Phenytoin Sodium interactions
Checked as Phenytoin in this data source.
Full monograph for Phenytoin SodiumCheck it against another medicine
Medicines
773 documented
| Medicine | Severity | Mechanism | Effect | Sources |
|---|---|---|---|---|
| Abemaciclib | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of abemaciclib and its pharmacologically active… | 6 sources — open the full entry |
| Abiraterone Acetate | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of abiraterone, which is partially metabolized by the… | 8 sources — open the full entry |
| Acalabrutinib | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of acalabrutinib, which is primarily metabolized by… | 7 sources — open the full entry |
| Alpelisib | Major | Metabolism | Coadministration of alpelisib with potent inducers of CYP450 3A4 may significantly reduce the plasma concentrations of alpelisib. The proposed mechanism, based… | 8 sources — open the full entry |
| Amiodarone Hydrochloride | Major | Metabolism | Coadministration of amiodarone and phenytoin may alter the plasma concentrations of both drugs. Specifically, phenytoin concentrations may increase due to… | 34 sources — open the full entry |
| Amlodipine Besilate | Major | Metabolism | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized… | 35 sources — open the full entry |
| Amlodipine Besilate + Atenolol | Major | Metabolism · Unknown | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized…2 documented mechanisms | 35 sources — open the full entry |
| Amlodipine Besilate + Atorvastatin | Major | Metabolism | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized…2 documented mechanisms | 47 sources — open the full entry |
| Amlodipine Besilate + Benazepril Hydrochloride | Major | Metabolism · Unknown | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized…2 documented mechanisms | 35 sources — open the full entry |
| Amlodipine Besilate + Olmesartan Medoxomil | Major | Metabolism | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized… | 35 sources — open the full entry |
| Amlodipine Besilate + Telmisartan | Major | Metabolism · Unknown | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized…2 documented mechanisms | 35 sources — open the full entry |
| Amlodipine Besilate + Valsartan | Major | Metabolism · Unknown | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized…2 documented mechanisms | 35 sources — open the full entry |
| Apixaban | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 that also induce P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of apixaban… | 8 sources — open the full entry |
| Apremilast | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of apremilast, which is primarily metabolized by the… | 5 sources — open the full entry |
| Artemether + Lumefantrine | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of artemether and lumefantrine, both of which are…2 documented mechanisms | 10 sources — open the full entry |
| Articaine Hydrochloride + Epinephrine Bitartrate | Major | Synergy · Unknown | Coadministration of local anesthetics with other oxidizing agents that can also induce methemoglobinemia such as antimalarials (e.g., chloroquine, primaquine…2 documented mechanisms | 5 sources — open the full entry |
| Asciminib | Major | Metabolism | Coadministration of asciminib with CYP450 2C9 substrates that are also potent CYP450 3A4 inducers such as phenytoin or fosphenytoin may lead to altered plasma… | 1 sources — open the full entry |
| Avatrombopag | Major | Metabolism | Concomitant use of avatrombopag with moderate to potent dual inducers of CYP450 2C9 and 3A4 may decrease the systemic exposure (AUC) of avatrombopag which may… | 4 sources — open the full entry |
| Axitinib | Major | Metabolism | Coadministration with potent and moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of axitinib, which is primarily… | 9 sources — open the full entry |
| Benzocaine + Butamben + Tetracaine Hydrochloride | Major | Synergy | Coadministration of local anesthetics with other oxidizing agents that can also induce methemoglobinemia such as antimalarials (e.g., chloroquine, primaquine…2 documented mechanisms | 12 sources — open the full entry |
| Bisoprolol Fumarate + Amlodipine Besilate | Major | Metabolism · Unknown | Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of calcium channel blockers, the majority of which are primarily metabolized…2 documented mechanisms | 35 sources — open the full entry |
| Bortezomib | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of bortezomib, which is primarily… | 10 sources — open the full entry |
| Brigatinib | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of brigatinib, which is partially metabolized by the… | 9 sources — open the full entry |
| Cabozantinib | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of cabozantinib, which is a substrate of the isoenzyme. | 7 sources — open the full entry |
| Capmatinib Hydrochloride | Major | Metabolism | Coadministration with strong or moderate CYP450 3A4 inducers may decrease the plasma concentrations and anti-tumor activity of capmatinib. The proposed… | 5 sources — open the full entry |
| Caspofungin Acetate | Major | Metabolism | Coadministration with inducers or mixed inducer/inhibitors of certain metabolic pathways may produce clinically meaningful reductions in the plasma… | 1 sources — open the full entry |
| Cenobamate | Major | Metabolism | Coadministration of cenobamate and phenytoin may lead to increased plasma concentrations of phenytoin and reduced plasma concentrations of cenobamate. The… | 17 sources — open the full entry |
