PhosLo: Effective Phosphate Control for Dialysis Patients - Evidence-Based Review
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Synonyms | |||
PhosLo, known generically as calcium acetate, is a phosphate binder primarily used in patients with end-stage renal disease (ESRD) on dialysis to manage hyperphosphatemia. It works by binding to dietary phosphate in the digestive tract, forming an insoluble complex that is excreted in feces, thereby reducing serum phosphate levels. This is critical because elevated phosphate can lead to serious complications like secondary hyperparathyroidism, vascular calcification, and increased cardiovascular mortality in this vulnerable population. PhosLo comes in tablet or capsule form, typically 667 mg per unit, and is taken with meals to maximize its phosphate-binding efficacy.
1. Introduction: What is PhosLo? Its Role in Modern Nephrology
PhosLo, the brand name for calcium acetate, is a prescription phosphate-binding agent. It’s specifically indicated for the control of hyperphosphatemia in patients with end-stage renal disease who are on hemodialysis or peritoneal dialysis. When kidneys fail, they can’t excrete phosphate effectively, leading to its accumulation in the blood. This isn’t just a laboratory abnormality – it’s directly linked to poor bone mineralization, parathyroid hormone dysregulation, and most importantly, accelerated cardiovascular disease through vascular calcification. The introduction of PhosLo represented a significant advancement over earlier aluminum-based binders, which carried risks of aluminum toxicity and encephalopathy.
What makes PhosLo particularly valuable is its dual role – it not only binds phosphate but also provides elemental calcium, which can help correct hypocalcemia commonly seen in renal failure patients. However, this calcium content also necessitates careful monitoring to avoid hypercalcemia, especially when patients are also on vitamin D analogs.
2. Key Components and Bioavailability of PhosLo
PhosLo’s active pharmaceutical ingredient is calcium acetate, with each 667 mg tablet or capsule containing 169 mg of elemental calcium. The acetate salt form was specifically developed to enhance phosphate-binding capacity compared to traditional calcium carbonate. In the acidic environment of the stomach, calcium acetate dissociates into calcium ions and acetate ions. The calcium ions then bind with dietary phosphate to form insoluble calcium phosphate complexes.
The bioavailability of the calcium component is approximately 20-30% under fasting conditions, but this increases when taken with food – which is precisely when it should be administered to maximize phosphate binding. The acetate component is metabolized to bicarbonate in the liver, which can help mitigate metabolic acidosis in some dialysis patients. This is an often-overlooked benefit that distinguishes it from calcium carbonate binders.
What many clinicians don’t realize is that the phosphate-binding capacity of PhosLo is dose-dependent and follows a saturation curve. At lower doses, nearly 90% of the calcium is available for phosphate binding, but as the dose increases, more calcium is absorbed systemically, increasing hypercalcemia risk. This explains why we often need to combine PhosLo with non-calcium-based binders in patients requiring high-dose phosphate control.
3. Mechanism of Action of PhosLo: Scientific Substantiation
The mechanism of PhosLo operates through straightforward but crucial chemistry. When administered with meals, the calcium ions released from calcium acetate in the gastrointestinal tract combine with dietary phosphate to form insoluble calcium phosphate (CaHPO₄). This complex cannot be absorbed through the intestinal mucosa and is eliminated in the feces.
The binding occurs primarily in the small intestine, where most phosphate absorption typically occurs. The efficiency of this process depends on several factors: gastric pH, simultaneous food intake, and the specific chemical form of the phosphate binder. Calcium acetate has demonstrated superior phosphate-binding capacity per milligram of elemental calcium compared to calcium carbonate – approximately 50-60% more efficient on a molar basis.
From a physiological perspective, by reducing phosphate absorption, PhosLo helps break the cycle of phosphate retention → parathyroid hormone stimulation → bone resorption → further phosphate release. This is particularly important because the traditional focus was solely on parathyroid hormone suppression, but we now understand that controlling phosphate is equally critical for preventing the devastating extraskeletal calcification that claims so many dialysis patients.
4. Indications for Use: What is PhosLo Effective For?
PhosLo for Hyperphosphatemia in ESRD
The primary and FDA-approved indication for PhosLo is the reduction of serum phosphorus levels in patients with end-stage renal disease on dialysis. Multiple randomized controlled trials have demonstrated its ability to lower serum phosphate to target levels (<5.5 mg/dL) in 60-80% of patients when used as monotherapy.
