The aim was to determine the prescription patterns of cytochrome P450-inducing and -inhibiting drugs and their contraindicated and major pharmacological interactions in a group of patients from Colombia. This cross-sectional study included patients who received drugs that induce or inhibit metabolism and examined their contraindicated and major pharmacological interactions. The patients were identified from a population database and the Micromedex® tool. A total of 63,433 patients were analyzed. Antiepileptics (35.9%) and antifungals (27.6%) were the most commonly used inducers and inhibitors. A total of 30.1% of patients had potential contraindicated or greater interactions. The following factors were associated with a higher probability of presenting a potential pharmacological interaction: being male (OR:1.14; 95%CI:1.10–1.19), being between 18-39 years (OR:1.77; 95%CI:1.67–1.89) or between 40-64 years (OR:1.64; 95%CI:1.56–1.72), having neurological diseases (OR:1.28; 95%CI:1.21–1.35), having psychiatric diseases (OR:3.84; 95%CI:3.58–4.13), having rheumatologic diseases (OR:1.32; 95%CI:1.23–1.41), receiving comedications with statins (OR:1.14; 95%CI:1.08-1, 19), receiving comedications with analgesics (OR:1.33; 95%CI:1.27–1.38), receiving comedications with antiparasitics (OR:2.88; 95%CI:2.66–3.11), and an increase in the number of medications (OR:1.24; 95%CI:1.23–1.25). Among the users of cytochrome P450 inhibitors and inducers, potential contraindications and greater interactions are very common, especially in men under 65 years of age with comorbidities and polypharmacy.