E, Expected; HP, Highly predictable. Interaction occurs in almost all patients receiving the interacting combination; P, Predictable. Interaction occurs in most patients receiving the combination; NP, Not predictable. Interaction occurs only in some patients receiving the combination; NE, Not established. Insufficient data available on which to base estimate of predictability.
TABLE 66–1 Important drug interactions.
HMG-CoA reductase inhibitors (statins) (cont.)
Iron Binds with drugs in gastrointestinal tract, reducing absorption.
Levodopa Levodopa degraded in gut prior to reaching sites of absorption. Agents that alter gastrointestinal motility may alter degree of intraluminal degradation. Antiparkinsonism effect of levodopa susceptible to inhibition by other drugs.
Lithium Renal lithium excretion sensitive to changes in sodium balance. (Sodium depletion tends to cause lithium retention.) Susceptible to drugs enhancing central nervous system lithium toxicity.
Gemfibrozil: [NP] Increased plasma lovastatin and simvastatin and increased risk of myopathy. Kinase inhibitors: [P] Decreased metabolism of atorvastatin, lovastatin, and simvastatin by ceritinib, dasatinib, imatinib, idelalisib, and lapatinib.
Macrolide antibiotics: [P] Clarithromycin and erythromycin inhibit the elimination of statins. Nefazodone: [NP] Decreased atorvastatin, lovastatin, and simvastatin metabolism. Phenytoin: [P] Increased atorvastatin, lovastatin, and simvastatin metabolism. Rifampin: [P] Increased atorvastatin, lovastatin, and simvastatin metabolism. St. John’s wort: [NP] Increased atorvastatin, lovastatin, and simvastatin metabolism. See also Azole antifungals; Calcium channel blockers; Cyclosporine. Methyldopa: [NE] Decreased methyldopa absorption. Mycophenolate: [P] Decreased mycophenolate absorption. Quinolones: [P] Decreased absorption of ciprofloxacin and other quinolones. Tetracyclines: [P] Decreased absorption of tetracyclines; decreased efficacy of iron. Thyroid hormones: [P] Decreased thyroxine absorption. See also Antacids. Clonidine: [NE] Inhibited antiparkinsonism effect. Haloperidol: [NP] Inhibited antiparkinsonism effect.
Metoclopramide: [NP] Inhibited antiparkinsonism effect. Monoamine oxidase inhibitors (MAOIs): [P] Hypertensive reaction (carbidopa prevents the interaction).