rifampin and Drug-Overdose

Determining the optimal dosages of isoniazid, rifampicin, pyrazinamide and ethambutol in children is necessary to obtain therapeutic serum concentrations of these drugs. Revised dosages have improved the exposure of 1st line anti-tubercular drugs to some extent; there is still scope for modification of the dosages to achieve exposures which can lead to favourable outcome of the disease. High dose of rifampicin is being investigated in clinical trials in adults with some benefit; studies are required in children. Inter-individual pharmacokinetic variability and the effect of age, nutritional status, Human immunodeficiency virus (HIV) infection, acetylator genotype may need to be accounted for in striving for the dosages best suited for an individual.

Topics: Age Factors; Antitubercular Agents; Child; Drug Overdose; Ethambutol; Food; Genotype; HIV Infections; Humans; Isoniazid; Malnutrition; Nutritional Status; Polymorphism, Genetic; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis

In clinical toxicology, gastric endoscopic decontamination is rarely used, and only a few cases of pharmacobezoar removal after intentional ingestion of slow-release drugs have been described. Our case describes the use of gastric endoscopic decontamination to remove potential pharmacobezoar in an adolescent after ingestion of a lethal dose of isoniazid and rifampin, even long after gastric lavage. This technique allowed the removal of pharmacobezoars still present in the stomach while preventing further deterioration of the patient.

Topics: Adolescent; Drug Overdose; Gastric Lavage; Humans; Isoniazid; Rifampin; Stomach

Since six decades, Isoniazid and Rifampicin are used as first line drugs for treatment of tuberculosis. The minimum acute lethal or toxic dose of Rifampicin is not well established. However, non-fatal acute overdoses in adults have been reported with doses ranging from 9 to 12 gm and fatal acute overdoses with doses ranging from 14 to 60 gm. Isoniazid, if acutely ingested, even 1.5 to 2 gram may cause toxicity in adults. We report a case of Pott's spine on ATT, who took massive overdose of Rifampicin (>18 gm) and Isoniazid (>12 gm) and reported late (almost 36 hours) after ingestion. He was treated successfully with pyridoxine, hemodialysis and supportive care.

Topics: Adult; Antitubercular Agents; Drug Overdose; Humans; Isoniazid; Male; Rifampin; Severity of Illness Index; Tuberculosis, Spinal

A 19-years old, previously healthy male, ingested the higher amount of rifampicin, isoniazyd, pyrazinamide, ketoprofene and alcohol. Within less than 20 hours he developed dyspnoe, pruritus, red man syndrome, and ECG changes suggesting acute coronary syndrome appeared - ST interval elevation. In the next few hours chest pain appeared and troponin I concentration was elevated (13.54 ng/ml). The performed echocardiography revealed global hypokinesis with the decreased left ventricular ejection fraction (approx. 30%). There was no significant pathological changes in coronarography, except for slowed blood flow. Further patient developed cardiogenic shock, pulmonary oedema and died within 32 hours from medication overdose.

Topics: Acute Coronary Syndrome; Antitubercular Agents; Drug Overdose; Echocardiography; Ethanol; Fatal Outcome; Humans; Isoniazid; Ketoprofen; Male; Pyrazinamide; Rifampin; Shock, Cardiogenic; Suicide; Young Adult

A 14-year-old girl was inadvertently immunised with an excessively large dose of BCG-Connaught vaccine (1.0 ml instead of 0.1 ml). Examination of the patient a few hours later revealed a subcutaneous fluctuant tender lump at the injection site. This was surgically excised within 12h of immunisation and she was treated with isoniazid and rifampicin for six weeks. The patient developed no complications, other than a minor surgical scar. This case highlights the importance of the correct administration and dosing of BCG vaccine and suggests a management option that may prevent the severe local and systemic complications that are frequently associated with BCG overdose.