| Ceritinib | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of ceritinib, which is a substrate of the isoenzyme. | 3 sources — open the full entry |
| Crizotinib | Major | Metabolism | Coadministration with strong CYP450 3A4 inducers may decrease plasma concentrations and pharmacologic effects of crizotinib, which is primarily metabolized by… | 6 sources — open the full entry |
| Cyproterone Acetate + Ethinyl Estradiol | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may… | 65 sources — open the full entry |
| Dabigatran Etexilate Mesylate | Major | Absorption | Coadministration with potent inducers of P-glycoprotein (P-gp) may significantly reduce the bioavailability of dabigatran following oral administration of… | 5 sources — open the full entry |
| Daclatasvir | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentration of daclatasvir, which is primarily metabolized by the… | 6 sources — open the full entry |
| Daclatasvir + Sofosbuvir | Major | Absorption · Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentration of daclatasvir, which is primarily metabolized by the…2 documented mechanisms | 11 sources — open the full entry |
| Darolutamide | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 that also induce P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of… | 6 sources — open the full entry |
| Dasatinib | Major | Metabolism | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of dasatinib, which is primarily metabolized by the… | 11 sources — open the full entry |
| Deflazacort | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of 21-desdeflazacort, the active… | 6 sources — open the full entry |
| Desogestrel | Major | Antagonism | Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may reduce the… | 33 sources — open the full entry |
| Dienogest | Major | Antagonism · Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may…2 documented mechanisms | 98 sources — open the full entry |
| Dienogest + Estradiol Valerate | Major | Antagonism · Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may…3 documented mechanisms | 148 sources — open the full entry |
| Drospirenone | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may… | 65 sources — open the full entry |
| Drospirenone + Estetrol | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may… | 65 sources — open the full entry |
| Drospirenone + Estradiol | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may…2 documented mechanisms | 115 sources — open the full entry |
| Drospirenone + Ethinyl Estradiol0.02 mg0.03 mg | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may…2 documented mechanisms | 65 sources — open the full entry |
| Drospirenone + Ethinyl Estradiol + Levomefolate | Major | Antagonism · Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may…3 documented mechanisms | 91 sources — open the full entry |
| Elacestrant | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of elacestrant, which is primarily… | 1 sources — open the full entry |
| Erdafitinib | Major | Metabolism | Coadministration with potent inducers of CYP450 2C9 or 3A4 may decrease the plasma concentrations and therapeutic effects of erdafitinib. The mechanism is… | 2 sources — open the full entry |
| Ethinyl Estradiol + Desogestrel0.02 mg0.03 mg | Major | Antagonism · Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may…2 documented mechanisms | 98 sources — open the full entry |
| Ethinyl Estradiol + Gestodene | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may… | 65 sources — open the full entry |
| Ethinyl Estradiol + Levonorgestrel + Ferrous Fumarate | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may…2 documented mechanisms | 65 sources — open the full entry |
| Ethinyl Estradiol + Lynestrenol0.0375 mg0.05 mg | Major | Metabolism | RECOMMENDED: Coadministration with certain anticonvulsants such as carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, and primidone may… | 65 sources — open the full entry |
Food & lifestyle
food
ModerateAbsorption
Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen.
What to do: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.
16 sources
- Sandor P, Sellers EM, Dumbrell M, Khouw V "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther 30 (1981): 390-7
- Holtz L, Milton J, Sturek JK "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr 11 (1987): 183-6
- Sellers EM, Holloway MR "Drug kinetics and alcohol ingestion." Clin Pharmacokinet 3 (1978): 440-52
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- Doak KK, Haas CE, Dunnigan KJ, et al. "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy 18 (1998): 637-45
- Rodman DP, Stevenson TL, Ray TR "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy 15 (1995): 801-5
- Au Yeung SC, Ensom MH "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother 34 (2000): 896-905
- Ozuna J, Friel P "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs 16 (1984): 289-91
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- Faraji B, Yu PP "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs 30 (1998): 55-9
- Marvel ME, Bertino JS "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr 15 (1991): 316-8
- Fleisher D, Sheth N, Kou JH "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr 14 (1990): 513-6
- Haley CJ, Nelson J "Phenytoin-enteral feeding interaction." DICP 23 (1989): 796-8
- Guidry JR, Eastwood TF, Curry SC "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med 150 (1989): 659-61
- Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia 28 (1987): 706-12
- Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
- Cerner Multum, Inc. "Australian Product Information." O 0
Conditions
Conditions in which Phenytoin Sodium needs care, as documented in this source.
