Anhydrous Citric Acid

Dosage for Anhydrous Citric Acid is highly individualized and is typically based on the patient's acid-base status and urinary pH goals.

• For Metabolic Acidosis: The standard adult dose of a common oral solution (containing 334 mg of sodium citrate and 200 mg of citric acid per 5 mL) is 10 to 30 mL, diluted in water, taken four times daily after meals and at bedtime.
• For Urinary Alkalization/Stone Prevention: The typical dose ranges from 10 to 20 mL of solution diluted in a full glass of water or juice, taken three to four times per day. The goal is often to maintain a urinary pH between 6.0 and 7.0.

Anhydrous Citric Acid is used in pediatric populations, but dosing must be calculated carefully by a specialist, often based on body weight or surface area.

• Standard Pediatric Dosing: For children, the typical dose is 5 to 15 mL of oral solution, diluted in water or juice, taken two to four times daily.
• Monitoring: Children require frequent monitoring of serum electrolytes (sodium, potassium, chloride, and bicarbonate) to ensure the dose is effective and safe.

Renal Impairment

Patients with significant renal impairment (low GFR) require extreme caution. In patients with chronic kidney disease (CKD), the sodium or potassium load associated with citric acid salts can lead to fluid overload or life-threatening hyperkalemia. Doses may need to be reduced, or the medication may be contraindicated in severe cases.

Hepatic Impairment

Since the liver is the primary site for the metabolism of citrate to bicarbonate, patients with severe hepatic insufficiency may not experience the full alkalizing effect, and citrate levels could theoretically accumulate, though this is rarely a clinical concern compared to renal risks.

Elderly Patients

Older adults often have age-related declines in renal function. Starting at the lower end of the dosing range is recommended, with frequent monitoring of renal function and electrolyte levels.

Proper administration is critical to prevent gastrointestinal side effects and ensure efficacy:

1. 1Dilution is Mandatory: Oral solutions are highly concentrated and can cause severe irritation to the mouth, throat, and stomach. Always mix the prescribed dose with at least 6 to 8 ounces of cold water or fruit juice.
2. 2Timing: Take this medication after meals to minimize stomach upset and to help the body process the bicarbonate produced during digestion.
3. 3Consistency: For stone prevention, it is vital to take the medication at the same times every day to maintain a consistent urinary pH throughout a 24-hour cycle.
4. 4Storage: Store the medication at room temperature (20°C to 25°C). Do not freeze solutions. Keep the bottle tightly closed to prevent evaporation or contamination.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular schedule. Do not double the dose to catch up, as this can lead to acute electrolyte imbalances.

Signs of an Anhydrous Citric Acid overdose (or citrate salt overdose) include:

• Severe muscle twitching or cramps (signs of low ionized calcium)
• Numbness or tingling in the hands, feet, or lips
• Rapid or irregular heartbeat
• Severe diarrhea or abdominal pain
• Difficulty breathing

In the event of a suspected overdose, contact your local poison control center or seek emergency medical attention immediately. Treatment typically involves stabilizing electrolyte levels and supporting renal excretion.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or stop the medication without medical guidance, as this can cause a rapid shift in your body's pH balance.

Most side effects associated with Anhydrous Citric Acid involve the gastrointestinal tract and are often related to the concentration of the solution.

• Gastrointestinal Distress: Nausea, vomiting, and mild stomach pain are common, especially when the medication is not properly diluted.
• Diarrhea: The osmotic effect of the citrate salts can lead to loose stools or frequent bowel movements. This is usually transient and improves as the body adjusts to the medication.
• Laxative Effect: Some patients may experience a mild laxative effect, which can be managed by adjusting the dose or increasing water intake.

• Fluid Retention: Because many citric acid formulations contain sodium, some patients may experience swelling (edema) in the ankles, feet, or hands.
• Metabolic Alkalosis: Excessive dosing can lead to the blood becoming too alkaline, resulting in symptoms such as confusion, irritability, and muscle tremors.
• Electrolyte Shifts: Mild decreases in serum calcium or increases in serum sodium/potassium depending on the specific salt used.

• Tetany: A rare but serious condition characterized by involuntary muscle contractions, caused by a rapid decrease in ionized calcium levels due to citrate chelation.
• Severe Hyperkalemia: Specifically with potassium citrate/citric acid formulations, which can lead to cardiac arrhythmias.
• Gastrointestinal Ulceration: Extremely rare with liquid forms, but more common if tablets are not swallowed with sufficient water.

