Lithostat for Chronic Urea-Splitting Urinary Infections

For the treatment of chronic urea-splitting urinary infections

Lithostat^® enhances the effectiveness of antimicrobial agents to allow an increased cure rate of chronic urea-splitting urinary infections.

About infection stones

Infection calculi (struvite) comprise 5% to 15% of all stones. Because they occur most commonly in those most susceptible to urinary tract infections, women are more commonly affected than are men. Struvite stones (magnesium ammonium phosphate) occur only in association with urinary infection by urea-splitting bacteria.¹

How infection stones are formed

They form in the presence of alkaline urine (pH above 7.2) and in an ammonia-rich environment. The ammonia derives from the splitting of urea by colonization with bacteria that produce urease. Many bacterial organisms are able to produce this enzyme, with Proteus mirabilis the most common.^1,2

Populations at increased risk for infection stones

In addition to women, there are special populations that are at increased risk for infection stones:¹

The elderly
Premature infants
Infants born with congenital urinary tract malformation
Diabetics
Patients with urinary stasis as a result of urinary tract obstruction, urinary diversion, or neurologic disorders
Spinal cord-injured patients (they are at particular risk for both infection and metabolic stones owing to neurogenic urinary tract dysfunction and hypercalciuria related to immobility)

The role of Lithostat^® (acetohydroxamic acid) in treatment

Lithostat^® is indicated as an adjunct to antimicrobial therapy in patients with chronic urea-splitting urinary infection. It is intended to decrease urinary ammonia and alkalinity. Long-term treatment may be warranted to maintain urease inhibition as long as urea-splitting infection is present.

The clinical pharmacology and benefits of 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. The reduced ammonia levels and decreased pH enhance the effectiveness of antimicrobial agents and allow an increased cure rate of these infections.

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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