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Doxorubicin (Doxorubicin Hydrochloride) - Indications and Dosage

 
 



INDICATIONS AND USAGE

Ovarian Cancer


Doxorubicin hydrochloride liposome injection is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

AIDS-Related Kaposi’s Sarcoma


Doxorubicin hydrochloride liposome injection is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.

DOSAGE AND ADMINISTRATION

Usage and Administration Precautions


Liposomal encapsulation can substantially affect a drug’s functional properties relative to those of the unencapsulated drug. Therefore DO NOT SUBSTITUTE one drug for the other.
 
Do not administer as a bolus injection or an undiluted solution. Rapid infusion may increase the risk of infusion-related reactions [see Warnings and Precautions ]. Doxorubicin hydrochloride liposome injection must not be given by the intramuscular or subcutaneous route.
 
Until specific compatibility data are available, it is not recommended that doxorubicin hydrochloride liposome injection be mixed with other drugs.
 
Doxorubicin hydrochloride liposome injection should be considered an irritant and precautions should be taken to avoid extravasation. With intravenous administration of doxorubicin hydrochloride liposome injection, extravasation may occur with or without an accompanying stinging or burning sensation, even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the infusion should be immediately terminated and restarted in another vein. The application of ice over the site of extravasation for approximately 30 minutes may be helpful in alleviating the local reaction.

Patients With Ovarian Cancer


Doxorubicin hydrochloride liposome injection should be administered intravenously at a dose of 50 mg/m2 (doxorubicin hydrochloride equivalent) at an initial rate of 1 mg/min to minimize the risk of infusion reactions. If no infusion-related adverse reactions are observed, the rate of infusion can be increased to complete administration of the drug over one hour. The patient should be dosed once every 4 weeks, for as long as the patient does not progress, shows no evidence of cardiotoxicity [see Warnings and Precautions], and continues to tolerate treatment. A minimum of 4 courses is recommended because median time to response in clinical trials was 4 months. To manage adverse reactions such as hand-foot syndrome (HFS), stomatitis, or hematologic toxicity the doses may be delayed or reduced [see Dosage and Administration ]. Pretreatment with or concomitant use of antiemetics should be considered.

Patients With AIDS-Related Kaposi’s Sarcoma


Doxorubicin hydrochloride liposome injection should be administered intravenously at a dose of 20 mg/m2 (doxorubicin hydrochloride equivalent). An initial rate of 1 mg/min should be used to minimize the risk of infusion-related reactions. If no infusion-related adverse reactions are observed, the infusion rate should be increased to complete the administration of the drug over one hour. The dose should be repeated once every three weeks, for as long as patients respond satisfactorily and tolerate treatment.

Dose Modification Guidelines


Doxorubicin hydrochloride liposome injection exhibits nonlinear pharmacokinetics at 50 mg/m2; therefore, dose adjustments may result in a non-proportional greater change in plasma concentration and exposure to the drug [see Clinical Pharmacology].

Patients should be carefully monitored for toxicity. Adverse reactions, such as HFS, hematologic toxicities, and stomatitis may be managed by dose delays and adjustments. Following the first appearance of a Grade 2 or higher adverse reactions, the dosing should be adjusted or delayed as described in the following tables. Once the dose has been reduced, it should not be increased at a later time.
Recommended Dose Modification Guidelines Table 1: Hand-Foot Syndrome (HFS)
Toxicity Grade Dose Adjustment
1
(mild erythema, swelling, or desquamation not interfering with daily activities)
Redose unless patient has experienced previous Grade 3 or 4 HFS. If so, delay up to 2 weeks and decrease dose by 25%. Return to original dose interval.
2
(erythema, desquamation, or swelling interfering with, but not precluding normal physical activities; small blisters or ulcerations less than 2 cm in diameter)
Delay dosing up to 2 weeks or until resolved to Grade 0-1. If after 2 weeks there is no resolution, doxorubicin hydrochloride liposome injection should be discontinued. If resolved to Grade 0-1 within 2 weeks, and there are no prior Grade 3-4 HFS, continue treatment at previous dose and return to original dose interval. If patient experienced previous Grade 3-4 toxicity, continue treatment with a 25% dose reduction and return to original dose interval.
3
(blistering, ulceration, or swelling interfering with walking or normal daily activities; cannot wear regular clothing)
Delay dosing up to 2 weeks or until resolved to Grade 0-1. Decrease dose by 25% and return to original dose interval. If after 2 weeks there is no resolution, doxorubicin hydrochloride liposome injection should be discontinued.
4
(diffuse or local process causing infectious complications, or a bed ridden state or hospitalization)
Delay dosing up to 2 weeks or until resolved to Grade 0-1. Decrease dose by 25% and return to original dose interval. If after 2 weeks there is no resolution, doxorubicin hydrochloride liposome injection should be discontinued
Table 2: Hematological Toxicity
Grade ANC Platelets Modification
1
1,500 to 1,900
75,000 to 150,000
Resume treatment with no dose reduction
2
1,000 to <1,500
50,000 to <75,000
Wait until ANC ≥ 1,500 and platelets ≥ 75,000; redose with no dose reduction
3
500 to 999
25,000 to <50,000
Wait until ANC ≥ 1,500 and platelets ≥ 75,000; redose with no dose reduction
4
<500
<25,000
Wait until ANC ≥ 1,500 and platelets ≥ 75,000; redose at 25% dose reduction or continue full dose with cytokine support