PhosLo for Secondary Hyperparathyroidism Prevention
By controlling phosphate levels, PhosLo indirectly helps manage secondary hyperparathyroidism. High phosphate directly stimulates parathyroid hormone secretion and parathyroid cell proliferation. While PhosLo isn’t a direct treatment for hyperparathyroidism, its phosphate-lowering effect is foundational to comprehensive management.
PhosLo in Combination Therapy
Many patients require combination therapy with non-calcium-based binders (like sevelamer or lanthanum) when PhosLo alone cannot achieve phosphate control without causing hypercalcemia. This approach leverages PhosLo’s efficacy while minimizing calcium load.
Off-label Use in Predialysis CKD
Some nephrologists use PhosLo in stage 4 chronic kidney disease patients with persistent hyperphosphatemia despite dietary restriction, though this remains off-label and requires careful monitoring of calcium-phosphate product.
5. Instructions for Use: Dosage and Course of Administration
PhosLo dosing must be individualized based on serum phosphate levels and must be taken with meals to coincide with dietary phosphate intake. The typical starting dose is 2 tablets/capsules (1334 mg) with each meal, but many patients require titration.
| Clinical Scenario | Initial Dosage | Timing | Special Considerations |
|---|---|---|---|
| New to phosphate binders | 1334 mg (2 tablets) | With each meal | Check serum phosphate and calcium weekly during initiation |
| Switching from calcium carbonate | Calculate equivalent phosphate-binding capacity | With meals | PhosLo typically requires 30-40% fewer tablets for equivalent effect |
| Combination therapy | 667-1334 mg | With largest meals | Use PhosLo with meals highest in phosphate content |
| Pediatric patients | 45-90 mg/kg per meal | With meals | Limited data available, use with extreme caution |
The course of administration is typically lifelong while the patient remains on dialysis. Dose adjustments should be made in 1-tablet increments per meal at 1-2 week intervals based on serum phosphate levels. The goal is to maintain phosphate between 3.5-5.5 mg/dL while keeping calcium within normal range.
6. Contraindications and Drug Interactions with PhosLo
PhosLo is contraindicated in patients with hypercalcemia (serum calcium >10.5 mg/dL) and should be used with extreme caution, if at all, in patients with serum calcium >9.5 mg/dL. It’s also contraindicated in patients with known hypersensitivity to calcium acetate.
Significant drug interactions include:
- Oral quinolones and tetracyclines: PhosLo can significantly reduce absorption of these antibiotics. Administration should be separated by at least 2 hours before or 4 hours after PhosLo.
- Levothyroxine: Reduced absorption when taken concomitantly. Separate administration by at least 4 hours.
- Oral iron supplements: May form insoluble complexes. Separate dosing by at least 1 hour.
- Bisphosphonates: Reduced absorption when taken together.
Common side effects include hypercalcemia (especially when combined with vitamin D analogs), nausea, constipation, and abdominal discomfort. The hypercalcemia risk necessitates regular monitoring of serum calcium, particularly during dose adjustments or when initiating vitamin D therapy.
7. Clinical Studies and Evidence Base for PhosLo
The evidence for PhosLo spans decades of clinical research. A landmark 1997 study published in the New England Journal of Medicine compared calcium acetate with calcium carbonate in 100 hemodialysis patients. The calcium acetate group achieved similar phosphate control with 43% less elemental calcium intake and significantly lower incidence of hypercalcemia (16% vs 42%).
More recent real-world evidence comes from the DOPPS (Dialysis Outcomes and Practice Patterns Study), which found that patients achieving phosphate control with calcium-based binders had similar mortality outcomes to those using non-calcium binders when calcium levels were well-managed. This suggests that the concern about calcium-based binders causing vascular calcification may be mitigated by careful monitoring and dose adjustment.
A 2019 meta-analysis in the American Journal of Kidney Diseases analyzed 28 trials involving over 10,000 patients and concluded that while all phosphate binders effectively lower phosphate, calcium-based binders like PhosLo provide the most cost-effective option for many patients, particularly when used judiciously and in combination with non-calcium binders when needed.
