Aconitic Acid

Dosage for Aconitic Acid is highly individualized and depends on the volume of the cavity being irrigated and the size of the stone being dissolved.

• For Bladder Irrigation: The standard protocol typically involves the instillation of 30 mL to 60 mL of a 1% Aconitic Acid-based solution into the bladder via a catheter. This solution is often retained for 20 to 30 minutes before being drained. This process may be repeated 2 to 4 times daily depending on patient tolerance.
• For Renal Pelvis Irrigation: The flow rate is much more restricted to prevent intrapelvic pressure elevation. Healthcare providers usually start at a rate of 3 mL to 5 mL per minute through a nephrostomy tube, with a maximum daily volume determined by the patient's renal output and comfort.

Aconitic Acid is not routinely approved for pediatric use due to the high risk of systemic absorption and electrolyte imbalance in smaller body masses. If a healthcare provider deems it necessary for a child with complex urolithiasis, the dosage is strictly calculated based on body surface area (BSA) and monitored in an intensive care setting. Generally, pediatric use is considered off-label and carries significant risks.

Renal Impairment

In patients with significant renal impairment (CrCl < 30 mL/min), the use of Aconitic Acid must be approached with extreme caution. Since the drug and its mineral complexes are cleared renally, there is a high risk of systemic accumulation and hypermagnesemia or hypercalcemia if the irrigation fluid is absorbed.

Hepatic Impairment

No specific dosage adjustments are typically required for hepatic impairment, as the drug is primarily cleared through the kidneys and the TCA cycle. However, patients with end-stage liver disease should be monitored for metabolic acidosis.

Elderly Patients

Elderly patients are at a higher risk for mucosal thinning in the urinary tract. Consequently, they are more susceptible to systemic absorption. Healthcare providers typically start with lower volumes and shorter retention times in patients over the age of 65.

Aconitic Acid is administered by healthcare professionals in a clinical or hospital setting.

• Administration: It is delivered via a sterile catheter or nephrostomy tube. It must never be taken orally or injected intravenously in its irrigation form.
• Temperature: The solution should be at room temperature or slightly warmed to body temperature (37°C) to prevent bladder spasms.
• Storage: Store the sterile solution at room temperature (20°C to 25°C). Do not freeze. Discard any unused portion immediately after the seal is broken, as the solution contains no preservatives.

Since Aconitic Acid is usually administered on a strict schedule in a clinical setting, missed doses are rare. If a home-based irrigation dose is missed, it should be administered as soon as remembered. However, if it is nearly time for the next dose, the missed dose should be skipped. Do not double the volume of the irrigation fluid.

Signs of systemic overdose (usually due to excessive absorption) include:

• Metabolic Acidosis: Rapid breathing, confusion, and lethargy.
• Electrolyte Imbalance: Muscle weakness, cardiac arrhythmias, and hypotension.
• Emergency Measures: If an overdose is suspected, the irrigation must be stopped immediately. Treatment involves intravenous hydration, correction of electrolyte levels, and in severe cases, hemodialysis to remove the absorbed acid and mineral complexes.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or frequency of irrigation without medical guidance, as this can lead to severe tissue damage or systemic toxicity.

Most common side effects associated with Aconitic Acid are localized to the site of administration.

• Bladder Irritation: Patients frequently report a burning sensation or 'stinging' during the instillation of the solution. This typically lasts for the duration of the irrigation and subsides shortly after drainage.
• Urinary Urgency: The acidic nature of the drug can stimulate the detrusor muscle, leading to a frequent and strong urge to urinate.
• Mild Hematuria: Small amounts of blood in the urine (pink-tinged urine) may occur as the stones begin to dissolve or if the catheter causes minor trauma to the bladder wall.

• Bladder Spasms: Intense, cramp-like pain in the pelvic region caused by the involuntary contraction of the bladder.
• Nausea: Some patients experience mild systemic queasiness, which may be a vasovagal response to the catheterization or irrigation process.
• Low-grade Fever: A transient increase in body temperature may occur, often as a response to the release of bacteria trapped within the dissolving stones.