> Warning: Stop taking Anhydrous Citric Acid and call your doctor immediately if you experience any of these serious symptoms.

• Cardiac Arrhythmia: Palpitations, skipped beats, or a racing heart, which may indicate a potassium or calcium imbalance.
• Signs of Hypocalcemia: Numbness or "pins and needles" sensations around the mouth or in the extremities, and severe muscle cramps.
• Severe Abdominal Pain: Black, tarry stools or vomit that looks like coffee grounds (signs of GI bleeding).
• Mental Status Changes: Severe confusion, seizures, or unusual lethargy.
• Anaphylaxis: Though rare, seek help for hives, swelling of the face/tongue, or difficulty breathing.

Prolonged use of Anhydrous Citric Acid requires ongoing monitoring. Long-term risks include:

• Chronic Electrolyte Imbalance: Persistent shifts in sodium, potassium, and bicarbonate levels.
• Kidney Stone Composition Shift: While it prevents calcium oxalate stones, over-alkalization of the urine (pH > 7.5) can theoretically promote the formation of calcium phosphate (struvite) stones.
• Aluminum Toxicity: Long-term use in patients also taking aluminum-containing antacids can lead to aluminum accumulation in the bones and brain.

No FDA black box warnings currently exist for Anhydrous Citric Acid. However, it carries significant clinical warnings regarding its use in patients with renal failure and its potential for severe drug interactions (see Warnings section).

Report any unusual symptoms to your healthcare provider. You may also report side effects to the FDA at 1-800-FDA-1088.

Anhydrous Citric Acid is a potent metabolic agent. It must be used with caution in patients with underlying conditions that affect electrolyte balance or acid-base regulation. Patients must remain well-hydrated while taking this medication to ensure proper renal clearance and to prevent the formation of highly concentrated urine.

No FDA black box warnings for Anhydrous Citric Acid.

Allergic Reactions / Anaphylaxis Risk

While citric acid is an endogenous substance, synthetic formulations may contain dyes, preservatives, or flavoring agents that can trigger allergic reactions. Patients with known sensitivities to citrus-derived products should discuss this with their doctor.

Renal and Cardiac Risks

• Nephrotoxicity Risk: In patients with pre-existing kidney disease, the inability to excrete the sodium or potassium load from citrate salts can lead to toxic accumulations.
• Cardiotoxicity: Rapid changes in potassium or calcium levels can induce dangerous heart rhythms. This is a particular concern for patients on digoxin or those with heart failure.

Aluminum Toxicity Warning

This is one of the most critical warnings for Anhydrous Citric Acid. Citrate significantly increases the absorption of aluminum from the gut. If taken with aluminum-containing antacids, patients (especially those with renal impairment) can develop toxic levels of aluminum, which is associated with encephalopathy and osteomalacia (softening of the bones).

Metabolic Alkalosis

Patients with low chloride levels or those on high-dose diuretics are at increased risk for developing systemic alkalosis. Symptoms include slow breathing, confusion, and muscle twitching.

Patients on long-term Anhydrous Citric Acid therapy require regular laboratory testing:

• Serum Electrolytes: Monthly or quarterly checks of sodium, potassium, chloride, and bicarbonate.
• Renal Function: Monitoring of Creatinine and GFR (Glomerular Filtration Rate).
• Urinary pH: Patients are often asked to monitor their own urinary pH using dipsticks to ensure the dosage is maintaining the target range (usually 6.0–7.0).
• 24-Hour Urine Collection: To measure total citrate, calcium, and oxalate excretion.

Anhydrous Citric Acid generally does not affect the ability to drive or operate machinery. However, if a patient experiences dizziness or confusion due to electrolyte shifts, they should avoid these activities until the symptoms resolve.

Alcohol should be used with caution. Alcohol can contribute to dehydration and metabolic acidosis, which counteracts the therapeutic goals of citric acid therapy. Furthermore, alcohol can increase the risk of gastrointestinal irritation when taken alongside concentrated citrate solutions.

Do not stop taking this medication abruptly without consulting your doctor. Sudden discontinuation can lead to a rebound increase in urinary acidity, which may trigger the rapid formation of new kidney stones or a worsening of metabolic acidosis.

