Ferric orthophosphate
Also known as: Ferric phosphate, iron(III) phosphate, FePO4, Ferric orthophosphate
Overview
Ferric orthophosphate, also known as ferric phosphate or iron(III) phosphate (FePO4), is an iron salt utilized as both a dietary iron supplement and a phosphate binder. Its primary applications are in the treatment of iron deficiency anemia and hyperphosphatemia, particularly in patients with chronic kidney disease (CKD). While less soluble than ferrous salts, it offers the dual benefit of iron supplementation and phosphate control. Research indicates it generally causes less gastrointestinal irritation compared to ferrous salts, though its bioavailability may be lower. The efficacy and safety of ferric orthophosphate, especially related compounds like ferric citrate, are well-supported by multiple randomized controlled trials and meta-analyses.
Benefits
Ferric orthophosphate offers significant benefits, particularly for individuals with chronic kidney disease (CKD). Meta-analyses of ferric citrate, a related compound, demonstrate its effectiveness in reducing serum phosphate levels in CKD patients, with mean reductions ranging from -0.55 to -1.39 mg/dL compared to placebo. This makes it a valuable tool for managing hyperphosphatemia. Additionally, ferric phosphate compounds improve iron parameters such as hemoglobin, transferrin saturation, and ferritin, addressing iron deficiency anemia, which is common in CKD. A key advantage is its improved safety and tolerability profile, with fewer gastrointestinal side effects compared to traditional ferrous sulfate, leading to better patient compliance. These benefits are most pronounced in CKD populations requiring both phosphate control and iron supplementation, with improvements typically observed within weeks of treatment initiation.
How it works
Ferric orthophosphate functions through two primary mechanisms. As a phosphate binder, it binds to dietary phosphate within the gastrointestinal tract, forming insoluble complexes that prevent phosphate absorption into the bloodstream, thereby lowering serum phosphate levels. As an iron source, it provides ferric iron (Fe3+). This ferric iron is then reduced to ferrous iron (Fe2+) in the intestine, a form that can be absorbed. Once absorbed, the iron is utilized for hemoglobin synthesis, contributing to the correction of anemia. Its molecular targets include intestinal phosphate transporters and pathways involved in iron absorption. While its bioavailability is lower than ferrous salts, it is sufficient to achieve clinical efficacy in appropriate dosages, particularly in CKD patients.
Side effects
Ferric orthophosphate is generally considered safe with a low incidence of severe adverse effects. The most common side effects, affecting more than 5% of users, are mild gastrointestinal symptoms such as constipation and diarrhea. Less common side effects, occurring in 1-5% of individuals, may include nausea and abdominal discomfort. Rare side effects, affecting less than 1%, can include hypersensitivity reactions. It is important to note potential drug interactions: ferric orthophosphate may interfere with the absorption of certain antibiotics and levothyroxine, necessitating careful timing of administration. Contraindications include known hypersensitivity to iron compounds and conditions involving iron overload. While beneficial for CKD patients, these individuals require careful monitoring for both iron overload and phosphate levels to ensure safe and effective treatment.
Dosage
The minimum effective dose of ferric orthophosphate varies depending on the specific indication. For phosphate binding, typical doses of ferric citrate equivalents range from 1 to 6 grams per day. Optimal dosing is highly individualized, determined by the patient's serum phosphate and iron status, and requires adjustment based on clinical monitoring. The maximum safe dose is primarily guided by tolerability and the risk of iron overload; doses exceeding 6 grams per day are uncommon in clinical practice. To maximize both phosphate binding and iron absorption, ferric orthophosphate should be administered with meals. While ferric orthophosphate is the general compound, ferric citrate is the most extensively studied ferric phosphate compound for clinical use. Absorption can be influenced by other factors; for instance, Vitamin C may enhance iron absorption, while concurrent use of calcium or other phosphate binders might affect its overall efficacy.
FAQs
Is ferric orthophosphate effective for iron deficiency anemia?
Yes, it is effective for iron deficiency anemia, particularly in CKD patients, though its bioavailability may be less than that of ferrous salts.
Can it be used to lower phosphate in CKD?
Yes, ferric orthophosphate, and related compounds like ferric citrate, effectively reduce serum phosphate levels in patients with chronic kidney disease.
Are gastrointestinal side effects common?
Mild gastrointestinal symptoms like constipation and diarrhea can occur, but they are generally less frequent and severe compared to ferrous sulfate.
When are results typically seen?
Improvements in both phosphate levels and iron parameters are usually observed within a few weeks of initiating treatment.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5739813/ – This meta-analysis of 9 RCTs involving 1755 CKD patients found that ferric citrate significantly reduced serum phosphate levels (MD −1.39 mg/dL) and improved iron parameters, with an acceptable safety profile. The study, while focusing on ferric citrate, provides strong evidence for the efficacy of ferric phosphate compounds in this population.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10955115/ – This meta-analysis of 5 RCTs in non-dialysis dependent CKD patients demonstrated that ferric citrate lowered phosphate levels (WMD −0.55 mg/dL) and improved iron status without significantly affecting calcium or PTH. Despite high heterogeneity, the robust sensitivity analyses support the findings for ferric phosphate compounds.
- https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14643 – This systematic review and meta-analysis, while not specific to ferric orthophosphate, highlighted that the incidence of hypophosphatemia varies widely among iron formulations, with ferric compounds generally less associated with severe hypophosphatemia than some intravenous iron preparations. It contributes to the broader understanding of iron formulation safety.