum bilirubin) function prior to and periodically during therapy. Dose reduction is required for bilirubin >1.2 mg/dl or serum creatinine >3 mg/dl

» May cause ↑ serum and urine uric acid concentrations

Potential Nursing Diagnoses

• Risk for infection (Adverse Reaction)

• Decreased cardiac output (Adverse Reaction)

Implementation

• High Alert: Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings. Do not confuse doxorubicin hydrochloride liposome (Doxil) with doxorubicin hydrochloride (Adriamycin, Rubex) or with daunorubicin hydrochloride (Cerubidine)or daunorubicin citrate liposome (DaunoXome). Clarify orders that do not include generic and brand names

• Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers

» Aluminum needles may be used to administer doxorubicin but should not be used during storage, because prolonged contact results in discoloration of solution and formation of a dark precipitate. Solution is red

IV Adminstration:

• Intermittent Infusion:

Diluent: Dilute dose, up to 90 mg, in 250 ml of D5W. Do not dilute with other diluents or diluents containing a bacteriostatic agent. Solution is not clear, but a translucent red liposomal dispersion. Do not use in-line filters. Refrigerate diluted solutions and administer within 24 hr of dilution.
Concentration: 0.36 mg/ml

• Rate:
Initial rate of infusion should be 1 mg/min to minimize risk of infusion reactions. If no reactions occur, increase rate to complete administration within 1 hr. Do not administer as a bolus or undiluted solution. Rapid infusion may increase infusion-related reactions

• Y-Site Compatibility:

» acyclovir

» allopurinol

» aminophylline

» ampicillin

» aztreonam

» bleomycin

» butorphanol

» calcium gluconate

» carboplatin

» cefazolin

» cefepime

» cefoxitin

» ceftizoxime

» ceftriaxone

» chlorpromazine

» cimetidine

» ciprofloxacin

» cisplatin

» clindamycin

» cyclophosphamide

» cytarabine

» dacarbazine

» dexamethasone sodium phosphate

» diphenhydramine

» dobutamine

» dopamine

» droperidol

» enalaprilat

» etoposide

» famotidine

» fluconazole

» fluorouracil

» furosemide

» ganciclovir

» gentamicin

» granisetron

» haloperidol

» heparin

» hydrocortisone sodium succinate

» hydromorphone

» ifosfamide

» leucovorin

» lorazepam

» magnesium sulfate

» mesna

» methotrexate

» methylprednisolone sodium succinate

» metronidazole

» ondansetron

» piperacillin

» potassium chloride

» prochlorperazine

» ranitidine

» ticarcillin/clavulanate

» tobramycin

» trimethoprim/sulfamethoxazole

» vancomycin

» vinblastine

» vincristine

» vinorelbine

» zidovudine

• Y-Site Incompatibility:

» amphotericin B

» amphotericin B cholesteryl sulfate complex

» buprenorphine

» cefoperazone

» ceftazidime

» docetaxel

» mannitol

» meperidine

» metoclopramide

» mitoxantrone

» morphine

» ofloxacin

» paclitaxel

» piperacillin/tazobactam

» promethazine

» sodium bicarbonate

• Additive Incompatibility:
Do not admix with other solutions or medications

Patient/Family Teaching

• 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; 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; the usual duration is 3–7 days

• Advise patient that this medication may have teratogenic effects. Contraception should be used during and for at least 4 mo after therapy is concluded. Inform patient before initiating therapy that this medication may cause irreversible gonadal suppression

• 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 posttreatment

• Emphasize the need for periodic lab tests to monitor for side effects

Evaluation/Desired Outcomes

• Decrease in size or spread of malignancies

• Arrested progression of KS in patients with HIV infection