Phosphate binders: Uses, common brands, and safety info

Phosphates are a part of our everyday diet in the western world. They come from healthy, nutritious foods such as broccoli, whole grains, meats, and dried fruit. Unfortunately, phosphates are also contained in things such as soda which offers very little nutrition value but is often over consumed. Phosphate is an important electrolyte that is important to energy production and nerve function, but too much phosphate can be dangerous.

Phosphate binders, sometimes referred to as phosphorus binders, are a class of drugs used to treat abnormally high blood phosphate levels, known as hyperphosphatemia. Here we will discuss how they work, their side effects, and their safety.

Other phosphate binders

• PhosLo (calcium acetate)

• Eliphos (calcium acetate)

• Alternagel (aluminum hydroxide)

What are phosphate binders?

Phosphate binders are a class of drugs used to treat abnormally high blood phosphate levels, known as hyperphosphatemia. By preventing the absorption of phosphate into the bloodstream, phosphate binders lower phosphate levels and help to avoid the effects of high phosphorus levels such as bone loss and calcium deposit build-up. Calcium deposit build-up in your system can lead to vascular calcification and coronary artery calcification. 

Serum levels of calcium and phosphorus are typically naturally balanced by a combination of the parathyroid hormone (PTH) and vitamin D. Parathyroid hormone increases renal excretion of phosphorus but also increases phosphorus release from the bone into the blood. Fibroblast growth factor 23 (FGF23) is also a key player in phosphorus levels. There is a complex balance between PTH, FGF23, and vitamin D. CKD patients can not clear phosphorus through their kidneys as healthy individuals do. These rising phosphorus levels lead to secondary hyperparathyroidism because the release of FGF23 is stimulated. The management of hyperphosphatemia can be very complex because there are so many factors at play. For many patients, it will require the coordination of cardiovascular, nephrology, and internal medicine specialists. 

How do phosphate binders work?

Phosphate binders react with dietary phosphate in the intestinal tract to form an insoluble complex that can not be absorbed into the bloodstream from the intestinal tract. This insoluble complex is then excreted from the body in the stool. 

The absorption of phosphate occurs via two mechanisms in the gastrointestinal tract: paracellular absorption and transcellular transport. Paracellular absorption essentially has no limits to how much it can absorb, and therefore most phosphate is absorbed via this mechanism. When too much phosphate is absorbed, your serum phosphate levels increase. In response, your body pulls calcium from your bones. This bone disorder, known as osteopenia, leaves your bones weak. High serum levels of calcium and phosphates leads to dangerous cardiovascular calcification in your heart and blood vessels, as well as calcification in your lungs and eyes. These deposits can lead to fatal effects on these organs.

If patients take their phosphate binding drugs consistently when they eat, the serum phosphorus levels will decrease over time. 

What are phosphate binders used for?

• Hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis, chronic renal disease (CRD), or end-stage renal disease (ESRD)

Types of phosphate binders 

Calcium-based

Calcium-based phosphate binders can also serve as calcium supplements, though there is some concern about too much serum calcium since binders should be taken with each meal. Calcium binds to the phosphorus in foods to form an insoluble complex which is then excreted. Calcium acetate is the most common of the calcium-based binders. Calcium carbonate, the active ingredient in TUMS antacids, also has some binding ability, though that is not its primary intended use. Calcium levels may need to be monitored when taking calcium-based phosphate binders.

Examples of calcium-based phosphate binders: PhosLyra, Calphron, PhosLo, Eliphos

Aluminum-based

Aluminum-based binders are now mostly reserved for short-term use and when other binders have failed to sufficiently lower serum phosphorus levels. The reason long-term use is not recommended is that aluminum-based binders cause constipation and lead to increased levels of aluminum in the body. This can cause bone damage and nervous system impairment. These reasons are why aluminum-based binders are not frequently used in clinical practice. Aluminum-based binders should not be used in CKD patients, those on hemodialysis, and patients with dementia.

Examples of aluminum-based binders: Alternagel, Amphojel (no longer available in the United States)

Aluminum-free and calcium-free

Aluminum-free, calcium-free binders act as sponges to absorb phosphates in the intestinal tract, but because they do not contain aluminum or calcium, there is little concern over aluminum or calcium overload. Like other binders, they form an insoluble complex that undergoes excretion in the stool.