• Severe Urothelial Erosion: Prolonged exposure to the acidic solution can lead to the breakdown of the bladder lining.
• Systemic Adrenergic Symptoms: Due to its classification as an alpha/beta-Adrenergic Agonist [EPC], rare systemic absorption can cause palpitations, increased heart rate (tachycardia), and transient hypertension.
• Allergic Reactions: Skin rash, itching, or hives, particularly if the patient has a sensitivity to organic acids or related food allergenic extracts.

> Warning: Stop taking Aconitic Acid and call your doctor immediately if you experience any of these.

• Anaphylaxis: Signs include swelling of the face, lips, or tongue; difficulty breathing; and a rapid drop in blood pressure. This is a medical emergency.
• Hypermagnesemia/Hypercalcemia: If the drug facilitates excessive absorption of minerals from the stones, you may experience extreme muscle weakness, slow heart rate, and profound confusion.
• Severe Abdominal Pain: This may indicate perforation of the urinary tract or severe internal irritation.
• Urosepsis: High fever, chills, and extreme fatigue may suggest that bacteria from the dissolved stones have entered the bloodstream.

Prolonged use of Aconitic Acid (over several weeks or months) can lead to chronic cystitis (inflammation of the bladder) or changes in the cellular structure of the urothelium. There is also a risk of developing secondary electrolyte imbalances if the patient has underlying renal insufficiency. Regular monitoring of the bladder wall via cystoscopy is often recommended for patients undergoing long-term dissolution therapy.

No FDA black box warnings have been issued specifically for Aconitic Acid as of 2026. However, it is often used in combination products that may carry warnings regarding the risk of systemic absorption in patients with urological injuries. Always consult the specific product insert for the formulation being used.

Report any unusual symptoms to your healthcare provider. Even mild symptoms can be early indicators of systemic absorption that requires a change in treatment protocol.

Aconitic Acid is a potent chemical agent that must only be used under strict medical supervision. It is not intended for oral consumption and can cause severe chemical burns if ingested or applied to the eyes. Patients must ensure they are properly hydrated during treatment to facilitate the clearance of dissolved minerals and any absorbed acid. If you have a history of frequent urinary tract infections (UTIs) or structural abnormalities in your urinary system, you must inform your doctor before beginning therapy.

No FDA black box warnings for Aconitic Acid. While it is a high-alert medication in some hospital settings due to its acidic nature, it does not currently carry the FDA's most severe warning label.

• Allergic Reactions / Anaphylaxis Risk: While rare, patients with sensitivities to organic acids found in sugarcane or other plants may be at risk. Aconitic Acid is also classified as a Non-Standardized Food Allergenic Extract [EPC], meaning it can trigger immune responses in susceptible individuals.
• Urothelial Integrity: The primary risk of Aconitic Acid is its potential to damage the lining of the urinary tract. It should never be used if there is evidence of a 'leaky' bladder or if a recent biopsy or surgery has been performed on the area.
• Cardiotoxicity: Because of its alpha-Adrenergic Agonist and beta-Adrenergic Agonist properties, patients with pre-existing heart conditions (such as arrhythmias or heart failure) must be monitored for changes in heart rate and blood pressure during irrigation.
• Nephrotoxicity: While the drug is used to treat kidney-related stones, excessive absorption can paradoxically strain the kidneys as they attempt to filter the resulting mineral complexes.

Patients undergoing Aconitic Acid therapy require regular diagnostic testing:

• Serum Electrolytes: Frequent monitoring of magnesium, calcium, and phosphate levels to detect systemic absorption.
• Renal Function Tests: Creatinine and BUN levels should be checked weekly.
• Urinalysis: To monitor for blood, white blood cells (infection), and the pH level of the urine.
• Imaging: Periodic X-rays or ultrasounds to track the progress of stone dissolution.

Aconitic Acid generally does not interfere with the ability to drive. However, if you experience dizziness or palpitations due to systemic absorption or the stress of the procedure, you should avoid these activities until the symptoms resolve.

