Drug Safety - Case Reports最新文献

Tyrosine kinase inhibitors have revolutionized the chemotherapy arena as targeted therapies for a multitude of malignancies. They are more selective than conventional chemotherapy, and often elicit fewer systemic adverse events, however toxicities still exist. Cutaneous toxicities are common and their management presents a novel challenge to physicians and patients. Ponatinib is a third-generation tyrosine kinase inhibitor increasingly reported to cause cutaneous eruption. A 50-year-old woman with a history of chronic myelogenous leukemia presented with a 4-month history of worsening atrophic and ichthyosiform pink plaques involving the axillae, thighs and abdomen; red patches were also observed on the cheeks and forehead. She was started on the third-generation, ponatinib, 5 months earlier because of disease refractory to previous therapies including interferon, imatinib, dasatinib and bosutinib. A skin biopsy revealed perifollicular fibrosis, alternating orthokeratosis and parakeratosis, and a sparse perivascular lymphocytic infiltrate consistent with a pityriasis rubra pilaris-like reaction. Topical tretinoin 0.025% cream was initiated, resulting in resolution within 3 weeks without discontinuation of ponatinib. A review of previous reports identified significant similarities among the ponatinib-induced drug reactions. Here, we highlight not only that cutaneous eruptions occur on ponatinib therapy, but that the dermatologic manifestations are characteristic and unique, and benefit from retinoid therapy, without requiring interruption of vital chemotherapy.

Our case describes a 77-year-old, African American male who was experiencing recurrent hypoglycemic episodes, which resulted in two emergency department (ED) visits and a subsequent inpatient admission during his second ED visit. He was prescribed linezolid 600 mg twice daily for 14 days for the treatment of a Staphylococcus hominis urinary tract infection. Nine and a half days into therapy, the patient began having recurrent hypoglycemic episodes. These episodes persisted despite repeated intravenous dextrose boluses. The patient's linezolid was discontinued during the second day of his inpatient admission. After a brief lag period after the final linezolid administration, the patient's blood glucose level stabilized within normal limits. He was later discharged home. The Naranjo scale scores the causality of this reaction between 4 and 8, indicating possible to probable causality. The patient had a follow-up appointment with his primary care physician 2 weeks after discharge, with no noted blood glucose complications. Two months after discharge, he entered hospice care for his advancing heart failure and later expired due to causes unrelated to blood glucose complications.

A 66-year-old Caucasian male became unconscious 2 weeks after initiation of add-on therapy with empagliflozin for poorly controlled type 2 diabetes mellitus. The inpatient had recently suffered focal pontine stroke, rendering him bedridden and requiring increased nursing care, including assistance with drinking. The patient had received empagliflozin 10 mg once daily for glycaemic control. Investigations revealed hypernatraemia (164 mmol/l), a urine glucose level of 3935 mg/dl, and a creatinine level of 2.1 mg/dl. The patient was diagnosed with severe hypernatraemic dehydration due to iatrogenic glucosuria and prerenal kidney failure. Empagliflozin was discontinued and the patient received hypotonic fluids (including 5% dextrose and free water). Over the following 4 days, glucosuria subsided, blood sodium levels and kidney function normalized and the patient regained full consciousness. He was discharged for rehabilitation 40 days after admission. A Naranjo assessment score of 6 was obtained, indicating a probable relationship between the patient's hypernatraemic dehydration and administration of empagliflozin. In this care-dependent inpatient, who lost the ability to replace water loss autonomously because of a stroke, continuous administration of empagliflozin caused persistent glucosuria and contributed to progressive volume depletion. Excessive dehydration resulted from ignorance of both the populations that are susceptible to dehydration under sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy and the drug's mechanism of action. In patients who depend on support from others in daily tasks, including fluid intake, patients with an impaired sense of thirst and those who have lost the ability to communicate thirst, SGLT2 inhibitor therapy should not be initiated or might be (temporarily) discontinued.

Chronic lymphocytic leukemia is a lymphoproliferative disorder characterized by a gradual accumulation of neoplastic B-lymphocytes. Ibrutinib is a novel therapy for chronic lymphocytic leukemia. Ibrutinib therapy has been associated with nail plate abnormalities. Other common cutaneous adverse events caused by ibrutinib appear to be bruising, hair changes, pruritus, and rashes. We describe the clinical features of two patients with chronic lymphocytic leukemia: a 79-year-old woman and a 53-year-old man who developed nail plate abnormalities approximately 6 and 4 months, respectively, after beginning ibrutinib therapy. We also review the characteristics of other patients with chronic lymphocytic leukemia with ibrutinib-associated nail plate abnormalities. The PubMed database was used to search the following terms: abnormal, abnormalities, adverse, brittle, chronic, cutaneous, dystrophy, events, effects, ibrutinib, lymphocytic, leukemia, nail, plate, and side. The relevant referenced papers generated by the search were reviewed. In conclusion, ibrutinib is used to treat chronic lymphocytic leukemia. It is usually well-tolerated. Many patients receiving ibrutinib will develop nail plate abnormalities. This adverse event is not a drug-limiting toxicity.

