Interactions between Levoxyl and Rosiglitazone
1 drug interaction and 25 additional warnings found for the following 2 drugs:
- Levoxyl (levothyroxine)
- rosiglitazone
Drug interactions
Moderate drug interactions
Moderate:
levothyroxine rosiglitazone
Applies to: Levoxyl (levothyroxine) and rosiglitazone
Monitor
The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, sirolimus, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.
Management
Caution is advised when drugs that can interfere with glucose metabolism are prescribed to patients with diabetes. Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of these drugs, and the dosages of concomitant antidiabetic agents adjusted as necessary. Patients should be advised to notify their physician if their blood glucose is consistently high or if they experience symptoms of severe hyperglycemia such as excessive thirst and increases in the volume or frequency of urination. Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.
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Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
levothyroxine Food/Lifestyle
Applies to: Levoxyl (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)
- (2002) "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical
- (2022) "Product Information. Armour Thyroid (thyroid desiccated)." Forest Pharmaceuticals
- 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:
rosiglitazone Food/Lifestyle
Applies to: rosiglitazone
Generally avoid
Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.
Management
Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.
References (11)
- Jerntorp P, Almer LO (1981) "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand, 656, p. 33-6
- Jerntorp P, Almer LO, Holin H, et al. (1983) "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol, 24, p. 237-42
- Barnett AH, Spiliopoulos AJ, Pyke DA, et al. (1983) "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia, 24, p. 213-5
- Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A (1987) "Interaction of ethanol and glipizide in humans." Diabetes Care, 10, p. 683-6
- (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
- (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
- "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
- Skillman TG, Feldman JM (1981) "The pharmacology of sulfonylureas." Am J Med, 70, p. 361-72
- (2002) "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care, 25(Suppl 1), S50-S60
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2026) "Product Information. Awiqli FlexTouch (insulin icodec)." Novo Nordisk Pharmaceuticals Inc
Moderate:
levothyroxine multivitamins with minerals
Applies to: Levoxyl (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)
- Schneyer CR (1998) "Calcium carbonate and reduction of levothyroxine efficacy." JAMA, 279, p. 750
- Singh N, Singh PN, Hershman JM (2000) "Effect of calcium carbonate on the absorption of levothyroxine." JAMA, 283, p. 2822-5
- 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
- Neafsey PJ (2004) "Levothyroxine and calcium interaction: timing is everything." Home Healthc Nurse, 22, p. 338-9
Disease interactions
22 potential interactions Applies to: 20 conditions, including High Blood Pressure, Weight Loss, Heart Failure, Seizures, and Anemia.
Adrenal Insufficiency
Major:
Levoxyl
The levothyroxine in Levoxyl 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.
Anemia
Minor:
rosiglitazone
Rosiglitazone has a minor potential interaction with Anemia.
Thiazolidinediones can cause slight decreases in hemoglobin and hematocrit. In clinical studies, hemoglobin levels were reduced primarily within the first 4 to 12 weeks of therapy but remained relatively constant thereafter. These changes may be related to increased plasma volume and have rarely been associated with any significant hematologic clinical effects. Nevertheless, caution may be advisable when thiazolidinediones are prescribed to patients with certain anemias.
Diabetes, Type 1
Major:
rosiglitazone
Rosiglitazone has a major potential interaction with Diabetes, Type 1.
Thiazolidinediones exert their hypoglycemic effect only in the presence of insulin. Therefore, these agents should not be used in patients with type I diabetes or for the treatment of diabetic ketoacidosis.
Diabetes Insipidus
Moderate:
Levoxyl
The levothyroxine in Levoxyl 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:
Levoxyl
The levothyroxine in Levoxyl 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.
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Diabetes Mellitus.
New onset or worsening diabetic macular edema with decreased visual acuity have been reported in postmarketing reports in some diabetic patients who were taking thiazolidinedione drugs. Some patients presented with blurred vision or decreased visual acuity, but some patients appear to have been diagnosed on routine ophthalmologic examination. Most patients had peripheral edema at the time macular edema was diagnosed. Some patients had improvement in their macular edema after discontinuation of their thiazolidinedione. Patients with diabetes should have regular eye exams by an ophthalmologist according to current standards of care. Additionally, any diabetic who reports any kind of visual symptom should be promptly referred to an ophthalmologist, regardless of the patient's underlying medications or other physical findings.
Diabetic Ketoacidosis
Major:
rosiglitazone
Rosiglitazone has a major potential interaction with Diabetic Ketoacidosis.
