Drug–Drug, Drug–Food, Drug–Disease - NAPLEX

Buprenorphine. Buprenorphine's high mu-receptor affinity displaces full agonists, inducing acute withdrawal symptoms in dependent individuals.

Serotonin syndrome risk (MAOI activity). Linezolid's MAOI properties combined with serotonergic agents can cause excessive serotonin accumulation, leading to syndrome manifestations.

Strong induction lowers drug levels; reduced efficacy. Rifampin potently induces multiple CYP enzymes, decreasing substrate concentrations and compromising therapeutic outcomes.

Lithium levels increase; toxicity risk increases. Thiazides reduce lithium renal clearance, elevating serum levels and increasing toxicity risks like neurotoxicity.

Carbamazepine. Carbamazepine induces CYP3A4, accelerating estrogen metabolism and diminishing contraceptive reliability.

Reduced absorption; separate administration. Calcium and iron bind levothyroxine, impairing gastrointestinal absorption and necessitating timed separation for optimal efficacy.

Hypertensive crisis risk. Tyramine displaces norepinephrine in the presence of MAO inhibition, causing acute hypertension and potential cardiovascular emergencies.

Grapefruit juice. Grapefruit juice inhibits intestinal CYP3A4, reducing first-pass metabolism and elevating statin concentrations with myopathy risk.

Verapamil. Verapamil increases dofetilide exposure via P-glycoprotein inhibition, amplifying QT prolongation and torsades de pointes risk.

Hyperkalemia risk increases. Both classes promote potassium retention, leading to potentially life-threatening hyperkalemia.

INR increases; bleeding risk increases. Trimethoprim-sulfamethoxazole inhibits CYP2C9 and vitamin K-producing bacteria, potentiating warfarin's anticoagulant effects.

Chelation reduces absorption. Calcium in dairy forms insoluble complexes with tetracyclines, decreasing antibiotic bioavailability and therapeutic effectiveness.

Disulfiram-like reaction risk. Metronidazole inhibits aldehyde dehydrogenase, causing acetaldehyde buildup and symptoms like flushing and nausea upon alcohol ingestion.

Asthma. Nonselective beta-blockers antagonize beta-2 receptors in airways, exacerbating bronchoconstriction in asthmatic patients.

Chronic kidney disease. NSAIDs inhibit prostaglandins that maintain renal perfusion, leading to acute kidney injury and fluid retention in CKD patients.

Pregnancy. Isotretinoin is a potent teratogen, causing severe fetal malformations, thus contraindicated during pregnancy.

Severe renal impairment. Severe renal impairment reduces metformin clearance, increasing lactate accumulation and lactic acidosis risk.

Heart failure with reduced ejection fraction (HFrEF). Nondihydropyridine CCBs depress myocardial contractility, worsening systolic dysfunction in HFrEF patients.

CYP2C19 inhibition reduces clopidogrel activation. Omeprazole inhibits CYP2C19, impairing conversion of clopidogrel to its active metabolite and reducing antiplatelet efficacy.

Fluoroquinolones (especially ciprofloxacin). Fluoroquinolones inhibit CYP1A2, increasing tizanidine levels and risking severe hypotension or bradycardia.

Severe hypotension from additive vasodilation. Nitrates and PDE-5 inhibitors both promote vasodilation, leading to profound hypotension when combined.

Reduce warfarin dose and monitor INR closely. Amiodarone's inhibition of warfarin metabolism necessitates dose reduction and frequent INR monitoring to prevent bleeding complications.

CYP2C9 inhibition increases warfarin effect; INR rises. Amiodarone inhibits CYP2C9, reducing warfarin metabolism and potentiating its anticoagulant effects, which elevates INR levels.

CYP3A4 inhibition increases statin; rhabdomyolysis risk. Clarithromycin inhibits CYP3A4, elevating simvastatin levels and heightening the risk of muscle breakdown and kidney damage.