Drug Interactions between Prevpac and vitaMedMD RediChew Rx

MONITOR: Coadministration with clarithromycin may increase the plasma concentrations of lansoprazole. The proposed mechanism is clarithromycin inhibition of intestinal (first-pass) and hepatic metabolism of lansoprazole via CYP450 3A4. Although lansoprazole is primarily metabolized by CYP450 2C19 in the liver, 3A4-mediated metabolism is the predominant pathway in individuals who are 2C19-deficient (approximately 3% to 5% of the Caucasian and 17% to 20% of the Asian population). Additionally, inhibition of P-glycoprotein intestinal efflux transporter by clarithromycin may also contribute to the interaction, resulting in increased bioavailability of lansoprazole. In 18 healthy volunteers--six each of homozygous extensive metabolizers (EMs), heterozygous EMs, and poor metabolizers (PMs) of CYP450 2C19--clarithromycin (400 mg orally twice a day for 6 days) increased the peak plasma concentration (Cmax) of a single 60 mg oral dose of lansoprazole by 1.47, 1.71- and 1.52-fold, respectively, and area under the concentration-time curve (AUC) by 1.55-, 1.74- and 1.80-fold, respectively, in each of these groups compared to placebo. The AUC ratio of lansoprazole to lansoprazole sulphone, which is considered an index of CYP450 3A4 activity, was significantly increased by clarithromycin in all three groups. However, elimination half-life of lansoprazole was prolonged by 1.54-fold only in PMs. Mild diarrhea was reported in two subjects and mild abdominal disturbance in six subjects during clarithromycin coadministration. These side effects continued until day 6 and ameliorated the day after discontinuation of clarithromycin, whereas no adverse events were reported during placebo administration or after lansoprazole plus placebo. In another study, clarithromycin induced dose-dependent increases in the plasma concentration of lansoprazole in a group of 20 patients receiving treatment for H. pylori eradication. Mean 3-hour plasma lansoprazole concentration was 385 ng/mL for the control subjects who received lansoprazole 30 mg and amoxicillin 750 mg twice a day for 7 days; 696 ng/mL for patients coadministered clarithromycin 200 mg twice a day; and 947 ng/mL for patients coadministered clarithromycin 400 mg twice a day.

MANAGEMENT: Although lansoprazole is generally well tolerated, caution may be advised during coadministration with clarithromycin, particularly if higher dosages of one or both drugs are used. Dosage adjustment may be necessary in patients who experience excessive adverse effects of lansoprazole.

Switch to consumer interaction data

MONITOR: Inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may impair the gastrointestinal absorption of nonheme iron, a process that is dependent on an acidic environment. The interaction was suspected in two patients with iron deficiency anemia due to gastrointestinal blood loss that were unresponsive to oral iron replacement therapy, even after the bleeding had apparently stopped. Both patients had been on omeprazole for six months while being treated with ferrous sulfate. An iron-loading test was performed on one of the patients and indicated iron malabsorption. Within two months after discontinuation of omeprazole, notable improvements in hemoglobin level and mean corpuscular volume (MCV) were observed in both patients, and iron absorption was significantly increased in the patient who underwent absorption testing. In a case review of patients with hereditary hemochromatosis treated at one institution, investigators observed a reduced requirement for maintenance phlebotomy in seven patients following initiation of PPI therapy (mean 2.5 L blood removed/year before PPI therapy vs. 0.5 L/year during PPI therapy), presumably due to reduced tissue iron accumulation stemming from impaired absorption of dietary nonheme iron. Mean annual phlebotomy requirement during PPI therapy in these patients was also lower than that in controls who had never taken a PPI (mean 2.3 L blood removed/year). The same group of investigators also studied iron absorption in 14 patients fed an iron-loaded meal before and after PPI therapy for one week. PPI therapy was associated with a 51% reduction in area under the serum iron concentration-time curve (AUC 0 to 4 hours); a 55% reduction in maximum increase of serum iron following ingestion of iron-loaded meal; and a 46% reduction in percent recovery of administered iron at peak serum iron concentration. Interestingly, the interaction has not been reported in healthy, iron-replete individuals. In a study of 109 patients with Zollinger-Ellison syndrome who had not undergone gastric resection, omeprazole treatment for an average of 5.7 years did not significantly decrease body iron stores or cause iron deficiency compared to H2-receptor antagonist therapy or no gastric acid-suppressant treatment. It is possible that the interaction may not affect people with healthy iron stores because of compensation by dietary heme iron, which typically comprises only a small fraction of dietary iron but whose absorption is not dependent on gastrointestinal pH. In contrast, dietary heme iron alone may not be sufficient to restore normal iron balance in patients with anemia or those with defective regulatory mechanisms of iron absorption.

MANAGEMENT: Patients with iron deficiency may not respond adequately to oral iron replacement therapy during coadministration of PPIs or PCABs. If an interaction is suspected after ruling out other causes, it may be appropriate to discontinue the PPI or PCAB or consider administering iron parenterally.

Switch to consumer interaction data

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Switch to consumer interaction data