Phenytoin

Should be taken with food. When administering to patients on nasogastric or other enteral feeds, do not administer feeds 2 hr before or after a dose. Be consistent throughout therapy in relation to feed times. Do not switch dosage forms/brands w/o prior consideration.

History of acute hepatotoxicity attributable to phenytoin. IV/IM: Sinus bradycardia, sinoatrial block, 2nd- and 3rd-degree atrioventricular (AV) block, and Adams-Stokes syndrome. Concomitant use with delavirdine.

Patient with hypotension, cardiac disease, diabetes mellitus, hypothyroidism, hypoalbuminaemia, hyperbilirubinaemia, porphyria, myasthenia gravis; history of adverse haematologic reaction to any drug. Critically ill and debilitated patients. CYP2C9 intermediate and poor metabolisers, and patients who are positive for HLA-B*15:02 allele. Black patients. Avoid extravasation (IV). IM inj is not recommended for the treatment of status epilepticus. Not indicated for the treatment of myoclonic seizures, seizures due to hypoglycaemia or other metabolic causes, and absence (petit mal) seizures. Avoid abrupt withdrawal. Preparations containing phenytoin Na are not necessarily bioequivalent to those containing phenytoin base; dosage adjustments and monitoring of serum level may be necessary when switching dosage forms. Renal and hepatic impairment. Children and elderly. Pregnancy and lactation. Patient Counselling This drug may cause dizziness and drowsiness, if affected, do not drive or operate machinery. Women of childbearing potential must use proven birth control methods during therapy and for 1 month (for oral doses) after stopping the treatment. Consider using other reliable contraceptive methods recommended by the doctor as hormonal contraceptives may be ineffective. Monitoring Parameters Consider screening for HLA-B*15:02 allele in patients at increased risk of developing SCARs before therapy initiation. Pregnancy test may be considered in women of childbearing potential to rule out pregnancy before initiating treatment. Obtain CBC, comprehensive metabolic profile, plasma phenytoin concentration, and LFTs; 25-hydroxyvitamin D levels for chronic use. Monitor for signs and symptoms of suicidality, haematologic changes, and hypersensitivity or serious skin reactions. IV: Perform continuous cardiac (heart rate and rhythm, blood pressure) and respiratory monitoring during and after administration. Closely monitor for infusion site reactions.

Significant: Angioedema, transient increased serum transaminases, hyperglycaemia; precipitation or aggravation of absence or myoclonic seizures, dose-related CNS effects (e.g. somnolence, nystagmus, ataxia, incoordination, slurred speech), suicidal ideation and behaviour, exacerbation of porphyria; vitamin D deficiency, osteoporosis, osteomalacia, osteopenia, bone fractures, hypocalcaemia, hypophosphataemia (chronic use); lymphadenopathy; confusional states (delirium, psychosis, encephalopathy) or rarely, irreversible cerebellar dysfunction and/or atrophy (for plasma phenytoin levels sustained above the optimal range). IV: Soft tissue irritation and inflammation (e.g. tenderness, skin necrosis and sloughing) at the inj site, purple glove syndrome (oedema, discolouration, and pain distal to the inj site); hypotension (rapid IV administration). IM: Pain, necrosis, and abscess formation at the inj site. Ear and labyrinth disorders: Vertigo. Gastrointestinal disorders: Nausea, vomiting, constipation, taste perversion; gingival hyperplasia (mainly in children and patients with poor oral hygiene). Immune system disorders: Anaphylactoid reactions, anaphylaxis. Investigations: Abnormal thyroid function test. Musculoskeletal and connective tissue disorders: SLE, arthropathy. Rarely, Dupuytren's contracture. Nervous system disorders: Headache, dizziness, motor twitching, paraesthesia. Rarely, dyskinesia, dystonia, tremor, chorea, asterixis. Psychiatric disorders: Insomnia, transient nervousness. Renal and urinary disorders: Tubulointerstitial nephritis. Reproductive system and breast disorders: Rarely, Peyronie's disease. Respiratory, thoracic and mediastinal disorders: Pneumonitis. Skin and subcutaneous tissue disorders: Scarlatiniform or morbilliform rash, urticaria, hypertrichosis, hirsutism.
Potentially Fatal: Severe cardiac arrhythmias (including bradycardia, atrial and ventricular conduction depression, ventricular tachycardia or fibrillation progressing to asystole or cardiac arrest) associated with rapid IV administration; severe cutaneous adverse reactions (SCARs), including acute generalised exanthematous pustulosis, toxic epidermal necrolysis, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and exfoliative dermatitis; haematologic effects (e.g. agranulocytosis, leucopenia, granulocytopenia, megaloblastic anaemia, pure red cell aplasia, thrombocytopenia, pancytopenia with or without bone marrow depression); hepatotoxicity (e.g. toxic hepatitis, acute hepatic failure).

Serum phenytoin levels may be increased with halothane, cimetidine, fluvastatin, tacrolimus, tolbutamide, omeprazole, salicylates, antibiotics (e.g. chloramphenicol, erythromycin, isoniazid, sulfamethoxazole-trimethoprim), other anticonvulsants (e.g. oxcarbazepine, felbamate, topiramate, ethosuximide), antifungal agents (e.g. amphotericin B, itraconazole, ketoconazole), certain antineoplastic agents (e.g. capecitabine, fluorouracil), benzodiazepines or psychotropic drugs (e.g. disulfiram, methylphenidate, trazodone), CV agents (e.g. amiodarone, diltiazem, nifedipine), and SSRIs (e.g. fluoxetine, fluvoxamine). Serum phenytoin levels may be decreased with rifampicin, vigabatrin, theophylline, reserpine, folic acid, diazoxide, antiretrovirals (e.g. nelfinavir, ritonavir, fosamprenavir), and certain antineoplastic agents (e.g. bleomycin, cisplatin, doxorubicin). Concomitant use with ciprofloxacin, psychotropic agents (e.g. chlordiazepoxide, diazepam, phenothiazines), and certain anticonvulsants (e.g. carbamazepine, phenobarbital, valproic acid) may either increase or decrease serum phenytoin levels. May alter serum levels and/or effects of estrogens and oral contraceptives, vitamin D, doxycycline, rifampicin, ticagrelor, teniposide, furosemide, methadone, tolbutamide, anticoagulants (e.g. apixaban, warfarin), anticonvulsants (e.g. carbamazepine, lamotrigine, phenobarbital, valproic acid, lacosamide), antifungal agents (e.g. posaconazole, voriconazole), antiretrovirals (e.g. efavirenz, fosamprenavir, indinavir, ritonavir, saquinavir), CV agents (e.g. digoxin, disopyramide, mexiletine, verapamil), hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (e.g. atorvastatin, fluvastatin, simvastatin), neuromuscular blocking agents (e.g. pancuronium, rocuronium), and psychotropic agents/antidepressants (e.g. clozapine, paroxetine, quetiapine). Increased risk of hyperammonaemia with valproate.

Anticonvulsants

N03AB02 - phenytoin ; Belongs to the class of hydantoin derivatives antiepileptics.