Lipo-Dox Special Precautions

Cardiac Toxicity: All patients treating with Lipo-Dox should routinely undergo EKG monitoring. When T-wave flattening, S-T segment depression and benign arrhythmias occur, no need to discontinue therapy immediately. However, reduction of the QRS complex is considered more indicative of, it usually shows the cardiac toxicity. Endomyocardial biopsy should be considered to define for anthracycline myocardial injury (see Adverse Reactions).
Besides ECG, there are many specific methods for monitoring cardiac functions, such as a measurement of LVEF by echocardiography or preferably by Multigated Angiography (MUGA). These methods should be applied routinely before or during the Lipo-Dox treatment. In a phase III clinical trial comparing pegylated liposomal doxorubicin (50 mg/m²/every 4 weeks) versus conventional doxorubicin (60 mg/m²/every 3 weeks), the risk of developing a cardiac toxicity as a function of cumulative anthracycline dose was significant lower with pegylated liposomal doxorubicin than with conventional doxorubicin (HR=3.16, p<0.001). At cumulative doses between 450 mg/m² and 600 mg/m² there was no increased risk of cardiac toxicity with pegylated liposomal doxorubicin. The evaluation of left ventricular function is considered to be mandatory before each addition administration of pegylated liposomal doxorubicin which exceeds a lifetime cumulative anthracycline dose of 600 mg/m² in patients without prior anthracycline exposure. For patients who have received prior adjuvant anthracyclines (epirubicin or doxorubicin), LVEF assessments should be performed before each additional administration of pegylated liposomal doxorubicin that exceeds a lifetime, doxorubicin-equivalent, cumulative anthracycline dose of 450 mg/m².
The evaluation tests and monitoring of cardiac performance during anthracycline therapy should be employed in the following order: ECG monitoring, measurement of left ventricular ejection fraction, endomyocardial biopsy. If the test result indicates possible cardiac injury associated with pegylated liposomal doxorubicin therapy, the benefit of continued therapy must be carefully evaluated.
In patients with cardiovascular disease requiring treatment, administer Lipo-Dox only when the benefit outweighs the risk to the patient.
Caution should be exercised in patients with impaired cardiac function who receive pegylated liposomal doxorubicin.
If the test results indicate possible cardiac injure, such as the left ventricular ejection fraction lower than pre-treatment baseline and/or LVEF is lower than a prognostically relevant values (<45%), endomyocardial biopsy may be considered. The benefit of continued therapy must be carefully weighed against the risk of developing irreversible myocardial injury.
Moreover, congestive heart failure due to cardiomyopathy may occur suddenly, without prior ECG changes and may also be encountered several weeks after discontinuation of therapy.
Caution should be carefully monitored in patients who have received other anthracyclines, and the total dose of doxorubicin HCl should take into account any previous or concomitant therapy with cardiotoxic compounds such as other anthracyclines/anthraquinones or 5-fluorouracil. The cardiac toxicity also may occur at cumulative anthracycline doses lower than 450 mg/m² in patients with prior mediastinal irradiation or in those treating concurrent cyclophosphamide therapy.
The cardiac safety profile for the recommended dose for both breast and ovarian caner (50 mg/m²/every 4 weeks) is similar to the 20 mg/m²/every 2 weeks profile in AIDS-KS patients. (See Adverse Reactions.)
Myelosuppression: Many patients treated with pegylated liposomal doxorubicin have baseline myelosuppression due to such factors as their pre-existing HIV disease or concomitant or previous medications, or tumors involving bone marrow. In the ovarian cancer clinical trial, patients who treated with 50 mg/m² of pegylated liposomal doxorubicin, myelosuppression was generally mild to moderate, reversible, and was not related to the neutropenic infection or sepsis.
Besides these, the clinical results of ovarian cancer using topotecan as control group proved that the incidence of therapy-related sepsis was lower in pegylated liposomal doxorubicin group than in topotecan group. A similar low incidence of myelosuppression was seen in metastatic breast cancer patients receiving pegylated liposomal doxorubicin in a first-line clinical trial. In contrast to the experience in breast cancer and ovarian cancer patients, the myelosuppression appears to be the dose-limiting adverse event in AIDS-KS patients. Because of the potential for bone marrow suppression, periodic blood counts must be performed during the course of pegylated liposomal doxorubicin, and at least before each dose of pegylated liposomal doxorubicin.
Persistent severe bone marrow suppression is not seen in breast or ovarian cancer patients, but it may result in superinfection or hemorrhage.
Due to the different pharmacokinetic properties and dosing schedules, Lipo-Dox should not be used interchangeably with other doxorubicin HCl formulations. Combination chemotherapy with pegylated liposomal doxorubicin has been studied in solid tumor populations. Pegylated liposomal doxorubicin has been safely co-administered with standard doses of chemotherapeutic agents that are frequently used in the treatment of advanced breast cancer or ovarian cancer, however the efficacy of such combination regimens has not been established.
Diabetic Patients: Each vial of Lipo-Dox contains sucrose and is administered in Dextrose 5% in Water for intravenous infusion, so precaution should be exercised.
Infusion-related Adverse Reactions: Serious and sometimes life-threatening infusion reactions which are characterized by allergic-like or anaphylactoid-like reactions, with symptoms including asthma, flushing, urticarial rash, chest pain, fever, hypertension, tachycardia, pruritus, sweating, shortness of breath, facial edema, chills, back pain, tightness in the chest and throat and/or hypotension may occur within minutes of starting the infusion of pegylated liposomal doxorubicin. Temporarily stopping the infusion usually resolved these symptoms without further therapy. However, medications to treat these symptoms (e.g., antihistamines, corticosteroids, and adrenaline), as well as emergency equipment should be available for immediate use. In most patients can be resumed after all symptoms have resolved, without recurrence. Infusion reactions rarely recur after the first treatment cycle. To minimize the risk of infusion reactions, the initial dose should be administered at a rate no greater than 1 mg/minute. (See Adverse Reactions.)
Driving and Machine Operations: As reported, pegylated liposomal doxorubicin does not affect on patient's driving, but few people (<5%) occur dizziness and somnolence. Patients who suffer from these effects should avoid driving and machine operations.