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Drug Interactions between levothyroxine and Pepcid Complete

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

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Interactions between your drugs

Moderate

levothyroxine calcium carbonate

Applies to: levothyroxine and Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide)

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

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Moderate

levothyroxine magnesium hydroxide

Applies to: levothyroxine and Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide)

ADJUST DOSING INTERVAL: Concurrent administration of simethicone and/or antacid preparations may decrease the oral bioavailability of levothyroxine. Pharmacologic effects of levothyroxine may be reduced. The exact mechanism of interaction is unknown but may involve nonspecific adsorption of levothyroxine to polyvalent cations, resulting in an insoluble complex that is poorly absorbed from the gastrointestinal tract. Additionally, because gastric acidity is required for adequate levothyroxine absorption, agents that effect intragastric pH may reduce levothyroxine absorption. There have been case reports suggesting decreased efficacy of levothyroxine during coadministration of aluminum- and magnesium-containing antacids, as well as other products containing polyvalent cations such as calcium and iron. In one report, a man stabilized on levothyroxine 150 mcg/day developed significantly increased serum thyrotropin (thyroid-stimulating hormone, or TSH) levels while taking an aluminum and magnesium hydroxide antacid. The apparent interaction was also observed on two subsequent rechallenges. Other case reports have described increased dosage requirements of levothyroxine during antacid use. It is not known whether this interaction occurs with other thyroid hormone preparations.

MANAGEMENT: It is recommended to separate the times of administration of levothyroxine and simethicone and antacids or other antacid-containing preparations (e.g., didanosine buffered tablets or pediatric oral solution) 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. Sperber AD, Liel Y (1992) "Evidence for interference with the intestinal absorption of levothyroxine sodium by aluminum hydroxide." Arch Intern Med, 152, p. 183-4
  2. (2002) "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical
  3. Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC (1992) "Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism." Ann Intern Med, 117, p. 1010-3
  4. Liel Y, Sperber AD, Shany S (1994) "Nonspecific intestinal adsorption of levothyroxine by aluminum hydroxide." Am J Med, 97, p. 363-5
  5. Schneyer CR (1998) "Calcium carbonate and reduction of levothyroxine efficacy." JAMA, 279, p. 750
  6. Singh N, Singh PN, Hershman JM (2000) "Effect of calcium carbonate on the absorption of levothyroxine." JAMA, 283, p. 2822-5
  7. Csako G, McGriff NJ, Rotman-Pikielny P, Sarlis NJ, Pucino F (2001) "Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders." Ann Pharmacother, 35, p. 1578-83
  8. Neafsey PJ (2004) "Levothyroxine and calcium interaction: timing is everything." Home Healthc Nurse, 22, p. 338-9
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  10. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  11. Cerner Multum, Inc. "Australian Product Information."
View all 11 references

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Minor

famotidine calcium carbonate

Applies to: Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide) and Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide)

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

References

  1. Donn KH, Eshelman FN, Plachetka JR, et al. (1984) "The effects of antacid and propantheline on the absorption of oral ranitidine." Pharmacotherapy, 4, p. 89-92
  2. Albin H, Vincon G, Demotes-Mainard F, et al. (1984) "Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone." Eur J Clin Pharmacol, 26, p. 271-3
  3. Lin JH, Chremos AN, Kanovsky SM, Schwartz S, Yeh KC, Kann J (1987) "Effects of antacids and food on absorption of famotidine." Br J Clin Pharmacol, 24, p. 551-3
  4. Bodemar G, Norlander B, Walan A (1979) "Diminished absorption of cimetidine caused by antacids." Lancet, 02/24/79, p. 444-5
  5. Steinberg WM, Lewis JH, Katz DM (1982) "Antacids inhibit absorption of cimetidine." N Engl J Med, 307, p. 400-4
  6. Barzaghi N, Gatti G, Crema F, Perucca E (1989) "Impaired bioavailability of famotidine given concurrently with a potent antacid." J Clin Pharmacol, 29, p. 670-2
  7. Russell WL, Lopez LM, Normann SA, et al. (1984) "Effect of antacids on predicted steady-state cimetidine concentrations." Dig Dis Sci, 29, p. 385-9
  8. Shelly DW, Doering PL, Russell WL, Guild RT, Lopez LM, Perrin J (1986) "Effect of concomitant antacid administration on plasma cimetidine concentrations during repetitive dosing." Drug Intell Clin Pharm, 20, p. 792-5
  9. Albin H, Vincon G, Begaud B, Bistue C, Perez P (1987) "Effect of aluminum phosphate on the bioavailability of ranitidine." Eur J Clin Pharmacol, 32, p. 97-9
  10. Mihaly GW, Marino AT, Webster LK, Jones DB, Louis WJ, Smallwood RA (1982) "High dose of antacid (Mylanta II) reduces bioavailability of ranitidine." Br Med J, 285, p. 998-9
  11. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  12. Bachmann KA, Sullivan TJ, Jauregui L, Reese J, Miller K, Levine L (1994) "Drug interactions of h-2-receptor antagonists." Scand J Gastroenterol, 29, p. 14-9
View all 12 references

