Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
pegylated liposomal DOXOrubicin
pegylated liposomal DOXOrubicin
SYNONYM(S): Doxorubicin Hydrochloride Pegylated Liposomes
COMMON TRADE NAME(S): Caelyx®
Pegylated liposomal doxorubicin is doxorubicin hydrochloride encapsulated in long-circulating liposomes, microscopic vesicles composed of a phospholipid bilayer that are capable of encapsulating active drugs. The Stealth® liposomes are formulated with surface-bound methoxypolyethylene glycol (MPEG), a process often referred to as pegylation, to protect liposomes from detection by the mononuclear phagocyte system and to increase blood circulation time. It is hypothesized that pegylated liposomal doxorubicin molecules are able to penetrate the vasculature of tumours. Incorporation of doxorubicin into a liposomal preparation substantially alters the pharmacokinetic properties of the drug compared with those of the non-liposomal doxorubicin.
The pharmacokinetics of pegylated liposomal doxorubicin are non-linear, suggesting that there is a greater than dose-proportional increase in exposure as dose is increased, and that clearance is saturable. Pegylated liposomal doxorubicin distributes mainly in intravascular fluid.
Significantly higher doxorubicin concentrations were found in Kaposi sarcoma lesions than in normal skin.
| Cross blood brain barrier? |
Unknown |
| PPB | Approximately 70 % (doxorubicin) |
Liposomal doxorubicin undergoes metabolism mainly in the liver.
| Active metabolites | Doxorubicinol (major metabolite). |
| Inactive metabolites | Yes |
The elimination of doxorubicin is primarily via the biliary system. Very low or absent plasma concentrations of doxorubicin metabolites suggest that the metabolite elimination rate exceeds the metabolite production rate.
| Urine |
6% (in 72 hours) |
| Half-life | (apparent mean): 74 hours |
- Ovarian cancer
- Kaposi sarcoma (AIDS-related)
- Breast cancer
Refer to the product monograph for a full list and details of approved indications.
Other Uses:
- Hodgkin lymphoma
- Multiple myeloma
Emetogenic Potential:
Extravasation Potential: Irritant
The following adverse effects were reported mainly in single agent studies in breast cancer.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Arrhythmia (<1%) | E D | |||
| Arterial thromboembolism (<1%) | E D | ||||
| Cardiotoxicity (3-9%) | E | ||||
| Venous thromboembolism (<1%) | E D | ||||
| Dermatological | Alopecia (20%) | E | |||
| Hand-foot syndrome (48%) | E | ||||
| Nail disorder (<5%) | E | ||||
| Radiation recall reaction (rare) | E | ||||
| Rash (10%) (may be severe) | I | ||||
| Gastrointestinal | Abdominal pain (8%) | E | |||
| Anorexia (11%) | I | ||||
| Constipation (8%) | E | ||||
| Diarrhea (7%) | E | ||||
| Dyspepsia (<5%) | E | ||||
| Mucositis (23%) | E | ||||
| Nausea, vomiting (37%) | I | ||||
| Weight changes (≤5%) | E | ||||
| General | Fatigue (12%) | E | |||
| Pain (<5%) | E | ||||
| Hematological | Myelosuppression ± infection, bleeding (>10%) (may be severe) | E | |||
| Hepatobiliary | ↑ LFTs (2%) | E | |||
| Hypersensitivity | Infusion related reaction (11-13%) | I | |||
| Injection site | Phlebitis (rare) | E | |||
| Metabolic / Endocrine | Abnormal electrolyte(s) (≤5%) | E | |||
| Neoplastic | Secondary malignancy (rare) | D L | |||
| Nervous System | Dysgeusia (<5%) | I E | |||
| Respiratory | Cough (1-5%) | E | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects reported were infusion reactions, hand-foot syndrome, nausea/vomiting, mucositis, alopecia and fatigue.
In general, acute hypersensitivity infusion reactions occur during the first infusion of pegylated liposomal doxorubicin, usually within the first few minutes after the start of the infusion. Symptoms include flushing, rash, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest and throat, and hypotension. These acute reactions do not appear to occur during subsequent cycles of chemotherapy in patients who did not react to the first cycle. Hold the infusion if a patient experiences signs or symptoms of an infusion reaction. These symptoms usually resolve without further therapy; however, some patients may require treatment with antihistamines and/or corticosteroids.
