Lithostat (acetohydroxamic acid) Information for Patients

It has been known for many years that urinary infection may cause the formation of urinary stones. As these stones form, bacteria are trapped within the stones. The trapped bacteria cause the stones to grow, and the stones protect the bacteria from antibiotics. Surgical removal of the stone attempts to break this vicious cycle - many times successfully. However, if infection persists or if a small stone fragment persists, then there is an increased risk of stone recurrence. Multiple operations to remove kidney stones may result in damage and scarring of the kidney. In some situations removal of the kidney may be necessary.

In some instances stones may form initially as a result of non-infectious (i.e., metabolic) causes. If a metabolic stone becomes infected, then an "infection stone" may grow onto the "metabolic stone." Stone analysis and/or biochemical tests will usually determine which factors are present.

Experimental investigations have identified an enzyme called urease which is made by some (but not all) bacteria. Urease reacts with urine to make ammonia. Ammonia changes the acidity of the urine and the change in acidity encourages stone formation. Lithostat^® (acetohydroxamic acid) inhibits urease and thereby reduces urinary ammonia. In some instances, Lithostat^® enhances the effectiveness

What is Lithostat^® ?

Lithostat^® is a drug which prevents the excessive buildup of ammonia in your urine, which controls the acidity and alkalinity (pH) of your urine. The cause of excessive ammonia and alkalinity in your urine is a bacterial infection.

What can Lithostat^® do?

Treatment with Lithostat^® is prescribed to decrease urinary ammonia. This may increase the chance of controlling your infection with antibiotics and may help the treatment of your kidney stones. Dissolution of existing stones is unlikely.

LlTHOSTAT should not be used in place of surgical treatment. Surgical removal of all stones and elimination of all infection with antibiotics offers the possibility of curative treatment. Lithostat^® is likely to be more effective after large stones or obstructing stones have been removed.

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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