Lithostat (acetohydroxamic acid) Information for Health Providers

Acetohydroxamic acid has been evaluated clinically in patients with urea-splitting urinary infections, often accompanied by struvite stone disease, that were recalcitrant to other forms of medical and surgical management. In these clinical trials, AHA reduced the pathologically elevated urinary ammonia and pH levels that result from the hydrolysis of urea by the enzyme, urea.

About Lithostat^®

Lithostat^® reversibly inhibits the bacterial enzyme urease, thereby inhibiting the hydrolysis of urea and production of ammonia in urine infected with urea splitting organisms.

Lithostat^® is intended to decrease urinary ammonia and alkalinity, but it should not be used in lieu of curative surgical treatment (for patients with stones) or antimicrobial treatment.

The inhibition of urease by Lithostat^® in single clinical trials reduced ammonia levels and decreased urinary pH. The result of this intervention with Lithostat^® :

Allowed successful antibiotic treatment of urea-splitting Proteus infections after surgical removal of struvite stones in patients not cure by three months of antibacterial treatment alone.
Reduced the rate of stone growth in patients who were not candidates for surgical removal of stones.

About AHA

Acetohydroxamic acid (AHA) is a stable, synthetic compound derived from hydroxylamine and ethyl acetate. Its molecular structure is similar to urea.

AHA is weakly acidic, highly soluble in water, and chelates metals — notably iron. The molecular weight is 75.068. AHA has a pKa of 9.32 and a melting point of 89-91° C.

Important Safety Information

Warnings

A Coombs negative hemolytic anemia has occurred in patients receiving AHA. Gastrointestinal upset characterized by nausea, vomiting, anorexia and generalized malaise have accompanied the most severe forms of hemolytic anemia. Approximately 15% of patients receiving AHA have had only laboratory findings of an anemia. However, most patients developed a mild reticulocytosis. The untoward reactions have reverted to normal following cessation of treatment. A complete blood count, including a reticulocyte count, is recommended after two weeks of treatment. If the reticulocyte count exceeds 6%, a reduced dosage should be entertained. A CBC and reticulocyte count are recommended at 3-month intervals for the duration of treatment .

Precautions

Bone marrow depression (leukopenia, anemia, and thrombocytopenia) has occurred in experimental animals receiving large doses of AHA, but has not been seen in man to date. AHA is a known inhibitor of DNA synthesis and also chelates metals - notably iron. Its bone marrow suppressant effect is probably related to its ability to inhibit DNA synthesis, but anemia could also be related to depletion of iron stores. To date, the only clinical effect noted has been hemolysis, with a decrease in the circulating red blood cells, hemoglobin and hematocrit. Abnormalities in platelet or white blood cell count have not been noted. However, clinical monitoring of the platelet and white cell count is recommended.

Abnormalities of liver function have not been reported to date. However, a chloro-benzene derivative of acetohydroxamic acid caused significant liver dysfunction in an unrelated study. Therefore, close monitoring of liver function is recommended.

Since AHA is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored, and a reduction of daily dose may be needed to avoid excessive drug accumulation.

This material is intended to provide basic information. Patients should discuss all medical advice, diagnosis, and treatment with their healthcare provider.

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