Levothyroxine with Simvastatin Interaction Details

Brand Names Associated with Levothyroxine

Brand Names Associated with Simvastatin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 10, 2023

Interaction Effect

Decreased levothyroxine efficacy

Interaction Summary

Three case reports described increased thyroid stimulating hormone (TSH) levels following concomitant levothyroxine and simvastatin use. Excess formation of CYP3A4 in the liver by simvastatin resulting in accelerated levothyroxine metabolism is postulated as a possible mechanism for this interaction. If these agents are used concomitantly, monitoring the patient for an adequate response to levothyroxine therapy may be warranted.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Decreased levothyroxine efficacy was seen following concomitant use of levothyroxine and simvastatin as described in three case reports. Consider monitoring the patient for an adequate response to levothyroxine therapy if these agents are used concomitantly.

Mechanism Of Interaction

Increased levothyroxine metabolism

Literature Reports

A) An 85-year-old woman being treated with simvastatin 80 mg, levothyroxine 100 mcg, and her regular antihypertensive regimen experienced hypothyroidism and rhabdomyolysis 3 weeks after a simvastatin dose increase to improve lipid control. The patient, who had an extensive medical history of osteoporosis, hypertension, hypercholesterolemia, mild chronic renal impairment, and hypothyroidism, presented to the emergency room after 7 days of muscle pain, progressive lower limb weakness, and inability to bear weight. The patient had mild renal and hepatic impairment with a creatinine kinase (CK) value of 2228, as well as a free thyroxine (T4) level at the lower limit of normal and elevated thyroid stimulating hormone (TSH) of 28.6 International Units/L. Brain and spinal cord MRI demonstrated no intracranial abnormalities. Simvastatin was discontinued promptly and the levothyroxine dose was maintained at 100 mcg. Shortly after admission, CK reached 32,000 with continuing renal and hepatic function deterioration. Muscle biopsy demonstrated evidence of a statin-induced myopathy. Over the next month, renal and hepatic function as well as thyroid function tests slowly returned to normal. The patient was released from the hospital after 5 weeks with no long-term ill effects. The postulated mechanism of action is excess formation of CYP3A4 in the liver by simvastatin, thereby accelerating levothyroxine metabolism .

B) A 75-year-old woman being treated with levothyroxine 800 mcg/week, alendronate 10 mg/day, and calcium supplements experienced fatigue, abdominal pain, and increasing thyroid stimulating hormone (TSH) levels subsequent to being initiated on simvastatin 10 mg/day for hyperlipidemia. After 4 months of simvastatin therapy, her levothyroxine dose was increased to 900 mcg/week due to increasing TSH levels (47.83 micro-International Units/liter), with free thyroxine (T4) levels at the lower limit of normal). After 16 days of treatment with the higher levothyroxine dose, her symptoms had not improved (TSH level, 28.63 micro-International Units/liter. Liver function tests increased to slightly above normal during the hypothyroidism period. Upon subsequent discontinuation of simvastatin, her symptoms resolved and the levothyroxine dose was decreased to the original 800 mcg/week dose. In the next month, the patient's TSH level had returned to and remained within normal limits. Bezafibrate treatment was initiated with no ill effects. The postulated mechanism of action is excess formation of CYP3A4 in the liver by simvastatin, thereby accelerating levothyroxine metabolism .

C) An 81-year-old man experienced increasing thyroid stimulating hormone (TSH) after being initiated on levothyroxine for elevated TSH levels and shortly thereafter being started on simvastatin. Concomitant agents included vitamin D, allopurinol, isosorbide mononitrate, felodipine, alprazolam, furosemide, tamsulosin, clopidogrel, and erythropoietin. He had been successfully treated with levothyroxine in the past for an episode of amiodarone-induced hypothyroidism, and was in stable renal failure with plasma creatinine of approximately 4 mg/dL, with chronic anemia, following unilateral nephrectomy. Two years after initial therapy with levothyroxine, TSH levels of 11.76 micro-International Units/Liter with free thyroxine (T4) levels at the lower end of normal, prompted reinitiation of levothyroxine 50 mcg/day. Simvastatin 10 mg/day was added to his regimen soon thereafter. In the weeks following simvastatin initiation, his TSH level continued to increase to 23.9 micro-International Units/Liter. Simvastatin was immediately discontinued and, within 4 weeks, TSH levels decreased to within the normal range with no change in levothyroxine dose. Subsequently, he began receiving pravastatin for his elevated cholesterol level without any ill effects on his thyroid status .

Levothyroxine Overview

• Levothyroxine is used to treat hypothyroidism (condition where the thyroid gland does not produce enough thyroid hormone). It is also used with surgery and radioactive iodine therapy to treat thyroid cancer. Levothyroxine is in a class of medications called hormones. It works by replacing thyroid hormone that is normally produced by the body.

• Without thyroid hormone, your body cannot function properly, which may result in poor growth, slow speech, lack of energy, excessive tiredness, constipation, weight gain, hair loss, dry, thick skin, increased sensitivity to cold, joint and muscle pain, heavy or irregular menstrual periods, and depression. When taken correctly, levothyroxine reverses these symptoms.

Simvastatin Overview

• Simvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Simvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.