Near Fatal Poisoning by Isoniazid and Rifampicin.

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.

Fatal suicidal poisoning with antituberculosis agents with ST elevation and acute coronary syndrome symptoms--a case report.

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.

Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

BACKGROUND: Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. CASE PRESENTATION: A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had acute liver injury subsequently which gradually improved with supportive care. Her liver functions found to be completely normal 1 week after the discharge. CONCLUSIONS: Poisoning with fixed drug combination of isoniazid and rifampicin tablets is rare but can cause severe morbidity and mortality if not treated promptly. Oral pyridoxine can substitute for intravenous pyridoxine with almost similar efficacy at a low cost in managing patients with acute severe standard isoniazid poisoning in resource poor setting.

[Clinical presentation of ST-elevation acute coronary syndrome in the course of intoxication with megadose of rifampicin. A case report]. / Obraz ostrego zespolu wiencowego z uniesieniem odcinka ST w przebiegu zatrucia megadawka rifampicyny. Opis przypadku.

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.

Combined dapsone and clofazimine intoxication.

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.

Red/orange person syndrome.

We present a case of a patient whose skin turned orange overnight. The patient had tried to commit suicide by taking approximately forty 300 mg rifampicin capsules. Her case served as a stimulus for us to review the literature. Photographs taken during the initial work-up recorded the changes; her normal skin color returned within twenty-four hours, although her urine and tears remained orange for several days.

[Fatal rifampicin poisoning. Apropos of a case]. / Intoxication mortelle par la rifampicine. A propos d'une observation.

Successful suicide attempts by rifampicin are not commonly reported in literature. Fatal cases and mechanisms of death are most of the time unexplained. We report a suicidal case in a 33-aged man with fatal course occurring 27 hours after acute overdosage with 15 g rifampicin. Criterias of prognostic value are discussed: clinical signs in particular the redman syndrome, and biological data. None of them allows us to prevent fatal issue but, since cardiac arrest of unknown origin may rapidly occur, admission in intensive care must be carried out promptly with a total dose absorbed of 12 g and/or evident clinical signs.

[Acute renal failure, intravascular hemolysis and toxic hepatitis caused by repeated use of rifampicin (case report)]. / Akutno bubrezno zatajenje, intravaskularna hemoliza i toksicni hepatitis uzrokovani opetovanim uzimanjem rifampicina (prikaz bolesnika).

We report the case of a 57-year-old man treated with interrupted rifampicin therapy for urinary tract tuberculosis who experienced acute renal failure, intravascular hemolysis and toxic hepatitis. This combined adverse reactions are rare. Supportive treatment with dialysis and withdrawal of rifampicin result with complete recovery. Interrupted and intermittent therapy with rifampicin should be avoided and noncompliant patients should be given alternative treatment when possible.

A review of the Redman syndrome and rifampicin overdosage.

The literature was reviewed for cases of cutaneous pigmentation induced by rifampicin overdosage. 29 examples have been described, in which 2 general groups of individuals were observed. The first consisted of older individuals (average age 27.1 years) who attempted suicide. A prior history of suicide attempts, depression and substance abuse was a predominant factor in these patients. The second group included generally younger patients (average age 2.9 years) in whom misformulation of rifampicin preparations for treatment of Haemophilus influenzae Type B resulted in bright reddish-orange discoloration to the skin. The time to clinical appearance of skin discoloration was approximately 2.2 hours after administration. Periorbital or facial oedema occurred in 72.4% of the patients, pruritus in 62.1% and either nausea, vomiting or diffuse abdominal tenderness in 51.7%. Limited laboratory data are available but these indicate that all patients had elevated levels of total bilirubin. Histological examination in selected individuals revealed rifampicin crystal deposits in the nasopharynx, gastrointestinal tract and lining of the aorta. In adults, it appears that a dose of at least 14 g of rifampicin is necessary before cardiovascular-pulmonary arrest occurs. Other than general supportive measures, very few methods are described in the literature for the treatment of acute intoxications with this drug. A differential diagnosis of other causes of reddish-orange pigmentation is discussed, together with clinical information to differentiate these cases from toxic rifampicin ingestion.

Red child syndrome.

An acute overdose of rifampicin in an 18 month old white infant is described. The characteristic signs of the syndrome: orange-red discolouration of the skin, urine, and tears, facial pruritus, and periorbital oedema were present and the outcome was uneventful. Paediatricians should be aware of this peculiar yet easily identifiable syndrome.

A case of fatal poisoning by rifampicin.

The toxicologic findings of a fatal poisoning with rifampicin (Rimactan) are presented. The concentration of rifampicin and its two major metabolites 25-desacetylrifampicin and 3-formylrifamycin in post-mortem blood, urine, bile and liver at about 10 h after ingestion of 14-15 g was determined using a high-performance liquid chromatographic method. The results of the toxicological analyses were compared with findings in fatal and non-fatal intoxications and after therapeutic administration of the drug. Possible explanation for the fatal outcome is given.