Lipo-Dox Dosage/Direction for Use

Pegylated liposomal doxorubicin exhibits unique pharmacokinetic properties and must not be used interchangeably with other formulations of doxorubicin HCl.
Lipo-dox should only be administered under the supervision of a qualified oncologist specialized in the administration of cytotoxic agents.
Breast/Ovarian Cancer: Lipo-Dox should be administered intravenously at a dose of 50 mg/m² once every 4 weeks for as long as the disease does not progress and the patient continues to tolerate treatment.
For dose <90 mg: dilute Lipo-Dox in 250 mL Dextrose 5% in Water.
For dose >90 mg: dilute Lipo-Dox in 500 mL Dextrose 5% in Water.
To minimize the risk of infusion reactions, the initial dose is administered at a rate no greater than 1 mg/min. If no infusion reaction is observed, subsequent Lipo-Dox infusions can be increased to complete administration over 60 minute period. In the breast cancer trial program, modification of the infusion was permitted for those patients experiencing an infusion reaction as follows: 5% of the total dose was infused slowly over the 15 minutes. If tolerated without reaction, the infusion rate was doubled for the next 15 minutes. If tolerated, the infusion was completed over the next hour for total infusion time of 90 minutes.
Subsequent pegylated liposomal doxorubicin infusions may be administered over a 60 minute period.
AIDS-KS Patients: Lipo-Dox should be administered intravenously at 20 mg/m² every two to three weeks. The intervals should not be shorter than 10 days to avoid drug accumulation and increased toxicity. Patients should be treated for 2 to 3 months to achieve a therapeutic response. If necessary, keep on treatment to maintain a therapeutic response.
Dilute Lipo-Dox in 250 ml Dextrose 5% in Water and complete administration by intravenous infusion over 30 minutes.
All patients: If any signs or early symptoms of infusion reaction occur, the infusion should be immediately discontinued, give appropriate premedications (antihistamine and/or short acting corticosteroid) and restart at a slower rate.
Do not administer as a bolus injection or an undiluted solution. It is recommended that the pegylated liposomal doxorubicin infusion line be connected through the side port of an intravenous infusion of Dextrose 5% in Water to achieve further dilution and minimize the risk of thrombosis and extravasation. The infusion may given through a peripheral vein. Pegylated liposomal doxorubicin must not be given by the intramuscular or subcutaneous route. Do not use with in-line filters.
Adverse events, such as palmar-plantar erythrodysesthesia (PPE), hematologic toxicity or stomatitis, may be managed by dose reducing or delay. Guidelines for dose modification secondary to these adverse effects are provided in the table as follows. The toxicity grading is based on the National Cancer Institute Common Toxicity Criteria (NCI-CTC). (See Tables 2, 3 and 4.)

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Patients with Impaired Hepatic Function: Base on reports, in the small number of patients with elevated total bilirubin levels, the pharmacokinetics are similar with patients with normal total bilirubin. However, until further experience is gained, the pegylated liposomal doxorubicin dosage in patients with impaired hepatic function should be reduced based on the experience from the breast and ovarian cancer clinical trial programs as follows: at initiation of therapy, if the bilirubin 1.2 to 3.0 mg/dL, the initial dose is reduced by 25%. If the bilirubin >3.0 mg/dL, the initial dose is reduced by 50%. If the patient tolerates the initial dose without an increase in serum bilirubin or liver enzymes, the dose of cycle 2 can be increased to the next dose level, i.e., if reduced by 25% for the initial dose, increase to full dose for cycle 2; if reduced by 50% for the initial dose, increase to 75% of full dose for cycle 2. Then, if the patient well tolerates, the dosage can be increased to full dose for subsequent cycles. In the liver metastases patients with concurrent elevation of bilirubin and liver enzymes up to 4x the upper limit of the normal range, pegylated liposomal doxorubicin could be administered. Before pegylated liposomal doxorubicin administration, evaluate hepatic function using conventional clinical laboratory tests such as ALT/AST, alkaline phosphatase, and bilirubin.
Patients with Impaired Renal Function: Doxorubicin is metabolized by the liver and excreted in the bile, so no need to adjust the dose. From the pharmacokinetic analysis of special population, it is confirmed that the pharmacokinetic properties are not changed in the patients with the creatinine clearance between 30-156 mL/min. No pharmacokinetic data are available patients with the creatinine clearance of less than 30 mL/min.
AIDS-KS Patients with Splenectomy: No experience with pegylated liposomal doxorubicin in patients with splenectomy the bladder-excision AIDS-KS patients. Not recommended to use.
Pediatric Patients: Limited Phase Ⅰ safety clinical data indicated that doses up to 60 mg/m² pegylated liposomal doxorubicin every 4 weeks are well tolerated in pediatric patients; however the efficacy in patients under 18 years old has not been established.
Geriatric Patients: Base on population analysis, the pharmacokinetics of pegylated liposomal doxorubicin in 21-75 year-old patients are not changed.