Acetohydroxamic Acid

Mechanism-of-action class: Urease Inhibitors.

• 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.

• Acetohydroxamic acid should not be used in: a. patients whose physical state and disease are amenable to definitive surgery and appropriate antimicrobial agents b.contraindicated

AHA should be administered orally, one tablet 3-4 times a day in a total daily dose of 10-15 mg/kg/day. The recommended starting dose is 12 mg/kg/day, administered at 6-8 hour intervals at a time when the stomach is empty. The maximum daily dose should be no more than 1.5 grams, regardless of body weight. The dosage should be reduced in patients with reduced renal function. Patients whose serum creatinine is greater than 1.8 mg/dl should take no more than 1.0 gm/day; such patients should be dosed at q-12-h intervals. Further reductions in dosage to prevent the accumulation of toxic concentrations in the blood may also be desirable. Insufficient data exists to accurately characterize the optimum dose and/or dose interval in patients with moderate degrees of renal insufficiency. Patients with advanced renal insufficiency (i.e., serum creatinine more than 2.5 mg/dl) should not be treated with AHA. The risk of accumulation of toxic blood levels of AHA seems to be greater than the chances for a beneficial effect in such patients. In children an initial dose of 10 mg/kg/day is recommended. Close monitoring of the patient’s clinical condition and hematologic status is recommended. Titration of the dose to higher or lower levels may be required to obtain an optimum therapeutic effect and/or to reduce the risk of side effects.

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.

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.

(See Contraindications.)

Acute deliberate overdosage in man has not occurred, but would be expected to induce the following symptoms: anorexia, malaise, lethargy, diminished sense of well being, tremulousness, anxiety, nausea and vomiting. Laboratory findings are likely to include an elevated reticulocyte count and a severe hemolytic reaction requiring hospitalization, symptomatic treatment, and possibly blood transfusions. Concomitant reduction in platelets and/or white blood cells should be anticipated. Milder overdosages resulting in hemolysis have occurred in an occasional patient with reduced renal function after several weeks or months of continuous treatment. The acute LD 50 of AHA in animals (rats) is 4.8 gm/kg. Recommended treatment for an overdosage reaction consists of (1) cessation of treatment, (2) close monitoring of hematologic status, (3) symptomatic treatment, and (4) blood transfusions as required by the clinical circumstances. The drug is probably dialyzable, but this property has not been tested clinically.

• May 31, 1983NDANDA018749Mission Pharma

1. 1Headache1226%
2. 2Decreased Appetite1021%
3. 3Tremor919%
4. 4Asthenia511%
5. 5Nausea511%
6. 6Confusional State48.5%
7. 7Death48.5%
8. 8Fatigue48.5%
9. 9Rash48.5%
10. 10Somnolence48.5%
11. 11Abdominal Pain Upper36.4%
12. 12Alopecia36.4%
13. 13Diarrhoea36.4%
14. 14Dizziness36.4%
15. 15Feeling Abnormal36.4%

Recent PubMed references pinned to Acetohydroxamic Acid as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Design and discovery of urease and Helicobacter pylori inhibitors based on benzofuran/benzothiophene-sulfonate and sulfamate scaffolds for the treatment of ureolytic bacterial infections.
  International journal of biological macromolecules · 2024 · Hashem O, Zaib S, Zaraei SO, et al.
  PMID 38768915DOI 10.1016/j.ijbiomac.2024.132502
• Synthesis, crystal structure and biological evaluation of new phosphoramide derivatives as urease inhibitors using docking, QSAR and kinetic studies.
  Bioorganic chemistry · 2019 · Gholivand K, Pooyan M, Mohammadpanah F, et al.
  PMID 30772649DOI 10.1016/j.bioorg.2019.01.064
• Formation of struvite urinary stones and approaches towards the inhibition-A review.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2017 · Das P, Gupta G, Velu V, et al.
  PMID 29028588DOI 10.1016/j.biopha.2017.10.015
• Aminophosphinates against Helicobacter pylori ureolysis-Biochemical and whole-cell inhibition characteristics.
  PloS one · 2017 · Macegoniuk K, Grela E, Biernat M, et al.
  PMID 28792967DOI 10.1371/journal.pone.0182437
• Whole-cell Proteus mirabilis urease inhibition by aminophosphinates for the control of struvite formation.
  Journal of medical microbiology · 2016 · Grela E, Dziełak A, Szydłowska K, et al.
  PMID 27550502DOI 10.1099/jmm.0.000342
• Contemporary Management of Struvite Stones Using Combined Endourologic and Medical Treatment: Predictors of Unfavorable Clinical Outcome.
  Journal of endourology · 2016 · Iqbal MW, Youssef RF, Neisius A, et al.
  PMID 24251429DOI 10.1089/end.2013.0257
• Oxidation of N-hydroxy-l-arginine by hypochlorous acid to form nitroxyl (HNO).
  Journal of inorganic biochemistry · 2013 · Cline MR, Chavez TA, Toscano JP, et al.
  PMID 23102772DOI 10.1016/j.jinorgbio.2012.09.024
• Redox reactions of Pu(IV) and Pu(III) in the presence of acetohydroxamic acid in HNO(3) solutions.
  Inorganic chemistry · 2009 · Tkac P, Precek M, Paulenova A, et al.
  PMID 19904974DOI 10.1021/ic901081j

The 5 most recently updated of 5 ClinicalTrials.gov registrations naming Acetohydroxamic Acid as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Acetohydroxamic Acid Combined With a Short-Course Regimen for MDR-TB (AHA-PLUS)
  Not yet recruiting · Phase 2 · Interventional · 120 enrolled · Shanghai Pulmonary Hospital, Shanghai, China
  NCT07393438updated 2026-02-06
• MyHeart Counts Cardiovascular Health Study
  Active not recruiting · Interventional · 2,000,000 enrolled · Stanford University
  NCT03090321updated 2025-05-29
• Placebo-Controlled Study Assessing the Use of a Novel Exfoliative Serum With A Chemical Peel to Improve Photodamage in Adults
  Completed · Interventional · 34 enrolled · Austin Institute for Clinical Research
  NCT05908825updated 2024-07-19
• Manipulating the Gut Microbiome Study
  Terminated · Phase 1 · Phase 2 · Interventional · 4 enrolled · Nicholas Ah Mew
  NCT03181828updated 2021-12-15
• Acute High-risk Abdominal Surgery Study - an Optimized Perioperative Course
  Completed · Interventional · 1,200 enrolled · Hvidovre University Hospital
  NCT01899885updated 2015-06-12

Frequently asked questions

How does Acetohydroxamic Acid work?

Mechanism-of-action class: Urease Inhibitors.

What is Acetohydroxamic Acid used for?

According to FDA labeling, Acetohydroxamic Acid carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Acetohydroxamic Acid?

Acetohydroxamic Acid is classified as Other urologicals, Urease Inhibitor, Urease Inhibitors.

What are the brand names for Acetohydroxamic Acid?

Acetohydroxamic Acid is marketed under brand names including Lithostat.

What are the contraindications for Acetohydroxamic Acid?

Acetohydroxamic Acid labeling lists contraindications including: Acetohydroxamic acid should not be used in: a. patients whose physical state and disease are amenable to definitive surgery and appropriate antimicrobial agents b.. Always consult the full prescribing information and a clinician.