A 37-year-old woman experienced a significant increase in blood tacrolimus levels after starting Clarithromycin for an H. Pylori infection. Tacrolimus, used in organ transplant patients, has a narrow therapeutic index requiring close monitoring. The concurrent use of Clarithromycin, a CYP3A4 inhibitor, led to a dramatic spike in tacrolimus levels, causing signs of potential toxicity, such as elevated serum creatinine. This case highlights the critical importance of awareness of drug-drug interactions, especially involving CYP3A4 inhibitors, to prevent adverse effects and ensure patient safety. Clinicians should closely monitor tacrolimus levels when prescribing such medications.