Synthroid Drug Interactions: What to Avoid and What to Tell Your Doctor

Levothyroxine (Synthroid) has one of the most extensive drug interaction profiles of any commonly prescribed medication — there are over 247 known drug interactions. Most of these interactions affect how much levothyroxine your body absorbs or how quickly it's metabolized, which directly impacts whether your dose is keeping your thyroid levels in the right range.

The good news: most interactions are manageable. The key is knowing about them and telling your doctor and pharmacist about everything you take — including supplements and over-the-counter medications.

Medications That Reduce Synthroid Absorption (Most Common Problem)

The most clinically common and important interactions are those that reduce how much levothyroxine your body absorbs from the gut. Taking these drugs too close to Synthroid can cause your TSH to rise (signs of undertreatment) even if you haven't changed your dose.

Calcium carbonate (Tums, Os-Cal, supplements): Binds levothyroxine in the gut. Take Synthroid at least 4 hours before or after calcium.

Iron supplements (ferrous sulfate, ferrous gluconate, ferrous fumarate): All forms of iron reduce levothyroxine absorption. Separate by at least 4 hours.

Proton pump inhibitors (PPIs — omeprazole/Prilosec, esomeprazole/Nexium, lansoprazole/Prevacid): PPIs reduce stomach acid, which impairs dissolution and absorption of levothyroxine tablets. In one major study, nearly 70% of clinically significant levothyroxine interactions were with PPIs. Separating doses often isn't sufficient — monitor TSH if you start or stop a PPI.

Antacids (aluminum- and magnesium-containing): Reduce levothyroxine absorption; separate by 4 hours.

Cholestyramine, colesevelam (Welchol), colestipol (Colestid): Bile acid sequestrants that strongly bind levothyroxine. Take Synthroid at least 4–6 hours before these drugs.

Sevelamer (Renvela, Renagel): Phosphate binder used in kidney disease; binds levothyroxine. Separate by 4 hours.

Sucralfate: Used for ulcers; reduces levothyroxine absorption.

Orlistat (Alli, Xenical): Weight-loss drug that reduces fat absorption; also reduces levothyroxine absorption.

Medications That Increase Synthroid Metabolism (May Require Higher Dose)

Some medications activate liver enzymes that metabolize levothyroxine faster than normal, which means your dose may become less effective over time if you start one of these:

Carbamazepine (Tegretol): Anticonvulsant; increases hepatic metabolism of T4

Phenytoin (Dilantin): Anticonvulsant; also displaces T4 from protein binding

Phenobarbital: Barbiturate anticonvulsant; increases T4 clearance

Rifampin (Rifadin): Antibiotic for TB; powerful enzyme inducer; significantly increases T4 metabolism

Medications Whose Effects Are Changed by Synthroid

Levothyroxine doesn't just get affected by other drugs — it also affects other drugs:

Warfarin (Coumadin): Levothyroxine potentiates anticoagulant effects; INR can rise when levothyroxine is started or increased. Monitor INR closely and reduce warfarin if needed.

Digoxin: Levothyroxine reduces digoxin's effect; digoxin levels may need to be increased when starting or increasing levothyroxine.

Insulin and oral diabetes medications: Levothyroxine can worsen glycemic control by increasing blood sugar; diabetes medications may need dose adjustment when starting thyroid therapy.

Tricyclic antidepressants (amitriptyline, nortriptyline): Combination increases receptor sensitivity to catecholamines; risk of cardiac arrhythmias and CNS effects.

Propranolol (>160 mg/day): Levothyroxine increases heart rate, opposing beta-blocker effect; may require dose adjustment.

Food and Supplement Interactions

Coffee: Reduces levothyroxine absorption by up to 27% if taken within 15 minutes of the dose.

Soybean flour, soy products: Reduce levothyroxine absorption; soy-based infant formula is a known concern in newborns.

Walnuts and dietary fiber: Can bind and decrease levothyroxine absorption from the GI tract.

Grapefruit juice: May reduce levothyroxine absorption and reduce its effect.

Magnesium supplements: May adsorb to levothyroxine; separate by 4 hours.

Lycopus (Bugleweed) herbal supplement: CONTRAINDICATED — blocks conversion of T4 to T3; do not take with levothyroxine.

What to Tell Your Doctor

Before starting Synthroid — or when adding any new medication — tell your doctor and pharmacist:

All prescription medications, especially warfarin, digoxin, diabetes drugs, anticonvulsants, or antidepressants

All OTC medications, especially calcium, iron, antacids, and PPIs

All supplements and vitamins

Any herbal products, especially those containing bugleweed (lycopus), rose hips, or shepherd's purse

For side effects related to Synthroid itself, see our guide on Synthroid side effects. And if you need help finding Synthroid in stock, medfinder can locate it at pharmacies near you.