A case of tubulointerstitial nephritis and uveitis syndrome after suspected drug-induced acute interstitial nephritis

Distinguishing between late-onset TINU syndrome and drug-induced AIN remains difficult given that patients with TINU syndrome may develop uveitis long after the onset of AIN. Therefore, ophthalmic examination is required not only upon diagnosis but also continuously or when eye symptoms, and relapse of urinary findings are observed.

Who gets prescriptions for proton pump inhibitors and why? A drug-utilization study with claims data in Bavaria, Germany, 2010–2018

Purpose The German annual drug prescription-report has indicated overuse of proton pump inhibitors (PPIs) for many years; however, little was known about the characteristics of people using PPIs. This study aimed to provide comprehensive utilization data and describe frequencies of potential on- and off-label PPI-indications in Bavaria, Germany. Methods Claims data of statutorily insured people from 2010 to 2018 were used. Defined daily doses (DDDs) of PPIs by type of drug, prevalence of PPI-use and DDDs prescribed per 1000 insured people/day were analyzed. For 2018, proportions of users and DDDs per 1000 insured people were calculated by age and sex. To elucidate changes in prescribing practices due to a suspected drug-drug interaction, we examined co-prescribing of clopidogrel and PPIs between 2010 and 2018. For PPI new users, sums of DDDs and frequencies of potential indications were examined. Results PPI prescribing increased linearly from 2010 to 2016 and gradually decreased from 2016 to 2018. In 2018, 14.7% of women and 12.2% of men received at least one prescription, and 64.8 DDDs (WHO-def.) per 1000 insured people/day were prescribed. Overall, omeprazole use decreased over the observation period and was steadily replaced by pantoprazole, especially when co-prescibed with clopidogrel. An on-label PPI-indication was not reported at first intake in 52.0% of new users. Conclusions The utilization of prescribed PPIs has decreased since 2016. However, a large proportion of new PPI-users had no documentation of a potential indication, and the sums of DDDs prescribed often seemed not to comply with guidelines.

Therapeutic Drug Monitoring of Carbamazepine: A 20-Year Observational Study

Background: Carbamazepine (CBZ) is a first-generation anticonvulsant drug. Hence, in certain cases, therapeutic drug monitoring (TDM) supports pharmacotherapy. Methods: The presented research was based on a retrospective analysis including 710 ambulatory and hospitalized patients treated with CBZ between the years 1991 and 2011. The method used for the determination of the CBZ concentration was fluorescence polarization immunoassay (FPIA) performed using an Abbott GmbH TDx automatic analyzer, with the therapeutic range for carbamazepine being 4–12 µg/mL. Results: The therapeutic range was observed more often in patients between 3 and 17 years of age compared with the population ≥18 years of age (73.5% vs. 68.8%). The therapeutic level was exceeded less frequently in the population between 3 and 17 years of age despite them being given a significantly higher dose per kilogram of body weight than in the population ≥18 years of age (13.64 mg/kg vs. 10.43 mg/kg, p < 0.0001). Patients ≥18 years of age were statistically significantly more likely to be in the group with a suspected drug overdose (73.9% vs. 26.1%), and suicide attempts only occurred in elderly patients (100.0% vs. 0.0%, p = 0.003). Conclusion: The results of the TDM of CBZ showed that only 71% of all samples were at the therapeutic level. To ensure the maximum efficacy and safety of the therapy, it is necessary to monitor the concentration of CBZ regardless of sex and age.

“Tineariasis” (or plaque-psoriasis induced by Terbinafine)

Terbinafine is an anti fungal drug used worldwide to treat dermatophytosis. Although generally is well tolerated, several cutaneous side effects have been described. One of them is the induction or exacerbation of psoriasis, especially the pustular type. We describe a case of plaque-psoriasis induced by terbinafine in a young patient. Skin biopsy was performed to confirm the diagnosis and the suspected drug was discontinued. Biopsy showed regular epidermal hyperplasia with parakeratoses and neutrophils in the corneal layer. No fungal elements were observed. Improvement was observed after discontinuation of terbinafine. We present a new case of the induction of plaque-psoriasis after the use of oral terbinafine and conclude that this drug should be used with caution in predisposed patients. Keywords: psoriasis; pustular posriasis; plaque-psoriasis; terbinafine

Ashwagandha-Induced Gastric Upset in Post-Covid Patient-A Case Report and Brief Review of the Literature