Cardiotoxicity
MajorThe intravenous administration of phenytoin or its prodrug, fosphenytoin, is contraindicated in patients with sinus bradycardia, sino-atrial block, second and third degree AV block, and patients with Adam-Stokes syndrome. Severe cardiotoxic reactions related to depression of atrial and ventricular conduction and ventricular fibrillation have been reported with parenteral phenytoin, primarily in elderly or gravely ill patients. Hypotension and cardiovascular collapse have also been reported, usually when the drug was administered too rapidly. Therapy with intravenous phenytoin or fosphenytoin should be administered cautiously in patients with hypotension or severe myocardial insufficiency, particularly if they are elderly or seriously ill. The rate of injection should not exceed manufacturer recommendations and should be adjusted based on the patient's cardiovascular status. The rate of IV administration for SESQUIENT should not exceed 0.4 mg PE/kg/min in pediatric patients as safety at a faster rate has not been established.
13 sources
- Unger AH, Sklaroff HJ "Fatalities following intravenous use of sodium diphenylhydantoin for cardiac arrhythmias: report of two cases." JAMA 200 (1967): 159-60
- Barron SA "Cardiac arrhythmias after small intravenous dose of phenytoin." N Engl J Med 295 (1976): 678
- York RC, Coleridge ST "Cardiopulmonary arrest following intravenous phenytoin loading." Am J Emerg Med 6 (1988): 255-9
- Durelli L, Mutani R, Sechi GP, et al. "Cardiac side effects of phenytoin and carbamazepine: a dose related phenomenon?" Arch Neurol 42 (1985): 1067-8
- Isenstein D, Nasraway SA "Hypotension during slow phenytoin infusion in severe sepsis." Crit Care Med 18 (1990): 1036-8
- Earnest MP, Marx JA, Drury LR "Complications of intravenous phenytoin for acute treatment of seizures: recommendations for usage." JAMA 249 (1983): 762-5
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- Browne TR, Kugler AR, Eldon MA "Pharmacology and pharmacokinetics of fosphenytoin." Neurology 46 (6 supp (1996): s3-7
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- Ramsay RE, DeToledo J "Intravenous administration of fosphenytoin: options for the management of seizures." Neurology 46 (6 supp (1996): s17-9
- Sloan EP "Emergency department seizure treatment." P&T 21(suppl 5) (1996): s24-9
- Boucher BA, Feler CA, Dean JC, et al. "The safety, tolerability, and pharmacokinetics of fosphehytoin after intramuscular and intravenous administration in neurosurgery patients." Pharmacotherapy 16 (1996): 638-45
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
- "Product Information. Sesquient (fosphenytoin)." Emergent BioSolutions Inc. (2021):
Hematologic Diseases
MajorHematologic toxicities have been associated with the use of hydantoin anticonvulsants, particularly mephenytoin. Thrombocytopenia, leukopenia, neutropenia, agranulocytosis, pancytopenia and, rarely, hemolytic anemia, aplastic anemia and pure red cell aplasia have been reported. Therapy with hydantoin anticonvulsants should be administered cautiously in patients with preexisting blood dyscrasias and/or bone marrow depression. Complete blood counts, including platelets, should be performed prior to initiating therapy and regularly for several months thereafter. For mephenytoin, the manufacturer recommends performing counts after 2 weeks on a low dosage, after another 2 weeks when full dosage is reached, then monthly for a year, and every 3 months thereafter. Marked depression of blood counts may be indication for withdrawal of hydantoin therapy.
