What is already known about this subject
• In several case reports the use of omeprazole has been associated with interstitial nephritis.
• Recently there have been reports linking other proton pump inhibitors (PPIs) with interstitial nephritis.
What this study adds
• We present supplementary cases received by the Netherlands Pharmacovigilance Centre Lareb, concerning interstitial nephritis in users of PPIs including omeprazole, pantoprazole and rabeprazole.
• In this case series seven patients are presented. In six cases they recovered spontaneously after cessation of the PPI, in one case the patient recovered after treatment with a corticosteroid.
• Further support for this association comes from the worldwide adverse drug reaction database of the World Health Organization.
• This report shows that interstitial nephritis can occur with all PPIs. Health professionals should be aware of this potential serious adverse drug reaction.
Aim
To investigate the association between the use of proton pump inhibitors (PPIs) and acute interstitial nephritis (AIN).
Methods
The Netherlands Pharmacovigilance Centre Lareb received seven case reports of AIN induced by various PPIs. In five of the reports it was mentioned that the diagnosis was confirmed by a renal biopsy.
Results
The time to onset varied between hours to 4 months. In all cases but one the patient spontaneously recovered after withdrawal of the offending agent. In one case the patient received treatment with prednisolone and recovered. In one patient a rechallenge was done 9 days after the initial event. Within 12 h of re‐exposure the patient developed symptoms of AIN.
Conclusions
The mechanism of drug‐induced AIN is unknown, but an immunological mechanism is suspected. Our reports show no relation between dosage, latency, time to recovery, age or gender, supporting the hypothesis that the aetiology of AIN is immunological. Lareb has received reports of AIN with the use of omeprazole, pantoprazole and rabeprazole. This shows that AIN is a complication associated with the whole group of PPIs and not only omeprazole. It is important for health professionals to be aware of this adverse drug reaction, because an accurate and timely diagnosis and withdrawal of the offending drug can prevent potentially life‐threatening renal failure.
Severe psychosis in patients with Cushing's syndrome is rare and generally difficult to treat. We report a 46-yr-old woman suffering from Cushing's syndrome caused by an inoperable ACTH-producing lung carcinoma. She was initially treated with chemotherapy and radiotherapy. Six months later she presented with severe psychosis. Laboratory findings revealed a severe hypokalemia and metabolic alkalosis, which was caused by extremely high serum ACTH (788 ng/l) and cortisol (4.2 micromol/l). She was unresponsive to treatment with conventional antipsychotic drugs; she was therefore sedated and intubated. Treatment was started i.v. with etomidate, which blocks the cortisol synthesis, and orally by nasogastric tube with mifepristone, which competes with cortisol for binding to their receptors. To counteract adrenal insufficiency, she received corticosteroids. After 5 days there was a normalization of the ACTH, cortisol levels, and the metabolic disorders. After discontinuing etomidate she was extubated; there were no signs of psychosis observed. Computed tomography (CT) scan of the brain showed no metastasis, however CT scan of the abdomen showed liver metastasis and bilateral adrenal enlargement. Unfortunately, the clinical situation worsened and the patient died due to progression of the metastasis. This case report demonstrates the efficacy of a treatment of mifepristone with etomidate in a patient with an ectopic ACTH-producing Cushing's syndrome.
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