Isoniazid toxicity: liver, nerve and skin side effects of this TB medicine

Isoniazid is an antibacterial medicine. The product leaflet explains that it works by killing the bacteria that cause tuberculosis and that it is used for TB both in and outside the lungs. The NHS says TB treatment is usually a course of antibiotics lasting at least 6 months, and that for latent TB, where there are no symptoms, antibiotics are usually taken for 3 to 6 months. It stresses taking antibiotics correctly and completing the course, because if you stop early TB could come back.

Because it is taken for months, side effects matter. The leaflet says side effects are more common in people aged over 35 and in people who break down isoniazid more slowly, and that the risk increases with high doses. The aim of this guide is to explain the serious effects so that they can be recognised and reported quickly, not to discourage treatment. Never stop isoniazid on your own: the leaflet says not to stop without first talking to your doctor, and to take the full course.

The prescribing information lists hepatitis as an uncommon effect and, with unknown frequency, acute hepatic failure, liver injury and jaundice. It says the risk increases with age, especially over 35, and that it may be serious and sometimes fatal. It identifies advanced age, female gender, slow acetylators (people who break the medicine down slowly), malnutrition, HIV infection, pre-existing liver disease and extra-pulmonary TB as risk factors.

The leaflet describes the warning symptoms: yellowing of the skin or whites of the eyes, urine getting darker and stools paler, fatigue, weakness, malaise, loss of appetite, nausea or vomiting. It says to contact your doctor as soon as possible if these occur. The prescribing information advises that if symptoms of hepatitis such as malaise, fatigue, anorexia and nausea develop, isoniazid should be discontinued immediately, and that treatment should be withdrawn if the liver enzyme AST rises to more than three times normal or bilirubin rises. These are decisions for the treating team, not for patients to make alone.

Peripheral neuropathy, the pins and needles or numbness in the hands and feet, is listed in the prescribing information, along with optic neuritis, seizures and psychiatric effects such as psychotic disorder. The leaflet lists tingling or numbness in the hands or feet, fits, mental disturbances including hallucinations and delusions, and eye problems such as visual disturbances and eye pain.

The prescribing information explains that nicotinic acid deficiency may be related to an isoniazid-induced pyridoxine (vitamin B6) deficiency, and that patients at risk of neuropathy or pyridoxine deficiency should be given pyridoxine, with supplementation recommended in pregnancy. The prescribing information says isoniazid should be used with caution in people with a history of psychosis, and the leaflet lists psychosis, epilepsy and ever having had fits among the reasons to check with your doctor before taking it.

The leaflet and prescribing information describe serious skin reactions reported with isoniazid, including Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS and acute generalised exanthematous pustulosis. The leaflet says to stop and seek medical attention immediately if symptoms appear, including a red, scaly widespread rash with bumps under the skin and blisters with fever, or severe extensive skin damage. The prescribing information says that if a serious reaction has occurred, isoniazid must not be restarted at any time.

Other effects the leaflet lists include pancreatitis (severe pain in the abdomen and back), a lupus-like syndrome with swollen joints, tiredness and rashes, blood disorders that make infections more likely, and high blood sugar.

The leaflet says isoniazid should be taken on an empty stomach, at least 30 minutes before a meal or two hours after, and that alcohol should be avoided. It may interact with foods containing histamine or tyramine, such as matured cheeses, cured meat, some fish like tuna, salmon and mackerel, wine and beer, causing headache, sweating, flushing, palpitations and dizziness, so these foods should be avoided.

It lists medicines that need review, including some used for epilepsy (carbamazepine, phenytoin, primidone), disulfiram, other TB medicines such as rifampicin, diazepam, levodopa, and itraconazole and ketoconazole. The prescribing information adds that there may be an increased risk of liver damage when rifampicin and isoniazid are given together. Always tell your doctor or pharmacist about every medicine you take, including those bought without a prescription.

The leaflet says that if you accidentally take too much you should immediately contact the nearest hospital casualty department or your doctor, and that taking too much may cause feeling and being sick, dizziness or a spinning feeling, fits and acidosis (an upset of the acid balance in the body), which may require emergency treatment in hospital. The prescribing information adds that the commonly reported events are nausea, vomiting and central nervous system toxicity such as vertigo, seizures and coma, and that treatment includes controlling convulsions and giving large intravenous doses of pyridoxine.

Do not take a double dose to make up for a missed one, the leaflet says. If a child has swallowed tablets, or if someone is drowsy, vomiting or fitting after taking too much, call 999 or go to A&E and take the packet with you.

Contact your TB nurse, specialist or GP promptly if you notice yellowing of the skin or eyes, dark urine, pale stools, persistent sickness, unusual tiredness or weakness, numbness or tingling, vision changes, a rash or blistering, or mental changes. The leaflet says to seek medical attention immediately for serious skin symptoms and for liver warning signs to speak with your doctor or go to casualty. Report suspected side effects through the MHRA Yellow Card scheme, as the leaflet suggests.

The NHS notes more general TB warning signs: coughing up blood needs urgent GP or NHS 111 advice, and a stiff neck with severe headache, a seizure, sudden confusion or weakness could mean TB has spread to the brain and needs 999 or A&E.

TB treatment is organised through NHS TB services, with specialist nurses and clinics monitoring liver tests and side effects. The medicine and the monitoring are the same whichever service prescribes it. Whoever prescribes it, ask when blood tests will be done and who to contact if you feel unwell.