Examples of calcium-free, aluminum-free binders: Renvela, Renagel, Fosrenol

Iron supplement binders

Iron compounds also bind to phosphorus in the intestinal tract to form an insoluble precipitate that is excreted in the stool. These can be used in patients undergoing dialysis. This non-calcium also serves the purpose of treating anemia and low iron levels.

Examples of iron supplements: Velphoro, Auryxia 

Who can take phosphate binders?

Can men take phosphate binders?

Men can take phosphate binders. Caution should be used in men with pre-existing constipation, and high levels of electrolytes such as calcium and magnesium. Some phosphate binders are not safe for some dialysis patients. Consult with your healthcare provider for more information.

Can women take phosphate binders?

Women can also take phosphate binders. Like in men, women should use phosphate binders with caution in pre-existing constipation, and high levels of electrolytes such as calcium and magnesium. Some phosphate binders are not safe for women undergoing certain types of dialysis.

Can you take phosphate binders while pregnant or breastfeeding?

There are no adequate studies in pregnant women across the different types of protein binders. Other factors should be considered when weighing the risk of use in pregnant women, including the need for healthy levels of electrolytes. Some phosphate binders, such as Renvela, have been shown not to cross into breast milk, making them an acceptable choice in breastfeeding patients when necessary.

Can children take phosphate binders?

Some phosphate binders are appropriate for children. Dosage form considerations are important as solid oral dosage forms tend to be large and could not be swallowed easily. Chewable or liquid preparations are appropriate for children in some cases.

Can seniors take phosphate binders?

Caution should be used in seniors taking phosphate binders. Seniors tend to already suffer from chronic constipation, and phosphate binders can make this worse. Electrolyte imbalances can lead to worsening dementia, central nervous system damage, and chronic renal failure.

Are phosphate binders safe?

Recalls

Currently, there are no FDA recalls associated with phosphate binders.

Restrictions

Do not take phosphate binders if you have had a hypersensitivity reaction to a related phosphate binder. 

Patients with pre-existing constipation and digestive issues should use phosphate binders with caution as they can worsen constipation and lead to ileus, impaction, and other serious gastrointestinal issues. 

Some phosphate binders are not recommended for hemodialysis patients. Make sure your healthcare provider is aware of all of your medical conditions. 

Aluminum-based phosphate binders may raise serum aluminum levels, and therefore blood levels must be monitored.

Patients with pre-existing electrolyte imbalances such as high calcium or aluminum levels should be very selective about which phosphate binder formulations they utilize. Your doctor will make the best selection for your treatment of hyperphosphatemia based on your medical history and the potential for adverse effects. 

Treatment with phosphate binders can create a significant pill burden for patients, meaning there are a lot of doses to remember over the course of the day. It is important to utilize methods to ensure you are compliant with your therapy such as pill reminders, alarms, or pill organizers.

Are phosphate binders controlled substances?

No, phosphate binders are not controlled substances.

Common phosphate binders side effects

Serious adverse effects:

• Hypercalcemia (calcium acetate products)

• Hypersensitivity or anaphylactic reaction

• Iron overload (iron-containing binders)

• Aluminum toxicity (aluminum-based binders)

• Osteomalacia

• Encephalopathy

• Fecal impaction

• Colitis

• Dysphagia

• Intestinal perforation

• Intestinal necrosis

• Ileus

Common side effects:

• Nausea

• Vomiting 

• Diarrhea

• Constipation

• Fecal discoloration

• Change in taste

• Abdominal pain

• Hypophosphatemia

• Dyspepsia

• Flatulence

How much do phosphate binders cost?

There is a great deal of variability in the cost of phosphate binders. Alternagel (aluminum hydroxide) is a very cost-effective medication, available generically for less than $8 per pint with a coupon from SingleCare. However, it is important to consider the cost of aluminum blood level monitoring that must occur when you take an aluminum-based phosphate binder. This can raise the total cost of treatment considerably.

Calcium-based phosphate binders are also relatively cost-effective. A one-month supply of generic Calphron is less than $20 with SingleCare. Insurance coverage can vary, and it may be cheaper or more expensive with insurance. Your pharmacist can help answer questions about your coverage.

Products such as Renvela can be quite costly in their brand-name form. Thankfully, SingleCare offers savings on the generic lowering the price to less than $35 at participating pharmacies.

Auryxia does not have a generic available on the market. With costs between $750-$800 per month, the cost is considerable. SingleCare can help you save significantly on this and other phosphate binders when your insurance does not offer adequate coverage. Your pharmacist can help you understand your prescription coverage of most phosphate binders and work with your prescriber to find the best option for you.