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Dilantin Disease Interactions

There are 12 disease interactions with Dilantin (phenytoin).

Major

Hydantoins (applies to Dilantin) blood dyscrasias

Major Potential Hazard, Low plausibility. Applicable conditions: Bone Marrow Depression/Low Blood Counts

Hematologic 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.

References

  1. Schweiger FJ, Kelton JG, Messner H, et al. "Anticonvulsant-induced marrow suppression and immune thrombocytopenia." Acta Haematol 80 (1988): 54-8
  2. Travin M, Macris NT, Block JM, Schwimmer D "Reversible common variable immunodeficiency syndrome induced by phenytoin." Arch Intern Med 149 (1989): 1421-2
  3. Dessypris EN, Redline S, Harris JW, Krantz SB "Diphenylhydantoin-induced pure red cell aplasia." Blood 65 (1985): 789-94
  4. 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
  5. Eisenstein SJ, Coleman GC "Reversible bone marrow granulomata and fever induced by phenytoin administration." J Fam Pract 29 (1989): 564-5
  6. Cacatian AA, Rando J "Diphenylhydantoin-induced pseudolymphoma syndrome with severe thrombocytopenia." N Y State J Med June (1981): 1085-7
  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
  8. 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
  9. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  10. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  11. Thompson DF, Gales MA "Drug-induced pure red cell aplasia." Pharmacotherapy 16 (1996): 1002-8
  12. "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
  13. "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
View all 13 references
Major

Hydantoins (applies to Dilantin) liver disease

Major Potential Hazard, High plausibility.

Hydantoin 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.

References

  1. 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
  2. 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
  3. Mullick FG, Ishak KG "Hepatic injury associated with diphenylhydantoin therapy: a clinicopathologic study of 20 cases." Am J Clin Pathol 74 (1980): 442-52
  4. Aaron JS, Bank S, Ackert G "Diphenylhydantoin-induced hepatotoxicity." Am J Gastroenterol 80 (1985): 200-2
  5. Gennis MA, Vemuri R, Burns EA, et al. "Familial occurrence of hypersensitivity to phenytoin." Am J Med 91 (1991): 631-4
  6. Taylor JW, Stein MN, Murphy MJ, Mitros FA "Cholestatic liver dysfunction after long-term phenytoin therapy." Arch Neurol 41 (1984): 500-1
  7. 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
  8. Egerton-Vernon JM, Fisk MJ, Snell AP "Phenytoin-induced hepatotoxicity." N Z Med J 96 (1983): 467-9
  9. Korman LB, Olson MJ "Phenytoin-induced hepatitis, rhabdomyolysis, and renal dysfunction." Clin Pharm 8 (1989): 514-5
  10. Prosser TR, Lander RD "Phenytoin-induced hypersensitivity reactions." Clin Pharm 6 (1987): 728-34
  11. 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
  12. Roy AK, Mahoney HC, Levine RA "Phenytoin-induced chronic hepatitis." Dig Dis Sci 38 (1993): 740-3
  13. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  14. Browne TR, Kugler AR, Eldon MA "Pharmacology and pharmacokinetics of fosphenytoin." Neurology 46 (6 supp (1996): s3-7
  15. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  16. "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
  17. "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
View all 17 references
Major

Hydantoins (applies to Dilantin) porphyria

Major Potential Hazard, Moderate plausibility.

The 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.

References

  1. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  2. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  3. 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):
Major

Phenytoin (applies to Dilantin) renal dysfunction

Major Potential Hazard, High plausibility.

The 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.

References

  1. 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
  2. Reynolds F, Jones NF, Ziroyanis PN, Smith SE "Salivary phenytoin concentrations in epilepsy and in chronic renal failure." Lancet 2 (1976): 384-9
  3. 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
  4. 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
  5. 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
  6. 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
  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
  8. Mabuchi H, Nakahashi H "A major inhibitor of phenytoin binding to serum protein in uremia." Nephron 48 (1988): 310-4
  9. Tiula E, Neuvonen PJ "Effect of total drug concentration on the free fraction in uremic sera." Ther Drug Monit 8 (1986): 27-31
  10. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  11. Browne TR, Kugler AR, Eldon MA "Pharmacology and pharmacokinetics of fosphenytoin." Neurology 46 (6 supp (1996): s3-7
  12. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
View all 12 references
Major

Phenytoin IV (applies to Dilantin) cardiotoxicity

Major Potential Hazard, High plausibility. Applicable conditions: Heart Disease, Hypotension

The 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.

