Assist

The dosage of Ammonium Chloride varies significantly based on the intended therapeutic goal and the patient's current acid-base status.

• For Metabolic Alkalosis: The dose is calculated based on the patient's chloride deficit. A common formula used by clinicians is: Dose (mEq) = [0.2 x Body Weight (kg)] x [Desired Chloride Change (mEq/L)]. In practice, adults may receive 100 to 200 mEq per day, often divided into multiple doses or administered as a slow IV infusion.
• For Urinary Acidification: To maintain an acidic urine pH (usually below 5.5), adults are typically prescribed 1 to 2 grams (1000-2000 mg) every 4 to 6 hours. The total daily dose should generally not exceed 12 grams.
• As an Expectorant: In OTC preparations, the standard dose is usually 250 mg to 500 mg every 4 to 6 hours as needed for cough.

Ammonium Chloride must be used with extreme caution in children, as their renal and hepatic systems are still developing, making them more susceptible to acidosis.

• For Alkalosis/Acidification: Pediatric dosing is strictly weight-based. A common range is 75 mg/kg per day, divided into 4 to 6 doses.
• General Safety: It is not recommended for use in neonates (infants under 28 days old) due to the high risk of metabolic acidosis and immature urea cycle function. Always consult a pediatrician before administering any ammonium-containing product to a child.

Renal Impairment

Ammonium Chloride is strictly contraindicated in patients with severe renal impairment. In mild to moderate cases, the dose must be significantly reduced, and the patient must be monitored for signs of hyperchloremic acidosis. If the kidneys cannot excrete the chloride load, the drug will quickly become toxic.

Hepatic Impairment

This medication is contraindicated in patients with severe liver disease or cirrhosis. Because the liver is responsible for converting ammonium to urea, hepatic failure leads to the accumulation of ammonia in the blood, which can cause life-threatening hepatic encephalopathy (brain swelling and dysfunction).

Elderly Patients

Elderly patients often have a natural decline in renal function (reduced GFR). Dosing should start at the lower end of the spectrum, and frequent monitoring of serum electrolytes and bicarbonate levels is mandatory to prevent the sudden onset of metabolic acidosis.

• Oral Forms: Tablets should be taken with a full glass of water (8 oz) to minimize irritation of the throat and stomach. If using enteric-coated tablets, they must be swallowed whole; do not crush, chew, or break them, as this destroys the coating designed to protect your stomach.
• With Food: Taking Ammonium with a meal can significantly reduce the 'upset stomach' or nausea often associated with the medication.
• IV Administration: This is performed only in a hospital. The solution must be highly diluted (e.g., 2.14% solution) and infused at a rate not exceeding 5 mL per minute in adults to avoid vein irritation and toxicity.
• Storage: Store at room temperature (68°F to 77°F) away from moisture and heat. Keep the bottle tightly closed.

If you miss a dose of the oral medication, 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 timing. Do not double the dose to catch up, as this significantly increases the risk of developing metabolic acidosis.

An overdose of Ammonium Chloride is a medical emergency. Signs of overdose include:

• Rapid, deep breathing (Kussmaul respirations)
• Confusion or extreme drowsiness
• Nausea and violent vomiting
• Irregular heartbeat
• Seizures or coma

Emergency Measures: If an overdose is suspected, contact a poison control center or seek emergency medical care immediately. Treatment usually involves the intravenous administration of sodium bicarbonate or sodium lactate to neutralize the excess acidity, along with supportive care for electrolyte imbalances.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as acid-base imbalances can shift rapidly.

Most patients taking Ammonium Chloride will experience some level of gastrointestinal discomfort. These effects are usually dose-dependent and may include:

• Nausea and Vomiting: This is the most frequent complaint. It often feels like a sharp 'gnawing' sensation in the upper stomach shortly after ingestion.
• Gastric Irritation: A burning sensation in the chest or stomach (heartburn). This occurs because the ammonium ion can be irritating to the mucosal lining.
• Increased Thirst: As the body attempts to balance the increased salt (chloride) load, patients may feel a persistent need to drink water.

• Hyperventilation: You may notice your breathing becoming slightly faster or deeper as your body tries to exhale carbon dioxide to compensate for the mild increase in blood acidity.
• Drowsiness: A general feeling of lethargy or 'fogginess' can occur as the pH of the blood shifts.
• Diarrhea: The salt load in the intestines can sometimes draw water in, leading to loose stools.
• Injection Site Reaction: If given intravenously, redness, swelling, or pain at the site of the needle may occur.