Thiazolidinediones exert their hypoglycemic effect only in the presence of insulin. Therefore, these agents should not be used in patients with type I diabetes or for the treatment of diabetic ketoacidosis.
Diabetic Macular Edema
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Diabetic Macular Edema.
New onset or worsening diabetic macular edema with decreased visual acuity have been reported in postmarketing reports in some diabetic patients who were taking thiazolidinedione drugs. Some patients presented with blurred vision or decreased visual acuity, but some patients appear to have been diagnosed on routine ophthalmologic examination. Most patients had peripheral edema at the time macular edema was diagnosed. Some patients had improvement in their macular edema after discontinuation of their thiazolidinedione. Patients with diabetes should have regular eye exams by an ophthalmologist according to current standards of care. Additionally, any diabetic who reports any kind of visual symptom should be promptly referred to an ophthalmologist, regardless of the patient's underlying medications or other physical findings.
Fluid Retention
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Fluid Retention.
Thiazolidinediones can cause dose-related edema. Therapy with thiazolidinediones should be administered cautiously in patients at risk for congestive heart failure as well as those with fluid overload or other conditions that may be adversely affected by excess fluid such as hypertension. Patients should be monitored for signs and symptoms of heart failure such as dyspnea, swelling of legs or ankles, and weight gain.
Heart Disease
Major:
Levoxyl
The levothyroxine in Levoxyl 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.
Heart Failure
Major:
rosiglitazone
Rosiglitazone has a major potential interaction with Heart Failure.
The use of thiazolidinediones, alone or in combination with other antidiabetic agents, has been associated with fluid retention and new onset or exacerbation of heart failure. An increased risk of cardiovascular events (heart failure worsening; new or worsening edema; new or worsening dyspnea; increases in heart failure medication; myocardial infarction; angina; cardiovascular hospitalization and deaths) has been reported with rosiglitazone therapy in type II diabetic patients with New York Heart Association (NYHA) Class I or II congestive heart failure compared to placebo. Likewise, overnight hospitalization for CHF was observed in 9.9% of diabetic patients with NYHA Class II and III heart failure on pioglitazone compared to 4.7% of patients on glyburide. An increased incidence of cardiovascular adverse events including edema and cardiac failure has also been reported in patients receiving a thiazolidinedione in combination with insulin relative to insulin and placebo. Therapy with thiazolidinediones should be administered cautiously and initiated at the lowest recommended dosage in patients with congestive heart failure. Thiazolidinediones are contraindicated for the treatment of patients with NYHA Class III or IV cardiac status. Patients should be monitored for signs of worsening heart failure such as increased dyspnea, edema, and weight gain. Therapy should be discontinued if any deterioration in cardiac status occurs.
High Blood Pressure
Major:
Levoxyl
The levothyroxine in Levoxyl 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.
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with High Blood Pressure.
Thiazolidinediones can cause dose-related edema. Therapy with thiazolidinediones should be administered cautiously in patients at risk for congestive heart failure as well as those with fluid overload or other conditions that may be adversely affected by excess fluid such as hypertension. Patients should be monitored for signs and symptoms of heart failure such as dyspnea, swelling of legs or ankles, and weight gain.
History - Myocardial Infarction
Major:
rosiglitazone
Rosiglitazone has a major potential interaction with History - Myocardial Infarction.
Safety data from a pooled analysis of 42 randomized, controlled clinical studies suggest that patients treated with rosiglitazone may have an increased risk of myocardial infarction and/or death from heart-related causes. The overall incidence of myocardial ischemia was 1.99% in patients receiving rosiglitazone-containing therapies (n = 8,604) for at least 24 weeks, compared to 1.51% in patients receiving placebo or other antidiabetic therapies (n = 5,633) for a similar duration. The hazard ratio was 1.31 (95% CI, 1.01 to 1.70) for rosiglitazone-treated patients relative to the comparators, which represents a greater than 30% excess risk of myocardial ischemic events in the rosiglitazone group. However, other published and unpublished data from long-term clinical trials of rosiglitazone provide contradictory evidence about the potential risks. Until more data are available, caution may be advisable when rosiglitazone is prescribed to patients with underlying heart disease or a history of myocardial infarction.
Hyperthyroidism
Major:
Levoxyl
The levothyroxine in Levoxyl 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.
