dexrazoxane

REMS

Reducing incidence and severity of cardiomyopathy from doxorubicin in women with metastatic breast cancer who have already received a cumulative dose of doxorubicin >300 mg/m² and who will continue to receive doxorubicin therapy to maintain tumor control.
Treatment of extravasation resulting from IV anthracycline chemotherapy.

Action ⬆ ⬇

Acts as an intracellular chelating agent.

Therapeutic effects:

Diminishes the cardiotoxic effects of doxorubicin.
Decreased damage from extravasation of anthracyclines.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Some metabolism occurs; 42% eliminated in urine.

Half-Life: 2.1–2.5 hr.

Time/Action Profile ⬆ ⬇

(cardioprotective effect)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Any other type of chemotherapy except other anthracyclines (doxorubicin-like agents);
Hepatic impairment (for treatment of extravasation only);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment (CCr <40 mL/min) (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

GU: ↓fertility (males)

Hemat: leukopenia, neutropenia, thrombocytopenia

Local: pain at injection site

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Myelosuppression may be ↑ by antineoplastics or radiation therapy.
Antitumor effects of concurrent combination chemotherapy with fluorouracil and cyclophosphamide may be ↓ by dexrazoxane.

Route/Dosage ⬆ ⬇

Cardioprotective

IV (Adults ): 10 mg of dexrazoxane/1 mg doxorubicin.

Renal Impairment

IV (Adults ): CCr <40 mL/min:↓ dose by 50%.

Extravasation Treatment

IV (Adults ): 1000 mg/m² (maximum 2000 mg) given on days 1 and 2, and followed by a dose of 500 mg/m² (maximum 1000 mg) on day 3.

Renal Impairment

IV (Adults ): CCr <40 mL/min:↓ dose by 50%.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 250 mg/vial; 500 mg/vial

Assessment ⬆ ⬇

Cardioprotective: Assess extent of cardiomyopathy (cardiomegaly on x ray, basilar rales, S₃ gallop, dyspnea, decline in left ventricular ejection fraction) prior to and periodically during therapy.
Extravasation protection: Assess site of extravasation for pain, burning, swelling, and redness. Assess site during and after therapy until resolution. Dexrazoxane is not effective against the effects of vesicants other than anthracyclines.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC and platelet count before each course of therapy and frequently during therapy. Thrombocytopenia, leukopenia, neutropenia, and granulocytopenia from chemotherapy may be more severe at nadir with dexrazoxane therapy.
- Monitor liver function tests periodically during therapy. May cause reversible ↑ of liver enzymes.

Implementation ⬆ ⬇

IV Administration:

Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
- Solution is slightly yellow. Do not administer solutions that are discolored or contain particulate matter. Reconstituted solution and diluted solution are stable in an IV bag for 6 hr at room temperature or if refrigerated. Discard unused solutions.
Extravasation Protection: Administer as soon as possible within 6 hr of extravasation in a large caliber vein in an extremity/area other than the one affected by the extravasation. Remove cooling procedures, such as ice packs, at least 15 min before administration to allow sufficient blood flow to area of extravasation. Start treatment on Day 2 and Day 3 at same hr (+/- 3 hr) as on first day.
: Intermittent Infusion: Reconstitution: Reconstitute with 50 mL sterile water for injection.Concentration: 10 mg/mLDiluent: Withdraw dose volume within 30 min of reconstitution and inject into 1000 mL bag of LR. Solution is stable for 4 hr at room temperature or 12 hr if refrigerated.
Rate: Infuse over 1–2 hr in a large caliber vein.
Cardioprotective: Doxorubicin should be administered within 30 min following dexrazoxane administration.
: Intermittent Infusion: Reconstitution: Reconstitute with 25 mL sterile water for injection for 250-mg vial or 50 mL for 500-mg vial.Concentration: 10 mg/mL.Diluent: Dilute reconstituted solution further in LR1.3–5 mg/mL. Solution is stable for 1 hr at room temperature or 4 hr if refrigerated.
Rate: Infuse over 15 min. Administer doxorubicin within 30 min of completion of infusion. Do not administer via IV push.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of the medication to the patient.
Emphasize the need for continued monitoring of cardiac function.
Rep: Dexrazoxane may cause fetal harm. Advise females of reproductive potential to use highly effective contraception during and for 6 mo after last dose of dexrazoxane and to avoid breastfeeding during and for 2 wk after last dose. Advise males with female partners of reproductive potential to use highly effective contraception during and for 3 mo after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected. May impair fertility in males.

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Pronunciation ⬇

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