> Important: Discuss all your medical conditions, especially heart disease, kidney disease, or high blood pressure, with your healthcare provider before starting Anhydrous Citric Acid.

• Aluminum-Containing Antacids (e.g., Aluminum Hydroxide): Citric acid dramatically increases the intestinal absorption of aluminum. This can lead to acute aluminum toxicity, particularly in patients with reduced kidney function. This combination must be strictly avoided.
• Potassium-Sparing Diuretics (e.g., Spironolactone, Triamterene): When used with potassium-based citric acid formulations, this can lead to life-threatening hyperkalemia (high potassium).

• ACE Inhibitors and ARBs (e.g., Lisinopril, Losartan): These blood pressure medications can increase potassium levels. Using them with potassium citrate/citric acid requires frequent electrolyte monitoring.
• Digoxin: Changes in calcium and potassium levels caused by citric acid can increase the risk of digoxin toxicity, leading to dangerous heart arrhythmias.
• Salicylates (e.g., Aspirin): Alkalinizing the urine increases the renal excretion of salicylates, which may reduce their effectiveness for anti-inflammatory or analgesic purposes.

• Amphetamines: Alkalinizing the urine decreases the excretion of amphetamines, potentially increasing their blood levels and the risk of side effects (e.g., insomnia, tachycardia).
• Lithium: Urinary alkalinizers can increase the excretion of lithium, potentially lowering its therapeutic effectiveness for mood stabilization.
• Quinine/Quinidine: Increased urinary pH can reduce the excretion of these drugs, leading to increased serum levels and potential toxicity.

• High-Sodium Diet: For patients taking sodium citrate/citric acid, a high-salt diet can worsen fluid retention and increase the risk of high blood pressure.
• Dairy Products: Large amounts of calcium-rich foods may interact with the chelation mechanism of citrate, although this is usually managed through dosing rather than restriction.
• Hydration: Not an interaction, but a requirement—low water intake significantly reduces the efficacy of the medication.

• Calcium Supplements: Taking calcium supplements at the same time as citric acid may lead to the formation of calcium citrate complexes in the gut, reducing the absorption of both. It is often recommended to space these apart.
• Licorice Root: Can affect electrolyte balance (lowering potassium), which may complicate the management of patients on citrate therapy.

Anhydrous Citric Acid can affect several laboratory parameters:

• Urinary pH: Will be intentionally increased.
• Serum Bicarbonate: Will be increased.
• Serum Calcium: May appear slightly decreased if ionized calcium is measured during rapid administration.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter antacids and vitamins.

Anhydrous Citric Acid should NEVER be used in the following circumstances:

1. 1Severe Renal Impairment: In patients with oliguria (low urine output) or azotemia (high nitrogen levels in the blood), the body cannot handle the electrolyte or acid-base load, leading to rapid toxicity.
2. 2Untreated Addison’s Disease: These patients have an inability to regulate sodium and potassium, making the use of citrate salts extremely dangerous.
3. 3Adynamic Ileus: Since the medication is an oral irritant and relies on GI absorption, it should not be used in patients with paralyzed bowel function.
4. 4Acute Dehydration: Using concentrated salts in a dehydrated patient can cause severe osmotic shifts and worsen the condition.
5. 5Severe Myocardial Damage: Especially for potassium-containing versions, where any shift in potassium can cause cardiac arrest.

Conditions requiring a careful risk-benefit analysis include:

• Congestive Heart Failure (CHF): The sodium load in many formulations can trigger fluid overload and pulmonary edema.
• Hypertension: Sodium-based formulations may make blood pressure more difficult to control.
• Peripheral or Pulmonary Edema: Any condition characterized by salt retention.
• Active Peptic Ulcer Disease: The acidic nature of the undiluted solution can exacerbate gastric ulcers.

Patients who have had severe reactions to other citrate salts (such as sodium citrate or potassium citrate) should be considered cross-sensitive to Anhydrous Citric Acid formulations. While the acid itself is endogenous, the flavoring agents (like lemon or orange extracts) are common sources of sensitivity.

> Important: Your healthcare provider will evaluate your complete medical history, including your heart and kidney health, before prescribing Anhydrous Citric Acid.

