Should fosfomycin be taken on an empty stomach?

Fosfomycin Administration: Empty Stomach vs. With Food

Fosfomycin can be taken without regard to food, as the cumulative amount of fosfomycin excreted in the urine is the same whether taken with food or on an empty stomach, though food may slightly delay peak urinary concentration. 1

Pharmacokinetic Considerations

• Oral fosfomycin tromethamine is rapidly absorbed following administration and converted to the free acid, fosfomycin, with an absolute bioavailability of 37% under fasting conditions 1
• When taken with a high-fat meal, oral bioavailability is reduced to 30%, with maximum serum concentration (Cmax) decreasing from 26.1 mcg/mL (fasting) to 17.6 mcg/mL (fed) 1
• Although food delays the rate of urinary excretion, the cumulative amount of fosfomycin excreted in the urine remains equivalent: 1,118 mg (fed) vs. 1,140 mg (fasting) 1
• Importantly, urinary concentrations equal to or greater than 100 mcg/mL are maintained for the same duration (26 hours) regardless of food intake 1

Clinical Implications

• Fosfomycin tromethamine is typically administered as a single 3-gram oral dose for uncomplicated urinary tract infections in women 2
• The European Association of Urology recommends fosfomycin as a first-line treatment for uncomplicated UTIs, providing therapeutic urinary concentrations for 24-48 hours 2
• Despite the slight reduction in peak concentration when taken with food, the therapeutic efficacy is maintained as urinary levels remain above the minimum inhibitory concentration for common uropathogens 1, 3

Administration Recommendations

• The FDA-approved label explicitly states that "fosfomycin tromethamine can be taken without regard to food" 1
• For patients who experience gastrointestinal side effects (diarrhea, nausea, vomiting), taking fosfomycin with food might help reduce these adverse events 2
• The standard dosing for uncomplicated UTIs remains a single 3-gram oral dose, regardless of food intake 2, 3

Special Considerations

• For patients taking metoclopramide, be aware that co-administration lowers serum concentrations and urinary excretion of fosfomycin 1
• Cimetidine does not affect the pharmacokinetics of fosfomycin when co-administered 1
• For patients with renal impairment, the half-life of fosfomycin increases significantly, but no dosage adjustment is necessary for the standard single-dose regimen 1

In conclusion, while taking fosfomycin on an empty stomach results in slightly higher peak concentrations, the FDA-approved labeling confirms that the therapeutic efficacy is maintained regardless of food intake, making patient preference and tolerability reasonable factors in determining administration timing.