Left ventricular failure is less common than with doxorubicin but is reported and is more common in patients who have received high cumulative lifetime doses of doxorubicin (> 550mg/m2), other anthracyclines or anthracenediones, who have had doxorubicin doses > 400mg/m2 plus mediastinal radiation or have other cardiac risk factors. Congestive heart failure and/or myocardiopathy may occur suddenly or may happen several weeks after treatment completion.
A frequent dose-limiting adverse effect of pegylated liposomal doxorubicin is myelosuppression, predominantly leukopenia, with higher incidence and greater severity in patients with Kaposi sarcoma who are immuno-compromised at baseline. In patients with ovarian cancer, myelosuppression is generally mild to moderate, reversible and is not associated with neutropenic infection or sepsis. Growth factor support is infrequently required. Pegylated liposomal doxorubicin does not appear to offer any advantage over standard doxorubicin in terms of hematological adverse events.
Palmar-plantar erythrodysesthesia (PPE; hand-foot syndrome) is another common dose and schedule-related adverse effect associated with pegylated liposomal doxorubicin. The syndrome is characterized by painful, macular reddening skin eruptions, swelling, pain, and, for some patients, desquamation of the skin on the hands and feet. PPE is generally seen after 2 or 3 cycles of treatment but may occur earlier. Strategies to prevent and treat PPE, which may be initiated 4-7 days after treatment, include keeping hands and feet cool, avoiding excessive heat/hot water and keeping them unrestricted. Emollients and petroleum-based balms may also provide some relief.
Pegylated liposomal doxorubicin associated stomatitis is dose and schedule-dependent and occurs in up to 39% of patients. Mouth care with regular rinsing should be encouraged as prophylaxis. Mouth sores usually subside with dosage reduction and treatment delay (see Dosing), along with appropriate stomatitis treatment protocol.
Secondary oral cancers, including fatal cases were reported during treatment and up to 6 years following treatment completion. Patients should be monitored regularly for oral ulceration or discomfort.
Refer to protocol by which patient is being treated.
Pegylated liposomal doxorubicin is not interchangeable with other doxorubicin formulations.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Dose adjustment is required in patients with history of prior anthracyclines use, prior mediastinal irradiation, concurrent cyclophosphamide therapy, or pre-existing cardiovascular disease.
Ovarian or breast cancer:
- q4 weeks: 50mg/m2 IV
AIDS-related Kaposi Sarcoma:
- q2-3 weeks: 20mg/m2 IV
Dosage modifications for toxicity differ for ovarian/breast cancer and Kaposi sarcoma. This is due to differences in the population group, immunity status, and dose of pegylated liposomal doxorubicin indicated for specific use.
Ovarian or Breast Cancer:
|
Worst Toxicity & Toxicity on day of planned dosing |
Action*: Week 4-5
|
Action*: Week 6
|
|
Grade 1 skin/stomatitis
|
If was ≥ grade 3, delay for 1-2 weeks; otherwise treat on time
|
If still grade 1, ↓ dose by 25%
|
|
Grade 2 skin/stomatitis
|
Delay for 1-2 weeks;
|
If still grade 1 or 2, ↓ dose by 25%
|
|
Grade 3 or 4 skin/stomatitis
|
Delay for 1-2 weeks;
|
Discontinue if still ≥ grade 3
Consider discontinuing if was grade 4
Otherwise ↓ dose by 25%
|
|
Grade 4 ANC, platelets, febrile neutropenia or thrombocytopenic bleeding |
↓ dose by 25%
|
|
|
Significant cardiotoxicity
|
Discontinue
|
|
|
Grade 3 other
|
↓ dose by 25%
|
|
|
Grade 4 other
|
Discontinue
|
|
|
*Do not retreat until ANC > 1.5 x 109/L, platelets > 75-100 x 109/L and other toxicity ≤ grade 2 / or as indicated above |
||
AIDS-related Kaposi Sarcoma:
|
Worst Toxicity & Toxicity on day of planned dosing |
Action*: Week 3
|
Action*: Week 4
|
|
Grade 1 skin
|
If was ≥grade 3, delay for 1 week; otherwise treat on time
|
If still grade 1, ↓ dose by 25%
|
|
Grade 1 stomatitis
|
Treat on time with no dose modification
|
Not applicable
|
|
Grade 2 skin
|
Delay for 1 week
|
If still grade 2, ↓ dose by 50%
