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Drug Interaction Report

3 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

No drug ⬌ drug interactions were found between the drugs in your list. However, this does not necessarily mean no drug interactions exist. Always consult your healthcare provider.

Drug and food interactions

Major

buprenorphine food

Applies to: buprenorphine

GENERALLY AVOID: Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection. The mechanism of interaction probably involves some degree of additive pharmacologic effects. Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

References

  1. (2002) "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc
  2. Kilicarslan T, Sellers EM (2000) "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry, 157, p. 1164-6
  3. Reynaud M, Petit G, Potard D, Courty P (1998) "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction, 93, p. 1385-92
  4. Tracqui A, Kintz P, Ludes B (1998) "Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities." J Anal Toxicol, 22, p. 430-4
  5. Reynaud M, Tracqui A, Petit G, Potard D, Courty P (1998) "Six deaths linked to misuse of buprenorphine-benzodiazepine combinations." Am J Psychiatry, 155, p. 448-9
  6. Kintz P (2002) "A new series of 13 buprenorphine-related deaths." Clin Biochem, 35, p. 513-6
  7. Martin HA (2011) "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs, 37, p. 200-2
  8. Hakkinen M, Launiainen T, Vuori E, Ojanpera I (2012) "Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning." Eur J Clin Pharmacol, 68, p. 301-9
  9. Substance Abuse and Mental Health Services Administration (US) (2013) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series, No. 40 http://www.ncbi.nlm.nih.gov/books/NBK64245/
  10. Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ (2013) "Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes." Drug Alcohol Depend, 132, p. 580-6
  11. Ferrant O, Papin F, Clin B, et al. (2011) "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int, 204, e8-11
  12. Pirnay S, Borron SW, Giudicelli CP, Tourneau J, Baud FJ, Ricordel I (2004) "A critical review of the causes of death among post-morten toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths." Addiction, 99, p. 978-88
  13. Kintz P (2001) "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int, 121, p. 65-9
  14. Sekar M, Mimpriss TJ (1987) "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia, 42, p. 567-8
  15. Gueye PN, Borron SW, Risede P, et al. (2002) "Buprenorphine and midazolalm act in combination to depress respiration in rats." Toxicol Sci, 65, p. 107-14
  16. US Food and Drug Administration (2016) FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf
View all 16 references

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Moderate

levothyroxine food

Applies to: Synthroid (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

levothyroxine food

Applies to: Synthroid (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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Therapeutic duplication warnings

No duplication 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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Further information

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