Page 1183 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 66 Important Drug Interactions & Their Mechanisms 1169

TABLE 66–1 Important drug interactions.

Drug or Properties Promoting
Drug Group Drug Interaction Clinically Documented Interactions
Nonsteroidal Prostaglandin inhibition may result ACE inhibitors (ACEIs): [P] Decreased antihypertensive response.
anti- in reduced renal sodium excretion,
inflammatory impaired resistance to hypertensive Angiotensin II receptor blockers (ARBs): [P] Decreased antihypertensive response.
drugs (NSAIDs) stimuli, and reduced renal lithium Furosemide: [P] Decreased diuretic, natriuretic, and antihypertensive response to
excretion. Most NSAIDs inhibit furosemide.
platelet function; may increase
likelihood of bleeding due to other Hydralazine: [NE] Decreased antihypertensive response to hydralazine.
drugs that impair hemostasis.
Methotrexate: [NP] Possibly increased methotrexate toxicity (especially with
anticancer doses of methotrexate).
Selective serotonin reuptake inhibitors (SSRIs): [P] Increased risk of bleeding due to
platelet inhibition.
Thiazide diuretics: [P] Decreased diuretic, natriuretic, and antihypertensive response.
Triamterene: [NE] Decreased renal function noted with triamterene plus indomethacin
in both healthy subjects and patients.
See also Anticoagulants, oral; β-Adrenoceptor blockers; Lithium.
Opioid Opioid analgesics that are Amiodarone: [NP] Decreased CYP3A4-dependent opioid metabolism. Expect similar
analgesics substrates of CYP3A4 (alfentanil, interactions with dronedarone.
fentanyl, oxycodone, sufentanil,
and to a lesser extent methadone) Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine,
are susceptible to inhibitors and fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir
inducers. Methadone is primarily inhibit the metabolism of CYP3A4-dependent opioids.
metabolized by CYP2B6. Additive Boceprevir: [P] Decreased metabolism of CYP3A4-dependent opioids.
central nervous system depression
with other central nervous system Bosentan: [P] Increased CYP3A4-dependent opioid metabolism.
depressants.
Cobicistat: [P] Decreased metabolism of CYP3A4-dependent opioids.
Conivaptan: [P] Decreased metabolism of CYP3A4-dependent opioids.
Efavirenz: [P] Increased metabolism of CYP3A4-dependent opioids.
Kinase inhibitors: [P] Decreased metabolism of CYP3A4-dependent opioid by
ceritinib, dasatinib, imatinib, idelalisib, and lapatinib.
Nefazodone: [NP] Decreased CYP3A4-dependent opioid metabolism.
Nevirapine: [P] Increased metabolism of CYP3A4-dependent opioids.
Phenytoin: [P] Increased CYP3A4-dependent opioid metabolism.
Rifampin: [P] Increased CYP3A4-dependent opioid metabolism.
St. John’s wort: [NP] Increased CYP3A4-dependent opioid metabolism.
See also Azole antifungal agents; Barbiturates; Carbamazepine; Cimetidine; Macrolides;
Monoamine oxidase inhibitors.
Phenytoin Induces hepatic microsomal Drugs whose metabolism is stimulated by phenytoin:
drug metabolism. Susceptible to
inhibition of metabolism by CYP2C9 Corticosteroids: [P] Decreased serum corticosteroid levels.
and, to a lesser extent, CYP2C19. Doxycycline: [P] Decreased serum doxycycline levels.
Mexiletine: [NE] Decreased serum mexiletine levels.
Quinidine: [P] Decreased serum quinidine levels.
Theophylline: [NP] Decreased serum theophylline levels.
See also Calcium channel blockers; Cyclosporine; Estrogens; Opioid analgesics.
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.
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