Lithostat

Acidifying Agents

For store information, see the specific product information within the How Supplied section.

Administer on an empty stomach (i.e., 1 hour before or 2 hours after a meal) with plenty of fluids.

hemolytic anemia / Delayed / 15.0-15.0
pulmonary embolism / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known

depression / Delayed / 6.0-20.0
leukopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
palpitations / Early / Incidence not known
phlebitis / Rapid / Incidence not known

headache / Early / 30.0-30.0
nausea / Early / 20.0-25.0
malaise / Early / 20.0-25.0
anorexia / Delayed / 20.0-25.0
vomiting / Early / 20.0-25.0
tremor / Early / 6.0-20.0
anxiety / Delayed / 6.0-20.0
fatigue / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
alopecia / Delayed / Incidence not known

Lithostat

Rx

Unique agent that inhibits hydrolysis of urea and production of ammonia in urine infected with urea-splitting organisms; has no direct antimicrobial effect and is not considered an acidifying agent.
Used as an adjunct in the treatment of chronic urea-splitting urinary tract infections.
Also used off-label for hepatic encephalopathy (not first-line).

250 mg PO 3 or 4 times daily given at 6- or 8-hour intervals on an empty stomach for a total daily dose of 10 to 15 mg/kg/day PO; usual starting dose is 12 mg/kg/day. Do not exceed 1.5 grams/day PO, regardless of body weight.

Detailed studies regarding dosage and dose intervals have not been established. Begin with 10 mg/kg/day PO, administered in two or three divided doses given on an empty stomach every 6 to 8 hours, and titrate as to obtain optimum therapeutic effect and to reduce the risk of side effects. Maximum dose is 15 mg/kg/day, not to exceed 1.5 grams/day PO, regardless of body weight.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

CrCl >= 20 mL/min and serum creatinine > 1.8 mg/dL: No more than 1 gram/day PO administered in 2 divided doses. Further reductions may be required. Adequate data do not exist to determine the optimum dose and/or dose interval in patients with renal impairment.
CrCl < 20 mL/min or serum creatinine > 2.5 mg/dL: Contraindicated.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Acetaminophen; Aspirin: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aluminum Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Carbonate: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Antacids: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aspirin, ASA: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Carisoprodol: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Dipyridamole: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Omeprazole: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Oxycodone: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Bismuth Subsalicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Choline Salicylate; Magnesium Salicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Colchicine: (Moderate) Colchicine is an alkaloid that is inhibited by acidifying agents. The colchicine dose may need adjustment.
Ethanol: (Major) Advise patients to avoid alcohol-containing beverages while taking acetohydroxamic acid. Concomitant use of acetohydroxamic acid and alcohol can cause a flushing reaction and a nonpruritic, macular rash on the upper extremities and face. The rash typically occurs within 30 to 45 minutes of alcohol ingestion and disappears 30 to 60 minutes later.
Ferric Maltol: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Food: (Major) Acetohydroxamic acid chelates heavy metals, including dietary iron. Absorption of iron and acetohydroxamic acid from the intestinal lumen may be reduced. Acetohydroxamic acid should be taken without food, on an empty stomach.
Iron Salts: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Iron: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Magnesium Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Magnesium Salicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Methadone: (Minor) As methadone is a weak base, the renal elimination of methadone is increased by urine acidification. Thus acidifying agents may lower the serum methadone concentration. The limited amounts of circulating methadone that undergo glomerular filtration are partially reabsorbed by the kidney tubules, and this reabsorption is pH-dependent. Several studies have demonstrated that methadone is cleared faster from the body with an acidic urinary pH as compared with a more basic pH.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Polysaccharide-Iron Complex: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
Probenecid; Colchicine: (Moderate) Colchicine is an alkaloid that is inhibited by acidifying agents. The colchicine dose may need adjustment.
Salsalate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.

Lithostat Oral Tab: 250mg

1.5 grams/day PO.

1.5 grams/day PO.

15 mg/kg/day PO, not to exceed 1.5 grams/day PO.

Detailed studies have not established optimum dosage or dose intervals. 15 mg/kg/day PO, not to exceed 1.5 grams/day PO, whichever is less.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Acetohydroxamic acid inhibits the hydrolysis of urea and production of ammonia in urine infected with urea-splitting bacteria. By inhibiting the enzyme, there is a reduction of both urine alkalinity and ammonia concentration. Acetohydroxamic acid does not directly acidify the urine or have any direct antimicrobial effect. The effectiveness of antibacterial medications is enhanced and the formation of urinary calculi, including struvite stones, is reduced.

Acetohydroxamic acid is administered orally. Acetohydroxamic acid is distributed throughout body water. There is no known binding to tissue. A significant portion of the dose (36—65%) is excreted unchanged in the urine. The half-life is approximately 5—10 hours in patients with normal renal function. An increase in the dose of acetohydroxamic acid corresponds to an increase in half-life.
 
The drug inhibits urease, which results in inhibition of the hydrolysis of urea and production of ammonia in urine infected with urea-splitting organisms (see Mechanism of Action). The therapeutic effect of acetohydroxamic acid is due to excretion of unchanged drug in the urine. The concentration of acetohydroxamic acid in the urine that is needed to inhibit urease is unknown. Therapeutic benefit may be seen from concentrations as low as 8 mcg/mL, but higher concentrations (i.e., 30 mcg/mL) are expected to provide urease inhibition.

Acetohydroxamic acid is well absorbed orally. Peak plasma concentrations are reached 0.25—1 hour after oral dosing. Chelation to dietary iron in the gut which may interfere with oral absorption of acetohydroxamic acid and iron (see Drug Interactions).

Acetohydroxamic acid is classified as FDA pregnancy risk category X and is contraindicated in women who are or may become pregnant. Acetohydroxamic acid may cause fetal harm when administered to pregnant women. Acetohydroxamic acid was found to be teratogenic when given intraperitoneally to rats. Teratogenic effects included retarded and/or clubbed rear legs, exencephaly, and encephalocele. Acetohydroxamic acid is contraindicated in females who are not using appropriate contraception. If a woman becomes pregnant while taking acetohydroxamic acid, the physician and patient should discuss the potential hazard to the fetus.

According to the manufacturer, it is not known whether acetohydroxamic acid is excreted into breast milk. However, due to the potential toxicity of acetohydroxamic acid, breast-feeding is not recommended due to the potential harm to the infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.