Sucralfate–Levothyroxine Interaction Resulting in Functional Hypothyroidism

Patient Background

Robert H. is a 62-year-old male with a history of primary hypothyroidism, gastroesophageal reflux disease, prior peptic ulcer disease, type 2 diabetes mellitus, hyperlipidemia, and hypertension. He has no known drug allergies. His hypothyroidism had been clinically and biochemically stable for several years on levothyroxine 100 mcg once daily, with a TSH of 2.1 mIU/L documented three months prior to the current presentation.

Clinical Presentation

Following an upper endoscopy that demonstrated gastric erosions, the patient was started on sucralfate 1 g four times daily, administered before meals and at bedtime. In an effort to simplify his medication schedule, Robert began taking his morning dose of sucralfate concurrently with levothyroxine.

Over the subsequent four weeks, he developed progressive fatigue, cold intolerance, constipation, dry skin, cognitive slowing, and a six-pound weight gain. At follow-up, his vital signs were notable for a blood pressure of 138/86 mmHg and heart rate of 58 beats per minute. Repeat thyroid function testing revealed a TSH of 8.9 mIU/L with a low-normal free T4, consistent with a recurrence of hypothyroidism

Clinical Issue Identified

The patient’s laboratory abnormalities and symptoms were inconsistent with primary thyroid disease progression and instead reflected reduced absorption of levothyroxine. Sucralfate is a potent gastrointestinal binding agent that can complex with levothyroxine in the gut, significantly decreasing its bioavailability when administered concurrently.

This represented a drug–drug interaction related to improper medication timing, rather than inadequate levothyroxine dosing. The temporal relationship between sucralfate initiation, altered administration timing, and the emergence of hypothyroid symptoms strongly supported this mechanism.

Pharmacist Intervention and Clinical Management

Identification of Absorption-Based Interaction

• Recognize sucralfate as a binding agent capable of impairing levothyroxine absorption.
• Correlate symptom onset with the change in medication timing rather than dose.

Therapeutic Optimization

• Reinforce proper levothyroxine administration: taken alone on an empty stomach with water, ideally 30–60 minutes before breakfast.
• Instruct the patient to separate levothyroxine and sucralfate administration by at least four hours.
• Avoid unnecessary levothyroxine dose escalation while absorption issues are being corrected.

Monitoring and Follow-Up

• Repeat thyroid function testing 6–8 weeks after correcting medication timing.
• Monitor for resolution of hypothyroid symptoms and normalization of TSH.

Patient Education

• Educate the patient on medications that can impair levothyroxine absorption, including sucralfate, calcium, iron, aluminum-containing antacids, and bile acid sequestrants.
• Emphasize the importance of reporting new medications or supplements prior to adjusting thyroid therapy.

Interprofessional Communication

• Communicate findings to the prescribing provider to prevent unnecessary dose changes and reinforce correct administration practices.

Clinical Rationale and Ramifications

This case highlights a common and preventable cause of apparent levothyroxine treatment failure—drug-induced malabsorption due to gastrointestinal binding interactions. When a patient with long-standing stable hypothyroidism presents with biochemical and clinical deterioration, clinicians should first evaluate medication timing and interactions before increasing the levothyroxine dose.

Failure to recognize absorption-related interactions can lead to inappropriate dose escalation, increased pill burden, and potential future thyrotoxicosis once the interacting agent is discontinued. In this case, the patient’s hypothyroid symptoms were fully attributable to administration error rather than disease progression.

This scenario reinforces a key clinical principle: unexpected changes in thyroid control after years of stability should prompt assessment for binding drug interactions before altering levothyroxine dosing. Careful medication reconciliation and patient education are essential to maintaining endocrine stability and preventing avoidable harm.