LITHOSTAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LITHOSTAT (LITHOSTAT).
Acetohydroxamic acid inhibits bacterial urease, reducing urinary ammonia and pH, thereby decreasing urinary saturation of struvite and calcium phosphate and preventing formation of infection stones.
| Metabolism | Primarily hepatic; approximately 65% of a dose is metabolized to acetamide, carbon dioxide, and water. |
| Excretion | Primarily renal (urinary) elimination; approximately 63% of the absorbed dose is excreted unchanged in urine within 24 hours. A small fraction (less than 5%) is eliminated via feces via biliary excretion. |
| Half-life | Terminal elimination half-life is approximately 17 hours (range 9–28 hours) in patients with normal renal function. Half-life is prolonged in renal impairment and can exceed 50 hours in severe cases. |
| Protein binding | Negligible to minimal binding to plasma proteins (less than 5%). |
| Volume of Distribution | Apparent volume of distribution is approximately 0.3–0.6 L/kg, indicating distribution mainly in extracellular fluid. |
| Bioavailability | Oral bioavailability is 55–65% with significant interindividual variability; food may reduce absorption. |
| Onset of Action | Oral administration: clinical effect (reduction in urinary calcium oxalate supersaturation) is typically seen within 24 to 48 hours of initiating therapy. |
| Duration of Action | Duration of action is around 12–24 hours; sustained inhibition of urine supersaturation persists with regular dosing. Clinical effect wanes over 2–3 days after discontinuation. |
Adults: 250 mg orally twice daily, with or after meals.
| Dosage form | TABLET |
| Renal impairment | CrCl 30–59 mL/min: 250 mg once daily; CrCl 15–29 mL/min: 250 mg every 48 hours; CrCl <15 mL/min: 250 mg twice weekly; on hemodialysis: 250 mg after each dialysis session. |
| Liver impairment | No data for Child-Pugh A; Child-Pugh B or C: avoid use or reduce dose with caution; no specific dosing available. |
| Pediatric use | Children >2 years: 15–20 mg/kg/day in 2 divided doses, max 1 g/day. |
| Geriatric use | Start at low end of dosing range; monitor renal function closely; adjust based on CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LITHOSTAT (LITHOSTAT).
| Breastfeeding | It is not known whether acetohydroxamic acid is excreted into human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Lithostat, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. No M/P ratio is available. |
| Teratogenic Risk | Lithostat (acetohydroxamic acid) is contraindicated in pregnancy. In animal studies, it has been associated with teratogenic effects including skeletal malformations and fetal resorption. There are no adequate and well-controlled studies in pregnant women. The potential risk to the fetus outweighs any possible benefit. Use during pregnancy should be avoided; if pregnancy occurs, the patient should be apprised of the hazard to the fetus. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to acetohydroxamic acid; severe renal impairment (CrCl <25 mL/min); pregnancy (Category X).
| Precautions | Monitor for hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency; use with caution in renal impairment (CrCl <25 mL/min is not recommended); can cause reversible myelosuppression. |
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| Fetal Monitoring | For women of childbearing potential, pregnancy testing should be performed before initiating therapy and periodically during treatment. Effective contraception is mandatory. If pregnancy is suspected, immediate discontinuation is required. |
| Fertility Effects | Acetohydroxamic acid may impair fertility in animal studies. In rats, decreased fertility and increased preimplantation loss were observed at doses comparable to human therapeutic doses. The clinical relevance to human fertility is unknown. |