No Clinically Significant Interaction Between Synthroid and Macrobid
There is no documented drug interaction between levothyroxine (Synthroid) and nitrofurantoin (Macrobid), and these medications can be safely taken together without dose adjustments or special timing considerations.
Why This Combination Is Safe
The available evidence demonstrates no pharmacokinetic or pharmacodynamic interaction between these two medications:
Levothyroxine is absorbed in the small intestine and metabolized primarily through conjugation and deiodination, not through cytochrome P450 enzymes 1, 2
Nitrofurantoin does not affect thyroid hormone metabolism, absorption, or protein binding, and there are no reports in the literature of interactions between these agents 3
Macrolides (clarithromycin, erythromycin, azithromycin) are the antibiotics that cause drug interactions through CYP3A4 inhibition, but nitrofurantoin is not a macrolide and does not share this mechanism 4, 5
Important Distinction: Macrobid vs. Macrolides
A common source of confusion is the similar-sounding names:
Macrobid (nitrofurantoin) is a urinary tract antibiotic that does NOT interact with most medications 3
Macrolides (erythromycin, clarithromycin, azithromycin) are a different class of antibiotics that DO cause multiple drug interactions through enzyme inhibition 4, 5
Practical Administration Guidance
You can take both medications at the same time or separately—timing does not matter for this combination:
Take levothyroxine on an empty stomach, 30-60 minutes before breakfast, as is standard practice 2
Take nitrofurantoin with food to minimize gastrointestinal upset, which is its most common side effect 3
When to Exercise Caution With Levothyroxine
While nitrofurantoin is safe, be aware that levothyroxine DOES interact with other medications that may require dose adjustments or timing separation:
Calcium supplements, iron, antacids, and proton pump inhibitors reduce levothyroxine absorption and should be taken at least 4 hours apart 1, 2
Rifampin dramatically increases levothyroxine metabolism, requiring dose increases of 25-50% 6
Phenytoin can both increase levothyroxine metabolism and displace it from binding proteins 7
Monitoring Recommendations
No additional monitoring is required specifically for this drug combination:
Continue routine TSH monitoring every 6-12 months for stable hypothyroid patients on levothyroxine 2
Monitor for nitrofurantoin side effects (nausea, headache) as you would for any patient, but these are unrelated to levothyroxine 3
If TSH becomes abnormal during nitrofurantoin treatment, consider other causes (non-adherence, dietary changes, other new medications) rather than attributing it to the antibiotic 1, 2