acetohydroxamic acid
Regulatory sources consulted
Approved indications
- Adjunctive treatment of chronic urinary infection caused by urease-producing organisms, together with antimicrobial therapy and surgery when appropriate.
Contraindications
Absolute
- Pregnancy or lack of effective contraception; advanced renal impairment; infection caused by non-urease-producing organisms or controllable with antibiotics/definitive surgery.
Clinical warnings
- Major warning · May cause Coombs-negative hemolytic anemia. Check CBC and reticulocytes at 2 weeks and then every 3 months; consider dose reduction if reticulocytes exceed 6%. — FDA/DailyMed, set_id 6660b616-a82d-9109-19ce-2bdf9747acea
- Major warning · Monitor renal and liver function; accumulation and adverse reactions increase with renal impairment. — FDA/DailyMed, set_id 6660b616-a82d-9109-19ce-2bdf9747acea
Drug interactions
- ModerateOral iron
Mechanism: Acetohydroxamic acid chelates iron and may reduce absorption of both agents.
Recommendation: Avoid simultaneous oral administration; consider an alternative route for iron.
FDA/DailyMed, set_id 6660b616-a82d-9109-19ce-2bdf9747aceahttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6660b616-a82d-9109-19ce-2bdf9747acea
- ModerateAlcohol
Mechanism: The combination has been associated with rash and warmth.
Recommendation: Avoid alcohol during treatment.
FDA/DailyMed, set_id 6660b616-a82d-9109-19ce-2bdf9747aceahttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6660b616-a82d-9109-19ce-2bdf9747acea
Adverse events
Common (≥1%)
Headache · Nausea, vomiting, or anorexia · Malaise · Reticulocytosis or anemia
Rare but serious
Clinically significant hemolytic anemia · Thrombophlebitis or pulmonary embolism · Alcohol-associated rash
Pregnancy and lactation
Contraindicated during pregnancy; effective contraception is required. Decide whether to stop breastfeeding or the drug because of the risk of serious reactions in the infant.
Recent literature (PubMed)
Recurrent kidney stones are unpleasant and may lead to kidney damage, sepsis, or invasive procedures. To assess benefits and harms of diet, pharmacologic therapy, and surveillance imaging to prevent recurrent nephrolithiasis. PubMed, Cochrane Library, and trial registries through December 2025. Randomized controlled trials (RCTs) or nonrandomized studies of interventions (NRSIs) in nonpregnant adults or children. One reviewer extracted data, and a second reviewer checked for accuracy. Dual independent assessments of risk of bias and strength of evidence (SOE) were done. Among 31 studies (26 RCTs and 5 NRSIs), none evaluated imaging strategies. All but 3 included adults only. For adults with calcium oxalate or phosphate stones, increased water intake; a diet with normal to high calcium, low protein, and low sodium; thiazides; alkali treatment; and allopurinol may reduce stone recurrence (low SOE). There may be no difference between selective and empirical pharmacotherapy (low SOE). Acetohydroxamic acid may reduce stone growth in adults with infection-related stones (low SOE) but had insufficient evidence on prevention of recurrent stones and probably increased adverse events (moderate SOE). There may be increased minor adverse events with lemon juice but no increased harm due to serious adverse events with thiazides and allopurinol (low SOE). Studies not published in English or with fewer than 30 participants per group were excluded. Increased fluid intake; a diet with normal to high calcium, low protein, and low sodium; thiazides; alkali therapy; and allopurinol may prevent stone recurrence in adults with calcium oxalate or calcium phosphate stones. Evidence is limited on other interventions, including imaging strategies, in children and on harms and other outcomes. Patient-Centered Outcomes Research Institute and Agency for Healthcare Research and Quality (contract no. 75Q80120D00007/75Q80124F32010). (PROSPERO: CRD42024617257).
The prevalence of nephrolithiasis is increasing across all demographic groups. Apart from the morbidity associated with an acute occurrence, preventative treatment is essential for stone disease, which can become a long-term problem. Simple interventions like fluid intake optimization and dietary modification are effective for most stone types. However, patients with specific metabolic abnormalities may require pharmaceutical therapy if lifestyle changes are insufficient to reduce the risk of stone recurrence. The treatment of citrates and/or pyridoxines may help eliminate or prevent recurrences of kidney stones, especially when they are composed of uric acid, calcium oxalate, calcium phosphate, or the latter two together. In cases of struvite stones, which often necessitate a surgical approach, acetohydroxamic acid emerges as a valuable second-line treatment option. Thiol-binding agents may be needed for cystinuria, as well as lifestyle modifications. Successful treatment reduces stone recurrence and the need to remove stones surgically.
Urease is an attractive drug target for designing anti-infective agents against pathogens such as Helicobacter pylori, Proteus mirabilis, and Ureaplasma urealyticum. In the past century, hundreds of medicinal chemists focused their efforts on explorations of urease inhibitors. Despite the FDA's approval of acetohydroxamic acid as a urease inhibitor for the treatment of struvite nephrolithiasis and the widespread use of N-(n-butyl)thiophosphoric triamide as a soil urease inhibitor as nitrogen fertilizer synergists in agriculture, urease inhibitors with high potency and safety are urgently needed. Exploration of novel urease inhibitors has therefore become a hot research topic recently. Herein, inhibitors identified worldwide from 2016 to 2021 have been reviewed. They structurally belong to more than 20 classes of compounds such as urea/thioure analogues, hydroxamic acids, sulfonamides, metal complexes, and triazoles. Some inhibitors showed excellent potency with IC50 values lower than 10 nM, having 10000-fold higher potency than the positive control thiourea.
Urease is a nickel-dependent metalloenzyme that catalyzes urea hydrolysis, generating ammonia and elevating local pH, a process implicated in the pathogenesis of Helicobacter pylori-associated peptic ulcer disease (PUD). To identify effective urease inhibitors, acetohydroxamic acid (AHA) remains the only FDA-approved agent, with clinical use constrained by toxicity. This review synthesizes current evidence on urease inhibition strategies, encompassing metal-based complexes, organic derivatives, natural products, peptide inhibitors, nanotechnology-enabled systems, and emerging gene-based approaches. Several candidates, including copper-based compounds and the natural alkaloid palmatine (PAL), demonstrate potent urease inhibition and favorable effects in preclinical models. However, translation to clinical practice is limited by safety concerns, instability, and a paucity of human trials. Advancing hybrid molecules, optimized delivery platforms, and combination therapies may enhance therapeutic efficacy. Rigorous clinical evaluation remains essential to establish urease inhibition as a viable strategy in urease-mediated diseases. We assessed the comparative effectiveness and harms of diet and pharmacologic therapy to prevent recurrent nephrolithiasis in adults and children, as well as surveillance imaging strategies. Evidence for preventive interventions in adults was updated based on a prior review. Medline® via PubMed®, Cochrane Library, trial registry, reference lists of relevant articles from January 2000 (imaging) or 2011 (update on preventive interventions) through May 2025. Randomized controlled trials (RCTs) in nonpregnant adults or children evaluating diet, pharmacologic, or surveillance imaging strategies reporting health outcomes (e.g., symptomatic stone recurrence, quality of life), adverse events, or other outcomes. Nonrandomized studies of interventions (NRSIs) were eligible if no RCT was available. Active, placebo, and no treatment controls were eligibl