Levothyroxine with Ritonavir Interaction Details

Brand Names Associated with Levothyroxine

Brand Names Associated with Ritonavir

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 05, 2023

Interaction Effect

Loss of levothyroxine efficacy

Interaction Summary

An HIV-positive woman with prior thyroidectomy was observed to have signs and symptoms of hypothyroidism despite levothyroxine dose increases while taking an antiretroviral regimen including ritonavir. The levothyroxine dosage was continually increased, and symptoms of fatigue, anorexia, and anemia were present, while TSH and free T4 levels remained elevated. After antiretroviral therapy was changed to a regimen without ritonavir, her TSH normalized and remained normal for 18 months thereafter while on a stable dosage of levothyroxine. A patient stabilized on levothyroxine experienced loss of efficacy when ritonavir was added to his therapeutic regimen, necessitating a doubling of the levothyroxine dose. Following the discontinuation of ritonavir, levothyroxine was decreased to the previous daily dose and the patient remained asymptomatic. Levothyroxine undergoes conjugation with glucuronic and sulfuric acids, and ritonavir may have induced glucuronyl transferases . In another case report, an HIV-positive female on lopinavir/ritonavir experienced persistent hypothyroidism, despite increasing doses of levothyroxine. The hypothyroidism resolved upon discontinuation of lopinavir/ritonavir and recurred upon rechallenge .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Monitor TSH levels in patients receiving levothyroxine and ritonavir. Doses of levothyroxine may need to be increased when ritonavir is initiated and decreased when ritonavir is discontinued. However, increased levothyroxine dosages may not always resolve TSH elevations, according to case reports.

Mechanism Of Interaction

Induction of glucuronyl transferases by ritonavir

Literature Reports

A) A 37-year-old HIV-positive woman with prior thyroidectomy due to multinodular goiter was observed to have signs and symptoms of hypothyroidism despite levothyroxine dose increases while taking an antiretroviral regimen including ritonavir. As her viral load was undetectable on abacavir 600 mg/lamivudine 300 mg once daily and lopinavir 200 mg/ritonavir 50 mg twice daily (initiated due to pregnancy at the time), this regimen was continued after her thyroidectomy and through 2 additional pregnancies. Post-thyroidectomy, her TSH increased from 1.32 to 94.3 milli-international units/L (reference range: 0.3 to 0.6 milli-international units/L), and free T4 decreased from 0.89 to 0.47 nanograms/dL (11.5 to 6.1 picomol/L; reference range: 0.7 to 1.9 nanogram/dL (9 to 23 picomol/L)). After her final pregnancy, the presumed interaction between ritonavir and levothyroxine was managed by increasing the levothyroxine dosage, starting with 75 mcg/day and increasing to 175 mcg/day. She had symptoms of fatigue, anorexia, and anemia while TSH and free T4 levels remained elevated. After antiretroviral therapy was changed to abacavir 600 mg/lamivudine 300 mg once daily with dolutegravir 50 mg daily instead of ritonavir-boosted therapy, her TSH decreased to 0.12 milli-international units/L, and remained normal for 18 months thereafter, while taking levothyroxine 125 mcg/day .

B) An HIV-positive female on lopinavir/ritonavir experienced persistent hypothyroidism, despite increasing doses of levothyroxine. Approximately 2 years after starting lopinavir/ritonavir, zidovudine, and lamivudine, she required a total thyroidectomy followed by radioiodine therapy for thyroid papillary carcinoma. Levothyroxine was started. Despite increases in levothyroxine dose to 225 mcg/day and addition of liothyronine, the TSH remained elevated at 47.5 mU/L; T4 remained low at 8.5 pmol/L (T3, 3.2 pmol/L); and the patient was symptomatic. Normal values were 0.2 to 5.1 mU/L for TSH, 11 to 24 pmol/L for serum free T4, and 2.5 to 7 pmol/L for serum free T3. Within 2 months after discontinuation of lopinavir/ritonavir, TSH, T4, and T3 normalized . A rechallenge with lopinavir/ritonavir 9 months later resulted in elevated TSH (18.1 mU/L to 42.9 mU/L) and reduced T4 (8.5 pmol/L to 10.6 pmol/L). Within 3 months of discontinuation of lopinavir/ritonavir and initiation of 3 nucleoside reverse transcriptase inhibitors, the TSH and T4 normalized .

C) An HIV-positive male receiving long-term therapy with interferon-alfa was diagnosed with autoimmune thyroiditis secondary to interferon use when his thyroid stimulating hormone (TSH) level increased to 9.25 mU/L. He responded to levothyroxine 0.125 mg daily and his thyroid indices returned to normal levels. One year later, ritonavir was added to his antiretroviral regimen because of increasing viral load. One month after initiating ritonavir 600 mg twice daily, his TSH level was 18.47 mU/L and the patient was extremely lethargic. Increasing his levothyroxine dose to 0.25 mg daily reduced his TSH to 7.35 mU/L. Because of hepatotoxicity, indinavir was substituted for ritonavir and levothyroxine was reduced to 0.125 mg daily to avoid toxicity. He remained asymptomatic on this levothyroxine dose and his TSH stabilized at 7.32 mU/L .

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.

Ritonavir Overview

• Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

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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.