Drug Interactions between Augmentin and teriflunomide

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.

Immunosuppressive agents may increase the risk of progressive multifocal leukoencephalopathy (PML). Certain agents are contraindicated in patients who have or have had PML. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not be treated with these agents. Health care professionals should monitor patients for any new sign or symptom suggestive of PML. Therapy dosing should be withheld immediately and an appropriate diagnostic evaluation should be performed at the first sign or symptom suggestive of PML.

Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents. Patients receiving immunosuppressants are at increased risk of developing bacterial, viral, fungal, and protozoal infections, and new or reactivated viral infections including opportunistic infections. Caution should be exercised when considering their use in patients with severe or chronic infections. It is recommended to interrupt therapy in patients who develop a new infection while undergoing treatment and to monitor these patients closely for any sign or symptom indicative of infection.

The administration of amoxicillin-clavulanate has infrequently been associated with hepatotoxicity such as elevations in serum transaminases, bilirubin, and/or alkaline phosphatase. The histologic findings on liver biopsy have consisted of predominantly cholestatic and/or hepatocellular changes. Symptoms may occur during or several weeks after therapy. The hepatotoxicity is generally reversible, although deaths have been reported on rare occasions, mostly in patients with serious underlying diseases or concomitant use of other medications. Liver enzyme abnormalities have also been observed with the use of amoxicillin or ampicillin alone. According to the manufacturer, therapy with amoxicillin-clavulanate should be administered cautiously in patients with evidence of hepatic dysfunction. Periodic monitoring of liver function is recommended during prolonged therapy. The use of amoxicillin-clavulanate is contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with the drug.

Teriflunomide is contraindicated in patients with severe hepatic impairment. No dosage adjustment is necessary for patients with mild and moderate hepatic impairment. Severe liver injury including fatal liver failure have been reported in patients treated with leflunomide. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of teriflunomide with other potentially hepatotoxic drugs may increase the risk of severe liver injury. If drug-induced liver injury is suspected, discontinue therapy with teriflunomide and start an accelerated elimination procedure with cholestyramine or charcoal. Patients with preexisting liver disease may be at increased risk of developing elevated serum transaminases while on therapy with teriflunomide. It is recommended to obtain transaminase and bilirubin levels within 6 months before initiation of therapy. Monitor ALT levels at least monthly for six months after starting therapy.

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.

Peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), has been reported with the use of teriflunomide. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. Care should be taken when prescribing this agent to patients at risk and if a patient develops symptoms consistent with peripheral neuropathy, such as bilateral numbness or tingling of hands or feet, consider discontinuing teriflunomide therapy and performing an accelerated elimination procedure.

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.

Teriflunomide may increase the blood pressure. Caution should be taken when using this agent in hypertensive patients. It is recommended to check blood pressure before the start of teriflunomide treatment and periodically thereafter and elevated blood pressure should be appropriately managed during treatment with teriflunomide.

Cases of decrease in white blood cell count and in platelet count have been observed with the use teriflunomide. Care should be taken when using this agent in immunosuppressed patients. It is recommended to obtain a complete blood cell count within 6 months before the initiation of treatment and further monitoring should be based on signs and symptoms suggestive of bone marrow suppression.

Interstitial lung disease and worsening of preexisting interstitial lung disease, including acute interstitial pneumonitis, have been reported during treatment with teriflunomide. Caution should be exercised when prescribing this agent to patients with pulmonary complication. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of therapy and if discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure.

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.

Peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), has been reported with the use of teriflunomide. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. Care should be taken when prescribing this agent to patients at risk and if a patient develops symptoms consistent with peripheral neuropathy, such as bilateral numbness or tingling of hands or feet, consider discontinuing teriflunomide therapy and performing an accelerated elimination procedure.

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).

Interstitial lung disease and worsening of preexisting interstitial lung disease, including acute interstitial pneumonitis, have been reported during treatment with teriflunomide. Caution should be exercised when prescribing this agent to patients with pulmonary complication. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of therapy and if discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure.

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.

Cases of tuberculosis have been observed with the use of teriflunomide. It is recommended to screen patients for latent tuberculosis infection before initiating therapy with teriflunomide. The safety of teriflunomide in patients with a positive tuberculosis screen, and in individuals with latent tuberculosis infection is unknown. Care should be exercised and in those patients testing positive, standard medical practice treatment should be given prior to teriflunomide therapy initiation.

Cases of tuberculosis have been observed with the use of teriflunomide. It is recommended to screen patients for latent tuberculosis infection before initiating therapy with teriflunomide. The safety of teriflunomide in patients with a positive tuberculosis screen, and in individuals with latent tuberculosis infection is unknown. Care should be exercised and in those patients testing positive, standard medical practice treatment should be given prior to teriflunomide therapy initiation.

Vaccination with live vaccines is not recommended in patients treated with teriflunomide. No clinical data are available on the efficacy and safety of live vaccinations in patients taking teriflunomide. The long half-life of teriflunomide should be considered when contemplating administration of a live vaccine after stopping treatment.