LITHOSTAT- acetohydroxamic acid tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ACETOHYDROXAMIC ACID (UNII: 4RZ82L2GY5) (ACETOHYDROXAMIC ACID - UNII:4RZ82L2GY5)

Available from:

Mission Pharmacal Company

INN (International Name):

ACETOHYDROXAMIC ACID

Composition:

ACETOHYDROXAMIC ACID 250 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic 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. 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. Children with chronic, recalcitrant, urea-splitting urinary infection may benefit from treatment with AHA. However, detailed studies involving dosage and dose intervals in children have not been established. Children have tolerated a dose of 10 mg/kg/day, taken in two or three divided doses, satisfactorily for periods up to one year. Close monitoring of such patients is mandatory.

Product summary:

LITHOSTAT ® , NDC 0178-0500-01, is available for oral administration as 250 mg white, round tablets, in unit of use packages of 100 tablets. Each LITHOSTAT ® tablet is debossed MPC 500 on one side and blank on the other side. LITHOSTAT ® should be stored in a dry place at room temperature, 15° - 30°C (59° - 86°F). Container should be closed tightly. L050001R0620

Authorization status:

New Drug Application

Summary of Product characteristics

LITHOSTAT- ACETOHYDROXAMIC ACID TABLET
MISSION PHARMACAL COMPANY
----------
LITHOSTAT
(ACETOHYDROXAMIC ACID) TABLETS
DESCRIPTION
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. AHA
is a urease inhibitor. Available as 250 mg tablets.
CLINICAL PHARMACOLOGY
®
AHA 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.
AHA is well absorbed from the gastrointestinal tract after oral
administration; peak blood
levels occur from 0.25 to 1 hour after dosing. The compound is
distributed throughout
body water, and there is no known binding to any tissue. AHA chelates
with dietary iron
within the gut. This reaction may interfere with absorption of AHA and
with iron.
Concomitant hypochromic anemia should be treated with intramuscular
iron.
In rodents, the metabolic fate of AHA is well known; 55% is excreted
unchanged in
urine, 25% is excreted as acetamide or acetate and 7% is excreted by
the lungs as
carbon dioxide. Less than 1% is excreted in the feces. Approximately
5% of the
administered dose is unaccounted for. In rodents, AHA shows a
dose-related change in
pharmacokinetics; with increasing dose, there is an increase in the
half-life and an
increase in the percent of the administered dose recovered in urine as
unchanged AHA.
Pharmacokinetics in man are generally similar to rodents including the
dose-related
increase in half-life, but they are not as well characterized as in
the rodent. Thirty-six to
sixty-five percent (36-65%) of the oral dosage is excreted unchanged
in the urine. It is
unaltered AHA