What dosing schedule should a female patient on levothyroxine (Synthroid) for hypothyroidism, an oral iron supplement for iron deficiency, and oral estradiol (Estrace) for hormone therapy follow to ensure levothyroxine is taken on an empty stomach (30–60 minutes before food) and at least four hours apart from both iron and estradiol doses?

Medication Scheduling for Levothyroxine, Iron, and Estradiol

Take levothyroxine first thing in the morning on an empty stomach (30–60 minutes before breakfast), iron at lunch or mid-afternoon, and estradiol at bedtime—this schedule ensures optimal levothyroxine absorption while maintaining at least 4 hours separation from interfering medications. 1

Morning: Levothyroxine Administration

• Take levothyroxine immediately upon waking, 30–60 minutes before breakfast, with a full glass of water to maximize absorption and prevent choking or gagging 1
• Levothyroxine absorption is maximized when taken on an empty stomach because gastric acidity is critical for the absorption process 2, 3
• Taking levothyroxine with food reduces its therapeutic efficacy, as demonstrated by studies showing increased TSH levels when administration timing is changed 4

Midday: Iron Supplement Administration

• Take iron supplement at lunch (approximately 4–6 hours after levothyroxine) to ensure adequate separation 1
• Iron supplements significantly decrease levothyroxine absorption and must be separated by at least 4 hours 1
• This midday timing provides maximum separation from both the morning levothyroxine dose and the evening estradiol dose

Evening: Estradiol Administration

• Take estradiol at bedtime (at least 4 hours after iron and 12+ hours before next levothyroxine dose) 1
• While estradiol does not have the same absorption requirements as levothyroxine, maintaining 4-hour separation from levothyroxine is recommended 1
• Bedtime administration ensures the medication is taken consistently and maintains appropriate spacing from levothyroxine

Sample Daily Schedule

• 6:00 AM: Levothyroxine with full glass of water (on empty stomach)
• 7:00 AM: Breakfast (at least 30–60 minutes after levothyroxine)
• 12:00 PM: Iron supplement with lunch
• 10:00 PM: Estradiol at bedtime

Critical Pitfalls to Avoid

• Never take levothyroxine within 4 hours of iron or calcium-containing products, as this dramatically reduces levothyroxine absorption and can lead to inadequate thyroid hormone replacement 1
• Do not take levothyroxine with breakfast or coffee, as food and beverages (except water) impair absorption 2, 3
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses that either fully suppress or inadequately control TSH due to inconsistent administration timing and drug interactions 5
• Avoid taking all three medications together, as this would result in subtherapeutic levothyroxine levels requiring dose escalation and potentially causing iatrogenic hyperthyroidism when medications are later separated 5

Monitoring and Adjustment

• TSH and free T4 should be monitored every 6–8 weeks during dose titration to ensure adequate thyroid hormone replacement despite the complex medication schedule 5, 1
• Once stable, repeat thyroid function tests every 6–12 months or if symptoms change 5
• If TSH remains elevated despite adequate levothyroxine dosing, verify medication timing and separation from iron supplements before increasing the levothyroxine dose 5, 1