Urease Inhibitor

Lithostat

Approved 31 May 1983OralTablet

Indications

Acetohydroxamic acid is indicated as adjunctive therapy in patients with chronic urea-splitting urinary infection. AHA 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. Long-term treatment with AHA may be warranted to maintain urease inhibition as long as urea-splitting infection is present. Experience with AHA does not go beyond 7 years.

A patient package insert should be distributed to each patient who receives AHA.

Contraindications

Acetohydroxamic acid should not be used in: a. patients whose physical state and disease are amenable to definitive surgery and appropriate antimicrobial agents b. patients whose urine is infected by non-urease producing organisms c. patients whose urinary infections can be controlled by culture-specific oral antimicrobial agents d. patients whose renal function is poor (i.e., serum creatinine more than 2.5 mg/dl and/or creatinine clearance less than 20 ml/min) e. female patients who do not evidence a satisfactory method of contraception f. patients who are pregnant Acetohydroxamic acid may cause fetal harm when administered to a pregnant woman.

AHA was teratogenic (retarded and/or clubbed rear leg at 750 mg/kg and above and exencephaly and encephalocele at 1,500 mg/kg) when given intraperitoneally to rats. AHA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the fetus.

Warnings and precautions

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.

At a glance

Brand name: Lithostat
Active substance: acetohydroxamic acid
Pharmacologic class: Urease Inhibitor
Route: Oral
Dosage form: Tablet
Applicant: Mission Pharma
Status: Prescription
FDA approval: 31 May 1983
Application: NDA018749-001

Indications

A patient package insert should be distributed to each patient who receives AHA.

Contraindications

Warnings and precautions

Adverse reactions

Experience with AHA is limited. About 150 patients have been treated, most for periods of more than a year. Adverse reactions have occurred in up to thirty percent (30%) of the patients receiving AHA. In some instances the reactions were symptomatic; in others only changes in laboratory parameters were noted. Adverse reactions seem to be more prevalent in patients with preexisting thrombophlebitis or phlebothrombosis and/or in patients with advanced degrees of renal insufficiency.

The risk of adverse reactions is highest during the first year of treatment. Chronic treatment does not seem to increase the risk nor the severity of adverse reactions. The following reactions have been reported: NEUROLOGICAL: Mild headaches are commonly reported (about 30%) during the first 48 hours of treatment. These headaches are mild, responsive to oral salicylate-type analgesics, and usually disappear spontaneously.

The headaches have not been associated with vertigo, tinnitus, or visual or auditory abnormalities. Tremulousness and nervousness have also been reported. GASTROINTESTINAL: Gastrointestinal symptoms, nausea, vomiting, anorexia, and malaise have occurred in 20-25% of patients. In most patients the symptoms were mild, transitory, and did not result in interruption of treatment. Approximately 3% of patients developed a hemolytic anemia of sufficient magnitude to warrant interruption in treatment; several of these patients also had symptoms of gastrointestinal upset.

HEMATOLOGICAL: Approximately 15% of patients have had laboratory findings characteristic of a hemolytic anemia. A mild reticulocytosis (5- 6%) without anemia, is even more prevalent. The laboratory findings are occasionally accompanied by systemic symptoms such as malaise, lethargy and fatigue, and gastrointestinal symptoms. Symptoms and laboratory findings have invariably improved following cessation of treatment with AHA.

The hematological abnormalities are more prevalent in patients with advanced renal failure. DERMATOLOGICAL: A nonpruritic, macular skin rash has occurred in the upper extremities and on the face of several patients taking AHA on a long-term basis, usually when AHA has been taken concomitantly with alcoholic beverages, but in a few patients in the absence of alcohol consumption. The rash commonly appears 30-45 minutes after ingestion of alcoholic beverages; it characteristically disappears spontaneously in 30-60 minutes.

The rash may be associated with a general sensation of warmth. In some patients the rash is sufficiently severe to warrant discontinuation of treatment, but most patients have continued treatment, avoiding alcohol or using smaller quantities of it. Alopecia has also been reported in patients taking AHA. CARDIOVASCULAR: Superficial phlebitis involving the lower extremities has occurred in several patients on AHA during the early (Phase II) clinical trials.

Several of the affected patients had had phlebitic episodes prior to treatment. One patient developed deep vein thrombosis of the lower extremities. The patient with phlebothrombosis had an associated traumatic injury to the groin. It is unclear whether the phlebitis was related to or exacerbated by treatment with AHA. No patient in the three (3) year controlled (Phase III) clinical trial developed phlebitis. In all instances these vascular abnormalities returned to normal following appropriate medical therapy.

Embolic phenomena have been reported in three patients taking AHA in the Phase II trial. The phlebitis and emboli resolved following discontinuation of AHA and implementation of appropriate medical therapy. Several patients have resumed treatment with AHA without ill effect. Palpitations have also been reported in patients taking AHA. RESPIRATORY: No symptoms have been reported. Radiographic evidence of small pulmonary emboli has been seen in three patients with phlebitis in their lower legs.

PSYCHIATRIC: Depression, anxiety, nervousness, and tremulousness have been observed in approximately 20% of patients taking AHA. In most patients the symptoms were mild and transitory, but in about 6% of patients the symptoms were sufficiently distressing to warrant interruption or discontinuation of treatment.

Lithostat

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Lithostat

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Official product information