Levothyroxine: side effects and drug interactions

Levothyroxine (brand names Synthroid, Unithroid, Levoxyl) is a synthetic version of thyroid hormone known as T4. The medication works the same way in the body as the thyroid hormone produced by your thyroid gland. Levothyroxine is prescribed for thyroid-hormone replacement therapy in people with low thyroid hormone levels (hypothyroidism). In combination with other treatments, it can also be used to treat some forms of thyroid cancer (DailyMed, 2019).

Levothyroxine works by replacing the thyroid hormone that your thyroid gland usually produces. Adequate levels of thyroid hormone are necessary for your body to regulate many of its normal processes. Without enough thyroid hormone, you may find yourself with low energy levels, constipation, weight gain, hair loss, increased sensitivity to cold, among other things (MedLinePlus, 2019). You can reduce these symptoms by taking levothyroxine to supplement your low thyroid hormone levels.

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Most of the side effects of levothyroxine are mainly due to getting too much of the drug, leading to symptoms of hyperthyroidism (too much thyroid hormone).

Black box warning issued by the U.S. Food and Drug Administration (FDA, 2017): Do not use thyroid hormones, like levothyroxine, for weight loss or to treat obesity. Large doses of levothyroxine can lead to serious and life-threatening effects.

Common side effects include (DailyMed, 2019):

• Increased appetite

• Weight loss

• Inability to tolerate high temperatures (heat intolerance)

• Fever

• Excessive sweating (hyperhidrosis)

• Nervousness/anxiety

• Tiredness

• Hyperactivity

• Muscle tremors

• Diarrhea

• Hair loss

• Decreased bone mineral density

• Irregular menstrual cycles

• Fertility problems

Serious side effects can occur, especially if the levothyroxine dose is too high. They mainly involve the heart and may include (DailyMed, 2019):

• Fast heartbeat (tachycardia or palpitations)

• Irregular heartbeat (arrhythmia)

• High blood pressure

• Heart failure

• Chest pain (angina)

• Heart attack (myocardial infarction)

• Cardiac arrest (heart stops working)

If you experience any of these side effects, seek medical attention right away.

This list does not include all possible side effects and others may exist. Check with your pharmacist or healthcare provider for more information.

Before starting levothyroxine, be sure to seek medical advice regarding your other medications to avoid any potential drug interactions. Some medicines can increase the risk of side effects, while others may make levothyroxine less effective. Also, levothyroxine may change the effectiveness of other medications you are taking. Drug interactions include (DailyMed, 2019):

• Calcium carbonate (like over-the-counter antacids) and ferrous sulfate (iron supplements) can prevent levothyroxine from being absorbed. Make sure to take calcium carbonate or ferrous sulfate at least four hours apart from your levothyroxine.

• Bile acid sequestrants (like colesevelam, cholestyramine, colestipol, kayexalate, sevelamer) are medications used to lower cholesterol; they may prevent levothyroxine from being absorbed. Take these medications at least four hours apart from your levothyroxine.

• Proton pump inhibitors (PPIs) and other antacids (brand names Maalox, Mylanta, etc.) interfere with the absorption of levothyroxine because they lower the stomach acid levels. Levothyroxine needs stomach acid to work properly. By reducing your stomach acid, these drugs make levothyroxine less effective.

• Diabetic medications, like insulin, metformin, etc., are less effective if taken with levothyroxine, and your healthcare provider may need to adjust your doses.

• Anticoagulants (blood thinners), like warfarin, are more likely to cause bleeding if you are also taking levothyroxine. Your healthcare provider may need to decrease your anticoagulant dose while you are taking the thyroid hormone.

• Digoxin, a drug used to regulate your heartbeat, is less effective in the presence of levothyroxine, and your healthcare professional may increase your dose.

• Antidepressants interact with levothyroxine in various ways. Taking tricyclic antidepressants, like amitriptyline, with levothyroxine increases the potential toxicity of both medications. Toxic effects may include cardiac arrhythmias (abnormal heartbeats) or nervous system problems. However, the antidepressant sertraline decreases the effectiveness of levothyroxine, and you may need to take more levothyroxine to get the desired effect.

• Ketamine and levothyroxine together increase your risk of significantly high blood pressure (hypertension) and fast heart rate (tachycardia).

• Sympathomimetic drugs (albuterol, dopamine, ephedrine, etc.) taken with levothyroxine may increase the risk of toxicity of both the thyroid hormone and the sympathomimetic drugs. People with heart disease are especially at risk of having serious heart problems if the two are taken together.

• Tyrosine-kinase inhibitors are a type of cancer medication that may decrease the effectiveness of levothyroxine.

• Orlistat, a weight loss medication, may prevent levothyroxine absorption by binding to the drug (Filippatos, 2008).

In addition to drug interaction, some foods can affect how levothyroxine is processed in your body. Foods like soybean flour, soy, walnuts, dietary fiber, espresso coffee, and grapefruit may all decrease the absorption of levothyroxine (UpToDate, n.d.).

This list does not include all possible drug interactions with levothyroxine and others may exist. Check with your pharmacist or healthcare provider for more information.

• People with adrenal insufficiency should have their adrenal gland function restored before starting levothyroxine.

• People with heart disease (cardiovascular disease) and the elderly are at higher risk of developing cardiac symptoms like chest pain or irregular heartbeats when taking levothyroxine.

• People with diabetes may need to have their diabetic medication adjusted if they are also taking levothyroxine.

• People with osteoporosis run the risk of worsening bone mineral density loss if they are on levothyroxine over long periods. Postmenopausal women are especially at risk.

• People taking blood thinners need to be extra careful when taking levothyroxine because it can increase their risk of bleeding.

Levothyroxine is considered pregnancy Category A by the FDA—studies looking at pregnant women taking levothyroxine have not shown an increased risk to the fetus (FDA, 2017). Similarly, levothyroxine does get into breastmilk, but there are no reports of harm to the baby. In both pregnancy and lactation, having low levels of thyroid hormone is worse than taking levothyroxine.

While it is available in a liquid form, most people who need thyroid hormone replacement with levothyroxine take the capsule or tablet form. Levothyroxine sodium pills are available in a variety of doses, including 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg, and 300 mcg (UpToDate, n.d.). You should take levothyroxine on an empty stomach, at least 30–60 minutes before eating any food. If you are taking the capsule, you should swallow it whole and do not crush or chew it. However, levothyroxine sodium tablets can be crushed and mixed with water. This medication is covered by most prescription plans and costs in the range of $4-$15, depending on the quantity and the dose (GoodRx.com). 

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Current version

August 17, 2020

Written by

Chimene Richa, MD

Fact checked by

Mike Bohl, MD, MPH, ALM

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About the medical reviewer

Mike Bohl, MD, MPH, ALM

Dr. Mike is a licensed physician and a former Director, Medical Content & Education at Ro.