13 sources
- Schweiger FJ, Kelton JG, Messner H, et al. "Anticonvulsant-induced marrow suppression and immune thrombocytopenia." Acta Haematol 80 (1988): 54-8
- Travin M, Macris NT, Block JM, Schwimmer D "Reversible common variable immunodeficiency syndrome induced by phenytoin." Arch Intern Med 149 (1989): 1421-2
- Dessypris EN, Redline S, Harris JW, Krantz SB "Diphenylhydantoin-induced pure red cell aplasia." Blood 65 (1985): 789-94
- Guerra IC, Fawcett WA, Redmon AH, et al. "Permanent intrinsic B cell immunodeficiency caused by phenytoin hypersensitivity." J Allergy Clin Immunol 77 (1986): 603-8
- Eisenstein SJ, Coleman GC "Reversible bone marrow granulomata and fever induced by phenytoin administration." J Fam Pract 29 (1989): 564-5
- Cacatian AA, Rando J "Diphenylhydantoin-induced pseudolymphoma syndrome with severe thrombocytopenia." N Y State J Med June (1981): 1085-7
- Arbiser JL, Goldstein AM, Gordon D "Thrombocytopenia following administration of phenytoin, dexamethasone and cimetidine: a case report and a potential mechanism." J Intern Med 234 (1993): 91-4
- Rawanduzy A, Sarkis A, Rovit RL "Severe phenytoin-induced bone marrow depression and agranulocytosis treated with human recombinant granulocyte-macrophage colony- stimulating factor. Case report." J Neurosurg 79 (1993): 121-4
Show all 13 sourcesShow fewer sources
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
- Thompson DF, Gales MA "Drug-induced pure red cell aplasia." Pharmacotherapy 16 (1996): 1002-8
- "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
- "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
Kidney Diseases
MajorThe plasma protein binding of phenytoin may be significantly decreased in patients with renal impairment, resulting in elevated free drug concentrations and increased risk of toxicity. This effect is proportional to the degree of renal impairment and stems from quantitative differences in serum albumin as well as qualitative differences in the ability to bind phenytoin. Therapy with phenytoin should be administered cautiously in patients with impaired renal function. Both the therapeutic and toxic plasma total phenytoin levels may be lower than normal in these patients and should be considered in dosing. Alternatively, the monitoring of unbound phenytoin concentrations may be appropriate.
12 sources
- Tiula E, Haapanen EJ, Neuvonen PJ "Factors affecting serum protein binding of phenytoin, diazepam and propranolol in acute renal diseases." Int J Clin Pharmacol Ther Toxicol 25 (1987): 469-75
- Reynolds F, Jones NF, Ziroyanis PN, Smith SE "Salivary phenytoin concentrations in epilepsy and in chronic renal failure." Lancet 2 (1976): 384-9
- Reidenberg MM "The binding of drugs to plasma proteins and the interpretation of measurements of plasma concentrations of drugs in patients with poor renal function." Am J Med 62 (1977): 466-70
- Vanholder R, Van Landschoot N, De Smet R, Schoots A, Ringoir S "Drug protein binding in chronic renal failure: evaluation of nine drugs." Kidney Int 33 (1988): 996-1004
- Hooper WD, Bochner F, Eadie MJ, Tyrer JH "Plasma protein binding of diphenylhydantoin: effects of sex hormones, renal and hepatic disease." Clin Pharmacol Ther 15 (1974): 276-82
- Reidenberg MM, Odar-Cederlof I, Bahr C, von Borga O, Sjoqvist F "Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function." N Engl J Med 285 (1971): 264-7
- Odar-Cederlof I, Borga O "Kinetics of diphenylhydantoin in uraemic patients: consequences of decreased plasma protein binding." Eur J Clin Pharmacol 7 (1974): 31-7
- Mabuchi H, Nakahashi H "A major inhibitor of phenytoin binding to serum protein in uremia." Nephron 48 (1988): 310-4
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- Tiula E, Neuvonen PJ "Effect of total drug concentration on the free fraction in uremic sera." Ther Drug Monit 8 (1986): 27-31
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- Browne TR, Kugler AR, Eldon MA "Pharmacology and pharmacokinetics of fosphenytoin." Neurology 46 (6 supp (1996): s3-7
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
Liver Diseases
MajorHydantoin anticonvulsants are primarily metabolized by the liver. Both metabolic activity and plasma protein binding may be significantly altered in patients with liver disease, resulting in elevated drug levels (total and unbound fraction) and increased risk of toxicity. Therapy with hydantoin anticonvulsants should be administered cautiously in patients with impaired hepatic function. Reduced dosages and slower titration may be necessary. In addition, periodic monitoring of liver function is recommended, since the use of anticonvulsants, including hydantoins, has been associated with hepatotoxicity related to drug hypersensitivity. Hepatic failure and death have occurred. Hydantoin therapy should be discontinued and not readministered if evidence of liver damage is observed and felt to be drug-related.
