mycophenolic-acid and Drug-Overdose

Literature regarding acute human toxicity of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) is limited.. Our objectives were to describe all cases of overdose with MMF or EC-MPS reported to the Swiss Toxicological Information Centre (STIC) or in the literature between 1995 and 2013. Therefore, we performed an observational case-series and systematic literature search to determine circumstances, magnitude, management and outcome of overdose with MMF or EC-MPS.. Of 152,762 reports to STIC, 15 (7 pediatric) involved overdose with MMF (n = 13) or EC-MPS (n = 2). Three cases from other centers were identified from a systematic literature search. The magnitude of overdose ranged from 1.2 to 16.7 (median 2.9) times usual dose. Six (33%) MMF overdoses had attributable symptoms, which included abdominal pain, vomiting, headache and dizziness. The majority of findings were minor, although a 9-fold MMF overdose caused hypotension 8 h after ingestion and a 12.5-fold overdose caused leukopenia after 5 days. Symptoms did not occur in patients who took 2.5 times or less of their usual MMF dose. Gastrointestinal decontamination measures with activated charcoal were undertaken in one-third of cases.. Acute MMF and EC-MPS overdoses had a favorable outcome in all cases reported to STIC and in the literature.

Topics: Adolescent; Adult; Antidotes; Charcoal; Child; Child, Preschool; Drug Overdose; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Treatment Outcome; Young Adult

To discuss the significance of the recent observational case series from the Swiss Toxicological Information Centre (STIC). Mycophenolic acid (MPA) and its prodrug mycophenolate mofetil are immunosuppressive agents that are frequently prescribed in renal transplant recipients, and their safety profiles must be established.. This case series and systemic literature analysis consists of 15 cases of MPA overdose from the STIC and a systemic analysis of the literature over the past 18 years. This study focuses on acute overdosing, the effects of which are presumably mild. In contrast, the effects of long-term overdosing may be much more severe. Substantial underreporting is likely. The pharmacokinetic monitoring of MPA is rarely performed, which is both striking and does not coincide with findings in academic literature. The scant data on pharmacokinetic monitoring presented demonstrated that MPA has a short terminal half-life, which suggests that decontamination and activated charcoal treatment in acute overdose may not be necessary.. The case series and systematic literature analysis of acute mycophenolate overdose represent an important contribution toward increasing the safety of MPA therapy.

Topics: Drug Overdose; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid

Enteric-coated mycophenolate sodium (EC-MPS) has a mean half-life of 11.7 hours, which encouraged hope of using this drug once daily in a nonadherent adolescent SLE patient. This is a case report on a 17-year-old adolescent with a history of noncompliance who was switched from twice-daily mycophenolate mofetil (MMF) to once-daily EC-MPS. The EC-MPS dose was equimolar to the daily MMF dose (1 g MMF BID and 1.44 g of EC-MPS OD). The active compound of both drugs, mycophenolic acid, was measured using a commercially available EMIT assay. Both drugs were well-tolerated and maintained remission of the SLE. The average of three 12-hour areas under the time-concentration curves (AUC) on 1 g of MMF BID was 59.0 mgxh/L. In contrast, the 24-hour AUC after 1.44 g EC-MPS OD was 283.2 mgxh/L, more than double the expected 118.0 mgxh/L of two MMF dosing intervals. A repeat 24-hour AUC after 1.08 g of EC-MPS was 218.2 mgxh/L. EC-MPS once daily may be a well-tolerated therapeutic option for nonadherent adolescent lupus patients, but may be associated with a significantly higher exposure than the equivalent MMF BID dose.

Topics: Adolescent; Drug Administration Schedule; Drug Overdose; Female; Humans; Lupus Erythematosus, Systemic; Mycophenolic Acid; Tablets, Enteric-Coated

Mycophenolate mofetil is an immunosuppressive drug used for prevention of graft rejection following solid organ transplant and for treatment of autoimmune disorders. We report a case of a 24-year-old female with lupus nephritis that presented following ingestion of 10 grams of mycophenolate in a suicide gesture. Serum levels confirmed ingestion. The patient was treated with decontamination and supportive care and recovered with no adverse effect.

Topics: Adult; Antidotes; Blood Cell Count; Charcoal; Drug Overdose; Female; Hemodynamics; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Suicide, Attempted