Lipo-Dox Special Precautions



TTY Biopharm


Onco Care Pharma


American Taiwan Biopharma
Full Prescribing Info
Special Precautions
Cardiac Toxicity: All patients treating with Lipo-Dox should routinely undergo ECG monitoring. When T-wave flattening, S-T segment depression and arrhythmia occur, therapy discontinuance immediately is not necessary. However, when the reduction of the QRS complex occurs, it usually shows the cardiac toxicity. Endomyocardial biopsy should be considered to define for anthracycline-induced myocardial injury. (See Adverse Reaction).
Besides ECG, there are many specific methods for monitoring cardiac functions, such as a measurement of LVEF by cardiac echo 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 ) with conventional doxorubicin (60 mg/m2 every 3 weeks), the risk of cardiac toxicity development as a function of cumulative anthracycline dose was significantly lower with pegylated liposomal doxorubicin than with conventional doxorubicin (HR=3.16, p<0.001). At cumulative doses between 450 mg/m2 to 600 mg/m, 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 and each time when the accumulated dosage increment of pegylated liposomal doxorubicin is 100 mg/m2, the patients must receive the evaluation of LVEF.
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 indicated possible cardiac injury associated with pegylated liposomal doxorubicin therapy, the benefit of continuance of therapy or not must be carefully evaluated.
In patients with cardiovascular disease requiring treatment, administer Lipo-Dox only when the benefit outweighs the risk to the patients.
Caution should be exercised in patients with impaired cardiac function who receive pegylated liposomal doxorubicin.
If the test results indicate possible cardiac injury, such as the left ventricular ejection fraction lower than pre-treatment baseline and/or LVEF is lower that a prognostically relevant values (<45%), endomyocardial biopsy might be considered. The benefit of continuance of 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 be taken 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 that 450 mg/m2 in patients with prior mediastinal irradiation or in those with concurrent cyclophosphamide therapy.
The cardiac safety profile for the recommended dose for both breast and ovarian cancer (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 preexisting HIV disease or concomitant or previous medications or tumors involving bone marrow. In the ovarian cancer clinical trial, patients who were treated with 50 mg/m2 of 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 ach dose of pegylated liposomal doxorubicin.
Persistent severe bone marrow suppression is not seen in breast or ovarian cancer patients, but it may result in recurrent infection hemorrhage.
Due to the different pharmacokinetic properties and dosing schedule, Lipo-Dox should not be interchanged with other doxorubicin HCl formulations. Combination chemotherapy with 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 regiments 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: Severe and sometimes life-threatening infusion reactions which are characterized by allergic-like or anaphylactoid-like reactions with symptoms including asthma, flushing, urticaria 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. Discontinuance of infusion temporarily usually resolved 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. The initial rate of infusion should not be over 1 mg/min to help minimize the risk of infusion reactions. (See Adverse Reactions.)
Driving and Machine Operations: As reported, pegylated liposomal doxorubicin does not affect patient's driving but dizziness occur and somnolence occur in a few people (<5%). Driving and machine operations should be avoided in patients who suffer from these effects.
Use in Pregnancy & Lactation: Pegylated liposomal doxorubicin is embryotoxic in rats and embryotoxic and abortifacient in rabbits. Teratogenicity cannot be excluded. There is no experience in pregnant women with pegylated liposomal doxorubicin, therefore administration to pregnant women is not recommended. Avoid pregnancy in women of child-bearing potential and their male partner within 6 months after discontinuation of Lipo-Dox therapy.
It is not known whether Lipo-Dox is excreted in human milk and because of the potential for severe adverse reactions in nursing infants, mothers should discontinue nursing. Medical experts recommend that HIV-infected women should not nurse infants under any circumstances in order to avoid transmission of HIV.
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