17 sources
- Affrime M, Reidenberg MM "The protein binding of some drugs in plasma from patients with alcoholic liver disease." Eur J Clin Pharmacol 8 (1975): 267-9
- Olsen GD, Bennett WM, Porter GA "Morphine and phenytoin binding to plasma proteins in renal and hepatic failure." Clin Pharmacol Ther 17 (1975): 677-84
- Mullick FG, Ishak KG "Hepatic injury associated with diphenylhydantoin therapy: a clinicopathologic study of 20 cases." Am J Clin Pathol 74 (1980): 442-52
- Aaron JS, Bank S, Ackert G "Diphenylhydantoin-induced hepatotoxicity." Am J Gastroenterol 80 (1985): 200-2
- Gennis MA, Vemuri R, Burns EA, et al. "Familial occurrence of hypersensitivity to phenytoin." Am J Med 91 (1991): 631-4
- Taylor JW, Stein MN, Murphy MJ, Mitros FA "Cholestatic liver dysfunction after long-term phenytoin therapy." Arch Neurol 41 (1984): 500-1
- Sherertz EF, Jegasothy BV, Lazarus GS "Phenytoin hypersensitivity reaction presenting with toxic epidermal necrolysis and severe hepatitis." J Am Acad Dermatol 12 (1985): 178-81
- Egerton-Vernon JM, Fisk MJ, Snell AP "Phenytoin-induced hepatotoxicity." N Z Med J 96 (1983): 467-9
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- Korman LB, Olson MJ "Phenytoin-induced hepatitis, rhabdomyolysis, and renal dysfunction." Clin Pharm 8 (1989): 514-5
- Prosser TR, Lander RD "Phenytoin-induced hypersensitivity reactions." Clin Pharm 6 (1987): 728-34
- Hooper WD, Bochner F, Eadie MJ, Tyrer JH "Plasma protein binding of diphenylhydantoin: effects of sex hormones, renal and hepatic disease." Clin Pharmacol Ther 15 (1974): 276-82
- Roy AK, Mahoney HC, Levine RA "Phenytoin-induced chronic hepatitis." Dig Dis Sci 38 (1993): 740-3
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- Browne TR, Kugler AR, Eldon MA "Pharmacology and pharmacokinetics of fosphenytoin." Neurology 46 (6 supp (1996): s3-7
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
- "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
- "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
Porphyrias
MajorThe use of phenytoin has rarely been associated with exacerbation of porphyria. Therapy with phenytoin should be administered cautiously in patients with porphyria. The same precaution should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.
3 sources
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
- Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division (1998):
Alcoholism
ModerateThe use of acute alcoholic intake may increase phenytoin serum levels while chronic alcoholic use may decrease serum levels. Caution is recommended in alcoholic patients. The same precaution should also be observed with fosphenytoin as this agent is a prodrug of phenytoin.
2 sources
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
Anemia, Megaloblastic
ModerateHydantoin anticonvulsants may interfere with folate metabolism and precipitate macrocytosis and megaloblastic anemia, which usually respond to folic acid therapy. These reactions have been fairly uncommon but may be of concern in patients with megaloblastic anemia or folate deficiency receiving hydantoin therapy.
5 sources
- Goggin T, Gough H, Bissessar A, et al. "A comparative study of the relative effects of anticonvulsant drugs and dietary folate on the red cell folate status of patients with epilepsy." Q J Med 65 (1987): 911-9
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
- "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
- "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
Arrhythmias, Cardiac
ModerateAromatic antiepileptic drugs such as phenytoin, carbamazepine, and oxcarbazepine, inhibit voltage- gated sodium channels and reduce membrane excitability in neurons and muscle and can be associated with cardiovascular effects. Individual agents have demonstrated AV heart block, including second and third-degree block following treatment. This occurred generally, but not solely in patients with underlying EKG abnormalities or risk factors for conduction abnormalities. Therapy with these agents should be considered and administered cautiously in patients with a history of cardiovascular disease and conduction abnormalities.
