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Interactions between Epinephrine / prilocaine and Synthroid

1 drug interaction and 21 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

levothyroxine EPINEPHrine

Applies to: Synthroid (levothyroxine) and epinephrine / prilocaine
Monitor

The concomitant use of thyroid hormones, especially large doses, with sympathomimetic drugs may potentiate sympathomimetic effects and increase the risk of cardiac insufficiency in patients who have coronary artery disease.

Management

Monitoring for increased sympathomimetic effects and cardiac function may be advisable.

References (4)
  1. (2002) "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical
  2. (2022) "Product Information. Armour Thyroid (thyroid desiccated)." Forest Pharmaceuticals
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  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

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

levothyroxine Food/Lifestyle

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 (3)
  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
Moderate:

levothyroxine multivitamins with minerals

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 (4)
  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
Moderate:

EPINEPHrine Caffeine

Applies to: epinephrine / prilocaine
Monitor

Coadministration of two or more sympathomimetic or noradrenergic agents may increase the risk of nervousness, irritability, tachycardia, and/or increased blood pressure. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic and/or noradrenergic agents, including norepinephrine transporter inhibitors. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

Management

Caution is advised if two or more sympathomimetic or noradrenergic agents are coadministered. Pulse and blood pressure should be closely monitored. Consultation with individual product labeling, as well as relevant institutional protocols, may be advisable for further guidance.

References (20)
  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2024) "Product Information. Ephedrine (ephedrine)." Hameln Pharma Ltd
  8. (2023) "Product Information. Ephedrine Hydrochloride (ephedrine)." Wockhardt UK Ltd
  9. (2026) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
  10. (2025) "Product Information. Atomoxetine (atomoxetine)." Zentiva Pharma UK Ltd
  11. (2026) "Product Information. Atomoxetine (Apo) (atomoxetine)." Arrotex Pharmaceuticals Pty Ltd
  12. Angita Pharma, Inc (2026) AG-ATOMOXETINE Product Monograph (Health Canada) https://pdf.hres.ca/dpd_pm/00059014.PDF
  13. (2026) "Product Information. Boots Decongestant (Pseudoephedrine) (pseudoephedrine)." The Boots Company Plc
  14. (2023) "Product Information. Sinus and Nasal Decongestant (Trust) (pseudoephedrine)." Noumed Pharmaceuticals Pty Ltd
  15. (2019) "Product Information. Ephedrine (ephedrine)." Pfizer Australia Pty Ltd
  16. (2024) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Amneal Pharmaceuticals LLC
  17. (2024) "Product Information. Lemsip Cough Max for Mucus Cough and Cold (guaifenesin/paracetamol/phenylephrine)." Reckitt Benckiser Healthcare (UK) Ltd
  18. emc (2026) Product information: sudafed plus blocked nose 1mg/50mg/ml nasal spray. https://www.medicines.org.uk/emc/product/14256/smpc?utm_source=chatgpt.com
  19. (2023) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Baxter Corporation
  20. Neo Health (OTC) Pty Ltd (2026) Product information: pseudoephedrine hydrochloride-paracetamol capsules. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2024-PI-02603-1&d=20260804172310101&d=20260827172310101

Disease interactions

18 potential interactions Applies to: 16 conditions, including High Blood Pressure, Seizures, Hyperthyroidism, Heart Disease, and Diabetes Insipidus.

Acidosis

Moderate:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a moderate potential interaction with Acidosis.

Acidosis, hypoxia, and hypercapnia may reduce the effectiveness of sympathomimetic amines in raising blood pressure. These conditions should be corrected before initiating therapy with sympathomimetic amines, if possible. Monitoring the patients acid-base balance, carbon dioxide levels, and oxygen saturation is recommended.

Adrenal Insufficiency

Major:

Synthroid

The levothyroxine in Synthroid has a major potential interaction with Adrenal Insufficiency.

The use of thyroid hormones is contraindicated in patients with uncorrected adrenal insufficiency. Thyroid hormones increase tissue demand for adrenocortical hormones and may precipitate acute adrenal crisis. In patients with controlled adrenal insufficiency or other endocrine disorders, therapy for these concomitant disorders may need to be adjusted following thyroid replacement, since hypothyroidism often obscure or diminish the signs and symptoms of these conditions. Clinical monitoring of thyroid and adrenal function as well as any other appropriate endocrine function is recommended during thyroid hormone therapy.

Cardiovascular Conditions and Disorders

Major:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a major potential interaction with Cardiovascular Conditions and Disorders.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Dehydration

Major:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a major potential interaction with Dehydration.

The use of sympathomimetic amines has been infrequently associated with significant hypotension especially in dehydrated patients secondary to the drug's beta-2 mediated vasodilation. Hypovolemia should be corrected, if possible, before administering sympathomimetic amines. Blood pressure and ECG should be monitored at regular intervals. Monitoring of cardiac output and pulmonary wedge pressure may also be desired.

Diabetes Insipidus

Moderate:

Synthroid

The levothyroxine in Synthroid has a moderate potential interaction with Diabetes Insipidus.

Since hypothyroidism often obscure or diminish the signs and symptoms of endocrine disorders such as diabetes mellitus or diabetes insipidus, thyroid replacement therapy may aggravate the intensity of symptoms associated with these conditions. Patients with endocrine disorders should be monitored more closely during thyroid hormone therapy, and their medication regimen adjusted accordingly. If thyroid medication is later discontinued, a downward readjustment of insulin or oral hypoglycemic agent may be necessary in patients with diabetes mellitus to avoid hypoglycemia.