Page 3, Table 2, 'Renal function indexes at different dates after admission': The cell entry in column 2, detailing the patient's urea concentration (μmol/L) on Day 1.

In this report we address an unusual adverse effect of finasteride (Propecia 1 mg tablets) that was associated with painless hematuria and hematospermia in a 38-year-old healthy male during treatment of androgenic alopecia at a dose of 1 mg/day. It was found that the bleeding was linked to finasteride use as it occurred 2-3 days after use and stopped upon discontinuation of the drug. The patient was subjected to urological examination, laboratory investigations, and radiological imaging to identify the probable cause of bleeding. It appeared the bleeding was most probably of prostatic origin in the absence of obvious underlying pathology. The frequency of such unusual bleeding remains to be investigated in large clinical trials to address its exact mechanism, predisposing factors, clinical significance, and potential long-term consequences.

International guidelines consider quetiapine at medium doses (300-400 mg/day) as valid options for the treatment of bipolar depression for the supposed lower risk of a switch to hypomania/mania than antidepressants. Norquetiapine is an active metabolite with antidepressant action. We describe three cases of induced hypomania in bipolar type 2 subjects who received quetiapine extended-release monotherapy (300 mg/day) for a mild/moderate major depressive episode. Quetiapine and norquetiapine plasma concentrations were measured after 1 week of treatment. Hypomania appeared after 7-10 days of quetiapine extended-release monotherapy and all subjects had a quetiapine/norquetiapine plasma concentration ratio <1. We propose a ratio value <1 as a predictor of risk for a switch to hypomania in bipolar depressed subjects receiving quetiapine extended-release monotherapy. Future research should ascertain the validity of this laboratory parameter to assess the risk of quetiapine-induced hypomania in large samples of bipolar patients.

Spontaneous hemothorax due to anticoagulant use is extremely rare in clinical practice. Dabigatran is a novel anticoagulant to prevent stroke or thromboembolic episodes in patients with nonvalvular atrial fibrillation. We report on an 83-year-old man who received dabigatran therapy (110 mg twice daily) for 7 months and developed massive spontaneous hemothorax and acute renal failure. The patient was admitted to the hospital with complaint of a dull ache in the chest and dyspnea. Chest computed tomography scan revealed massive pleural effusion in the left hemithorax with atelectasis. Acute renal failure was observed 4 days later after admission. Almost 2500 mL of blood was repeatedly drained by ultrasound-guided thoracocentesis, followed by a dramatic decrease in serum red blood cell count, hemoglobin and hematocrit. After excluding other possible causes, diagnostic withdrawal was performed for dabigatran, and plasma transfusion was conducted to supply the lost blood volume. A causal relationship was established, because the patient's renal function gradually improved and no further pleural effusion developed after dabigatran was discontinued. This is a rare case report of massive spontaneous hemothorax caused by dabigatran. Therefore, practitioners should be aware of hemothorax as a potential complication of dabigatran therapy.

This article, which encourages physicians to publish case reports of adverse drug reactions (ADRs), is a review of how well-documented published case reports have contributed to promoting public safety and health and thus served to advance basic pharmacology. The origin of a number of regulatory guidelines can ultimately be traced to safety concerns triggered by such reports. It illustrates how case reports of ADRs, when coupled with simultaneous monitoring of drug pharmacokinetics, have also led to further investigations resulting in major advances in pharmacology, especially pharmacogenetics, mechanisms of drug-drug interactions and modulation of drug metabolism during inflammatory co-morbidities. Published case reports differ significantly from spontaneous case reports since they enjoy quality-compliant peer review and an immediate wider visibility among the readership, triggering others to report similar cases, and ultimately leading to prescribing restrictions on or withdrawals of the drug from the market depending on the risk. Therefore, the reporter should not be discouraged by (a) the unusual or bizarre nature of the reaction; (b) the interval, however long, from commencing drug administration to the onset of the suspected reaction; (c) however well-known the drug or the period for which it has been on the market; and (d) any pressure not to publish. Case reports should be published in reputable journals that are searchable through databases such as PubMed.