MACROBID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MACROBID (MACROBID).
Nitrofurantoin is a urinary tract antibacterial agent that inhibits bacterial acetyl-CoA carboxylase, disrupting cell wall synthesis and bacterial respiration. It is reduced by bacterial nitroreductases to reactive intermediates that damage DNA, ribosomes, and other macromolecules.
| Metabolism | Primarily metabolized in the liver, with minor metabolism in the kidney. Nitrofurantoin is reduced by various reductases to active metabolites; the parent drug and metabolites are excreted renally. |
| Excretion | Renal: 36% (unchanged nitrofurantoin) and 15% (metabolites) within 24 hours. Total renal elimination: 51%. Biliary/fecal: 1-2%. Additional 30% undergoes rapid metabolic degradation in tissues. |
| Half-life | Terminal elimination half-life: 0.3-1.0 hour (short) due to rapid renal clearance and tissue metabolism; no accumulation with twice-daily dosing. The short half-life is adequate for urinary tract exposure. |
| Protein binding | 40-60% bound mainly to albumin. |
| Volume of Distribution | 0.9-1.2 L/kg; large Vd indicates extensive tissue distribution but does not achieve therapeutic levels in plasma due to rapid metabolism. |
| Bioavailability | Oral: 87% (macrocrystalline formulation). Food increases absorption. |
| Onset of Action | Oral: Clinical effect (bacteriuria reduction) occurs within 1-2 hours due to rapid absorption and renal excretion achieving urinary concentrations above MIC within 1 hour. |
| Duration of Action | Oral: Urinary bactericidal concentrations persist for 12 hours in patients with normal renal function; duration is 12 hours allowing twice-daily dosing. Not prolonged in renal impairment. |
| Action Class | Macrolides |
100 mg orally twice daily with food for 7 days.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated if CrCl < 30 mL/min. For CrCl ≥ 30 mL/min: no adjustment needed. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh C) due to potential accumulation. |
| Pediatric use | For patients ≥12 years: 100 mg orally twice daily with food for 7 days. Safety and efficacy in children <12 years not established. |
| Geriatric use | Use with caution; monitor for pulmonary and hepatic toxicity. No dose adjustment recommended in elderly with adequate renal function (CrCl ≥ 30 mL/min). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MACROBID (MACROBID).
| Breastfeeding | Nitrofurantoin is excreted into breast milk in low concentrations (M/P ratio approximately 0.06). It is considered compatible with breastfeeding by the AAP, but caution is advised in nursing infants with G6PD deficiency or if the infant is jaundiced due to potential for hemolysis. |
| Teratogenic Risk | Macrobid (nitrofurantoin) is generally avoided in the first trimester due to a potential increased risk of neural tube defects and oral clefts observed in some studies, though the absolute risk is low. In the second and third trimesters, it is considered safer, but it is contraindicated near term (after 38 weeks) due to the risk of hemolytic anemia in the newborn, particularly in G6PD-deficient infants. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Anuria, oliguria, or significant impairment of renal function (creatinine clearance <60 mL/min); known hypersensitivity to nitrofurantoin; pregnant patients at term (38-42 weeks gestation), during labor and delivery, or if pregnancy is confirmed; use in neonates (<1 month of age) due to risk of hemolytic anemia from immature enzyme systems (e.g., glutathione instability).
| Precautions | Pulmonary reactions (acute, subacute, chronic) including fibrosis; hepatotoxicity (hepatitis, cholestatic jaundice, necrosis); peripheral neuropathy; hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; optic neuritis; pseudomembranous colitis; superinfection with resistant organisms; caution in renal impairment (CrCl <60 mL/min), elderly, and patients with anemia, diabetes, electrolyte imbalance, vitamin B deficiency, or debilitating disease. |
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| Fetal Monitoring | Monitor for signs of hemolytic anemia, especially in G6PD-deficient patients. Assess pulmonary symptoms (acute and chronic pulmonary reactions). Monitor liver function tests and renal function periodically. In late pregnancy, assess newborn for jaundice. |
| Fertility Effects | No known adverse effects on fertility. Animal studies have not shown impaired fertility at clinically relevant doses. |