Drug interactions involving therapeutic radiopharmaceuticals: a systematic review

Drug interactions with diagnostic radiopharmaceuticals are well recognized, as they can modify biodistribution and lead to false or misleading diagnostic results. However, little is known about such interactions in the field of therapeutic radiopharmaceuticals, despite their rapid expansion-particularly with targeted radionuclide therapies such as Radioligand Therapy (RLT). This review aims, for the first time, to systematically compile and analyze available data on drug interactions involving therapeutic radiopharmaceuticals, in order to support safer and more effective patient care.

Eighty-three articles investigating drug interactions with [¹⁷⁷Lu]Lu-oxodotreotide (Lutathera®), [¹⁷⁷Lu]Lu-vipivotide tetraxetan (Pluvicto®), [¹³¹I]INa, [¹³¹I]I-meta-iodobenzylguanidine ([¹³¹I]I-MIBG), [²²³Ra]RaCl₂ (Xofigo®), [⁹⁰Y]Y-ibritumomab tiuxetan (Zevalin®) or [¹⁵³Sm]Sm-lexidronam pentasodium (Quadramet®) were included. These studies reported 133 drug interactions, 69% of which were not mentioned in the corresponding summaries of product characteristics. Interactions could be beneficial (e.g., reducing renal toxicity) or harmful (e.g., decreasing therapeutic efficacy or potentiating toxicity). Three interactions involved complementary and alternative medicines (quercetin, Ginkgo biloba and ouabain). Overall, the evidence level for reported interactions was low: 88% were classified as level 3 or 4 according to the Centre for Evidence-Based Medicine (CEBM) scale.

Drug interactions with therapeutic radiopharmaceuticals remain underreported, yet they may have significant clinical consequences. Clinical radiopharmacy plays a key role in detecting and preventing these interactions. Radiopharmacists, through their expertise, can identify potential interactions, influence therapeutic decisions, and positively impact patient management. Their involvement throughout the care pathway is essential to ensure the safe and effective use of these innovative therapies. Nuclear medicine physicians should also be aware that such interactions can alter biodistribution, compromise therapeutic efficacy, and increase the risk of adverse effects.