1 source
- "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals (2002):
Depressive Disorder
ModerateAntiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
16 sources
- "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals (2002):
- "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
- "Product Information. Mysoline (primidone)." Elan Pharmaceuticals (2001):
- "Product Information. Lyrica (pregabalin)." Pfizer U.S. Pharmaceuticals Group (2005):
- "Product Information. Sabril (vigabatrin)." Lundbeck Inc (2009):
- "Product Information. Potiga (ezogabine)." GlaxoSmithKline (2011):
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- "Product Information. Qsymia (phentermine-topiramate)." Vivus Inc (2012):
- "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
- "Product Information. Briviact (brivaracetam)." UCB Pharma Inc (2016):
- "Product Information. Diacomit (stiripentol)." Biocodex USA (2018):
- "Product Information. Epidiolex (cannabidiol)." Greenwich Biosciences LLC (2018):
- "Product Information. Xcopri (cenobamate)." SK Life Science, Inc. (2020):
- "Product Information. Fintepla (fenfluramine)." Zogenix, Inc (2020):
- "Product Information. Ztalmy (ganaxolone)." Marinus Pharmaceuticals, Inc (2022):
Hyperglycemia
ModeratePhenytoin, particularly in high dosages, may cause hyperglycemia by inhibiting insulin release. The drug may also raise serum glucose levels in diabetic patients. Therapy with phenytoin should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during phenytoin therapy, and their antidiabetic regimen adjusted accordingly. The same precautions should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.
6 sources
- Carter BL, Small RE, Mandel MD, Starkman MT "Phenytoin-induced hyperglycemia." Am J Hosp Pharm 38 (1981): 1508-12
- Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
- "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
- "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
Osteomalacia
ModeratePhenytoin may interfere with vitamin D metabolism. Hypocalcemia and osteomalacia have been reported. Therapy with phenytoin should be administered cautiously in patients with preexisting vitamin D deficiency. The same precaution should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.
9 sources
- Hahn TJ, Hendin BA, Scharp CR, Haddad JG "Effect of chronic anticonvulsant therapy on serum 25-hydroxycalciferol levels in adults." N Engl J Med 287 (1972): 900-4
- Anast CS "Anticonvulsant drugs and calcium metabolism." N Engl J Med 292 (1975): 587-8
- Bell RD, Pak CY, Zerwekh J, et al. "Effect of phenytoin on bone and vitamin d metabolism." Ann Neurol 5 (1979): 374-8
- Ronin DI, Wu Y, Sahgal V, MacLean IC "Intractable muscle pain syndrome, osteomalacia, and axonopathy in long-term use of phenytoin." Arch Phys Med Rehabil 72 (1991): 755-8
- Schmitt BP, Nordlund DJ, Rodgers LA "Prevalence of hypocalcemia and elevated serum alkaline phosphatase in patients receiving chronic anticonvulsant therapy." J Fam Pract 18 (1984): 873-7
- Alderman CP, Hill CL "Abnormal bone mineral metabolism after long-term anticonvulsant treatment." Ann Pharmacother 28 (1994): 47-8
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- Siddiqui MA "Osteomalacia and phenytoin therapy." Ann Intern Med 121 (1994): 550
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- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
Thyroid Diseases
ModeratePhenytoin may decrease serum PBI (protein-bound iodine) levels without associated thyroid disturbance. Free thyroxine concentrations may also be decreased, while resin or red cell T3 uptake values may be increased. Clinicians should be cognizant of these effects when prescribing or administering phenytoin therapy to patients with thyroid disorders.
3 sources
- Isojarvi JI, Pakarinen AJ, Myllyla VV "Thyroid function with antiepileptic drugs." Epilepsia 33 (1992): 142-8
- "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
- "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
Therapeutic duplication
Drug classes that overlap with Phenytoin Sodium, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.
antiarrhythmics
The recommended maximum number of medicines in the 'antiarrhythmics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antiarrhythmics' category.
Example product in the source data (US market): Trandolapril/verapamil
group i antiarrhythmics
The recommended maximum number of medicines in the 'group I antiarrhythmics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'group I antiarrhythmics' category.
Example product in the source data (US market): Bupivacaine/lidocaine/triamcinolone
group i antiarrhythmics
The recommended maximum number of medicines in the 'group I antiarrhythmics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'group I antiarrhythmics' category.
Example product in the source data (US market): Nuedexta
group i antiarrhythmics
The recommended maximum number of medicines in the 'group I antiarrhythmics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'group I antiarrhythmics' category.
Example product in the source data (US market): Epinephrine/lidocaine