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Drug Interactions between doxepin and Levothroid

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

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Interactions between your drugs

Moderate

doxepin levothyroxine

Applies to: doxepin and Levothroid (levothyroxine)

MONITOR: Coadministration of thyroid hormone replacement therapy with tricyclic antidepressants may accelerate the onset or potentiate the action of tricyclic antidepressants, increasing the risk of cardiac arrhythmias and CNS stimulation. The proposed mechanism may be an increased receptor sensitivity to catecholamines. Some clinicians have used this interaction therapeutically. However, individual cases of paroxysmal tachycardia, hypothyroidism, and thyrotoxicosis have also been reported.

MANAGEMENT: Patients receiving concomitant thyroid hormone replacement therapy and tricyclic antidepressant therapy should be closely monitored for cardiac arrhythmias and CNS stimulation. Advise patients to contact their doctor if they experience toxicity symptoms such as: anxiety, agitation, insomnia, shortness of breath, irregular or fast heartbeat, and lightheadedness or dizziness.

References

  1. Prange AJ, Wilson IC, Rabon AM, Lipton MA "Enhancement of imipramine antidepressant activity by thyroid hormone." Am J Psychiatry 126 (1969): 457-69
  2. Wilson IC, Prange AJ, McClane TK, Rabon AM, Lipton MA "Thyroid-hormone enhancement of imipramine in nonretarded depressions." N Engl J Med 282 (1970): 1063-7
  3. Wheatley D "Potentiation of amitriptyline by thyroid hormone." Arch Gen Psychiatry 26 (1972): 229-33
  4. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals PROD (2002):
  5. "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical PROD (2002):
  6. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals PROD (2001):
  7. "Product Information. Cytomel (liothyronine)." Monarch Pharmaceuticals Inc PROD (2001):
  8. Altshuler LL, Bauer M, Frye MA, et al. "Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature." Am J Psychiatry 158 (2001): 1617-22
  9. Joffe RT "The use of thyroid supplements to augment antidepressant medication." J Clin Psychiatry 59 Suppl 5 (1998): 26-9; discussion 30-1
  10. Joffe RT, Singer W, Levitt AJ, MacDonald C "A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression." Arch Gen Psychiatry 50 (1993): 387-93
  11. Cooke RG, Joffe RT, Levitt AJ "T3 augmentation of antidepressant treatment in T4-replaced thyroid patients." J Clin Psychiatry 53 (1992): 16-8
  12. Cooke RG "T3 augmentation of a tricyclic antidepressant in a patient receiving T4 maintenance therapy." Am J Psychiatry 147 (1990): 255
  13. Extein IL, Gold MS "Thyroid hormone potentiation of tricyclics." Psychosomatics 29 (1988): 166-74
  14. Schwarcz G, Halaris A, Baxter L, Escobar J, Thompson M, Young M "Normal thyroid function in desipramine nonresponders converted to responders by the addition of L-triiodothyronine." Am J Psychiatry 141 (1984): 1614-6
  15. Goodwin FK, Prange AJ Jr, Post RM, Muscettola G, Lipton MA "Potentiation of antidepressant effects by L-triiodothyronine in tricyclic nonresponders." Am J Psychiatry 139 (1982): 34-8
  16. Swartz CM "Dependency of tricyclic antidepressant efficacy on thyroid hormone potentiation: case studies." J Nerv Ment Dis 170 (1982): 50-2
  17. "Product Information. Triostat (liothyronine)." JHP Pharmaceuticals (2005):
  18. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  19. Cerner Multum, Inc. "Australian Product Information." O 0
  20. Posternak M, Novak S, Stern R, et al. "A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response." Int J Neuropsychopharmacol 11 (2008): 15-25
View all 20 references

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Drug and food interactions

Moderate

levothyroxine food

Applies to: Levothroid (levothyroxine)

ADJUST DOSING INTERVAL: Consumption of certain foods as well as the timing of meals relative to dosing may affect the oral absorption of T4 thyroid hormone (i.e., levothyroxine). T4 oral absorption is increased by fasting and decreased by foods such as soybean flour (e.g., infant formula), cotton seed meal, walnuts, dietary fiber, calcium, and calcium fortified juices. Grapefruit or grapefruit products may delay the absorption of T4 thyroid hormone and reduce its bioavailability. The mechanism of this interaction is not fully understood.

MANAGEMENT: Some manufacturers recommend administering oral T4 as a single daily dose, on an empty stomach, one-half to one hour before breakfast. In general, oral preparations containing T4 thyroid hormone should be administered on a consistent schedule with regard to time of day and relation to meals to avoid large fluctuations in serum levels. Foods that may affect T4 absorption should be avoided within several hours of dosing if possible. Consult local guidelines for the administration of T4 in patients receiving enteral feeding.

References

  1. "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical PROD (2002):
  2. "Product Information. Armour Thyroid (thyroid desiccated)." Forest Pharmaceuticals (2022):
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

doxepin food

Applies to: 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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Moderate

levothyroxine food

Applies to: Levothroid (levothyroxine)

ADJUST DOSING INTERVAL: Concurrent administration of calcium-containing products may decrease the oral bioavailability of levothyroxine by one-third in some patients. Pharmacologic effects of levothyroxine may be reduced. The exact mechanism of interaction is unknown but may involve nonspecific adsorption of levothyroxine to calcium at acidic pH levels, resulting in an insoluble complex that is poorly absorbed from the gastrointestinal tract. In one study, 20 patients with hypothyroidism who were taking a stable long-term regimen of levothyroxine demonstrated modest but significant decreases in mean free and total thyroxine (T4) levels as well as a corresponding increase in mean thyrotropin (thyroid-stimulating hormone, or TSH) level following the addition of calcium carbonate (1200 mg/day of elemental calcium) for 3 months. Four patients had serum TSH levels that were higher than the normal range. Both T4 and TSH levels returned to near-baseline 2 months after discontinuation of calcium, which further supported the likelihood of an interaction. In addition, there have been case reports suggesting decreased efficacy of levothyroxine during calcium coadministration. It is not known whether this interaction occurs with other thyroid hormone preparations.

MANAGEMENT: Some experts recommend separating the times of administration of levothyroxine and calcium-containing preparations by at least 4 hours. Monitoring of serum TSH levels is recommended. Patients with gastrointestinal or malabsorption disorders may be at a greater risk of developing clinical or subclinical hypothyroidism due to this interaction.

References

  1. Schneyer CR "Calcium carbonate and reduction of levothyroxine efficacy." JAMA 279 (1998): 750
  2. Singh N, Singh PN, Hershman JM "Effect of calcium carbonate on the absorption of levothyroxine." JAMA 283 (2000): 2822-5
  3. Csako G, McGriff NJ, Rotman-Pikielny P, Sarlis NJ, Pucino F "Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders." Ann Pharmacother 35 (2001): 1578-83
  4. Neafsey PJ "Levothyroxine and calcium interaction: timing is everything." Home Healthc Nurse 22 (2004): 338-9
View all 4 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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