Topics: Adolescent; Antitubercular Agents; BCG Vaccine; Dermatologic Surgical Procedures; Drug Overdose; Female; Humans; Isoniazid; Rifampin; Skin

We report here the successful treatment of a 16-year-old female who ingested 20 tablets of digoxin each containing 0.25 mg (total dose ingested equivalent to 0.1 mg/kg), 32 tablets of warfarin each containing 5mg (equivalent to 3.2 mg/kg), and approximately 15 tablets of propafenone each containing 300 mg (equivalent to 90 mg/kg). The patient developed hypotension and sinus bradycardia necessitating external cardiac pacing 17 hours after drug ingestion. In addition to gastric lavage, activated charcoal, blood alkalinisation, administration of vitamin K and temporary cardiac pacing, the authors performed plasma exchange for drug removal and administered rifampicin in order to increase the metabolism of digoxin, propafenone and warfarin. The patient was discharged without any sequelae. Plasma exchange may be lifesaving in drug ingestions where there is a low volume of distribution and high plasma protein binding. Rifampicin, an inducer of cytochrome p450, may be used in intoxications for elimination of drugs with inactive metabolites.

Topics: Adolescent; Anti-Arrhythmia Agents; Anticoagulants; Bradycardia; Cytochrome P-450 Enzyme System; Digoxin; Drug Overdose; Enzyme Induction; Female; Humans; Hypotension; Plasma Exchange; Propafenone; Rifampin; Warfarin

We present a case of 29-year-old male, with coronary artery disease in mother's history, after suicidal poisoning with 30 g of rifampicin, who presented severe chest pain, ST elevations in ECG, low values of blood pressure and elevated troponin I. Echocardiography revealed generalised hypokinesia, and depressed contractility--left ventricle ejection fraction was 7%. Urgent coronary angiography has shown normal epicardial arteries with slow contrast inflow. The toxic properties of rifampicin as well as hypotension due to dehydration are considered reasons of symptoms in the presented case.

Topics: Acute Disease; Adult; Angina, Unstable; Cardiac Output, Low; Chest Pain; Coronary Angiography; Diagnosis, Differential; Drug Overdose; Electrocardiography; Humans; Male; Rifampin; Suicide, Attempted; Treatment Outcome; Troponin I

Topics: Adolescent; Antibiotics, Antitubercular; Antitubercular Agents; Disease-Free Survival; Drug Overdose; Female; Humans; Isoniazid; Rifampin; Suicide, Attempted; Syndrome

We report clinical findings and pharmacokinetic data regarding a combined dapsone and clofazimine intoxication in a man, who ingested 50 tablets of dapsone (100 mg) 20 capsules of clofazimine (100 mg) and two tablets of rifampicin (600 mg). Oral administration of activated charcoal (50 grams) and sodium sulphate (20 grams) after gastric lavage resulted in an elimination half-life in plasma of 11.1 and 10.8 h for dapsone and its main metabolite, monoacetyldapsone, respectively. A rapid initial decrease of the plasma concentration of clofazimine was observed after gastric lavage and administration of activated charcoal and sodium sulphate. 15 h after this treatment, clofazimine plasma levels remained relatively constant. Dapsone-induced methaemoglobinaemia (48% at admission) was treated successfully with methylene blue.

Topics: Adult; Charcoal; Clofazimine; Dapsone; Drug Overdose; Gastric Lavage; Humans; Leprostatic Agents; Male; Methemoglobinemia; Methylene Blue; Rifampin; Suicide, Attempted; Sulfates

We report three patients who experienced hepatotoxic reactions in association with acetaminophen ingestion while undergoing treatment for active tuberculosis with isoniazid, rifampin, and other agents. All were young adult women. One patient intentionally took a large amount of acetaminophen and had typical signs and symptoms of acetaminophen overdosage; another took acetaminophen in combination form for a minor upper respiratory illness. She experienced no symptoms. The remaining patient took acetaminophen to ameliorate the symptoms of fever and malaise that were subsequently attributed to tuberculosis. She had the rapid onset of signs and symptoms of isoniazid hepatotoxicity. The patterns of liver function abnormalities were similar: each patient experienced pronounced serum elevations of hepatocellular enzymes with at most only modest rises in those of bilirubin. All antituberculous drugs were withheld until symptoms resolved and laboratory values became normal; then treatment for tuberculosis was resumed without isoniazid and was successfully completed in all three patients. These cases plus similar reports in the literature suggest that isoniazid or rifampin, or both, may potentiate the hepatotoxicity of acetaminophen, perhaps by induction of cytochrome P450 isozymes that oxidize acetaminophen to its toxic metabolites.

Topics: Acetaminophen; Adult; Capreomycin; Ciprofloxacin; Drug Combinations; Drug Overdose; Ethambutol; Female; Humans; Isoniazid; Liver; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary