Phenytoin Disease Interactions

There are 10 disease interactions with phenytoin:

Hydantoins (Includes Phenytoin) ↔ 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. "Product Information. Mesantoin (mephenytoin)" Novartis Pharmaceuticals, East Hanover, NJ.
  3. Schweiger FJ, Kelton JG, Messner H, et al "Anticonvulsant-induced marrow suppression and immune thrombocytopenia." Acta Haematol 80 (1988): 54-8
View all 13 references

Hydantoins (Includes Phenytoin) ↔ 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. 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. Taylor JW, Stein MN, Murphy MJ, Mitros FA "Cholestatic liver dysfunction after long-term phenytoin therapy." Arch Neurol 41 (1984): 500-1
View all 17 references

Hydantoins (Includes Phenytoin) ↔ 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.

Phenytoin (Includes Phenytoin) ↔ 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. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis, Morris Plains, NJ.
  3. Mabuchi H, Nakahashi H "A major inhibitor of phenytoin binding to serum protein in uremia." Nephron 48 (1988): 310-4
View all 12 references

Phenytoin Iv (Includes Phenytoin) ↔ 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
View all 12 references

Antiepileptics (Includes Phenytoin) ↔ 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.

Hydantoins (Includes Phenytoin) ↔ 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.
View all 6 references

Hydantoins (Includes Phenytoin) ↔ Megaloblastic Anemia

Moderate Potential Hazard, Moderate plausibility

Applies to: 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. Mesantoin (mephenytoin)" Novartis Pharmaceuticals, East Hanover, NJ.
  3. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis, Morris Plains, NJ.
View all 5 references

Hydantoins (Includes Phenytoin) ↔ 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. 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
View all 9 references

Phenytoin (Includes Phenytoin) ↔ 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

You should also know about...

phenytoin drug Interactions

There are 1075 drug interactions with phenytoin

phenytoin alcohol/food Interactions

There are 2 alcohol/food interactions with phenytoin

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.

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

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