Ritonavir-boosted nirmatrelvir (Paxlovid) is a treatment for COVID-19. However, ritonavir, a cytochrome P450 (CYP) CYP3A4 inhibitor, poses a risk of significant drug-drug interactions. In our case, coprescribed nirmatrelvir-ritonavir and verapamil, with concomitant acute kidney injury, resulted in complete heart block and shock. Following fluid resuscitation, blood pressure support with norepinephrine, and calcium therapy for verapamil toxicity, the patient recovered and was discharged home in normal sinus rhythm. To our knowledge, only 2 cases with this drug-drug interaction have been documented, making this a rare, but serious interaction poorly described in the literature. Understanding the pharmacokinetic relationship between these 2 medications and the risks of coprescribing them is crucial for both diagnosing toxicity and reducing preventable morbidity and mortality.