Ischemic Heart Disease
Major:
rosiglitazone
Rosiglitazone has a major potential interaction with Ischemic Heart Disease.
Safety data from a pooled analysis of 42 randomized, controlled clinical studies suggest that patients treated with rosiglitazone may have an increased risk of myocardial infarction and/or death from heart-related causes. The overall incidence of myocardial ischemia was 1.99% in patients receiving rosiglitazone-containing therapies (n = 8,604) for at least 24 weeks, compared to 1.51% in patients receiving placebo or other antidiabetic therapies (n = 5,633) for a similar duration. The hazard ratio was 1.31 (95% CI, 1.01 to 1.70) for rosiglitazone-treated patients relative to the comparators, which represents a greater than 30% excess risk of myocardial ischemic events in the rosiglitazone group. However, other published and unpublished data from long-term clinical trials of rosiglitazone provide contradictory evidence about the potential risks. Until more data are available, caution may be advisable when rosiglitazone is prescribed to patients with underlying heart disease or a history of myocardial infarction.
Liver Disease
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Liver Disease.
Initiation of rosiglitazone or pioglitazone therapy is not recommended in patients who exhibit clinical evidence of active liver disease or increased baseline serum transaminase levels (ALT exceeding 2.5 times upper limit of normal). Use of these agents is also not recommended in patients who have experienced jaundice during treatment with troglitazone. The use of troglitazone, another agent in the thiazolidinedione class, has been associated with clinically significant elevations in liver enzymes, reversible jaundice, and idiosyncratic hepatocellular injury including rare cases of liver failure, liver transplants, and death. Injury has occurred after both short- and long-term treatment. While these effects have not been associated with other thiazolidinediones in clinical trials, concerns exist because of their structural similarities. In addition, isolated cases of hepatitis and hepatic enzyme elevations to 3 or more times the upper limit of normal have been reported with both rosiglitazone and pioglitazone during postmarketing use. Rarely, these events have involved hepatic failure with and without fatal outcome, although causality has not been established. Until more safety data are available, patients who are prescribed thiazolidinedione therapy should have serum transaminase levels checked at baseline and periodically thereafter as clinically necessary. Mild to moderate elevations (ALT less than or equal to 2.5 times ULN) require cautious use with more frequent monitoring to determine if the elevations resolve or worsen. Patients who develop potential symptoms of hepatic injury such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, and dark urine should have liver enzymes checked. Therapy should be withdrawn if ALT is elevated and persists above 3 times ULN or if jaundice develops.
Pleural Effusion
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Pleural Effusion.
Thiazolidinediones can cause dose-related edema. Therapy with thiazolidinediones should be administered cautiously in patients at risk for congestive heart failure as well as those with fluid overload or other conditions that may be adversely affected by excess fluid such as hypertension. Patients should be monitored for signs and symptoms of heart failure such as dyspnea, swelling of legs or ankles, and weight gain.
Premenopausal Anovulation
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Premenopausal Anovulation.
In premenopausal, anovulatory patients with insulin resistance, treatment with thiazolidinediones may result in resumption of ovulation. Due to improved insulin sensitivity, pregnancy can occur if adequate contraception is not used.
Pulmonary Edema
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Pulmonary Edema.
Thiazolidinediones can cause dose-related edema. Therapy with thiazolidinediones should be administered cautiously in patients at risk for congestive heart failure as well as those with fluid overload or other conditions that may be adversely affected by excess fluid such as hypertension. Patients should be monitored for signs and symptoms of heart failure such as dyspnea, swelling of legs or ankles, and weight gain.
Seizures
Moderate:
Levoxyl
The levothyroxine in Levoxyl 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.
Weight Loss
Moderate:
rosiglitazone
Rosiglitazone has a moderate potential interaction with Weight Loss.
Thiazolidinediones can cause dose-related weight gain, which may be undesirable in obese patients attempting to lose weight. The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation. In postmarketing experience with rosiglitazone, there have been reports of unusually rapid increases in weight, greater than those generally observed in clinical trials. Patients who experience such increases should be assessed for fluid retention and volume-related events such as excessive edema and congestive heart failure.
More resources
Levoxyl
A total of 254 drugs are known to interact with Levoxyl.
- Levoxyl is in the drug class thyroid drugs.
- Levoxyl is used to treat the following conditions:
rosiglitazone
A total of 364 drugs are known to interact with rosiglitazone.
- Rosiglitazone is in the drug class thiazolidinediones.
- Rosiglitazone is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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