Inh metabolism has been thought to be associated with inhinduced liver injury. Isoniazid is almost completely absorbed from the gastrointestinal tract and penetrates all body fluid cavities, in which drug levels are similar to serum. It is believed that the toxicity may have resulted from a previously unrecognized interaction between isoniazid and acetaminophen and a molecular basis for this interaction has been proposed. Exclusive and selective toxicity enhancing effects have been detected for isoniazid inh which could be related to certain substituent effects of the 1,4dhps. People taking isoniazid and acetaminophen are at risk of acetaminophen toxicity. Isoniazid syrup fda prescribing information, side effects. The related drug information index provides comprehensive access to all drug information related to a specific drug types of content include full prescribing information, drug summaries, full prescribing information continuing medication education full pi cme, medication guides, risk evaluation and mitigation strategies rems summaries, rems continuing medication education rems cme, and. Chemotherapy of mycobacterium tuberculosis infections in mice. Oral, category 4 skin corrosionirritation, category 2. One dose of plg microparticles cleared bacteria more effectively from lungs and liver in an experimental murine. Sixteen patients 10% were unable to complete the therapy, 12 of these because of symptomatic reactions. Acetaminophen, isoniazid, and hepatic toxicity annals of. Pharmacokinetic characteristics of inh are presented.
Earlier studies were selected for their historical value and relevance to the clinical setting. Symptoms suggestive of liver toxicity include nausea, vomiting, abdominal pain, dark urine, right upper quadrant pain, and loss of appetite. Hepatotoxicity of antituberculosis therapy american thoracic society. A large portion of the worlds population is infected with tb. A higher level of free inh might be the cause of the high incidence of liver injury directly as inh can bind to liver proteins and cause.
We present two cases of acute isoniazid poisoning in patients who ingested 7. The authors surmised that isoniazid was not a metabolic antagonist of pyridoxine but that it combined with it to form a hydrazone that was excreted in the urine. Use of isoniazid for latent tuberculosis infection in a public health clinic. Severe isoniazid associated liver injuries among persons being treated for latent tuberculosis infection united states, 20042008. Isoniazid therapy is often associated with minor, transient and asymptomatic elevations in serum aminotransferase levels but, more importantly, isoniazid is a well known cause of acute clinically apparent liver injury which can be severe and is sometimes fatal. Early signs of toxicity include nausea, vomiting, slurred speech, diziness, mydriasis, tachycardia followed by recurrent seizures, severe metabolic acidosis and coma. A high dose of isoniazid disturbs endobiotic homeostasis in mouse. Pyridoxine and the isoniazidinduced neuropathy diseases of. Pyridoxine and the isoniazidinduced neuropathy diseases.
Although the disease is inactive in the majority, up to 10 percent of these persons may become infectious in their lifetime. Isoniazid has a boxed warning for severe and sometimes fatal hepatitis, which is agedependent at a rate of 0. Inh induces a state of functional pyridoxine deficiency by at least two mechanisms. Acetyl isoniazid free isoniazid and and metabolites hydrazone conjugates. Peripheral neuropathy is a rare adverse effect associated with isoniazid, and it occurs after the prolonged use of this drug 1. Acute ingestion of over 20 mgkg can cause convulsions. Chronic isoniazid toxicity produces nausea, vomiting, restlessness, fever and many. This product also contains as inactive ingredients. You may need to take other tb medicines in combination with isoniazid. Isoniazid toxicity in health care workers pdf paperity. Isoniazid investigated as a drug, hormone, mutagen, primary irritant, reproductive effector, and. Isoniazid is the most reliable and most commonly used medication for tuberculosis. Acute inh toxicity leads to central nervous system cns toxicity, including seizures, whereas chronic inh toxicity results in hepatotoxicity. If it is still the same day, take the dose as soon as you remember.
Discovery of novel enhancers of isoniazid toxicity in. The influence on the antituberculotic drug toxicity has been investigated for three prominent antituberculotic drugs. An acute overdose of inh is potentially fatal and is characterized by repetitive seizures, unresponsive to usual anticonvulsants, metabolic acidosis with a high anion gap and coma. Successful treatment with pyridoxine and hemodialysis find, read and. Each 5 ml teaspoonful of syrup contains 50 mg of isoniazid.
Mar 23, 2011 isoniazid inh monotherapy has gained widespread acceptance as an efficacious therapy for latent tuberculosis infection ltbi especially in lowprevalence settings. In addition, the characteristics of the liver toxicity in these studies were. Find information about common, infrequent and rare side effects of isoniazid oral. A report of severe acetaminophen toxicity was reported in a patient receiving isoniazid. Nervous system toxicity with current antituberculosis pharmacotherapy is relatively uncommon, although the frequency of the usage of antituberculosis therapy requires that physicians should be aware of such toxicity. Treatment with inh therapy has a risk of toxicity, which can be acute or. Ingestion at concentrations greater than 30 mgkg can often produce seizures.
With isoniazid toxicosis, pyridoxine vitamin b 6 should be administered promptly. Isoniazid isoniazid side effects, images, uses, dosage. Adverse effects of isoniazid have been reported by different researchers based on their clinical studies such as renal failure, liver injury and liver failure, development of agranulocytosis, isoniazid induced tenosynovitis etc. Dec 01, 2019 isoniazid tends to raise plasma concentrations of phenytoin and carbamazepine by inhibiting their metabolism in the liver. Serious and sometimes fatal liver problems may occur during treatment with isoniazid or after you stop taking this medicine, especially if you are between the ages of 35 and 65.
