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Drug Interactions between Adzenys ER and Sinequan

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

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Interactions between your drugs

Moderate

doxepin amphetamine

Applies to: Sinequan (doxepin) and Adzenys ER (amphetamine)

MONITOR: The use of tricyclic antidepressants in combination with amphetamines or sympathomimetic appetite suppressants may produce additive cardiovascular effects, increasing the risk of hypertension, cardiac arrhythmias, tachycardia, and fever. The mechanism involves additive pharmacodynamic effects resulting from increased norepinephrine release by sympathomimetic agents and inhibition of norepinephrine reuptake by tricyclic antidepressants. A pharmacokinetic interaction is also possible between tricyclic antidepressants and amphetamines, since many of these agents are metabolized by CYP450 2D6. Increased plasma levels of one or both drugs may occur during coadministration.

MANAGEMENT: Close monitoring of cardiovascular status is recommended for patients receiving this combination. Patients should be advised to promptly report symptoms such as fever, headache, or fast or irregular heartbeats.

References

  1. Raisfeld IH "Cardiovascular complications of antidepressant therapy: interactions at the adrenergic neuron." Am Heart J 83 (1972): 129-33
  2. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
  3. Nielsen KK, Flinois JP, Beaune P, Brosen K "The biotransformation of clomipramine in vitro, identification of the cytochrome p450s responsible for the separate metabolic pathways." J Pharmacol Exp Ther 277 (1996): 1659-64
  4. Gunne LM, Antonijevic S, Jonsson J "Effect of fenfluramine on steady state plasma levels of amitriptyline." Postgrad Med J 51 Suppl 1 (1975): 117
  5. Markowitz JS, Patrick KS "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet 40 (2001): 753-72
  6. Kirchheiner J, Muller G, Meineke I, Wernecke KD, Roots I, Brockmoller J "Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics." J Clin Psychopharmacol 23 (2003): 459-66
  7. Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J "Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers." Pharmacogenetics 12 (2002): 571-80
  8. Haritos VS, Ghabrial H, Ahokas JT, Ching MS "Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin." Pharmacogenetics 10 (2000): 591-603
View all 8 references

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Drug and food interactions

Moderate

amphetamine food

Applies to: Adzenys ER (amphetamine)

GENERALLY AVOID: Alcohol may potentiate the cardiovascular effects of amphetamines. The exact mechanism of interaction is unknown. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state. The interaction was suspected in a case report of a 20-year-old male who experienced retrosternal chest pain shortly after drinking alcohol and taking a double dose of his amphetamine/dextroamphetamine medication (Adderall 15 mg X 2) to stay alert. The patient had no family history of cardiovascular diseases, and his past medical history was remarkable only for ADHD. Prior to the episode, the patient had not taken his medication for weeks and had been drinking whiskey the previous three nights before going to bed. The patient was diagnosed with myocardial infarction likely secondary to amphetamine-induced coronary vasospasm.

MANAGEMENT: Concomitant use of amphetamines and alcohol should be avoided if possible, especially in patients with a history of heart disease.

References

  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68
  2. Jiao X, Velez S, Ringstad J, Eyma V, Miller D, Bleiberg M "Myocardial infarction associated with Adderall XR and alcohol use in a young man." J Am Board Fam Med 22 (2009): 197-201

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Moderate

doxepin food

Applies to: Sinequan (doxepin)

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

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

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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.

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