Table 3: Stomatitis
Toxicity Grade Dose Adjustment
1
(painless ulcers,
erythema, or mild
soreness)
Redose unless patient has experienced previous Grade 3 or 4 toxicity. If so, delay up to 2 weeks and decrease dose by 25%. Return to original dose interval.
2
(painful erythema,
edema, or ulcers, but can eat)
Delay dosing up to 2 weeks or until resolved to Grade 0-1. If after 2 weeks there is no resolution, doxorubicin hydrochloride liposome injection should be discontinued. If resolved to Grade 0-1 within 2 weeks and there was no prior Grade 3-4 stomatitis, continue treatment at previous dose and return to original dose interval. If patient experienced previous Grade 3-4 toxicity, continue treatment with a 25% dose reduction and return to original dose interval.
3
(painful erythema, edema, or ulcers, and cannot eat)
Delay dosing up to 2 weeks or until resolved to Grade 0-1. Decrease dose by 25% and return to original dose interval. If after 2 weeks there is no resolution, doxorubicin hydrochloride liposome injection should be discontinued.
4
(requires parenteral or enteral support)
Delay dosing up to 2 weeks or until resolved to Grade 0-1. Decrease dose by 25% and return to doxorubicin hydrochloride liposome injection original dose interval. If after 2 weeks there is no resolution, doxorubicin hydrochloride liposome injection should be discontinued.


Patients With Impaired Hepatic Function


Limited clinical experience exists in treating patients with hepatic impairment with doxorubicin hydrochloride liposome injection. Based on experience with doxorubicin hydrochloride, it is recommended that the doxorubicin hydrochloride liposome injection dosage be reduced if the bilirubin is elevated as follows: serum bilirubin 1.2 to 3 mg/dL - give ½ normal dose; serum bilirubin > 3 mg/dL - give ¼ normal dose.

Preparation for Intravenous Administration


Each 10 mL vial contains 20 mg doxorubicin hydrochloride at a concentration of 2 mg/mL.
Each 25 mL vial contains 50 mg doxorubicin hydrochloride at a concentration of 2 mg/mL.
 
Doxorubicin hydrochloride liposome injection doses up to 90 mg must be diluted in 250 mL of 5% Dextrose Injection, USP prior to administration. Doses exceeding 90 mg should be diluted in 500 mL of 5% Dextrose Injection, USP prior to administration. Aseptic technique must be strictly observed since no preservative or bacteriostatic agent is present in doxorubicin hydrochloride liposome injection. Diluted doxorubicin hydrochloride liposome injection should be refrigerated at 2°C to 8°C (36°F to 46°F) and administered within 24 hours.
 
Do not use with in-line filters.
 
Do not mix with other drugs.
 
Do not use with any diluent other than 5% Dextrose Injection.
 
Do not use any bacteriostatic agent, such as benzyl alcohol.
 
Doxorubicin hydrochloride liposome injection is not a clear solution but a translucent, red liposomal dispersion.
 
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if a precipitate or foreign matter is present.
 
Rapid flushing of the infusion line should be avoided.

Procedure for Proper Handling and Disposal


Caution should be exercised in the handling and preparation of doxorubicin hydrochloride liposome injection.

The use of gloves is required.
 
If doxorubicin hydrochloride liposome injection comes into contact with skin or mucosa, immediately wash thoroughly with soap and water.
 
Doxorubicin hydrochloride liposome injection should be considered an irritant and precautions should be taken to avoid extravasation. With intravenous administration of doxorubicin hydrochloride liposome injection, extravasation may occur with or without an accompanying stinging or burning sensation, even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the infusion should be immediately terminated and restarted in another vein. Doxorubicin hydrochloride liposome injection must not be given by the intramuscular or subcutaneous route.
 
Doxorubicin hydrochloride liposome injection should be handled and disposed of in a manner consistent with other anticancer drugs. Several guidelines on this subject exist [see References].

DOSAGE FORMS AND STRENGTHS

  • Single use vial: 20 mg/10 mL
  • Single use vial: 50 mg/25 mL

HOW SUPPLIED/STORAGE AND HANDLING


Doxorubicin hydrochloride liposome injection is supplied as a sterile, translucent, red liposomal dispersion in 10 mL or 25 mL glass, single use vials.

Each 10 mL vial contains 20 mg doxorubicin hydrochloride at a concentration of 2 mg/mL.
Each 25 mL vial contains 50 mg doxorubicin hydrochloride at a concentration of 2 mg/mL.

Refrigerate unopened vials of doxorubicin hydrochloride liposome injection at 2° to 8°C (36° to 46°F). Avoid freezing. Prolonged freezing may adversely affect liposomal drug products; however, short-term freezing (less than 1 month) does not appear to have a deleterious effect on doxorubicin hydrochloride liposome injection.

The following individually cartoned vials are available:
Table 19
mg in vial fill volume vial size NDC #s
20 mg vial
10 mL
10 mL
47335-049-40
50 mg vial
25 mL
30 mL
47335-050-40

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