"A deeper dive into data from the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS) with the type 2 diabetes drug sitagliptin (Januvia, Merck), confirming that the dipeptidyl peptidase-4 (DPP-4) is not associated with any "...
Signs And Symptoms
Nausea, vomiting, abdominal pain, pruritus, headache, and increasing lethargy will probably occur within a short time after ingestion; actual unconsciousness may occur with severe hepatic involvement. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces is proportional to amount ingested. Liver enlargement, possibly with tenderness, can develop within a few hours after severe overdosage, bilirubin levels may increase and jaundice may develop rapidly. Hepatic involvement may be more marked in patients with prior impairment of hepatic function. Other physical findings remain essentially normal. A direct effect upon the hematopoietic system, electrolyte levels, or acid-base balance is unlikely.
Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours. Nausea, vomiting, dizziness, slurring of speech, blurring of vision, visual hallucinations (including bright colors and strange designs), are among the early manifestations. With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, are to be expected, along with severe, intractable seizures. Severe metabolic acidosis, acetonuria, and hyperglycemia are typical laboratory findings.
The minimum acute lethal or toxic dose is not well established. However, nonfatal acute overdoses in adults have been reported with doses ranging from 9 to 12 gm rifampin. Fatal acute overdoses in adults have been reported with doses ranging from 14 to 60 gm. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal reports. Nonfatal overdoses in pediatric patients ages 1 to 4 years old of 100 mg/kg for one to two doses has been reported.
Untreated or inadequately treated cases of gross isoniazid overdosage can be fatal, but good response has been reported in most patients treated within the first few hours after drug ingestion. Ingested acutely, as little as 1.5 g isoniazid may cause toxicity in adults. Doses of 35 to 40 mg/kg have resulted in seizures. Ingestion of 80 to 150 mg/kg isoniazid has been associated with severe toxicity and, if untreated, significant mortality.
The airway should be secured and adequate respiratory exchange established. Only then should gastric emptying (lavage-aspiration) be attempted; this may be difficult because of seizures. Since nausea and vomiting are likely to be present, gastric lavage is probably preferable to induction of emesis.
Gastric lavage within the first 2 to 3 hours after ingestion should not be attempted until convulsions are under control. To treat convulsions, administer IV diazepam or short-acting barbiturates, and IV pyridoxine (usually 1 mg/1 mg isoniazid ingested). Activated charcoal slurry instilled into the stomach following evacuation of gastric contents can help absorb any remaining drug in the GI tract. Antiemetic medication may be required to control severe nausea and vomiting.
RAPID CONTROL OF METABOLIC ACIDOSIS IS FUNDAMENTAL TO MANAGEMENT. Intravenous sodium bicarbonate should be given at once and repeated as needed, adjusting subsequent dosage on the basis of laboratory findings (i.e., serum sodium, pH, etc.).
Forced osmotic diuresis must be started early and should be continued for some hours after clinical improvement to hasten renal clearance of drug and help prevent relapse. Fluid intake and output should be monitored.
Bile drainage may be indicated in presence of serious impairment of hepatic function lasting more than 24–48 hours. Under these circumstances and for severe cases, extracorporeal hemodialysis may be required; if this is not available, peritoneal dialysis can be used along with forced diuresis. Along with measures based on initial and repeated determination of blood gases and other laboratory tests as needed, meticulous respiratory and other intensive care should be utilized to protect against hypoxia, hypotension, aspiration, pneumonitis, etc.
Untreated or inadequately treated cases of gross isoniazid overdosage can terminate fatally, but good response has been reported in most patients brought under adequate treatment within the first few hours after drug ingestion.
RIFAMATE is contraindicated in patients with a history of hypersensitivity to rifampin or isoniazid, or any of the components, or to any of the rifamycins.
Rifampin is contraindicated in patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy and/or development of viral resistance.
Other contraindications include patients with severe hepatic damage; severe adverse reactions to isoniazid, such as drug fever, chills, and arthritis; patients with acute liver disease of any etiology; and patients with acute gout.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/15/2016
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