Isoniazid is an antibacterial available as a solution for oral administration. Isoniazid daily every day 9 months twice weekly m t w th f s sun your doctor may have you take vitamin b6 with your medicine. Keep inh out of reach from children to prevent accidental overdose. Isoniazid is the most widely used antituberculosis medication.
The hepatic toxicity of isoniazid among rapid and slow acetylators of the drug. Isoniazid isonicotinic acid hydrazide has been shown to be effective in preventing the development of active disease among asymptomatic, infected persons by 60% 95% 3, 4. Is isoniazid so safe to use in tuberculosis preventive. A single dose of plg microparticles exhibited a sustained release of isoniazid and rifampicin in vivo up to 7 and 6 weeks, respectively. We found that the levels of free heme increased in mouse. However, it can cause liver injury and even liver failure. Periodic clinical and liverfunction evaluations were made during the year of treatment. Acute inh overdose predominantly involves the brain and may cause prolonged seizures, anion gap metabolic acidosis, and coma. Pdf on jan 1, 1992, j m cash and others published isoniazid overdose. Inh toxicity stems from several causes, including deficiencies of pyridoxine vitamin b6 and gamma amino butyric acid gaba. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.
Isoniazid is an ideal agent because it is bactericidal, easily administered, inexpensive, and relatively nontoxic in children. Dosing should be based on the equivalent amount mg for mg of isoniazid that was ingested. The toxicity of isoniazid inh used as a secondary chemoprophylactic agent was evaluated in 160 adults. Isoniazid is used to treat and to prevent tuberculosis. Bhise sb lnbc institute of pharmacy, india klk consultants, india. This article focuses on the acute and chronic isoniazid isonicotinic acid hydrazide inh toxicity. The toxicity of isoniazid chemoprophylaxis was assessed in 83 health care workers hcws receiving a 6month course, in whom clinical toxicity and liver function were monitored. The absorption of isoniazid is impaired by aluminium hydroxide. Pyridoxine is considered the antidote for this toxicosis because it is a direct antagonist of isoniazid and will quickly reverse the clinical signs. Free drugs in combination injected in the same doses were detectable in vivo up to 24 h only. Inh metabolism has been thought to be associated with inhinduced. The isoniazidinduced peripheral neuropathy occurring in adult tuberculous patients results from a deficiency of biologically active pyridoxine. Nausea, vomiting, dizziness, blurred vision and slurring of speech occur within 30 minutes to 3 hours of overdosage.
Patients who ingest 80150 mgkg develop severe central nervous system cns symptoms. What you need to know about your medicine for latent. Aug 03, 2016 isoniazid inh is highly effective for the management of tuberculosis. Take all your medicines as prescribed by your doctor. In yet another case of inh toxicity, presence of epidural hematoma along with inh poisoning made it difficult to discriminate the cause of seizure 21.
Recommendations for the management of acute inh toxicity are highlighted. Take isoniazid at around the same time every scheduled day. Murphy and colleagues 1 recently reported a case of severe hepatotoxicity in a patient who had ingested both isoniazid and acetaminophen. The hydrazone was considered to result from a chemical reaction between the aldehyde group of pyridoxal 5phosphate, the active form of pyridoxine, and the free amine group of isoniazid.
Feb 07, 2019 this article focuses on the acute and chronic isoniazid isonicotinic acid hydrazide inh toxicity. If signs and symptoms of hepatotoxicity occur, isoniazid should be discontinued promptly. Furthermore, serial transaminase assays among patients receiving isoniazid indicate that some 12% of such individuals have enzyme elevations within the first two months. Jul 28, 2016 isoniazid is also not a safe drug and without toxicity, and side effects. Isoniazid has been reported to cause severe, and sometimes fatal, age related hepatitis. Your liver function may need to be checked every month while you are taking this medicine. It can be prevented by administration of pyridoxine whenever isoniazid is given. Pdf isoniazid inh is highly effective for the management of tuberculosis. Autooxidation of inh involving free radicals has also been reported 17. Although inh related hepatotoxicity is well recognized, progression to severe liver dysfunction requiring care at a transplant center remains unpredictable.
Isoniazid toxicity is associated with a high mortality rate. Pdf isoniazid metabolism and hepatotoxicity researchgate. See what others have said about isoniazid, including the effectiveness, ease of use and side effects. Isoniazid poisoning doesnt occur often, but can have extremely highrisk toxicity resulting in some cases from a misguided attempt to make up missed doses and in others from suicide attempts. Jul 06, 2018 a report of severe acetaminophen toxicity was reported in a patient receiving isoniazid. A case report indicating status epilepticus due to isoniazid toxicity has been reported 18.
Avoid prophylactic use of inh in the elderly, unless the potential benefit clearly outweighs the risk. Isoniazid neurotoxicity hepatotoxicity rhabdomyolysis case reports. Despite the benefits of preventive therapy, isoniazid is not widely applied because of missed opportunity, fears of toxicity, and poor adherence 5. Material may be irritating to the mucous membranes and upper respiratory tract. Since 1952, inh has been used as a frontline antimicrobial for tuberculosis tb. The deficiency is caused by the combination of isoniazid and pyridoxine to form a hydrazone which is excreted in the urine. When treating active tb, isoniazid must be used with other tb medicines. Tuberculosis can become resistant to treatment if isoniazid is used alone. The incidence of clinical hepatitis in young, healthy adults is 0.
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