EryPed and Trabectedin

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Erythromycin may increase the blood levels of trabectedin in some patients. This can increase the risk and/or severity of side effects such as nausea, vomiting, constipation, diarrhea, liver problems, heart muscle problems (e.G., heart failure), and impaired bone marrow function resulting in low numbers of different types of blood cells. You may be more likely to develop anemia, bleeding problems, and infections because of low blood cell counts. In addition, your may have an increased risk of developing a rare but serious condition called rhabdomyolysis that involves the breakdown of skeletal muscle tissue. In some cases, rhabdomyolysis can cause kidney damage and even death. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Let your doctor know immediately if you have unexplained muscle pain, tenderness, or weakness during treatment with trabectedin, especially if these symptoms are accompanied by fever or dark colored urine. You should also seek immediate medical attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of trabectedin, which is primarily metabolized by the isoenzyme. In eight study patients with advanced malignancies, administration of a single 0.58 mg/m2 infusion of trabectedin following the second dose of ketoconazole (200 mg twice daily for 15 doses), a potent CYP450 3A4 inhibitor, increased the dose-normalized mean trabectedin peak plasma concentration (Cmax) and systemic exposure (AUC) by 22% and 66%, respectively, compared to infusion of a single 1.3 mg/m2 dose of trabectedin alone.

MONITOR: Coadministration of trabectedin with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Reversible, acute increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have occurred frequently in patients treated with trabectedin alone or with pegylated liposomal doxorubicin in clinical trials. In one U.S. trial with 378 patients, grade 3 or 4 elevated liver function tests (defined as elevations in ALT, AST, total bilirubin, or alkaline phosphatase) were reported in 35% of patients receiving trabectedin. ALT or AST elevations greater than eight times the upper limit of normal (ULN) occurred in 18% of patients, and drug-induced liver injury (defined as concurrent elevations in ALT or AST more than three times ULN, alkaline phosphatase less than two times ULN, and total bilirubin at least two times ULN) occurred in 1.3% of patients.

MANAGEMENT: Caution is advised when trabectedin is prescribed with CYP450 3A4 inhibitors that are also potentially hepatotoxic (e.g., azole antifungal agents; bicalutamide; cyclosporine (high dosages); dronedarone; macrolide antibiotics; protein kinase inhibitors; zafirlukast). Patients should be monitored for toxicities such as myelosuppression, rhabdomyolysis, hepatotoxicity, and cardiomyopathy, and the trabectedin dosage adjusted accordingly or treatment discontinued as necessary. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of alkaline phosphatase, bilirubin, AST, and ALT should occur regularly during trabectedin treatment in accordance with the product labeling, or as often as necessary when clinical symptoms develop. Trabectedin must not be used in patients with elevated bilirubin at the time of initiation of cycle. Elevated liver function tests should be managed with treatment interruption, dosage reduction, or permanent discontinuation depending on the severity and duration of abnormality.

EryPed

Generic Name: erythromycin

Brand name: E. E. S, EryPed, EES. Granules, EES-400 Filmtab, EryPed 200, EryPed 400, Ery-Tab, Erythrocin Lactobionate, Erythrocin Stearate Filmtab, PCE Dispertab, Erythrocin, Erythromycin Filmtabs, Erythromycin Lactobionate - IV

Synonyms: n.a.

What is EryPed?

Trabectedin

Generic Name: trabectedin

Brand name: Yondelis

Synonyms: n.a.

What is Trabectedin?