Amoxicillin/omeprazole/rifabutin Disease Interactions

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Published observational studies suggest that proton pump inhibitor (PPI) use may be associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD), especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. It is recommended that patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Close monitoring is recommended in patients with diarrhea and in those taking antibacterial agents as CDAD has been reported with the use of nearly all these agents. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Patients with mononucleosis treated with an aminopenicillin antibiotic, may develop a pruritic erythematous maculopapular skin rash. The rash is usually self-limiting and resolves within days of discontinuing the offending agent. An altered drug metabolism or an immune-mediated process unrelated to drug hypersensitivity has been proposed as the underlying mechanism. Therapy with aminopenicillin antibiotics should not be administered in patients with mononucleosis.

High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using Clinitest®, Benedict's Solution or Fehling's Solution. Since this effect may also occur with amoxicillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix®) be used.

Some amoxicillin chewable tablets and suspensions products contain phenylalanine. The phenylalanine content should be considered when these products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).

Most beta-lactam antibiotics are eliminated by the kidney as unchanged drug and, in some cases, also as metabolites. The serum concentrations of beta-lactam antibiotics and their metabolites may be increased and the half-lives prolonged in patients with impaired renal function. Dosage adjustments may be necessary and modifications should be based on the degree of renal impairment as well as severity of infection in accordance with the individual product package labeling. Renal function tests should be performed periodically during prolonged and/or high-dose therapy, since nephrotoxicity and alterations in renal function have occasionally been associated with the use of these drugs.

Penicillin antibiotics (except for agents in the penicillinase-resistant class) are removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

Various published observational studies have reported that PPI therapy may be associated with an increased risk for osteoporosis related fractures of the hip, wrist or spine. The risk was increased in patients who received high doses (multiple daily doses), and long term treatment (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Caution should be used in patients at risk for osteoporosis related fractures and should be managed according to established treatment guidelines.

Symptomatic and asymptomatic hypomagnesemia has been reported rarely in patients treated with PPIs for at least 3 months, in most cases after a year of therapy. Serious adverse events can include tetany, seizures, and arrhythmias. Caution should be used in patients prone to magnesium imbalances such as patients taking other medications that can cause hypomagnesemia (e.g., diuretics). Regular monitoring is recommended.

The pharmacokinetics of rifabutin are not known in patients with moderate or severe liver dysfunction. No dosage adjustment is necessary for patients with mild liver dysfunction.

Rifabutin may be associated with neutropenia, and more rarely thrombocytopenia. Periodic hematologic studies should be considered in patients receiving prophylaxis with rifabutin, especially in patients with preexisting neutropenia and/or thrombocytopenia.

Rifabutin AUC increased by about 71% in patients with severe renal dysfunction (CrCl less than 30 mL/min) compared to patients with CrCl 61 to 74 mL/min. Patients with severe renal dysfunction should be carefully monitored for rifabutin associated adverse reactions; the dosage of rifabutin should be reduced in such patients if toxicity is suspected. No dosage adjustment is necessary for patients with mild or moderate renal dysfunction.

Rifabutin should not be given as monotherapy in patients with active tuberculosis (TB). The administration of rifabutin in the absence of appropriate antituberculosis agents may induce organisms resistant to rifabutin and rifampin. Likewise, patients must not have active TB when receiving rifabutin therapy for Mycobacterium avium complex prophylaxis or other indications where rifabutin might be used alone. Patients who develop symptoms consistent with active TB during rifabutin therapy should be evaluated promptly so that an effective antituberculosis regimen may be instituted if necessary.