• Hypokalemia (Low Potassium): As the body excretes chloride, it may also lose potassium, leading to muscle weakness or cramps.
• Rash: Allergic skin reactions, including itching or hives, are rare but possible.
• Glycosuria: The presence of glucose in the urine, even without diabetes, due to the effect of the drug on renal tubule function.

> Warning: Stop taking Ammonium and call your doctor immediately if you experience any of these symptoms. These may indicate life-threatening metabolic acidosis or ammonia toxicity.

• Severe Metabolic Acidosis: Symptoms include rapid, gasping breath (air hunger), profound confusion, and a bluish tint to the lips or fingernails.
• Ammonia Toxicity (Hyperammonemia): Characterized by tremors, twitching, a 'flapping' motion of the hands (asterixis), slurred speech, and extreme irritability or combativeness.
• Cardiac Arrhythmias: A feeling that your heart is skipping beats, fluttering, or racing, which can be caused by the electrolyte shifts (specifically potassium and calcium) triggered by ammonium.
• Seizures: Any sudden loss of consciousness or involuntary muscle contractions requires immediate emergency intervention.
• Profound Mental Status Changes: If the patient becomes unresponsive or impossible to wake up.

Prolonged use of Ammonium Chloride is generally discouraged. If used for extended periods, it can lead to:

• Demineralization of Bone: Chronic acidosis causes the body to leach calcium from the bones to act as a buffer, potentially increasing the risk of osteoporosis or fractures.
• Chronic Electrolyte Imbalance: Persistent low levels of potassium and calcium.
• Renal Stones: The changes in urinary pH and calcium excretion can increase the risk of developing certain types of kidney stones.

There are currently no FDA black box warnings specifically for Ammonium Chloride. However, the clinical literature emphasizes that it is a high-alert medication when administered intravenously. The primary danger is the rapid induction of metabolic acidosis if the infusion rate is not strictly controlled. Furthermore, its use in patients with primary hepatic disease is considered a 'never event' due to the certainty of inducing ammonia-related neurotoxicity.

Report any unusual symptoms to your healthcare provider. Even mild side effects should be monitored, as they can be the first signs of a worsening acid-base imbalance.

Ammonium is a potent pharmacological agent that directly alters the body's internal chemistry. It should never be used for self-medication without professional oversight. The most critical safety concern is the risk of Metabolic Acidosis, a condition where the blood becomes too acidic, which can impair the function of every major organ system, including the heart and brain.

No FDA black box warnings for Ammonium. However, healthcare providers treat Ammonium Chloride as a high-risk medication in the inpatient setting, particularly regarding its potential for causing severe pH shifts and hyperammonemia.

• Ammonia Toxicity Risk: This is the most significant risk for patients with liver impairment. If the liver cannot process the ammonium ion into urea, the ammonium remains in the blood and travels to the brain. This can cause swelling, permanent brain damage, and death.
• Anaphylaxis and Allergic Reactions: While rare, some patients may be allergic to the components of Ammonium Chloride injections or the proteins found in the 'Non-Standardized Plant Allergenic Extracts.' Symptoms include swelling of the face, tongue, or throat, and difficulty breathing.
• Cardiac and Respiratory Disease: Patients with existing heart failure or pulmonary edema must be monitored closely. The chloride load from the medication can lead to fluid retention, worsening these conditions.
• Metabolic Acidosis: Patients with underlying conditions that already cause acidity (such as poorly controlled diabetes or severe dehydration) are at a much higher risk for dangerous complications.

If you are prescribed Ammonium, your healthcare provider will require regular testing to ensure the drug is working safely. These tests include:

• Arterial Blood Gases (ABGs): To measure the exact pH and bicarbonate levels in your blood.
• Serum Electrolytes: Specifically checking levels of sodium, potassium, and chloride.
• Liver Function Tests (LFTs): To ensure your liver is capable of processing the ammonium.
• Renal Function Tests: Measuring creatinine and BUN to ensure your kidneys can excrete the waste products.
• Urinary pH: If the drug is being used for urinary acidification, your doctor will check your urine acidity regularly.

Ammonium can cause drowsiness, confusion, and dizziness, especially when you first start taking it or if the dose is adjusted. You should not drive or operate heavy machinery until you know how this medication affects you. If you feel 'foggy' or unusually tired, contact your doctor.

