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Drug Interactions between fosphenytoin and nortriptyline

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

nortriptyline fosphenytoin

Applies to: nortriptyline and fosphenytoin

MONITOR: Tricyclic antidepressants may increase serum phenytoin levels. In vitro studies suggest the mechanism may involve inhibition of CYP450 2C19-catalyzed phenytoin p-hydroxylation by tricyclic antidepressants, especially imipramine and amitriptyline. Phenytoin may induce the hepatic metabolism of desipramine resulting in decreased plasma concentrations. In addition, tricyclic antidepressants may lower the seizure threshold.

MANAGEMENT: Clinical monitoring of patient response, tolerance, and serum phenytoin concentrations is recommended. Patients should be advised to notify their doctor if they experience loss of seizure control or symptoms of phenytoin toxicity (drowsiness, visual disturbances, change in mental status, nausea, or ataxia). Phenytoin dosage may need to be adjusted.

References (9)
  1. Fogel BS, Haltzman S (1987) "Desipramine and phenytoin: a potential drug interaction of therapeutic relevance." J Clin Psychiatry, 48, p. 387-8
  2. Houghton GW, Richens A (1975) "Inhibition of phenytoin metabolism by other drugs used in epilepsy." Int J Clin Pharmacol, 12, p. 210-6
  3. Perucca E, Richens A (1977) "Interaction between phenytoin and imipramine." Br J Clin Pharmacol, 4, p. 485-6
  4. Shin JG, Park JY, Kim MJ, et al. (2002) "Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin." Drug Metab Dispos, 30, p. 1102-7
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  8. Cerner Multum, Inc. (2015) "Canadian Product Information."
  9. Cerner Multum, Inc (2015) "ANVISA Bulário Eletrônico."

Drug and food interactions

Moderate

nortriptyline food

Applies to: nortriptyline

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References (7)
  1. Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
  2. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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

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