Adverse drug reporting of herbal drugs is less common as they are generally considered as safe. It is also very common to use self-medication by people in the case of herbal drugs. But many times, mild to severe events have been seen with the use of herbal or ayurvedic medicines. We have reported a case of post-covid patient, who was having complained of headache, body ache, lethargy, backache, generalized weakness and excessive sweating since one weak. Patient had past history of hospitalization due to COVID-19 moderate pneumonia one month back. Patient also had history of type-2 diabetes mellitus, hypertension and dyslipidemia and was taking anti-diabetic and anti-hypertensive medications continuously. Ashwagandha powder (Withania somnifera), Maha yogaraj guggulu (herbal anti-inflammatory) and Syrup Amynity Plus (herbal immune-booster) were prescribed for these complain. Conversely, moderate severity adverse reaction like nausea, vomiting, diarrhea, and abdominal cramps were noted after the intake of suspected drug i.e. ashwagandha powder. Nevertheless, symptoms were relieved after the de-challenge. This shows a temporal relation of the event with the suspected drug. One more possibility of drug-drug interaction in this case cannot be ruled out completely. Causality assessment was done for this adverse event and it was considered as the “probable” category of the adverse event in WHO causality classification.

First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin

The multidrug resistance gene MDR1 encodes for an efflux transporter called P-glycoprotein (P-gp). In the canine Mdr1 gene, a nonsense mutation was identified in certain dog breeds causing increased drug sensitivity to various P-gp substrates such as antiparasitic macrocyclic lactones. Symptoms of neurologic toxicity include ataxia, depression, salivation, tremor, apparent blindness, and mydriasis. In the current report, a Thuringian goat developed similar neurological signs after treatment with doramectin, a compound from the macrocyclic lactone class. Therefore, Mdr1 might be defective in this individual goat. For diagnostic purposes, sequencing of the complete mRNA transcript coding for caprine Mdr1 was performed to investigate a potential missense mutation. The Mdr1 transcripts of two related goats without drug sensitivity were also sequenced to allow differential diagnosis and were compared to the suspected drug-sensitive goat. The only position where the Mdr1 sequence from the suspected drug-sensitive goat differed was in the 3′-untranslated region, being a heterozygous single nucleotide polymorphism c.3875C&gt;A. It can be suspected that this variant affects the expression level, stability, or translation efficiency of the Mdr1 mRNA transcript and therefore might be associated with the suspected drug sensitivity. To clarify this, further studies are needed, particularly investigating the Mdr1 mRNA and protein expression levels from brain material of affected goats. In conclusion, Mdr1 variants may exist not only in dogs, but also in individual goats. The current report provides the first Mdr1 mRNA transcript sequence of a goat and therefore represents the basis for more detailed Mdr1 sequence and expression analyses.

Panitumumab-Associated Drug-Induced Immune Thrombocytopenia in a Patient with Colorectal Cancer

Severe thrombocytopenia is a rare adverse event of panitumumab. Here, we report the first patient with metastatic colorectal cancer who developed severe thrombocytopenia, diagnosed as panitumumab-associated drug-induced immune thrombocytopenia (DITP). A clinical diagnosis of DITP can be obtained by excluding other causes of thrombocytopenia and is confirmed by the recovery of thrombocytopenia after the discontinuation of the suspected drug. Treatment includes permanent discontinuation of the suspected drug. Re-exposure should be avoided. It should be kept in mind that panitumumab can induce DITP in the case of a new, sudden, unexpected, and isolated drop in platelet count after excluding other causes of thrombocytopenia.

Detecting medication errors associated with the use of beta-lactams in the Russian Pharmacovigilance database

Background Comprehensive analysis of all available data in spontaneous reports (SRs) can reveal previously unidentified medication errors (MEs). Methods To detect MEs, we performed a retrospective analysis of SRs submitted to the Russian pharmacovigilance database in the period from January 01, 2012, to August 01, 2014. This study evaluated SRs of cases where beta-lactam antibiotics were the suspected drug. Results A total of 3608 SRs were analyzed. MEswere detected in 1043 reports (28.9% of all cases). The total number of detected errors was 1214. Reporters themselves indicated MEs in 29 SRs. A term denoting an ME was selected in the “Adverse Reactions” section in 18 of these SRs, whereas in the other 11 reports information on the ME was found only in the “Case narrative” section. MEs were associated with wrong indications in 32.5% of the cases; 61.0% of these cases were viral infections. Various dosing regimen violations constituted 29.7% of MEs. A contraindicated drug was administered in 17.3% of all detected MEs, most commonly to a patient with a history of allergy to the suspected drug or severe hypersensitivity reactions to other drugs of the same group. Conclusion Automatic identification of MEs in the pharmacovigilance database is sometimes precluded by the absence of a code for the respective episode in the “Adverse Reactions” section, even when the error was detected by the reporter. The most frequent types of MEs associated with the use of beta-lactams in Russia are the leading risk factors of growing bacterial resistance.