{"id":4291,"date":"2025-03-31T18:12:03","date_gmt":"2025-03-31T18:12:03","guid":{"rendered":"https:\/\/kidneydiseaseclinic.net\/kdc\/phenytoin-txt\/"},"modified":"2025-03-31T18:12:03","modified_gmt":"2025-03-31T18:12:03","slug":"phenytoin-txt","status":"publish","type":"post","link":"https:\/\/kidneydiseaseclinic.net\/kdc\/phenytoin-txt\/","title":{"rendered":"Phenytoin.txt"},"content":{"rendered":"

CLINICAL USE <\/H3>
\nAnti-epileptic agent Diabetic neuropathy Trigeminal neuralgia

DOSE IN NORMAL RENAL FUNCTION <\/H3>Oral: 150\u2013500 mg\/day or 3\u20134 mg\/kg\/day in 1\u20132 divided doses; higher doses can be used in exceptional casesStatus epilepticus (IV): 10\u201318 mg\/kg (with BP and ECG monitoring) then 100 mg every 6\u20138 hours according to levels

PHARMACOKINETICS <\/H3>
  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :252.3 (274.2 as sodium salt)<\/li>\n
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :90<\/li>\n
  • %Excreted unchanged in urine &nbsp &nbsp : up to 5<\/li>\n

  • Volume of distribution (L\/kg) &nbsp &nbsp &nbsp :0.52\u20131.19<\/li>\n

  • half-life \u2013 normal\/ESRD (hrs)&nbsp &nbsp &nbsp :7\u201342\/ Unchanged

    DOSE IN RENAL IMPAIRMENT <\/H3>

    GFR (mL\/MIN)<\/H4>
  • 20 to 50 &nbsp &nbsp : Dose as in normal renal function
  • 10 to 20 &nbsp &nbsp : Dose as in normal renal function
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES <\/H3>
  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function<\/p>\n
  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in normal renal function
  • HDF\/high flux &nbsp :Dialysed. Dose as in normal renal function.
  • CAV\/VVHD &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS <\/H3>Potentially hazardous interactions with other drugs\n
  • Analgesics: enhanced effect with NSAIDs; metabolism of methadone accelerated\n
  • Anti-arrhythmics: increased concentration with amiodarone; concentration of disopyramide and mexiletine reduced\n
  • Antibacterials: level increased by clarithromycin, chloramphenicol, isoniazid, metronidazole, co-trimoxazole and trimethoprim (+ antifolate effect); concentration increased or decreased by ciprofloxacin; concentration of doxycycline and telithromycin reduced; concentration reduced by rifampicin\n
  • Anticoagulants: increased metabolism of coumarins (reduced effect but also reports of enhancement)\n
  • Antidepressants: MAOIs, SSRIs and tricyclics antagonise anticonvulsant effect, concentration increased by fluoxetine and fluvoxamine; concentration of mianserin, mirtazepine and paroxetine and possibly tricyclics reduced; concentration reduced by St John\u2019s wort \u2013 avoid\n
  • Anti-epileptics: concentration of both drugs reduced with carbamazepine, concentration may also be increased by carbamazepine, ethosuximide, oxcarbazepine and topiramate; concentration of ethosuximide, active oxcarbazepine metabolite, primidone (but active metabolite increased), topiramate and valproate possibly reduced; concentration of lamotrigine, tiagabine and zonisamide reduced; primidone and valproate may alter concentration; concentration reduced by vigabatrin\n
  • Antifungals: concentration of ketoconazole, itraconazole, posaconazole, voriconazole and possibly caspofungin reduced \u2013 avoid with itraconazole, increase voriconazole dose and possibly caspofungin; levels increased by fluconazole, miconazole and voriconazole\n
  • Antimalarials: antagonise anticonvulsant effect; increased antifolate effect with pyrimethamine\n
  • Antipsychotics: antagonise anticonvulsant effect; possibly reduced aripiprazole concentration \u2013 increase aripiprazole dose; metabolism of clozapine, quetiapine and sertindole increased\n
  • Calcium-channel blockers: levels increased by diltiazem; concentration of diltiazem, felodipine, isradipine, nisoldipine and verapamil and possibly dihydropyridines, nicardipine and nifedipine reduced\n
  • Ciclosporin: reduced ciclosporin levels Corticosteroids: metabolism accelerated (effect reduced)Cytotoxics: metabolism inhibited by fluorouracil; increased antifolate effect .582 PHeNYtOINto avoid irritation. Cardiac monitoring recommended

    OTHER INFORMATION <\/H4>Aim for phenytoin levels of
  • 10 to 20 &nbsp &nbsp : mg\/L (40\u201380 micromol\/L)Total phenytoin levels must be adjusted for hypoalbuminaemia and uraemia (levels of 5\u201312 mcg\/mL may be enough)Decreased protein binding and volume of distribution in renal failureFree fraction of phenytoin is increased in uraemia to approximately 0.2Request free phenytoin serum levels, if possibleLoading dose 15 mg\/kg IV or oral, then 5 mg\/kg\/day. Steady state reached in 3\u20135 days if loading dose givenIncrease dose gradually (25\u201350 mg\/day at weekly intervals); demonstrates saturation kineticsPhenytoin absorption is markedly reduced by concurrent nasogastric enteral nutrition administration. Avoid concomitant administration with divalent cationsMay cause folate deficiency A useful equation: To correct a phenytoin level for low albumin: from Winters ME. Basic Clin Pharmacokinet, 3rd ed. Philadelphia PA. Lippincott Williams & Wilkins; 1994Cnormal Cobserved{(0.48) \u00d7 (1 0.1) \u00d7 albumin} + 0.1 4.4(g\/dl)with methotrexate; reduced phenytoin absorption; concentration of busulfan, etoposide and imatinib reduced \u2013 avoid with imatinibDisulfiram: levels of phenytoin increased\n
  • Diuretics: concentration of eplerenone reduced \u2013 avoid concomitant use; increased risk of osteomalacia with carbonic anhydrase inhibitors; antagonises effect of furosemideOestrogens and progestogens: metabolism increased (reduced contraceptive effect)Sulfinpyrazone: concentration increased by sulfinpyrazoneTheophylline: concentration of both drugs reduced\n
  • Ulcer-healing drugs: metabolism inhibited by cimetidine; absorption reduced by sucralfate; enhanced effect with esomeprazole and omeprazole

    ADMINISTRATION <\/H3>

    Reconstition<\/H4>\u2013

    Route <\/H4>IV, oral

    Rate of Administration <\/H4>

    IV infusion <\/H4> and bolus: not greater than 50 mg\/minute

    Comments<\/H4>Infusion: dilute in 50\u2013100 mL sodium chloride 0.9%; final concentration not exceeding 10 mg\/mLGive by slow IV injection into large vein followed by sodium chloride 0.9% flush,
    \n","protected":false},"excerpt":{"rendered":"

    CLINICAL USE Anti-epileptic agent Diabetic neuropathy Trigeminal neuralgia DOSE IN<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[7],"class_list":["post-4291","post","type-post","status-publish","format-standard","hentry","category-blog","tag-post-by-auto-php"],"_links":{"self":[{"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/posts\/4291","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/comments?post=4291"}],"version-history":[{"count":0,"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/posts\/4291\/revisions"}],"wp:attachment":[{"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/media?parent=4291"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/categories?post=4291"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/kidneydiseaseclinic.net\/kdc\/wp-json\/wp\/v2\/tags?post=4291"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}