Anticancer drug interaction with acid reducing agents and some recommendation to overcome this interaction

Pharmacist: Huda Jassim Muhammad
College of pharmacy
Tyrosine kinase inhibitors interaction with gastric acid reducing agents and some recommendation to overcome this interaction

Tyrosine kinase inhibitors TKIs such as (Dasatinib, Erlotinib, Gefitinib, Imatinib) show a high selective toxicity towards the cancer cells with minimal side effects. They have a superiority in the treatment of chronic myeloid leukemia, non-small cell lung cancer, renal cell carcinoma than traditional antineoplastic agents(1). Since the TKIs are administered orally, they offer great flexibility for the patient. However, the oral route can cause a drug interaction with the acid reducing agents. This interaction is mainly due to their pH-dependent solubility behaviors in physiological pH range (2). The solubility of TKIs is high in a low pH environment with poor solubility in neutral to alkaline medium. The acid reducing agents such as proton pump inhibitors (PPIs) or histamine H2-receptor blockers are prescribe for almost 50% of cancer patients (3). PPIs are considered the most widely prescribed drugs for gastroesophageal reflux, peptic ulcer, prevention of gastrointestinal bleeding when combined with non-steroidal anti-inflammatory drugs and Zollinger–Ellison syndrome (4).
The acid reducing agents increase the gastric pH which can decrease the solubility of the TKIs when taken together, resulting in low absorption, bioavailability, and sub-optimal clinical outcomes. Due to such significant interaction, the gastric acid reducing agents withdrawal are recommended (2, 5, 6)

Pervious research showed the administration of some TKIs with acidic beverages like Coca- Cola or apple juice resulted in clinically significant increase of absorption and bioavailability during PPIs therapy by decreasing the stomach pH temporarily or by increasing the solubility of the drug itself (7, 8). Therefore, administration of TKIs with acidic drinks can overcome the interaction with the acid reducing agents.

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