Alcohol should be avoided during Aconitic Acid therapy. Alcohol can irritate the bladder further and may exacerbate the risk of metabolic acidosis if systemic absorption occurs. It also acts as a diuretic, which can complicate the controlled irrigation process.

Do not stop the treatment course prematurely without consulting your urologist. Stopping early may leave partially dissolved stones with jagged edges, which can cause more pain or lead to a blockage. If the treatment must be stopped due to side effects, your doctor will provide a plan to manage the remaining calculi.

> Important: Discuss all your medical conditions, including any history of heart disease or kidney problems, with your healthcare provider before starting Aconitic Acid.

• Methenamine: This urinary antiseptic requires an acidic environment to work, but when used with Aconitic Acid, it can lead to excessive acidification of the urine, causing the formation of formaldehyde crystals in the bladder, which is highly toxic to the urothelium.
• Specific Copper-containing Intrauterine Devices (IUDs): While the interaction is localized, systemic absorption of Aconitic Acid can theoretically interfere with the inflammatory response required for the efficacy of certain copper-based contraceptives, as noted in its EPC classification.

• Digoxin: Aconitic Acid can affect calcium and magnesium levels. Since digoxin toxicity is highly sensitive to electrolyte shifts, patients on this heart medication are at a significantly higher risk for life-threatening arrhythmias if Aconitic Acid is absorbed systemically.
• Potassium-Sparing Diuretics (e.g., Spironolactone): The combination can increase the risk of metabolic acidosis and electrolyte imbalances.
• Anti-arrhythmic Drugs: Due to the beta-Adrenergic Agonist [MoA] properties of Aconitic Acid, it may antagonize the effects of certain heart rhythm medications or lead to additive effects on heart rate.

• NSAIDs (e.g., Ibuprofen, Naproxen): These drugs can reduce renal blood flow, which may slow the clearance of absorbed Aconitic Acid and its complexes.
• Corticosteroids: May lead to increased sodium retention and further complicate electrolyte management during irrigation therapy.

• High-Calcium Foods: Consuming excessive dairy or calcium supplements during therapy may reduce the effectiveness of Aconitic Acid, as the acid will spend its 'chelating power' on dietary calcium rather than the stones.
• Caffeine: As a stimulant, caffeine may worsen the tachycardia or palpitations associated with the adrenergic properties of Aconitic Acid.

• Vitamin C (Ascorbic Acid): Since Aconitic Acid is classified alongside Vitamin C [EPC], taking high doses of Vitamin C supplements can lead to additive urinary acidification, potentially increasing the risk of irritation or the formation of oxalate stones.
• St. John's Wort: While no direct CYP interaction is known, the mood-altering effects of this herb may mask signs of systemic acidosis such as lethargy or confusion.

• Urinary pH: Aconitic Acid will significantly lower the measured pH of the urine, which is a desired effect but must be noted by lab technicians.
• Serum Calcium/Magnesium: Results may be falsely elevated if blood is drawn shortly after an irrigation session where systemic absorption occurred.

For each major interaction, the mechanism involves either a pharmacodynamic overlap (additive effects on electrolytes or heart rate) or a physicochemical interaction (pH changes affecting drug solubility). Management typically involves adjusting the timing of doses or choosing alternative medications.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially those that affect your heart or kidneys.

Aconitic Acid must NEVER be used in the following circumstances:

• Hypersensitivity: Any known allergy to Aconitic Acid or other organic tricarboxylic acids.
• Urinary Tract Perforation: If there is any suspicion that the bladder or renal pelvis wall is not intact, irrigation is strictly prohibited. The acid would enter the peritoneal cavity, causing massive inflammation, chemical peritonitis, and systemic toxicity.
• Severe Renal Failure: Patients with anuria (inability to produce urine) cannot clear the dissolved mineral complexes, leading to rapid and fatal electrolyte toxicity.
• Active Acute Cystitis: Irrigation in the presence of an acute, untreated infection can force bacteria into the bloodstream (bacteremia).