Diabetes Mellitus

Moderate:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a moderate potential interaction with Diabetes Mellitus.

Sympathomimetic agents may cause increases in blood glucose concentrations. These effects are usually transient and slight but may be significant with dosages higher than those normally recommended. Therapy with sympathomimetic agents should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate.

Moderate:

Synthroid

The levothyroxine in Synthroid has a moderate potential interaction with Diabetes Mellitus.

Since hypothyroidism often obscure or diminish the signs and symptoms of endocrine disorders such as diabetes mellitus or diabetes insipidus, thyroid replacement therapy may aggravate the intensity of symptoms associated with these conditions. Patients with endocrine disorders should be monitored more closely during thyroid hormone therapy, and their medication regimen adjusted accordingly. If thyroid medication is later discontinued, a downward readjustment of insulin or oral hypoglycemic agent may be necessary in patients with diabetes mellitus to avoid hypoglycemia.

Heart Disease

Major:

Synthroid

The levothyroxine in Synthroid has a major potential interaction with Heart Disease.

Thyroid hormones cause increases in myocardial contractility and heart rate as a result of increased metabolic demands and oxygen consumption. Therapy with thyroid hormones should be administered cautiously and initiated at reduced dosages in patients with cardiovascular disorders such as angina, coronary artery disease, and hypertension. Clinical monitoring of cardiovascular function is recommended. If chest pain or exacerbation of cardiovascular disease occurs, the dosage of thyroid hormone should be reduced, even at the expense of achieving euthyroid state. Thyroid hormones should not be administered to patients with an acute myocardial infarction that is not complicated by hypothyroidism.

High Blood Pressure

Major:

Synthroid

The levothyroxine in Synthroid has a major potential interaction with High Blood Pressure.

Thyroid hormones cause increases in myocardial contractility and heart rate as a result of increased metabolic demands and oxygen consumption. Therapy with thyroid hormones should be administered cautiously and initiated at reduced dosages in patients with cardiovascular disorders such as angina, coronary artery disease, and hypertension. Clinical monitoring of cardiovascular function is recommended. If chest pain or exacerbation of cardiovascular disease occurs, the dosage of thyroid hormone should be reduced, even at the expense of achieving euthyroid state. Thyroid hormones should not be administered to patients with an acute myocardial infarction that is not complicated by hypothyroidism.

Hyperthyroidism

Major:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a major potential interaction with Hyperthyroidism.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Major:

Synthroid

The levothyroxine in Synthroid has a major potential interaction with Hyperthyroidism.

The use of thyroid hormones is contraindicated in patients with untreated thyrotoxicosis of any etiology, since thyroid hormones may exacerbate the condition.

Liver Disease

Moderate:

epinephrine / prilocaine

The prilocaine in epinephrine / prilocaine has a moderate potential interaction with Liver Disease.

Prilocaine topical is absorbed through intact skin and mucosal membranes. Prolonged exposure, large doses, and/or application to compromised skin or mucosa can result in elevated plasma concentrations of prilocaine. Prilocaine is metabolized by the liver and to some extent by the kidney. The pharmacokinetic disposition of prilocaine is altered by changes in hepatic and renal function. Therapy with prilocaine topical should be administered cautiously and dosing modified for patients with compromised hepatic and renal function.

Methemoglobinemia

Major:

epinephrine / prilocaine

The prilocaine in epinephrine / prilocaine has a major potential interaction with Methemoglobinemia.

Prilocaine has induced methemoglobinemia resulting in respiratory distress and cyanosis. Therapy with prilocaine topical should be administered cautiously to patients with or predisposed to methemoglobinemia. If life-threatening or severe methemoglobinemia develops, methylene blue infused at a dosage of 1 to 2 mg/kg body weight will rapidly reverse or improve the condition, except in G-6-PD-deficient patients.

Neurological Disorders

Moderate:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a moderate potential interaction with Neurological Disorders.

Epinephrine should be administered with caution to patients with Parkinson's disease as these patients may experience psychomotor agitation or notice a temporary worsening of symptoms.

Parkinsonism

Moderate:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a moderate potential interaction with Parkinsonism.

Epinephrine should be administered with caution to patients with Parkinson's disease as these patients may experience psychomotor agitation or notice a temporary worsening of symptoms.

Pheochromocytoma

Major:

epinephrine / prilocaine

The EPINEPHrine in epinephrine / prilocaine has a major potential interaction with Pheochromocytoma.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Renal Dysfunction

Moderate:

epinephrine / prilocaine

The prilocaine in epinephrine / prilocaine has a moderate potential interaction with Renal Dysfunction.

Prilocaine topical is absorbed through intact skin and mucosal membranes. Prolonged exposure, large doses, and/or application to compromised skin or mucosa can result in elevated plasma concentrations of prilocaine. Prilocaine is metabolized by the liver and to some extent by the kidney. The pharmacokinetic disposition of prilocaine is altered by changes in hepatic and renal function. Therapy with prilocaine topical should be administered cautiously and dosing modified for patients with compromised hepatic and renal function.

Seizures

Moderate:

Synthroid

The levothyroxine in Synthroid has a moderate potential interaction with Seizures.

Thyroid hormones may alter the seizure threshold. Seizures have been reported rarely following the initiation of levothyroxine therapy. Therapy with thyroid hormones should be administered cautiously in patients predisposed to seizures.

More resources

epinephrine / prilocaine

A total of 335 drugs are known to interact with epinephrine / prilocaine.

Synthroid

A total of 254 drugs are known to interact with Synthroid.

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.