AMMONIUM CHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMMONIUM CHLORIDE (AMMONIUM CHLORIDE).
Ammonium chloride is an acidifying agent. It dissociates to ammonium and chloride ions. The ammonium ion is converted to urea in the liver, releasing hydrogen ions, which lower blood and urinary pH. It also increases chloride concentration, promoting excretion of bicarbonate and other bases.
| Metabolism | Ammonium chloride is metabolized in the liver via the urea cycle, where ammonium is converted to urea, consuming bicarbonate and generating hydrogen ions. |
| Excretion | Renal: >99% as ammonium ion (NH4+) and chloride (Cl-), with acid excretion via conversion of NH4+ to urea in liver; minimal biliary/fecal. |
| Half-life | Terminal elimination half-life is approximately 8-12 hours in normal renal function; prolonged in renal impairment (up to 30 hours) due to reliance on renal acid excretion. |
| Protein binding | <10% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 0.3-0.5 L/kg, distributing mainly in extracellular fluid; minimal intracellular penetration. |
| Bioavailability | Oral: 70-80% (subject to first-pass hepatic conversion of NH4+ to urea); intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours for systemic acidifying effect; intravenous: within 30 minutes. |
| Duration of Action | Oral: 4-6 hours after a single dose; intravenous: 2-4 hours; duration depends on renal function and acid-base status. |
For metabolic alkalosis: 1-2 g orally 3-4 times daily; or 1 g (as 2 mmol/kg) intravenously over 4-6 hours, repeat as needed based on blood gas analysis.
| Dosage form | INJECTABLE |
| Renal impairment | Contraindicated in severe renal impairment (GFR <30 mL/min). For GFR 30-60 mL/min: reduce dose by 50% and monitor for acidosis. For GFR >60 mL/min: no adjustment necessary. |
| Liver impairment | No specific Child-Pugh dose adjustments; use with caution in severe hepatic impairment due to risk of encephalopathy. |
| Pediatric use | For metabolic alkalosis: 50-100 mg/kg orally every 6-8 hours, not to exceed 6 g/day. Intravenous: 2-3 mmol/kg over 4-6 hours, repeat based on blood pH. |
| Geriatric use | Start at low end of dosing range; monitor renal function and electrolytes closely due to age-related decline in GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMMONIUM CHLORIDE (AMMONIUM CHLORIDE).
| Breastfeeding | Ammonium chloride is excreted into breast milk in small amounts. The M/P ratio is not well-established. At therapeutic doses, exposure to the nursing infant is likely low and not expected to cause adverse effects. Caution is advised with high doses due to potential for maternal acidosis and subsequent infant effects. Consider monitoring infant for signs of acidosis if maternal therapy is prolonged or high-dose. |
| Teratogenic Risk | Ammonium chloride is not associated with major human teratogenicity. However, due to its potential to induce metabolic acidosis, high doses may pose theoretical fetal risks, including fetal acidosis and altered fetal pH homeostasis, particularly in the second and third trimesters. No specific trimester-specific risks are well-documented. |
■ FDA Black Box Warning
None.
| Serious Effects |
Severe hepatic or renal impairment, primary respiratory acidosis, and patients with uremia or high serum bicarbonate levels.
| Precautions | May cause metabolic acidosis, hyperammonemia in hepatic impairment, and electrolyte disturbances. Use with caution in patients with renal or hepatic disease, pulmonary insufficiency, or cardiac edema. |
| Food/Dietary | Avoid excessive consumption of alkaline foods (e.g., dairy products, fruits) as they may counteract the acidifying effect. Maintain a consistent diet to avoid fluctuations in acid-base balance. |
| Clinical Pearls |
Loading safety data…
| Fetal Monitoring | Monitor maternal serum electrolytes, chloride levels, and acid-base status (blood pH, bicarbonate, anion gap) regularly during therapy. In pregnancy, additional monitoring of fetal well-being (e.g., nonstress test, biophysical profile) may be warranted if high doses or prolonged therapy is used. Monitor for signs of maternal acidosis (hyperventilation, fatigue, confusion). |
| Fertility Effects | No known adverse effects on fertility in animal studies or human data. However, any drug-induced metabolic disturbances (e.g., acidosis) could theoretically impact reproductive function. There are no specific fertility warnings for ammonium chloride. |
| Ammonium chloride is used as a systemic acidifying agent to treat metabolic alkalosis. Monitor serum electrolytes and acid-base status closely during therapy. Avoid in severe hepatic or renal impairment. Use with caution in patients with respiratory acidosis. |
| Patient Advice | Take this medication exactly as prescribed. Do not exceed the recommended dose. · Notify your doctor if you experience nausea, vomiting, confusion, or rapid breathing. · Avoid taking with antacids or alkalinizing agents as they may reduce effectiveness. · Stay hydrated unless otherwise directed by your physician. · Inform your healthcare provider of all medications you are taking, especially diuretics or corticosteroids. |