Interactions between Macimorelin and Rubraca
1 drug interaction and 5 additional warnings found for the following 2 drugs:
- macimorelin
- Rubraca (rucaparib)
Drug interactions
Moderate drug interactions
Moderate:
rucaparib macimorelin
Applies to: Rubraca (rucaparib) and macimorelin
Generally avoid
Macimorelin can cause prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a dedicated thorough QT study consisting of 60 healthy subjects, a mean baseline- and placebo-adjusted change in QTcF of 9.6 msec was observed 4 hours following administration of a supratherapeutic dose of macimorelin 2 mg/kg (4 times the recommended dose), which occurred after the mean maximum macimorelin plasma concentration (0.5 hour). A similar increase in the QTcF interval was also observed in a single-ascending dose study, which included three dose levels: 0.5 mg/kg; 1 mg/kg (2 times the recommended dose); and 2 mg/kg (4 times the recommended dose). All three doses levels produced a similar magnitude of QTcF prolongation as reported in the thorough QT study, suggesting an absence of dose-dependent changes. The mechanism for the observed QTcF prolongation is unknown. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
Management
Coadministration of macimorelin with other drugs that can prolong the QT interval should generally be avoided. A sufficient washout period following discontinuation of these drugs is recommended prior to macimorelin administration. Patients treated with any medication that can cause QT prolongation should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
References (1)
- (2018) "Product Information. Macrilen (macimorelin)." Aeterna Zentaris
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
macimorelin Food/Lifestyle
Applies to: macimorelin
Adjust dosing interval
Food reduces the oral bioavailability of macimorelin. According to the product labeling, administration with a liquid meal decreased macimorelin peak plasma concentration (Cmax) and systemic exposure (AUC) by 55% and 49%, respectively, compared to administration under fasting conditions (i.e., for at least 8 hours).
Management
Macimorelin should be administered after fasting for at least 8 hours.
References (1)
- (2018) "Product Information. Macrilen (macimorelin)." Aeterna Zentaris
Disease interactions
4 potential interactions Applies to: 4 conditions, including Arrhythmia, Liver Disease, Renal Dysfunction, and Bone Marrow Depression/Low Blood Counts.
Arrhythmia
Moderate:
macimorelin
Macimorelin has a moderate potential interaction with Arrhythmia.
Macimorelin can cause an increase of about 11 msec in the corrected QT (QTc) interval that can lead to development of torsade de pointes-type ventricular tachycardia. It is recommended to avoid the concomitant use of macimorelin with drugs that are known to prolong the QT interval. Care should be exercised when using this agent in patients with arrhythmias or conduction disorders.
Bone Marrow Depression/Low Blood Counts
Moderate:
Rubraca
The rucaparib in Rubraca has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.
Cases of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) have been reported with the use of rucaparib. Rucaparib should not be started until patients have recovered from hematological toxicity caused by previous chemotherapy (grade 1 or less). It is recommended to monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during therapy. For hematologic toxicities exceeding 4 weeks, rucaparib should be interrupted or the dosage reduced according to the manufacturer product information; blood counts should be monitored weekly until recovery. If levels have not recovered to grade 1 or less after 4 weeks or if MDS/AML is suspected, the patient should be referred to a hematologist for further investigations (including bone marrow analysis and blood sample for cytogenetics). If MDS/AML is confirmed, rucaparib should be discontinued.
Liver Disease
Moderate:
Rubraca
The rucaparib in Rubraca has a moderate potential interaction with Liver Disease.
No dose adjustment is recommended for patients with mild to moderate liver dysfunction (total bilirubin up to 3 times the upper limit of normal [3 x ULN] or AST greater than ULN). Caution should be exercised when using this agent in patients with severe liver dysfunction (total bilirubin greater than 3 x ULN and any AST) as rucaparib has not been studied in these patients.
Renal Dysfunction
Moderate:
Rubraca
The rucaparib in Rubraca has a moderate potential interaction with Renal Dysfunction.
No dose adjustment is recommended for patients with mild to moderate renal dysfunction (CrCl between 30 and 89 mL/min [as estimated by Cockcroft-Gault method]). Caution should be exercised when using this agent in patients with severe renal dysfunction (CrCl less than 30 mL/min) or patients on dialysis as rucaparib has not been studied in these patients.
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More resources
macimorelin
A total of 361 drugs are known to interact with macimorelin.
- Macimorelin is in the drug class growth hormones.
- Macimorelin is used to treat Growth Hormone Reserve Test.
Rubraca
A total of 762 drugs are known to interact with Rubraca.
- Rubraca is in the drug class PARP inhibitors.
- Rubraca is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.