Interactions between Savella and Synthroid
No drug interactions found, but 23 warnings to review for the following 2 drugs:
- Savella (milnacipran)
- Synthroid (levothyroxine)
Drug interactions
There were no interactions found between Savella and Synthroid. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.
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)
- (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:
milnacipran Food/Lifestyle
Applies to: Savella (milnacipran)
Generally avoid
Use of milnacipran in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Milnacipran alone can increase serum transaminase levels. In placebo-controlled fibromyalgia trials, increases in ALT were more frequently observed in patients treated with milnacipran 100 mg/day (6%) and 200 mg/day (7%) compared to patients treated with placebo (3%). One patient receiving milnacipran 100 mg/day (0.2%) had an increase in ALT greater than 5 times the upper limit of normal (ULN) but did not exceed 10 times the ULN. Increases in AST were also more frequently observed in patients treated with milnacipran 100 mg/day (3%) and 200 mg/day (5%) than in patients treated with placebo (2%). There have been reported cases of increased liver enzymes and severe liver injury, including fulminant hepatitis, from foreign postmarketing experience with milnacipran. Significant underlying clinical conditions and/or use of multiple concomitant medications were present in the cases of severe liver injury.
Management
Due to the risk of liver injury, patients prescribed milnacipran should be counseled to avoid excessive use of alcohol. Milnacipran should generally not be prescribed to patients with substantial alcohol use.
References (1)
- (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
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)
- 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
20 potential interactions Applies to: 17 conditions, including High Blood Pressure, Depression, Bipolar Disorder, Urinary Tract Infection, and Seizures.
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.
Bipolar Disorder
Major:
Savella
The milnacipran in Savella has a major potential interaction with Bipolar Disorder.
Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Bipolar Disorder.
Therapy with SNRI antidepressants can cause activation of mania and hypomania and should be used with caution in patients with personal or family history of mania, hypomania, bipolar disorder, and other mood disorders.
Dehydration
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Dehydration.
Treatment with SNRI antidepressants can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.
Depression
Major:
Savella
The milnacipran in Savella has a major potential interaction with Depression.
Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.
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:
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.
Glaucoma, Narrow Angle
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Glaucoma, Narrow Angle.
SNRI antidepressants cause pupillary dilation that may trigger an angle closure attack in patients with anatomically narrow angle without iridectomy.
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.
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with High Blood Pressure.
Selective serotonin and norepinephrine reuptake inhibitor antidepressants (SNRIs) have been associated with sustained increases in blood pressure. Therapy with SNRI antidepressants should be administered cautiously in patients with preexisting hypertension. Blood pressure should be assessed prior to initiating treatment and monitored regularly. The dose should be reduced or discontinued if necessary.
Hyperthyroidism
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.
Hyponatremia
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Hyponatremia.
Treatment with SNRI antidepressants can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.
Liver Disease
Major:
Savella
The milnacipran in Savella has a major potential interaction with Liver Disease.
Postmarketing studies have reported that duloxetine and some other SNRIs like milnacipran may aggravate preexisting liver disease. The use of duloxetine delayed-release and milnacipran should be avoided in patients with chronic liver disease or cirrhosis.
Mania
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Mania.
Therapy with SNRI antidepressants can cause activation of mania and hypomania and should be used with caution in patients with personal or family history of mania, hypomania, bipolar disorder, and other mood disorders.
Renal Dysfunction
Major:
Savella
The milnacipran in Savella has a major potential interaction with Renal Dysfunction.
The clearance of SNRI antidepressants is decreased in subjects with renal impairment. SNRIs should be used with caution in this group of patients and a dose adjustment is recommended in those with moderate and severe renal impairment. The use of SNRIs is not recommended in patients with end-stage renal disease.
Seizures
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Seizures.
SNRI antidepressants may trigger seizures and should be administered with caution in patients with a seizure disorder.
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.
Urinary Tract Infection
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Urinary Tract Infection.
SNRI antidepressants have a noradrenergic effect and can affect urethral resistance. Caution should be used in patients with a history of dysuria, prostatic hypertrophy, prostatitis, and other lower urinary tract obstructive disorders.
Urinary Tract Obstruction
Moderate:
Savella
The milnacipran in Savella has a moderate potential interaction with Urinary Tract Obstruction.
SNRI antidepressants have a noradrenergic effect and can affect urethral resistance. Caution should be used in patients with a history of dysuria, prostatic hypertrophy, prostatitis, and other lower urinary tract obstructive disorders.
More resources
Savella
A total of 395 drugs are known to interact with Savella.
- Savella is in the drug class serotonin-norepinephrine reuptake inhibitors.
- Savella is used to treat Fibromyalgia.
Synthroid
A total of 254 drugs are known to interact with Synthroid.
- Synthroid is in the drug class thyroid drugs.
- Synthroid 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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.