Drug-Drug Interactions Associated with Kinase Inhibitors - Cancer Therapy and Drug Interactions

Importance of Drug-Drug Interactions in Cancer Therapy

Drug-drug interactions are an important consideration for patients undergoing cancer therapy as they often receive several drugs (oral or intravenous) as part of their anti-cancer therapy regimen, as well as additional therapies to manage comorbidities and side effects of therapy.¹ In addition, with the mean age of cancer patients increasing, older patients may be at higher risk for drug interactions as they have more comorbidities which require additional drug therapy.^2-4 In addition to age- and comorbidity- associated changes in drug absorption that are common in older patients.

Epidemiology

Nearly 60% of patients undergoing cancer therapy (regardless of mode of administration) are estimated to have had at least one potential drug-drug interaction.⁵ For patients receiving oral anticancer therapy, up to 50% have been reported to experience a potential drug-drug interaction, with 16% experiencing a major event.⁴ In addition, ~30% of drug-drug interactions associated with anticancer therapy required medical intervention,⁶ and drug-drug interactions are estimated to be the cause of death of ~4% of patients with cancer.⁷

When coadministered with anticancer therapies, drug-drug interactions occur most frequently with coumarin, quinolones, antiepileptics, hydrochlorothiazide and opioids.^4-6 Pharmacodynamic drug-drug interactions may cause QT prolongation, gastrointestinal toxicity and central nervous system depression.^4-6

Risk Factors

The risk of drug interactions is increased in certain patient groups, including patients using over-the-counter medications, patient subgroups with increased risk of drug interactions are:^3-5

• Patients who take multiple medications.
• Patients using over-the-counter drugs or complimentary medicines.
• Patient cancer type.

References

1. Riechelmann RP, Tannock IF, Wang L et al. Potential drug interactions and duplicate prescriptions among cancer patients. J Natl Cancer Inst 2007; 99: 592-600.
2. Yancik R, Ries LA. Aging and cancer in America. Demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 2000; 14: 17-23.
3. Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer 2006; 6: 546-558.
4. van Leeuwen RW, Brundel DH, Neef C et al. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer 2013; 108: 1071-1078.
5. van Leeuwen RW, Swart EL, Boven E et al. Potential drug interactions in cancer therapy: a prevalence study using an advanced screening method. Ann Oncol 2011; 22: 2334-2341.
6. van Leeuwen RW, Jansman FG, van den Bemt PM et al. Drug-drug interactions in patients treated for cancer: a prospective study on clinical interventionsdagger. Ann Oncol 2015; 26: 992-997.
7. Buajordet I, Ebbesen J, Erikssen J et al. Fatal adverse drug events: the paradox of drug treatment. J Intern Med 2001; 250: 327-341.