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Drug Interactions between Cytomel and Depo-Estradiol

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

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Interactions between your drugs

Moderate

estradiol liothyronine

Applies to: Depo-Estradiol (estradiol) and Cytomel (liothyronine)

MONITOR: Estrogens may increase serum thyrotropin concentration, which could be harmful in patients with thyroid cancer receiving thyroxine for thyrotropin suppression or increase dosage requirements in patients with hypothyroidism receiving thyroxine for replacement therapy. Estrogens are known to increase serum thyroid-binding globulin concentration in a dose-dependent manner. Consequently, there may be a reduction in unbound, or free, thyroxine available for hormone activity, which, in turn, leads to an increase in serum thyrotropin concentration. Normally, thyroxine secretion can increase to compensate for this effect, but patients with hypothyroidism lack the mechanism to adapt. Limited evidence suggests that transdermal estrogen therapy may not affect thyroid-binding globulin concentrations; however, more data are required to confirm that.

MANAGEMENT: In patients treated with thyroxine, serum thyrotropin should be measured approximately 12 weeks after estrogen therapy is initiated, changed or discontinued, and the thyroxine dosage adjusted accordingly. Patients should be advised to contact their physician if clinical manifestations of hypothyroidism occur, such as fatigue, cold intolerance, constipation, unexplained weight gain, depression, joint or muscle pain, thinning hair or hair loss, dry skin, hoarseness, and abnormal menstrual periods.

References

  1. "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical PROD (2002):
  2. Chetkowski RJ, Meldrum DR, Steingold KA, et al. "Biologic effects of transdermal estradiol." N Engl J Med 314 (1986): 1615-20
  3. Arafah BM "Increased need for thyroxine in women with hypothyroidism during estrogen therapy." N Engl J Med 344 (2001): 1743-9
  4. Utiger RD "Estrogen, thyroxine binding in serum, and thyroxine therapy." N Engl J Med 344 (2001): 1784-5
  5. Irving S, Vadiveloo T, Leese GP "Drugs that interact with levothyroxine; an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS)." Clin Endocrinol (Oxf) (2014):
  6. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):
View all 6 references

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Drug and food interactions

Moderate

liothyronine food

Applies to: Cytomel (liothyronine)

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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Minor

estradiol food

Applies to: Depo-Estradiol (estradiol)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

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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.

See also

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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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