If grade 1, ↓ dose by 25%
|
|
Grade 2 stomatitis
|
Delay for 1 week
|
If still grade 2, ↓ dose by 25%
|
|
Grade 3 skin
|
Delay for 1 week
|
If still grade 3, discontinue
If grade 2, then ↓ dose by 50%
If grade 1, ↓ dose by 25%
|
|
Grade 3 stomatitis
|
Delay for 1 week
|
If improved, ↓ dose by 25%
|
|
Grade 4 skin
|
Delay for 1 week
|
If still ≥ grade 3, discontinue
If ≤ grade 2, ↓ dose by 50%
|
|
Grade 4 stomatitis
|
Delay for 1 week
|
If still grade 4, discontinue
If improved, ↓ dose by 50%
|
|
Grade 3 myelosuppression
|
↓ dose by 25%
|
|
|
Grade 4 ANC, platelets, febrile neutropenia or thrombocytopenic bleeding |
↓ dose by 50%
|
|
|
Significant cardiotoxicity
|
Discontinue
|
|
|
Grade 3 other
|
↓ dose by 25%
|
|
|
Grade 4 other
|
Discontinue or ↓ dose by 50%
|
|
|
*Do not retreat until ANC > 1 x 109/L, platelets > 50-100 x 109/L and other toxicity ≤ grade 2 / or as indicated above
|
||
Management of Infusion-related reactions with Anthracyclines:
| Grade | Management | Re-challenge |
| 1 or 2 |
|
|
| 3 or 4 |
|
|
|
Bilirubin (µmol/L) |
Ovarian, Breast cancer |
HIV/AIDS |
|
|
% of Standard Dose
|
|||
|
Cycle 1 (% normal dose) |
Cycle 2 onwards if cycle 1 tolerated with no changes in liver function tests (% normal dose) |
Each cycle (% normal dose) |
|
|
21-51 |
75% |
100% |
50% |
|
>51 |
50% |
75%* |
25% |
No modifications are necessary for mild to moderate renal impairment (creatinine clearance > 30 mL/min). No studies have been done in patients with severe renal impairment.
Limited information in patients ≥ 60 years. Use with caution.
Safety and efficacy not established.
Pegylated liposomal doxorubicin is not interchangeable with other doxorubicin formulations.
- Pegylated liposomal doxorubicin is administered as an IV infusion.
- For dose < 90mg, dilute drug in 250mL D5W.
- For dose ≥ 90mg, dilute drug in 500mL D5W.
- Only use 5% Dextrose solution for further dilution. Use of other diluents or ones containing bacteriostatic agents (i.e. benzyl alcohol) may cause drug precipitation.
- Do not administer as a bolus injection or undiluted solution. The pegylated liposomal doxorubicin infusion line can be connected through the side port of a 5% Dextrose infusion for further diluent, or to minimize risk of thrombosis or extravasation.
- Do not use in-line filters. Do not admix pegylated liposomal doxorubicin with other drugs.
- To minimize 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 infusions may be administered over 60-minutes (in ovarian or breast cancer) and 30 minutes (for Kaposi sarcoma patients).
- The following graduated rate was used for patients who experienced an infusion reaction in the breast clinical trial: 5% of the total dose infused IV over 15 minutes. If tolerated, double the infusion rate for the next 15 minutes. If tolerated, complete the infusion over the next hour for a total infusion time of 90 minutes.
- Avoid extravasation. It may occur with or without an accompanying stinging or burning sensation, and even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation occur, the injection or infusion should be immediately terminated and restarted in another vein. Any known or suspected extravasation should be managed promptly.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
- Patients who have a history of hypersensitivity reactions to a conventional formulation of doxorubicin, other anthracyclines, anthracenediones, or components of the pegylated liposome
- Patients with Kaposi Sarcoma and HIV who have had splenectomy (no experience)
- Use with caution in patients with a history of cardiovascular disease and/or prior anthracycline use
- Care should be exercised in patients with diabetes as the infusate is dextrose water
- Pegylated liposomal doxorubicin is a unique formulation of doxorubicin and should never be used interchangeably with other formulations of doxorubicin
Other Drug Properties:
-
Carcinogenicity:
Yes
-
Mutagenicity:
Yes
-
Embryotoxicity:
Documented in animals
-
Abortifacient effects:
Documented in animals
-
Teratogenicity:
Probable
-
Pregnancy:
Pegylated liposomal doxorubicin is contraindicated in pregnancy.
