trandolapril and Drug-Overdose

Patients with fixed-dose combination product overdoses involving verapamil and trandolapril may present differently than sole calcium channel blocker (CCB) or angiotensin-converting enzyme inhibitor (ACE-I) overdose alone, and may have implications for the toxicological management. The ACE-I component may confound the traditional response to antidotal and supportive therapy recommended for CCB overdoses. In such cases, it may be prudent to manage the trandolapril component concurrently while administering traditional CCB antidotes.. To report a probable case and review the toxicological management of a fixed-dose antihypertensive combination product toxicity involving verapamil and trandolapril (Tarka®).. A 60-year-old man experienced dizziness and fell after ingesting five tablets of Tarka®. Eight hours later, he was found to be hypotensive and bradycardic. Therapy for CCB toxicity was initiated, including fluids, modified hyperglycemia-euglycemia insulin therapy, calcium chloride, activated charcoal, and glucagon. The patient's blood pressure and heart rate stabilized only after the administration and titration of dopamine and episodes of profuse vomiting in response to glucagon. The patient was transferred to the Cardiac Intensive Care Unit for further monitoring. He was considered stable to the point of all therapies being discontinued only 12 h post-ingestion. The patient was discharged 40 h after ingestion with no further sequelae.. Lack of familiarity with the components of fixed-dose combination products poses a problem during overdose situations and may confound the presentation and delay resuscitation and acute stabilization.

Topics: Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Overdose; Emergency Treatment; Follow-Up Studies; Humans; Hypertension; Indoles; Male; Middle Aged; Risk Assessment; Severity of Illness Index; Treatment Outcome; Verapamil

Verapamil blocks the rapid influx of calcium into the cardiac myocytes of the cardiac conduction system and smooth muscle of the vasculature, resulting in decreased myocardial contractility, prolonged conduction time, and vascular relaxation. A sustained-release form, verapamil SR (or ER), is available that contains higher levels of medication and requires only once-daily dosing. The majority of reported fatal cases of verapamil toxicity are due to massive, intentional overdoses. Herein, we present an unusual case of fatal verapamil SR toxicity in a 57-year-old female that resulted from accidental overdose of only 3 tablets (720 mg), as witnessed by the decedent's daughter. In spite of the low dose ingested, the postmortem cardiac blood verapamil level was clearly toxic (6000 ng/mL, or 6 mg/L). Her preexisting medical conditions included hypercholesterolemia, hypertension, iron deficiency anemia, diabetes mellitus, and associated mild chronic renal failure. Complicating factors, which likely include the decedent's preexisting renal and cardiac disease, and a review of the available literature will be discussed.

Topics: Accidents; Antihypertensive Agents; Calcium Channel Blockers; Drug Combinations; Drug Overdose; Female; Forensic Toxicology; Humans; Hypercholesterolemia; Hypertension; Indoles; Kidney Failure, Chronic; Middle Aged; Verapamil

Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 μg/L) and creatine kinase (219 μkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 μg/L and 57.5 μg/L, resp. (serum) and 8.15 μg/L and 602.3 μg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.

Topics: Acute Kidney Injury; Aged; Alcoholics; Anthraquinones; Anti-Inflammatory Agents; Antihypertensive Agents; Atorvastatin; Drug Overdose; Female; Forensic Toxicology; Gastrointestinal Contents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazoles; Indoles; Piperazines; Rhabdomyolysis; Suicide; Vasodilator Agents; Verapamil

Tarka® is a combination antihypertensive medication composed of verapamil hydrochloride and trandolapril. A 3.5-year-old female was brought to our hospital due to a sleepy condition 7 hours after an accidental ingestion of six tablets of Tarka® containing 240 mg verapamil hydrochloride and 4 mg trandolapril in each tablet. Five hours after hospitalization, her condition deteriorated and arterial pressure progressively decreased despite the treatment. Finally, a temporary pacemaker was implanted, after which the vital findings began to return to normal values. The pacemaker was removed 13 hours after implantation as normal heart rhythm was observed. There are no reports of intoxication with fixed-dose combination products, especially Tarka®, in young children in the literature. Therefore, we believe that our report can provide an insight on the toxic dose of this drug in younger children. Clinicians should keep in mind that lethargy can be the first symptom of a possible clinical deterioration, even in normotensive and normorhythmic individuals.

Topics: Child, Preschool; Drug Combinations; Drug Overdose; Electrocardiography; Female; Humans; Indoles; Pacemaker, Artificial; Treatment Outcome; Verapamil

The paper describes a case of suicidal poisoning with a combined hypotensive drug.. A 46-year old man ingested, with a suicidal intent, a 0.5 l of vodka and around 20 tabl. of Tarka contains 180 mg of verapamil and 2 mg of trandolapril in 1 tablet. Despite intensive supportive treatment no reperfusion was achieved, and it was necessary to amputate both legs below knees.. Acute overdoses of Tarka may be severe in spite of relatively small amounts of drug ingested by patients (from 5 to 20 tablets). In light of reports of severe ischemic complications, which seem to have thrombotic etiology, it seems advisable to employ prophylaxis with anticoagulants, especially in patients with resistant hypotension. Ischemic complications, which may result in amputation, may present long time after hemodynamic stabilization is achieved.

Topics: Amputation, Surgical; Drug Combinations; Drug Overdose; Ethanol; Humans; Indoles; Ischemia; Leg; Male; Middle Aged; Suicide, Attempted; Verapamil

Thrombotic microangiopathy (TMA) is a syndrome characterized by microangiopathic haemolytic anaemia, thrombocytopenia, and several variable signs of organ damage due to the platelet thrombi in the microcirculation. This article reports a case with TMA which developed after ingestion of a high-dose combination of verapamil and trandolapril. To the authors' knowledge, no prior cases of TMA induced by trandolapril (an angiotensin-converting enzyme inhibitor) and verapamil (a calcium channel blocker) have been reported in the literature.

Topics: Adult; Anemia, Hemolytic; Blood Cell Count; Drug Overdose; Female; Hematocrit; Hemoglobins; Humans; Indoles; Microcirculation; Thrombocytopenia; Time Factors; Verapamil