FDA Pregnancy Category C. Animal reproduction studies have not been conducted with Anhydrous Citric Acid. It is also not known whether it can cause fetal harm when administered to a pregnant woman. However, maintaining proper pH balance is crucial during pregnancy.

• Trimester-Specific Risks: There is no evidence of teratogenicity. The primary concern is the management of maternal electrolytes and blood pressure (due to sodium load).
• Clinical Use: It should be given to a pregnant woman only if clearly needed and under strict medical supervision.

Citric acid is a normal constituent of human milk. When used at therapeutic doses, it is unlikely to have an adverse effect on the nursing infant. However, the associated sodium or potassium salts could theoretically alter milk electrolyte composition in extreme cases. Most experts consider it compatible with breastfeeding, but monitoring the infant for gastrointestinal upset is advised.

Anhydrous Citric Acid is approved for use in children for the treatment of metabolic acidosis and certain types of kidney stones.

• Dosing: Must be strictly weight-based.
• Growth Effects: Long-term correction of acidosis is actually beneficial for growth, as chronic acidosis in children can lead to stunted growth and bone demineralization (rickets).
• Safety: Children are more susceptible to rapid electrolyte shifts and must be monitored closely.

Elderly patients are at a higher risk for adverse effects due to:

1. 1Reduced GFR: Age-related decline in kidney function increases the risk of potassium or sodium accumulation.
2. 2Polypharmacy: Increased likelihood of taking interacting drugs like ACE inhibitors, diuretics, or NSAIDs.
3. 3Blood Pressure: Older adults are more sensitive to the hypertensive effects of sodium-containing solutions.

In patients with mild to moderate renal impairment, dosage must be reduced and monitored with frequent serum bicarbonate and electrolyte checks. In severe renal failure (GFR < 30 mL/min), the medication is generally contraindicated due to the risk of metabolic alkalosis and electrolyte toxicity.

Since citrate is metabolized in the liver, severe hepatic failure could theoretically slow the conversion of citrate to bicarbonate. However, this is rarely a limiting factor in clinical use unless the patient is in end-stage liver failure.

> Important: Special populations, particularly the elderly and those with kidney disease, require individualized medical assessment and frequent lab monitoring.

Anhydrous Citric Acid acts as a systemic and urinary alkalinizer. Upon ingestion, the citrate anion is absorbed and enters the hepatic metabolic pathway. In the liver, citrate is oxidized via the tricarboxylic acid (TCA) cycle. The stoichiometry of this reaction results in the consumption of hydrogen ions or the generation of bicarbonate (HCO3-) ions.

In the kidneys, the increased filtered load of bicarbonate raises the pH of the urine. Additionally, the presence of citrate in the renal tubules provides a direct inhibitory effect on the crystallization of calcium salts. Citrate binds to calcium to form a soluble complex (calcium citrate), which effectively lowers the thermodynamic supersaturation of calcium oxalate and calcium phosphate.

• Onset of Action: The alkalinizing effect on the urine typically begins within 1 hour of ingestion.
• Duration of Effect: The effect lasts for approximately 4 to 6 hours, which is why dosing is required 3–4 times daily.
• Tolerance: There is no known pharmacological tolerance to the alkalizing effects of citrate; however, the body's compensatory mechanisms (renal excretion of excess bicarbonate) will eventually reach a steady state.

| Parameter | Value |

|---|---|

| Bioavailability | >95% (Rapidly absorbed) |

| Protein Binding | Negligible |

| Half-life | Short (Rapidly metabolized in the Krebs cycle) |

| Tmax | 0.5 - 1.0 hours |

| Metabolism | Hepatic (Oxidation to Bicarbonate) |

| Excretion | Renal (5-10% as unchanged citrate) |

• Molecular Formula: C6H8O7
• Molecular Weight: 192.12 g/mol
• Solubility: Highly soluble in water (approx. 59% w/w at 20°C); soluble in ethanol.
• Structure: A tricarboxylic acid with a hydroxyl group at the 3-carbon position. The anhydrous form is a white crystalline powder that is hygroscopic (absorbs moisture from the air).

Anhydrous Citric Acid is categorized as a Urinary Alkalinizer and a Calculi Dissolution Agent. It is often grouped with other mineral salts used for electrolyte replacement and acid-base balance.