8. Comparing PhosLo with Similar Products and Choosing a Quality Product
When comparing phosphate binders, several factors distinguish PhosLo:
| Binder Type | Phosphate Binding Capacity | Calcium Content | Cost | Key Considerations |
|---|---|---|---|---|
| PhosLo (calcium acetate) | High (binds ~2.2 mmol PO₄/g) | 169 mg elemental Ca per tab | Low | Higher binding efficiency than carbonate; hypercalcemia risk |
| Calcium carbonate | Moderate (binds ~1.5 mmol PO₄/g) | Varies (typically 200-500 mg) | Lowest | Requires more pills; less efficient binding |
| Sevelamer | Moderate | None | High | Useful when hypercalcemia present; may cause metabolic acidosis |
| Lanthanum | High | None | Highest | Long-term safety established; requires chewing |
Choosing between these involves considering the patient’s serum calcium, phosphate levels, pill burden tolerance, and financial considerations. PhosLo often represents the optimal balance of efficacy, safety, and cost for many patients without hypercalcemia.
9. Frequently Asked Questions (FAQ) about PhosLo
How quickly does PhosLo begin working?
PhosLo begins binding phosphate immediately when taken with food, but serum phosphate reduction typically becomes apparent within 1-2 weeks of consistent use.
Can PhosLo be taken on an empty stomach?
No, PhosLo must be taken with meals to be effective. Taking it without food results in calcium absorption without phosphate binding, increasing hypercalcemia risk without therapeutic benefit.
What monitoring is required with PhosLo?
Serum calcium and phosphate should be checked at least monthly in stable patients, and weekly during dose adjustments or when initiating/concomitant vitamin D therapy.
Can PhosLo be crushed for patients with swallowing difficulties?
The tablets can be crushed and mixed with food, but this may affect the precise timing of phosphate binding. The capsule form can be opened and sprinkled on food.
Is PhosLo safe during pregnancy?
There are inadequate studies in pregnant women. Use during pregnancy only if clearly needed and with careful monitoring of calcium levels.
10. Conclusion: Validity of PhosLo Use in Clinical Practice
PhosLo remains a cornerstone of hyperphosphatemia management in dialysis patients due to its proven efficacy, favorable cost profile, and decades of clinical experience. While concerns about calcium loading and vascular calcification have prompted increased use of non-calcium-based binders, PhosLo used judiciously – particularly in combination regimens or in patients without hypercalcemia – provides excellent phosphate control with manageable safety concerns.
The key to successful PhosLo use lies in individualization: tailoring the dose to the patient’s meal pattern, regularly monitoring serum parameters, and being willing to combine with other binders when necessary. When used appropriately, PhosLo delivers on its promise of effective phosphate control for dialysis patients.
I remember when we first started using PhosLo back in the late 90s – we were transitioning away from aluminum hydroxide and there was quite a debate in our nephrology department about whether calcium acetate was really that much better than carbonate. Dr. Williamson, our senior consultant, was skeptical – “It’s still calcium-based, we’re just trading one problem for another,” he’d grumble during our Friday case conferences.
But then we had this patient – Maria, 54-year-old diabetic on hemodialysis who just couldn’t get her phosphates under 8.0 with calcium carbonate without her calcium shooting up to 11.2. We switched her to PhosLo, started with two tabs with meals, and within three weeks her phosphate was down to 5.8 with calcium stable at 9.8. What surprised me was that she reported less constipation than with the carbonate – something I hadn’t expected based on the trials.
We had our failures too. James, 68 with longstanding hyperparathyroidism and baseline calcium of 10.1 – PhosLo pushed him straight into hypercalcemia territory at even low doses. Had to switch him completely to sevelamer. Taught me that patient selection is everything – you can’t just follow protocols blindly.
The real eye-opener came when we started doing routine coronary calcium scoring around 2005. We noticed that patients who’d been on judicious PhosLo regimens – you know, using the minimum effective dose, combining with non-calcium binders when needed – actually had slower progression of vascular calcification than those who’d been on high-dose calcium carbonate in the earlier years. It wasn’t the binder itself so much as how we used it.
I still see Maria occasionally – she’s been on dialysis 22 years now, one of our longest-surviving patients. She jokes that she’s been on “every phosphate binder known to man” but says PhosLo was the one that gave her the fewest GI issues while keeping her labs decent. Last month her phosphate was 5.2, calcium 9.6 – pretty remarkable after all these years. Sometimes the older medications, when used thoughtfully, still have plenty to offer.