{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T12:31:05Z","timestamp":1776947465337,"version":"3.51.4"},"reference-count":14,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2024,12,28]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Phenytoin is one of the most used antiepileptic drugs. Isoniazid, a first-line antitubercular drug, blocks the CYP2C19 enzyme, preventing phenytoin from being metabolised. Concomitant use of phenytoin and isoniazid predisposes to phenytoin toxicity. Here, we present the case of a female in her mid-30s with a known seizure disorder on phenytoin monotherapy. She was also started on antitubercular therapy, including isoniazid, after being diagnosed with pulmonary tuberculosis recently. This led to a catastrophic sequence of events including progressive loss of balance, psychosis, nystagmus, hyperreflexia and later, stupor. Her serum phenytoin level was found to exceed 40\u2009mg\/L. Her symptoms improved when phenytoin was switched to levetiracetam. Ours is the first case report of such an interaction in over 10 years and highlights the need to be extra-cautious while prescribing phenytoin and antitubercular therapy concomitantly, especially in a populations dominated by slow acetylators.<\/jats:p>","DOI":"10.1136\/bcr-2024-262164","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T07:00:46Z","timestamp":1736838046000},"page":"e262164","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Phenytoin toxicity caused by a drug-to-drug interaction between phenytoin and antitubercular therapy"],"prefix":"10.1136","volume":"18","author":[{"given":"Santhosh Shettigere","family":"Chandrappa","sequence":"first","affiliation":[{"name":"Internal Medicine, All India Institute of Medical Sciences \u2013 Rishikesh, Rishikesh, Uttarakhand, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-0112","authenticated-orcid":false,"given":"Rajat","family":"Ranka","sequence":"additional","affiliation":[{"name":"Internal Medicine, All India Institute of Medical Sciences \u2013 Rishikesh, Rishikesh, Uttarakhand, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minakshi","family":"Dhar","sequence":"additional","affiliation":[{"name":"Internal Medicine, All India Institute of Medical Sciences \u2013 Rishikesh, Rishikesh, Uttarakhand, India"},{"name":"Geriatric Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7590-8173","authenticated-orcid":false,"given":"Gaurav","family":"Karna","sequence":"additional","affiliation":[{"name":"Internal Medicine, All India Institute of Medical Sciences \u2013 Rishikesh, Rishikesh, Uttarakhand, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"2025082800330359000_18.1.e262164.1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-197904030-00001"},{"key":"2025082800330359000_18.1.e262164.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-001-0396-3"},{"key":"2025082800330359000_18.1.e262164.3","doi-asserted-by":"crossref","DOI":"10.1212\/01.WNL.0000163997.67472.C5","article-title":"Seizures following reduction in phenytoin level after orally administered folic acid","volume":"64","author":"Steinweg","year":"2005","journal-title":"Neurology (ECronicon)"},{"key":"2025082800330359000_18.1.e262164.4","unstructured":"Iorga A , Horowitz BZ . Phenytoin toxicity. In: StatPearls. Treasure Island (FL): StatPearls Publishing, 2023."},{"key":"2025082800330359000_18.1.e262164.5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2217\/pgs.13.2","article-title":"NAT2 sequence polymorphisms and acetylation profiles in Indians","volume":"14","author":"Khan","year":"2013","journal-title":"Pharmacogenomics"},{"key":"2025082800330359000_18.1.e262164.6","doi-asserted-by":"crossref","first-page":"924","DOI":"10.4103\/ijmr.IJMR_684_14","article-title":"Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity","volume":"144","author":"Sharma","year":"2016","journal-title":"Indian J Med Res"},{"key":"2025082800330359000_18.1.e262164.7","doi-asserted-by":"publisher","DOI":"10.1378\/chest.75.3.356"},{"key":"2025082800330359000_18.1.e262164.8","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/BF03256314","article-title":"Study of NAT2 Gene Polymorphisms in an Indian Population","volume":"13","author":"Singh","year":"2009","journal-title":"Mol Diag Ther"},{"key":"2025082800330359000_18.1.e262164.9","article-title":"Pharmacogenetics and enzyme induction\/inhibition properties of antiepileptic drugs","volume":"63","author":"Anderson","year":"2004","journal-title":"Neurol"},{"key":"2025082800330359000_18.1.e262164.10","article-title":"Inhibition of diphenylhydantoin metabolism in rats and in rat liver microsomes by antitubercular drugs","volume":"18","author":"Kutt","year":"1968","journal-title":"Neurol (ECronicon)"},{"key":"2025082800330359000_18.1.e262164.11","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1212\/WNL.16.6.594","article-title":"Depression of prahydroxylation of diphenylhydantoin by antituberculosis chemotherapy","volume":"16","author":"Kutt","year":"1966","journal-title":"Neurology (ECronicon)"},{"key":"2025082800330359000_18.1.e262164.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1985.tb05071.x"},{"key":"2025082800330359000_18.1.e262164.13","first-page":"1175","article-title":"Phenytoin toxicity due to concomitant antituberculosis therapy","volume":"85","author":"Walubo","year":"1995","journal-title":"S Afr Med J"},{"key":"2025082800330359000_18.1.e262164.14","doi-asserted-by":"publisher","DOI":"10.1177\/106002809502907-816"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2024-262164","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T07:33:12Z","timestamp":1756366392000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2024-262164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,14]]},"published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1136\/bcr-2024-262164"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2024-262164","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]}}}