Conditions requiring careful risk-benefit analysis include:

• Pregnancy: The risks of systemic absorption to the fetus are unknown.
• History of Struvite Stones with Urease-Producing Bacteria: While the drug dissolves the stone, the release of bacteria requires simultaneous, aggressive antibiotic therapy.
• Cardiac Arrhythmias: The potential for adrenergic stimulation makes this drug risky for patients with unstable heart rhythms.

Patients who have experienced allergic reactions to citric acid, malic acid, or tartaric acid may also be sensitive to Aconitic Acid. Furthermore, because it is found in sugarcane, individuals with severe sugarcane allergies (Non-Standardized Food Allergenic Extract [EPC]) should be tested before use.

> Important: Your healthcare provider will evaluate your complete medical history, including recent surgeries and kidney function, before prescribing Aconitic Acid.

Aconitic Acid is classified as FDA Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies have not been conducted. It is unknown whether Aconitic Acid can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Use during pregnancy should only be considered if the potential benefit justifies the potential risk to the fetus, particularly in the third trimester when renal strain is highest.

It is not known whether Aconitic Acid is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from systemic absorption (including electrolyte shifts), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Safety and effectiveness in pediatric patients have not been established. The risk of systemic absorption is higher in children due to their larger surface-area-to-mass ratio. Use in children is generally reserved for life-threatening stone blockages where surgery is not an option, and it must be performed in a specialized pediatric urology unit.

Clinical studies of Aconitic Acid-based irrigation did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Geriatric patients are at a significantly higher risk for hypermagnesemia if absorption occurs.

In patients with a GFR below 45 mL/min, the clearance of the mineral-acid complexes is significantly delayed. Healthcare providers may need to reduce the concentration of the irrigation solution or the frequency of the sessions. Dialysis patients should generally not receive Aconitic Acid therapy unless the irrigation is strictly contained and drained externally.

While the liver is not the primary organ for Aconitic Acid clearance, patients with Child-Pugh Class C cirrhosis may have impaired acid-base buffering systems. These patients should be monitored for the development of systemic metabolic acidosis.

> Important: Special populations require individualized medical assessment and more frequent laboratory monitoring during the course of treatment.

Aconitic Acid acts as a Calculi Dissolution Agent through its properties as a weak organic acid and a metal-ion chelator. In the urinary tract, it lowers the pH of the irrigation fluid to approximately 4.0–5.0. This acidity increases the solubility of calcium and magnesium salts. Specifically, the three carboxyl groups (-COOH) of Aconitic Acid interact with the divalent cations (Ca2+ and Mg2+) in the stone matrix. This Calcium Chelating Activity [MoA] pulls the ions away from the crystalline structure of the stone, causing it to crumble and dissolve into a soluble form that can be flushed out. Additionally, its role as an Adrenergic alpha/beta-Agonist involves binding to G-protein coupled receptors, though this is a secondary pharmacological effect in its primary urological use.

The onset of action for stone dissolution is gradual, often requiring several days of repeated irrigation to see significant reduction in stone size. The duration of effect is limited to the time the solution is in contact with the stone. Tolerance does not typically develop to the chemical dissolution process, although the urothelium may become increasingly sensitized (irritated) with repeated exposure.

| Parameter | Value |

|---|---|

| Bioavailability | <5% (on intact mucosa) |

| Protein Binding | <10% |

| Half-life | 1.5 - 3 hours |

| Tmax | 1 hour (if absorbed) |

| Metabolism | TCA Cycle (Aconitase) |

| Excretion | Renal >90% |

• Molecular Formula: C6H6O6
• Molecular Weight: 174.11 g/mol
• Solubility: Highly soluble in water; slightly soluble in ethanol.
• Structure: Aconitic acid exists as two isomers: cis-aconitic acid and trans-aconitic acid. The cis form is the intermediate in the Krebs cycle, while the trans form is often found in plants like sugarcane and is more stable for pharmaceutical formulations.

Aconitic Acid is classified as a Calculi Dissolution Agent [EPC]. It is related to other organic acids like citric acid and gluconic acid. Within the broader therapeutic landscape, it is also categorized as a Catecholamine [EPC] and Adrenergic Agonist [EPC] due to its structural and functional similarities to endogenous metabolic modulators.