- Adequate contraception should be used by patients who can become pregnant and their partners during treatment, and for 8 months after the last dose.
- Adequate contraception should be used by patients who produce sperm and their partners during treatment, and for at least 6 months after the last dose.
-
Breastfeeding:
Pegylated liposomal doxorubicin is contraindicated in breastfeeding.
-
Fertility effects:
Unknown
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| barbiturates | ↓ efficacy of doxorubicin | ↑ clearance of doxorubicin | monitor |
| cyclophosphamide | exacerbation of hemorrhagic cystitis | uncertain | Caution |
| cyclophosphamide | ↑ cardiotoxicity | uncertain | monitor, adjust as needed |
| digoxin | ↓ digoxin levels | ↓ digoxin absorption | monitor digoxin levels and patient |
| mercaptopurine | ↑ hepatotoxicity | uncertain | monitor |
| quinolones | ↓ efficacy of quinolones | ↓ absorption of quinolones | monitor, may need to modify dose of quinolones |
| High dose progesterone | ↑ hematologic toxicity | unknown | caution |
| Calcium channel blockers | ↑ cardiotoxicity | additive | avoid |
| Sorafenib | possibly ↑ doxorubicin toxicity | ↑ doxorubicin exposure | caution |
| cyclosporine | ↑ hematologic toxicity | ↓ doxorubicin clearance or metabolism | caution |
| cytarabine | typhlitis | uncertain | caution; treat appropriately |
| Streptozocin | ↑ toxicity of doxorubicin | liver damage due to streptozocin decreasing metabolism of doxorubicin | caution |
| zidovudine | ↓ effect of zidovudine | doxorubicin decreases intracellular activation | avoid |
| stavudine | ↓ effect of stavudine | inhibits stavudine phosphorylation/metabolism | avoid |
| radiation | ↑ toxicity | radiation sensitizer | caution; consider dose modification, especially in patients with prior mediastinal radiation |
| Paclitaxel followed by doxorubicin | ↑ neutropenia and stomatitis | ↓ doxorubicin clearance | use paclitaxel after doxorubicin |
| Dactinomycin | ↑ radiation recall pneumonitis | additive effects | caution |
| phenytoin | ↓ phenytoin levels | ↑ phenytoin metabolism | caution, check levels |
| Trastuzumab | ↑ cardiotoxicity | additive | avoid anthracycline-based therapy for up to 24 weeks after stopping Trastuzumab |
| Vincristine | seizures | unknown | caution |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
Cardiac function tests (Echo, RNA and/or MUGA scans) for all patients with cardiac risk factors. Regular cardiac function tests before each additional dose over the cumulative dose threshold of 450 mg/m2. (Cumulative dose lower for high risk patients) |
Baseline and as clinically indicated |
CBC |
Baseline and at each visit |
Liver function tests |
Baseline and at each visit |
Clinical toxicity assessment for stomatitis, rash, hand-foot syndrome, hypersensitivity, infection, bleeding and cardiac symptoms |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Liposomal Doxorubicin - Platinum-Resistant Ovarian Fallopian Tube or Primary Peritoneal Cancer
- Liposomal DOXOrubicin - Single Agent Treatment of Platinum Sensitive Ovarian Fallopian Tube or Primary Peritoneal Cancer
- Liposomal Doxorubicin with Carboplatin - Platinum-Sensitive Recurrent Ovarian Fallopian Tube and Primary Peritoneal Cancer
- Liposomal Doxorubicin - HIV-positive Kaposi's Sarcoma
Coukell AJ, Spencer CM. Polyethylene glycol-liposomal doxorubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the management of AIDS-related Kaposi's sarcoma. Drugs. 1997 Mar;53(3):520-38.
McEvoy GK, editor. AHFS Drug Information 2009. Bethesda: American Society of Health-System Pharmacists, p. 1046-55.
Doxorubicin drug monograph, Cancer Care Ontario, 2011.
Product Monograph: Caelyx® (pegylated liposomal doxorubicin). Janssen Inc., October 10, 2013.
Product Monograph: Caelyx® (pegylated liposomal doxorubicin). Baxter Corp., April 2, 2024.
March 2025 Modified Pharmacokinetics, Indications, Other Drug Properties, and Pregnancy/Lactation sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.