Alcohol should be avoided while taking Ammonium. Alcohol can irritate the stomach lining, compounding the gastric side effects of the drug. More importantly, alcohol can interfere with liver function and may worsen the CNS-depressing effects (drowsiness/confusion) caused by acid-base shifts.

Do not stop taking Ammonium suddenly if you are being treated for a chronic condition, as this can cause a 'rebound' effect where your body's pH swings too far in the opposite direction. Your doctor will likely taper your dose or transition you to another therapy while monitoring your blood chemistry.

> Important: Discuss all your medical conditions with your healthcare provider before starting Ammonium. Be sure to mention if you have a history of liver disease, kidney disease, or heart failure.

• Potassium-Sparing Diuretics (e.g., Spironolactone, Amiloride): These drugs should never be used with Ammonium Chloride. Both agents can increase potassium levels and promote acidosis. Combining them significantly raises the risk of life-threatening hyperkalemia (high potassium) and severe metabolic acidosis.
• Severe Hepatic Impairment Medications: Drugs that further stress the urea cycle or liver function should be avoided.

• Salicylates (e.g., Aspirin): Ammonium acidifies the urine. When urine is acidic, salicylates are reabsorbed back into the bloodstream rather than being excreted. This can lead to toxic levels of aspirin in the body, even at standard doses.
• Amphetamines: Similar to salicylates, amphetamines are weak bases. Acidifying the urine with Ammonium increases their ionization, which actually speeds up their excretion. This may reduce the effectiveness of amphetamine-based medications used for ADHD or narcolepsy.
• Lithium: Ammonium Chloride may increase the excretion of lithium, potentially lowering its concentration in the blood and reducing its effectiveness in treating bipolar disorder.

• Antacids: Taking antacids (like calcium carbonate or magnesium hydroxide) can neutralize the acidifying effect of Ammonium, making the treatment less effective.
• Sulfonylureas (Diabetes medications): The change in systemic pH can occasionally alter the glucose-lowering effects of these drugs. Blood sugar should be monitored more frequently.

• High-Protein Diets: A very high protein intake increases the nitrogen load on the liver and kidneys, which may compound the metabolic work required to process ammonium.
• Dairy Products: Large amounts of calcium-rich dairy may interact with the chloride ions and affect the risk of stone formation in the kidneys.
• Hydration: It is vital to maintain adequate water intake unless otherwise directed by a doctor, as dehydration can worsen the acidity caused by the drug.

• Licorice Root: Natural licorice (glycyrrhizic acid) can cause potassium loss and fluid retention, which may complicate the electrolyte imbalances managed or caused by Ammonium.
• St. John's Wort: While no direct metabolic interaction is known, the CNS effects of St. John's Wort may overlap with the drowsiness caused by ammonium-induced pH shifts.

• Urinary pH Tests: Ammonium will intentionally lower these results.
• Serum Bicarbonate: This will appear lower on lab reports as the drug neutralizes bicarbonate.
• Liver Function Tests: May show transient elevations if the liver is struggling to process the ammonium load.

For each major interaction, the mechanism usually involves a shift in the Henderson-Hasselbalch equilibrium, where the acidity of the environment determines whether a drug molecule is 'charged' (and excreted) or 'uncharged' (and reabsorbed).

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. This includes over-the-counter cough medicines, as many already contain ammonium.

There are several conditions where the use of Ammonium is strictly prohibited due to the risk of death or severe injury:

1. 1Severe Hepatic Impairment: Patients with cirrhosis, hepatitis, or liver failure cannot process the ammonium ion. This leads to Hyperammonemia, which causes brain swelling (cerebral edema) and hepatic coma.
2. 2Severe Renal Impairment: If the kidneys cannot excrete the chloride ions and the acid load, the patient will develop rapid, uncompensable metabolic acidosis.
3. 3Primary Respiratory Acidosis: If a patient is already acidic due to a lung problem (like severe COPD where they can't breathe out CO2), adding an acidifying agent like Ammonium can push their pH to lethal levels.
4. 4Metabolic Alkalosis due to Vomiting with Loss of Sodium: In cases where sodium loss is the primary issue rather than chloride loss, sodium chloride is the appropriate treatment, not ammonium chloride.

