Papaverine: [NE] Inhibited antiparkinsonism effect. Phenothiazines: [P] Inhibited antiparkinsonism effect. Phenytoin: [NE] Inhibited antiparkinsonism effect. Pyridoxine: [P] Inhibited antiparkinsonism effect (carbidopa prevents the interaction). ACE inhibitors (ACEIs): [NE] Reduce renal clearance of lithium; increase lithium effect. Angiotensin II receptor blockers (ARBs): [NE] Reduce renal clearance of lithium; increase lithium effect. Diuretics (especially thiazides): [P] Decreased excretion of lithium; furosemide may be less likely to produce this effect than thiazide diuretics. Haloperidol: [NP] Occasional cases of neurotoxicity in manic patients, especially with large doses of one or both drugs. Methyldopa: [NE] Increased likelihood of central nervous system lithium toxicity. Nonsteroidal anti-inflammatory drugs (NSAIDs): [NE] Reduced renal lithium excretion (except sulindac and salicylates). Theophylline: [P] Increased renal excretion of lithium; reduced lithium effect.
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.
Macrolides The macrolides clarithromycin and erythromycin are known to inhibit CYP3A4 and P-glycoprotein. Azithromycin does not appear to inhibit CYP3A4 but is a modest inhibitor of P-glycoprotein.
Monoamine Increased norepinephrine stored in oxidase adrenergic neuron. Displacement inhibitors of these stores by other drugs (MAOIs) may produce acute hypertensive response. MAOIs have intrinsic hypoglycemic activity.
Benzodiazepines: [P] Decreased metabolism of alprazolam, midazolam, triazolam. Eplerenone: [P] Decreased metabolism of eplerenone. Ergot alkaloids: [P] Decreased elimination of ergot alkaloids. Kinase inhibitors: [P] Decreased metabolism of axitinib, bosutinib, ceritinib, cabozantinib, cobimetinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, ibrutinib, idelalisib, imatinib, ixazomib, lapatinib, nilotinib, nintedanib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ruxolitinib, sunitinib, tofacitinib, vandetanib, and vemurafenib by clarithromycin and erythromycin.
Opioid analgesics: [P] Decreased elimination of alfentanil, fentanyl, methadone, oxycodone, and sufentanil. Phosphodiesterase inhibitors: [P] Decreased metabolism of phosphodiesterase inhibitor.
Pimozide: [P] Increased pimozide concentrations. Quinidine: [P] Increased serum quinidine concentrations. Theophylline: [P] Decreased metabolism of theophylline. See also Anticoagulants, oral; Calcium channel blockers; Carbamazepine; Cisapride;