References

  1. Unger AH, Sklaroff HJ "Fatalities following intravenous use of sodium diphenylhydantoin for cardiac arrhythmias: report of two cases." JAMA 200 (1967): 159-60
  2. Barron SA "Cardiac arrhythmias after small intravenous dose of phenytoin." N Engl J Med 295 (1976): 678
  3. York RC, Coleridge ST "Cardiopulmonary arrest following intravenous phenytoin loading." Am J Emerg Med 6 (1988): 255-9
  4. 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
  5. Isenstein D, Nasraway SA "Hypotension during slow phenytoin infusion in severe sepsis." Crit Care Med 18 (1990): 1036-8
  6. Earnest MP, Marx JA, Drury LR "Complications of intravenous phenytoin for acute treatment of seizures: recommendations for usage." JAMA 249 (1983): 762-5
  7. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  8. Browne TR, Kugler AR, Eldon MA "Pharmacology and pharmacokinetics of fosphenytoin." Neurology 46 (6 supp (1996): s3-7
  9. Ramsay RE, DeToledo J "Intravenous administration of fosphenytoin: options for the management of seizures." Neurology 46 (6 supp (1996): s17-9
  10. Sloan EP "Emergency department seizure treatment." P&T 21(suppl 5) (1996): s24-9
  11. 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
  12. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  13. "Product Information. Sesquient (fosphenytoin)." Emergent BioSolutions Inc. (2021):
View all 13 references
Moderate

Antiepileptics (applies to Dilantin) suicidal tendency

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Depression, Psychosis

Antiepileptic 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.

References

  1. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals (2002):
  2. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  3. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  4. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  5. "Product Information. Mysoline (primidone)." Elan Pharmaceuticals (2001):
  6. "Product Information. Lyrica (pregabalin)." Pfizer U.S. Pharmaceuticals Group (2005):
  7. "Product Information. Sabril (vigabatrin)." Lundbeck Inc (2009):
  8. "Product Information. Potiga (ezogabine)." GlaxoSmithKline (2011):
  9. "Product Information. Qsymia (phentermine-topiramate)." Vivus Inc (2012):
  10. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  11. "Product Information. Briviact (brivaracetam)." UCB Pharma Inc (2016):
  12. "Product Information. Diacomit (stiripentol)." Biocodex USA (2018):
  13. "Product Information. Epidiolex (cannabidiol)." Greenwich Biosciences LLC (2018):
  14. "Product Information. Xcopri (cenobamate)." SK Life Science, Inc. (2020):
  15. "Product Information. Fintepla (fenfluramine)." Zogenix, Inc (2020):
  16. "Product Information. Ztalmy (ganaxolone)." Marinus Pharmaceuticals, Inc (2022):
View all 16 references
Moderate

Aromatic antiepileptic drugs (applies to Dilantin) arrhythmias

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Cardiovascular Disease

Aromatic 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.

References

  1. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals (2002):
Moderate

Hydantoins (applies to Dilantin) hyperglycemia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Diabetes Mellitus, Abnormal Glucose Tolerance

Phenytoin, 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.

References

  1. Carter BL, Small RE, Mandel MD, Starkman MT "Phenytoin-induced hyperglycemia." Am J Hosp Pharm 38 (1981): 1508-12
  2. Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70
  3. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  4. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  5. "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
  6. "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
View all 6 references
Moderate

Hydantoins (applies to Dilantin) megaloblastic anemia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Anemia Associated with Folate Deficiency, Folic Acid/Cyanocobalamin Deficiency

Hydantoin 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.

References

  1. 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
  2. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  3. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  4. "Product Information. Peganone (ethotoin)." Abbott Pharmaceutical (2001):
  5. "Product Information. Mesantoin (mephenytoin)." Novartis Pharmaceuticals (2001):
View all 5 references
Moderate

Hydantoins (applies to Dilantin) osteomalacia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Vitamin D Deficiency

Phenytoin 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.

References

  1. 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
  2. Anast CS "Anticonvulsant drugs and calcium metabolism." N Engl J Med 292 (1975): 587-8
  3. Bell RD, Pak CY, Zerwekh J, et al. "Effect of phenytoin on bone and vitamin d metabolism." Ann Neurol 5 (1979): 374-8
  4. 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
  5. 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
  6. Alderman CP, Hill CL "Abnormal bone mineral metabolism after long-term anticonvulsant treatment." Ann Pharmacother 28 (1994): 47-8
  7. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  8. Siddiqui MA "Osteomalacia and phenytoin therapy." Ann Intern Med 121 (1994): 550
  9. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
View all 9 references
Moderate

Phenytoin (applies to Dilantin) alcoholism

Moderate Potential Hazard, Moderate plausibility.

The 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.

References

  1. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  2. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
Moderate

Phenytoin (applies to Dilantin) thyroid function tests

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Thyroid Disease

Phenytoin 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.

References

  1. Isojarvi JI, Pakarinen AJ, Myllyla VV "Thyroid function with antiepileptic drugs." Epilepsia 33 (1992): 142-8
  2. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  3. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):

Dilantin drug interactions

There are 805 drug interactions with Dilantin (phenytoin).

Dilantin alcohol/food interactions

There is 1 alcohol/food interaction with Dilantin (phenytoin).


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.