These conditions require a careful risk-benefit analysis by a physician:

• Mild to Moderate Kidney Disease: Requires frequent monitoring and lower doses.
• Cardiac Edema or Heart Failure: The chloride load can cause the body to retain water, which can lead to 'fluid overload' and strain the heart.
• Pregnancy: Use only if the potential benefit outweighs the unknown risks to the fetus.

Patients who have had a severe allergic reaction to other ammonium salts or components of allergenic extracts should avoid this medication. Additionally, because Ammonium is often packaged in vials with latex stoppers or contains specific preservatives, patients with Latex Allergies or sensitivities to parabens should inform their provider before receiving an IV dose.

> Important: Your healthcare provider will evaluate your complete medical history, including your liver and kidney function, before prescribing Ammonium.

Ammonium Chloride is classified as FDA Pregnancy Category C. This means that animal reproduction studies have not been conducted, and there are no adequate, well-controlled studies in humans. It is unknown if Ammonium can cause fetal harm when administered to a pregnant woman. However, severe metabolic acidosis in the mother can lead to reduced uterine blood flow and fetal distress. Therefore, Ammonium should be used during pregnancy only if clearly needed and under strict specialist supervision.

It is not known whether ammonium ions or their metabolites are excreted in human milk. Because many drugs are excreted in milk and the potential for serious adverse reactions in nursing infants (such as metabolic shifts) exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Ammonium is used in children primarily for the treatment of severe alkalosis. However, the safety margin is much narrower in pediatric patients. Infants, especially neonates, have immature renal function and a limited ability to excrete an acid load. Using Ammonium in this population carries a high risk of 'acidosis-induced' respiratory failure. It should only be used in a pediatric intensive care setting with continuous monitoring.

Clinical studies of Ammonium Chloride did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently from younger subjects. However, because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. The risk of falling may also be increased in the elderly if the drug causes confusion or dizziness due to pH changes.

In patients with a GFR (Glomerular Filtration Rate) below 30 mL/min, Ammonium is generally avoided. For those with mild impairment (GFR 60-89 mL/min), the dose should be reduced by at least 50%, and blood pH should be checked every few hours during the initial phase of treatment.

As previously noted, any degree of significant hepatic impairment is a major red flag. In patients with Child-Pugh Class B or C, the drug is absolutely contraindicated. Even in Class A (mild) impairment, the risk of triggering encephalopathy is considered too high for standard use.

> Important: Special populations require individualized medical assessment. Never share this medication with others, especially those in these high-risk groups.

Ammonium Chloride (NH4Cl) works by providing a source of chloride ions and hydrogen ions. Once it reaches the liver, the NH4+ ion is processed via the Urea Cycle. The chemical equation for this process is:

2NH4Cl + CO2 → (NH2)2CO (urea) + 2HCl + H2O.

The resulting Hydrochloric Acid (HCl) dissociates into H+ and Cl-. The H+ ions react with bicarbonate buffers in the blood, lowering the pH. This molecular 'titration' of the body's base reserve is the core of its pharmacological effect.

The onset of action for oral Ammonium Chloride is approximately 30 to 60 minutes, with the peak acidifying effect occurring between 1 and 3 hours. The duration of effect is typically 6 to 8 hours. The relationship between dose and response is linear in patients with healthy livers, but becomes unpredictable in those with hepatic dysfunction. Tolerance does not typically develop, but the body's compensatory mechanisms (like the lungs breathing out more CO2) will attempt to counteract the drug's effect over time.

| Parameter | Value |

|---|---|

| Bioavailability | ~90-100% (Oral) |

| Protein Binding | Negligible |

| Half-life | 2-4 hours (Metabolic conversion) |

| Tmax | 1-3 hours |

| Metabolism | Hepatic (Urea Cycle) |

| Excretion | Renal (as Urea and Chloride) |

• Molecular Formula: NH4Cl
• Molecular Weight: 53.49 g/mol
• Solubility: Highly soluble in water (370 g/L at 20°C); slightly soluble in alcohol.
• Structure: An inorganic salt consisting of a central nitrogen atom bonded to four hydrogen atoms, ionically bonded to a chloride anion.

Ammonium belongs to the therapeutic class of Acidifying Agents. In the context of the provided EPC data, it is also categorized as a 'Non-Standardized Plant Allergenic Extract' when used in diagnostic immunology. It is related to other acidifiers like dilute hydrochloric acid or lysine hydrochloride, though it is more commonly used due to its ease of administration.