Drugs In Practice

Drugs for GERD and Peptic Ulcer Disease tetracyclines should not be used during pregnancy or in children ≤8 years old. Levofloxacin can cause severe hypoglycemia, delirium, agitation, nervousness, and disturbances in attention, memory, and orientation. It can also cause persistent or permanent peripheral neuropathy and an increased risk of pseudotumor cerebri syndrome. Tendinitis, tendon rupture, exacerbation of myasthenia gravis, C. difficile infection, and QT-interval prolongation and torsades de pointes can also occur. Rifabutin can cause brown-orange discoloration of urine, feces, saliva, sputum, perspiration, tears, and skin. It can rarely cause myelotoxicity (generally with higherthanrecommended doses or prolonged use) and uveitis. Serious, sometimes fatal, hypersensitivity reactions and C. difficile infection has been reported with use of rifabutin. Clarithromycin commonly causes taste disturbances that some patients find intolerable, and it can cause QT-interval prolongation. 32 The labeling of clarithromycin contains a warning about an increased risk of cardiac adverse events and death in patients with coronary artery disease.33

Sucralfate is generally well tolerated, but patients often complain about its metallic taste. It can cause constipation and, particularly in patients with renal impairment, aluminum toxicity. Abdominal pain and dose-related diarrhea, which can be severe, are the most common adverse effects of misoprostol. Severe nausea, dyspepsia, and flatulence can also occur.

Drug Interactions

Metronidazole is an inhibitor of CYP2C9 and may increase serum concentrations of drugs metabolized by this isozyme, including warfarin. Coadministration of products containing calcium, magnesium, or iron can decrease absorption of tetracycline and levofloxacin; either should be taken 2 hours before or 6 hours after these products. Rifabutin is an inducer of CYP3A4, 2C8 and 2C9 and can reduce serum concentrations of drugs that are metabolized by these isozymes. Clarithromycin is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) and may increase serum concentrations of drugs that are CYP3A4 or P-gp substrates. 7 Taking clarithromycin with other drugs that prolong the QT interval, especially those metabolized by CYP3A4, can increase the risk of QTinterval prolongation and torsades de pointes. 33 Sucralfate decreases the absorption of many other drugs, including fluoroquinolones, tetracyclines, and levothyroxine; administration should be separated by at least 2 hours.

Pregnancy

Bismuth subsalicylate is converted to bismuth and salicylic acid in the GI tract. Bismuth is minimally absorbed. The FDA has required new warnings in the labels of NSAIDs, including aspirin, advising against their use during pregnancy beginning at 20 weeks’ gestation because of a risk of fetal renal dysfunction that could lead to low amniotic fluid levels and neonatal renal impairment. NSAIDs can cause premature closure of the ductus arteriosus and persistent neonatal pulmonary hypertension when used after 30 weeks’ gestation.34 Metronidazole is generally considered safe for use during pregnancy. An association between metronidazole exposure in utero and development of cleft lip was observed in one case-control study, but this finding has not been replicated in numerous other observational studies and meta-analyses. 35 Tetracyclines can cause fetal harm and reversible inhibition of bone growth when taken during pregnancy. Levofloxacin also should generally be avoided during pregnancy if possible. Fluoroquinolones have caused arthropathy in animal studies, but observational data in pregnant women suggest that teratogenic effects are unlikely to occur at therapeutic doses. Rifabutin and clarithromycin are generally not recommended for use during pregnancy. Sucralfate is minimally absorbed and does not appear to be associated with adverse fetal outcomes. Misoprostol is an abortifacient and should not be used in women who are or could become pregnant.

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