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Minor

famotidine magnesium hydroxide

Applies to: Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide) and Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide)

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

References

  1. Donn KH, Eshelman FN, Plachetka JR, et al. (1984) "The effects of antacid and propantheline on the absorption of oral ranitidine." Pharmacotherapy, 4, p. 89-92
  2. Albin H, Vincon G, Demotes-Mainard F, et al. (1984) "Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone." Eur J Clin Pharmacol, 26, p. 271-3
  3. Lin JH, Chremos AN, Kanovsky SM, Schwartz S, Yeh KC, Kann J (1987) "Effects of antacids and food on absorption of famotidine." Br J Clin Pharmacol, 24, p. 551-3
  4. Bodemar G, Norlander B, Walan A (1979) "Diminished absorption of cimetidine caused by antacids." Lancet, 02/24/79, p. 444-5
  5. Steinberg WM, Lewis JH, Katz DM (1982) "Antacids inhibit absorption of cimetidine." N Engl J Med, 307, p. 400-4
  6. Barzaghi N, Gatti G, Crema F, Perucca E (1989) "Impaired bioavailability of famotidine given concurrently with a potent antacid." J Clin Pharmacol, 29, p. 670-2
  7. Russell WL, Lopez LM, Normann SA, et al. (1984) "Effect of antacids on predicted steady-state cimetidine concentrations." Dig Dis Sci, 29, p. 385-9
  8. Shelly DW, Doering PL, Russell WL, Guild RT, Lopez LM, Perrin J (1986) "Effect of concomitant antacid administration on plasma cimetidine concentrations during repetitive dosing." Drug Intell Clin Pharm, 20, p. 792-5
  9. Albin H, Vincon G, Begaud B, Bistue C, Perez P (1987) "Effect of aluminum phosphate on the bioavailability of ranitidine." Eur J Clin Pharmacol, 32, p. 97-9
  10. Mihaly GW, Marino AT, Webster LK, Jones DB, Louis WJ, Smallwood RA (1982) "High dose of antacid (Mylanta II) reduces bioavailability of ranitidine." Br Med J, 285, p. 998-9
  11. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  12. Bachmann KA, Sullivan TJ, Jauregui L, Reese J, Miller K, Levine L (1994) "Drug interactions of h-2-receptor antagonists." Scand J Gastroenterol, 29, p. 14-9
View all 12 references

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Drug and food interactions

Moderate

levothyroxine food

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

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Moderate

calcium carbonate food

Applies to: Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide)

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  3. Cerner Multum, Inc. "Australian Product Information."
  4. 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
  5. Mangels AR (2014) "Bone nutrients for vegetarians." Am J Clin Nutr, 100, epub
  6. Davies NT (1979) "Anti-nutrient factors affecting mineral utilization." Proc Nutr Soc, 38, p. 121-8
View all 6 references

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Moderate

levothyroxine food

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

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Minor

famotidine food

Applies to: Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide)

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM (1990) "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol, 38, p. 165-9

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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