Caelyx Dosage/Direction for Use

Caelyx pegylated liposomal should only be administered under the supervision of a qualified oncologist specialised in the administration of cytotoxic agents.
Caelyx pegylated liposomal exhibits unique pharmacokinetic properties and must not be used interchangeably with other formulations of doxorubicin hydrochloride.
Posology: Breast cancer/Ovarian cancer: Caelyx pegylated liposomal is 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.
Multiple myeloma: Caelyx pegylated liposomal is administered at 30 mg/m² on day 4 of the bortezomib 3 week regimen as a 1 hour infusion administered immediately after the bortezomib infusion. The bortezomib regimen consists of 1.3 mg/m² on days 1, 4, 8, and 11 every 3 weeks. The dose should be repeated as long as patients respond satisfactorily and tolerate treatment. Day 4 dosing of both medicinal products may be delayed up to 48 hours as medically necessary. Doses of bortezomib should be at least 72 hours apart.
AIDS-related KS: Caelyx pegylated liposomal is administered intravenously at 20 mg/m² every two-to-three weeks. Avoid intervals shorter than 10 days as medicinal product accumulation and increased toxicity cannot be ruled out. Treatment of patients for two-to-three months is recommended to achieve a therapeutic response. Continue treatment as needed to maintain a therapeutic response.
For all patients: If the patient experiences early symptoms or signs of infusion reaction (see Precautions and Adverse Reactions), immediately discontinue the infusion, give appropriate premedications (antihistamine and/or short acting corticosteroid) and restart at a slower rate.
Guidelines for Caelyx pegylated liposomal dose modification: To manage adverse events such as palmar-plantar erythrodysesthesia (PPE), stomatitis or haematological toxicity, the dose may be reduced or delayed. Guidelines for Caelyx pegylated liposomal dose modification secondary to these adverse effects are provided in the following tables. The toxicity grading in these tables is based on the National Cancer Institute Common Toxicity Criteria (NCI-CTC).
The tables for PPE (Table 2) and stomatitis (Table 3) provide the schedule followed for dose modification in clinical trials in the treatment of breast or ovarian cancer (modification of the recommended 4 week treatment cycle): if these toxicities occur in patients with AIDS-related KS, the recommended 2 to 3 week treatment cycle can be modified in a similar manner.
The table for haematological toxicity (Table 4) provides the schedule followed for dose modification in clinical trials in the treatment of patients with breast or ovarian cancer only. Dose modification in patients with AIDS-KS is provided following Table 5. (See Tables 2, 3 and 4.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

For multiple myeloma patients treated with Caelyx pegylated liposomal in combination with bortezomib who experience PPE or stomatitis, the Caelyx pegylated liposomal dose should be modified as described previously in Table 2 and 3 respectively. Table 5, as follows provides the schedule followed for other dose modifications in the clinical trial in the treatment of patients with multiple myeloma receiving Caelyx pegylated liposomal and bortezomib combination therapy. For more detailed information on bortezomib dosing and dosage adjustments, see the package insert for bortezomib. (See Table 5.)

Click on icon to see table/diagram/image

For AIDS-KS patients treated with Caelyx pegylated liposomal, haematological toxicity may require dose reduction or suspension or delay of therapy. Temporarily suspend Caelyx pegylated liposomal treatment in patients when the ANC count is < 1,000/mm³ and/or the platelet count is < 50,000/mm³. G-CSF (or GM-CSF) may be given as concomitant therapy to support the blood count when the ANC count is < 1,000/mm³ in subsequent cycles.
Hepatic Impairment: Caelyx pegylated liposomal pharmacokinetics determined in a small number of patients with elevated total bilirubin levels do not differ from patients with normal total bilirubin; however, until further experience is gained, the Caelyx pegylated liposomal dosage in patients with impaired hepatic function should be reduced based on the experience from the breast and ovarian clinical trial programs as follows: at initiation of therapy, if the bilirubin is between 1.2-3.0 mg/dl, the first dose is reduced by 25%. If the bilirubin is > 3.0 mg/dl, the first dose is reduced by 50%. If the patient tolerates the first dose without an increase in serum bilirubin or liver enzymes, the dose for cycle 2 can be increased to the next dose level, i.e., if reduced by 25% for the first dose, increase to full dose for cycle 2; if reduced by 50% for the first dose, increase to 75% of full dose for cycle 2. The dosage can be increased to full dose for subsequent cycles if tolerated. Caelyx pegylated liposomal can be administered to patients with liver metastases with concurrent elevation of bilirubin and liver enzymes up to 4 x the upper limit of the normal range. Prior to Caelyx pegylated liposomal administration, evaluate hepatic function using conventional clinical laboratory tests such as ALT/AST, alkaline phosphatase, and bilirubin.
Renal Impairment: As doxorubicin is metabolised by the liver and excreted in the bile, dose modification should not be required. Population pharmacokinetic data (in the range of creatinine clearance tested of 30-156 ml/min) demonstrate that Caelyx pegylated liposomal clearance is not influenced by renal function. No pharmacokinetic data are available in patients with creatinine clearance of less than 30 ml/min.
AIDS-related KS patients with splenectomy: As there is no experience with Caelyx pegylated liposomal in patients who have had splenectomy, treatment with Caelyx pegylated liposomal is not recommended. Paediatric population: The experience in children is limited. Caelyx pegylated liposomal is not recommended in patients below 18 years of age.
Elderly: Population based analysis demonstrates that age across the range tested (21-75 years) does not significantly alter the pharmacokinetics of Caelyx pegylated liposomal.
Method of administration: Caelyx pegylated liposomal is administered as an intravenous infusion. For further instructions on preparation and special precautions for handling (see Special precautions for disposal and other handling under Cautions for Usage).
Do not administer Caelyx pegylated liposomal as a bolus injection or undiluted dispersion. It is recommended that the Caelyx pegylated liposomal infusion line be connected through the side port of an intravenous infusion of 5% (50 mg/ml) glucose to achieve further dilution and minimise the risk of thrombosis and extravasation. The infusion may be given through a peripheral vein. Do not use with in-line filters. Caelyx pegylated liposomal must not be given by the intramuscular or subcutaneous route (see Special precautions for disposal and other handling under Cautions for Usage).
For doses < 90 mg: dilute Caelyx pegylated liposomal in 250 ml 5% (50 mg/ml) glucose solution for infusion.
For doses ≥ 90 mg: dilute Caelyx pegylated liposomal in 500 ml 5% (50 mg/ml) glucose solution for infusion.
Breast cancer/Ovarian cancer/Multiple myeloma: To minimise the risk of infusion reactions, the initial dose is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent Caelyx pegylated liposomal infusions may be administered over a 60-minute period.
In those patients who experience an infusion reaction, the method of infusion should be modified as follows: 5% of the total dose should be infused slowly over the first 15 minutes. If tolerated without reaction, the infusion rate may then be doubled for the next 15 minutes. If tolerated, the infusion may then be completed over the next hour for a total infusion time of 90 minutes.
AIDS-related KS: The dose of Caelyx pegylated liposomal is diluted in 250 ml 5% (50 mg/ml) glucose solution for infusion and administered by intravenous infusion over 30 minutes.