Potassium Chloride
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Potassium Chloride: From Potassium Deficiency to Renal Tubular Acidosis
One-Sentence Summary
Potassium chloride is an electrolyte replacement originally used to treat potassium deficiency and constipation disorder. The TxGNN model predicts it may be useful for Renal Tubular Acidosis, but there are 0 registered clinical trials and only case-level and review-level literature (18 publications, mostly case reports) supporting this direction. The benefit would be supportive (correcting low potassium), not disease-modifying.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Potassium deficiency disease; constipation disorder (from the knowledge graph; no approved-label indication text is available) |
| Predicted New Indication | Renal tubular acidosis |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (all 15 listed authorizations are cancelled) |
| Number of NDAs | 15 (all ANDA or unnumbered listings, none currently valid) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, potassium chloride is a potassium salt that replaces body potassium, and its efficacy in potassium deficiency is well established.
Distal (type 1) renal tubular acidosis is caused by impaired acid (H+) secretion in the kidney’s distal tubule, which leads to hyperchloremic metabolic acidosis and renal potassium wasting. Many patients therefore develop low potassium, which can cause muscle weakness, paralysis and heart rhythm problems. Potassium chloride can treat this low potassium, as shown in several case reports where patients with Sjögren’s-related RTA and severe hypokalemia received intravenous or oral potassium chloride.
However, this is supportive, symptom-directed therapy rather than treatment of the underlying acidosis. Alkali therapy such as potassium citrate or bicarbonate is generally preferred because it corrects the acidosis and the potassium deficit together. Chloride salts may worsen hyperchloremic acidosis. The very high TxGNN score most likely reflects the known link between potassium chloride and hypokalemia (its original use) rather than a novel repurposing signal. Potassium supplementation would also be harmful in type 4 (hyperkalemic) RTA.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The available literature consists mainly of case reports, reviews and cohort descriptions. No RCTs were found. Several entries have not yet been classified or assessed for relevance.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38445406 | 2023 | Cohort (genotype-phenotype) | La Tunisie medicale | Distal RTA is a rare genetic disorder with hyperchloremic acidosis, hypokalemia and nephrocalcinosis |
| 10213645 | 1999 | Cohort | Am J Kidney Dis | Metabolic acidosis in 113 predialysis patients with advanced renal failure, comparing diabetic and nondiabetic patients (not specific to potassium chloride) |
| 786013 | 1976 | Review | Am J Med Sci | Causes, consequences and correction of hypokalemia |
| 6277192 | 1982 | Review | Am J Med | Review of distal nephron function disorders |
| 34595212 | 2021 | Case report | Case Rep Nephrol Dial | Type 1 RTA with severe hypokalemia (1.6 mEq/L) in Sjögren’s/lupus, treated with potassium chloride infusion |
| 40654398 | 2024 | Case report | JNMA | Sjögren’s syndrome presenting with severe hypokalemia and acidosis, treated with intravenous potassium chloride |
| 34748193 | 2022 | Case report | J Nephrol | Distal RTA with hypokalemic periodic paralysis during pregnancy |
| 40288831 | 2025 | Case report with review | Nefrologia | Primary RTA in pregnancy and perinatal prognosis |
| 37727491 | 2023 | Case report | World J Clin Cases | Incomplete distal RTA uncovered during pregnancy |
| 1468597 | 1992 | Case report | Nihon Naibunpi Gakkai Zasshi | Hashimoto’s thyroiditis with distal RTA and Sjögren syndrome; patient on oral potassium chloride for low potassium |
US Market Information
All 15 authorizations in the data are cancelled and none are currently valid. The data contain no approved-indication text. The main ones are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA211665 | Potassium Chloride (Strides Pharma) | Solution | Not available |
| ANDA214452 | Potassium Chloride Extended-Release (Vangard Labs) | Extended-release tablet | Not available |
| ANDA088908 | Potassium Chloride (Fresenius Kabi) | Injection, solution, concentrate | Not available |
| ANDA208445 | Potassium Chloride (Zydus) | Extended-release capsule | Not available |
| ANDA218979 | KLOR-CON (Upsher-Smith) | Film-coated extended-release tablet | Not available |
Safety Considerations
- Conditions flagged as contraindications in the knowledge graph (not taken from the label text): anuria, kidney disease, congestive heart failure, heart disease, coronary artery disease, hypertension, peptic/gastric ulcer, liver disease, pancreatitis, hypercalcemia, nephrocalcinosis, sickle cell anemia, Wilson disease and hereditary hemochromatosis, among others. Several of these (kidney disease, nephrocalcinosis) overlap with the RTA population, so caution is warranted.
- Drug interactions (100 interactions recorded; examples):
- Major: amiloride, benazepril, olmesartan, valsartan and azilsartan (risk of hyperkalemia with potassium-sparing or renin-angiotensin agents); anticholinergics such as atropine, hyoscyamine, glycopyrronium, benzatropine and biperiden (slowed gut motility can raise gastrointestinal injury risk with solid potassium forms); amitriptyline; antihistamines such as chlorpheniramine, brompheniramine and acrivastine.
- Moderate: ibuprofen, ketorolac, aliskiren.
- Minor: cyanocobalamin.
- Clinical consideration: potassium supplementation is inappropriate in hyperkalemic (type 4) RTA, and chloride salts may worsen hyperchloremic acidosis.
Package insert warnings were not available for this report; please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction mostly restates the drug’s original use (correcting hypokalemia), and no clinical trials or controlled studies exist for renal tubular acidosis. Potassium chloride is not disease-modifying here, and alkali-potassium salts such as potassium citrate are generally better suited. In addition, all US authorizations in the data are cancelled, and package insert safety data are missing.
To proceed, the following is needed:
- Package insert warnings and contraindications (currently unavailable)
- Mechanism of action data
- Comparative evidence against potassium citrate or bicarbonate in RTA, including RTA subtype stratification (type 1 vs. type 4)
- Review of the unclassified literature entries for relevance
- Confirmation of current US market availability and approved indications
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.