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Fosphenytoin Disease Interactions

There are 12 disease interactions with fosphenytoin:

Major

Hydantoins (Includes Fosphenytoin) ↔ Blood Dyscrasias

Severe Potential Hazard, Low plausibility

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

Hydantoins (Includes Fosphenytoin) ↔ Liver Disease

Severe Potential Hazard, High plausibility

Applies to: Liver Disease

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

Hydantoins (Includes Fosphenytoin) ↔ Porphyria

Severe Potential Hazard, Moderate plausibility

Applies to: Porphyria

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. Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL, eds. "Harrison's Principles of Internal Medicine. 14th ed." New York, NY: McGraw-Hill Health Professionals Division (1998):
  2. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis, Morris Plains, NJ.
  3. "Product Information. Dilantin (phenytoin)." Parke-Davis, Morris Plains, NJ.
Major

Phenytoin (Includes Fosphenytoin) ↔ Renal Dysfunction

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction

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

Phenytoin Iv (Includes Fosphenytoin) ↔ Cardiotoxicity

Severe Potential Hazard, High plausibility

Applies to: 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.

References

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

Antiepileptics (Includes Fosphenytoin) ↔ Suicidal Tendency

Moderate Potential Hazard, Moderate plausibility

Applies to: 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 across multiple indications in either monotherapy or adjunctive therapy for a median treatment duration of 12 weeks (up to a maximum of 24 weeks) showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. The estimated rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% for 16,029 placebo-treated patients, representing an increase of approximately one case for every 530 patients treated. There were four suicides in AED-treated patients and none in placebo-treated patients, although the number is too small to establish any causal relationship. The increased risk of suicidal thoughts or behavior was observed as early as one week after starting AEDs and persisted for the duration of treatment assessed. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Therapy with 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. For clinically significant or persistent symptoms, a dosage reduction or treatment withdrawal should be considered. If patients have symptoms of suicidal ideation or behavior, treatment should be discontinued.

Moderate

Fosphenytoin (Includes Fosphenytoin) ↔ Renal Dysfunction

Moderate Potential Hazard, Moderate plausibility

Applies to: Renal Dysfunction

Fosphenytoin injection provides a phosphate load of 0.0037 mmol per each mg of phenytoin sodium equivalent activity, which should be considered in patients who require phosphate restriction, such as those with severe renal impairment.

References

  1. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis, Morris Plains, NJ.
Moderate

Hydantoins (Includes Fosphenytoin) ↔ Hyperglycemia

Moderate Potential Hazard, Moderate plausibility

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

Hydantoins (Includes Fosphenytoin) ↔ Megaloblastic Anemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Folic Acid/Cyanocobalamin Deficiency, Anemia Associated with Folate 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. Mesantoin (mephenytoin)" Novartis Pharmaceuticals, East Hanover, NJ.
  3. "Product Information. Dilantin (phenytoin)." Parke-Davis, Morris Plains, NJ.
  4. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis, Morris Plains, NJ.
  5. "Product Information. Peganone (ethotoin)" Abbott Pharmaceutical, Abbott Park, IL.
View all 5 references
Moderate

Hydantoins (Includes Fosphenytoin) ↔ Osteomalacia

Moderate Potential Hazard, Moderate plausibility

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

Phenytoin (Includes Fosphenytoin) ↔ Alcoholism

Moderate Potential Hazard, Moderate plausibility

Applies to: Alcoholism

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.

Moderate

Phenytoin (Includes Fosphenytoin) ↔ Thyroid Function Tests

Moderate Potential Hazard, Moderate plausibility

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

fosphenytoin drug Interactions

There are 1115 drug interactions with fosphenytoin

fosphenytoin alcohol/food Interactions

There is 1 alcohol/food interaction with fosphenytoin

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
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 information available.

Do not stop taking any medications without consulting your healthcare provider.

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