Prophylaxis and Treatment - Prophylactic Management

Healthcare providers are pivotal in the prophylactic management of potential drug-drug interactions kinase inhibitor. General recommendations are listed below.

Concomitant Medication

Patients should be advised to tell their healthcare provider discuss any concomitant medications, including prescription and non-prescription medicines, vitamins and herbal and dietary supplements before they start taking them. It should be explained that the kinase inhibitor treatment they are taking may affect the way other medicines work, and other medicines may affect how the kinase inhibitor works.1,2

Checking Drug Medication Safety Systems

Healthcare providers should check for drug-drug interactions by entering all drugs (also over-the-counter drugs and herbals) in their medication safety system, such as the Micromedex interaction checker and the Drug Interaction Checker at Drugs.com, Stockley’s Drug Interactions and SiteGPR®. Importantly, pharmacists and physicians should work together to extrapolate known drug-drug interactions to other drugs, and act appropriately. Cytochrome P450 activity for kinase inhibitors can be determined using the P450 drug interaction table from Indian University.

ECG Monitoring

ECG monitoring is recommended 24-48 h before, and 1 week after, the start of the concomitant use of QTc interval prolonging drugs and CYP3A4 inhibitors together with kinase inhibitors.3,4

Timing of Drug Intake

Since concomitant use of acid suppressive drugs with kinase inhibitors can affect drug absorption of Tyrosine kinase inhibitors it is recommended that time of drug intake should be separated by at least several hours, if the combination cannot be avoided.4

Dose Adjustments

Dose adjustments are highly recommended with concomitant use of strong CYP3A4 inhibitors or inducers as they can significantly affect the exposure to kinase inhibitors.4 Importantly, the choice of dose should not be made on assumptions. Dosing should be readjusted based on observed toxicities despite the dose being adapted during the first cycle based on comedications etc.

Additional Checks

Lifestyle, food and drinks (e.g. grapefruit juice), herbal supplements (e.g. St John’s Wort), over-the-counter drugs, cardiac risk factors and physical examination should be checked, to improve safe use of kinase inhibitors.4

The patient’s medical history should be taken thoroughly and interactively, and updated periodically. Patients who have risk factors for potential DDIs should also be monitored more closely.5

Co-Administering Kinase Inhibitors with Protein Pump inhibitors

Avoid co-administering kinase inhibitors with PPIs if at all possible. If unavoidable, consult multidisciplinary team members including medical oncologists and clinical pharmacists to make a decision to proceed based on patient characteristics and known data.

Co-Administering Kinase Inhibitors with QT Prolongators

Avoid co-administering kinase inhibitors with QT prolongators if at all possible. Switch to a drug that is a non-QT prolongator. If this combination is unavoidable, consult a cardiologist and clinical pharmacologist and take ECG measurements within 24-48 hours of administration and 1 week after starting treatment.4

References

  1. Food and Drug Administration. Regorafenib (STIVARGA) Prescribing information. 2015.
  2. Food and Drug Administration. Sunitinib (Sutent) Prescribing information. 2015.
  3. van Leeuwen RW, Jansman FG, van den Bemt PM et al. Drug-drug interactions in patients treated for cancer: a prospective study on clinical interventions. Ann Oncol 2015; 26: 992-997.
  4. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 2014; 15: e315-326.
  5. Teo YL, Ho HK, Chan A. Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. Br J Clin Pharmacol 2015; 79: 241-253.
Last update: 17 July 2015