This is an article from medscape;
some things to keep in mind when we are considering Indian patients.
All studies were done in western populations where the daily calcium intake is high to begin with .
This may not hold true for Indian patients.
So still calcium acetate is a good cheaper choice.
Specially when patients are not taking the other costlier binders due to economic reasons.
Aluminum hydroxide is still a cheap way to combat high phosphate levels for acute short term administration.
When it comes to Indian brands and costs, the best bang for the buck is Lanthonate by Forcee
next best is Hypophos by samarth.
.
some things to keep in mind when we are considering Indian patients.
All studies were done in western populations where the daily calcium intake is high to begin with .
This may not hold true for Indian patients.
So still calcium acetate is a good cheaper choice.
Specially when patients are not taking the other costlier binders due to economic reasons.
Aluminum hydroxide is still a cheap way to combat high phosphate levels for acute short term administration.
When it comes to Indian brands and costs, the best bang for the buck is Lanthonate by Forcee
next best is Hypophos by samarth.
Accessed on Oct-3-2013
Phosphorus Binders: Relative Potency: Phosphate-Binding Agents
William F. Finn, MD
Differences among various binders may be due to variations in formulation (disintegration and dissolution), the nature of the chemical reaction between the binder and phosphorus and its modification by the changing pH of the gastrointestinal tract, the presence or absence of other anions that compete with phosphorus for binding sites, and the intrinsic transport characteristics of the small intestine.
Aluminum
Aluminum-based phosphate binders were the standard therapy for the treatment of hyperphosphatemia. With a very short disintegration time,[10] activity throughout a wide pH range,[8] and strong chemical affinity for phosphorus, aluminum-based compounds were and are considered to be the most effective binding agents. Unfortunately, the intestinal absorption of aluminum along with exposure to high concentrations of aluminum in dialysate water led to a significant accumulation of aluminum and toxicity. This was marked by dementia, anemia, osteomalacia, and (in some cases) the appearance of adynamic bone disease due to oversuppression of the parathyroid glands.[11]
Calcium Carbonate
As the evidence of serious complications due to aluminum accumulation increased, consideration was given to other agents. Calcium carbonate was first suggested as a potential binding agent in 1966,[12] although there were several theoretic disadvantages to its use. For example, the comparably long disintegration time[10] delays its dissolution. More importantly, there is a considerable fall in the binding of phosphorus with calcium carbonate at a low pH because the higher H+ concentration effectively competes with calcium for phosphorus.[8]
In early studies,[13] it was reported that the mean dose of calcium carbonate necessary to achieve a reduction in the serum phosphorus equal to that of aluminum (4.8 mg/dL; 1.55 mmol/L) was 8.5 g/day -- equal to 3.4 g of elemental calcium. Even with this, it was reported that 30% of the 20 patients in this study required supplemental doses of aluminum hydroxide to achieve the study goal.
More favorable results were reported in a group of 17 hemodialysis patients given either aluminum hydroxide at 3.36 g/day or calcium carbonate at 4.96 g/day (1.98 g of elemental calcium). In these patients, the mean serum phosphorus levels fell to 5.24 mg/dL (1.69 mmol/L) and 5.30 mg/dL (1.71 mmol/L), respectively.[14]
Calcium Acetate
On the basis of a number of theoretic calculations, in vitro experiments, and in vivo studies, a convincing argument was put forward that calcium acetate was a more effective phosphate binder than other calcium salts, including calcium carbonate. For example, when the same dose of elemental calcium was given to uremic patients with acetate (1 g of calcium acetate = 253 mg of elemental calcium; 1 g of elemental calcium = 3.95 g of calcium carbonate) rather than with carbonate (1 g of calcium carbonate = 400 mg of elemental calcium; 1 g of elemental calcium = 2.5 g of calcium carbonate), twice as much phosphorus was complexed,[15] leaving less calcium for absorption and presumably less hypercalcemia -- the most concerning side effect of calcium-based binder therapy.
A summary of several studies comparing calcium acetate with calcium carbonate can be found in Table 1 . The mean doses of elemental calcium in milligrams per day, as either calcium acetate or calcium carbonate given to achieve the serum phosphorus concentration in milligrams per deciliter and millimoles per liter, are listed. It should be noted that the same degree of phosphorus control was achieved with significantly less elemental calcium in the patients who were treated with calcium acetate.
Unfortunately, several of the studies reported a significant incidence of hypercalcemia that ranged from 13% to 27% with calcium acetate and 14% to 31% with calcium carbonate.[17,22] From these studies, it appears that it is not possible to achieve a reduction in the serum phosphorus concentration with calcium-based binders to or below the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline target of 5.5 mg/dL without the risk of hypercalcemia and its attendant consequences.[25]
Sevelamer Hydrochloride
Sevelamer hydrochloride is a cationic (allylamine hydrochloride) polymer that is resistant to intestinal degradation or absorption. It binds the phosphate anion by ion exchange and hydrogen bonding and is most effective in the physiologic range of approximately pH 7. Below pH 7, phosphate exists primarily as the monobasic ion H2PO4 -, which may not be as strongly absorbed as the dibasic ion HPO4 2-. As the pH rises above 7, the amines of sevelamer convert to the protonated form to the uncharged free base, taking away potentia binding sites, resulting in decreased binding at the high pH.[26,27]
Table 2 summarizes several studies comparing calcium-based phosphorus binders. The mean doses (grams per day) of sevelamer hydrochloride and elemental calcium (given as either calcium acetate or calcium carbonate) are listed. The doses (milligrams per deciliter and millimoles per liter) administered to achieve the serum phosphorus concentrations are also listed. In general, at the doses used, the patients receiving sevelamer hydrochloride were somewhat shy of reaching a serum phosphorus concentration at or below 5.5 mg/dL. The patients receiving calcium-based phosphorus binders tended to be more successful in this regard but at a dose of elemental calcium that sometimes exceeded the 1500-mg limit recommended by the K/DOQI guidelines.[25] Moreover, there were substantial differences in the percentage of study patients who exhibited at least 1 episode of hypercalcemia. This ranged from 0% to 17% in the sevelamer hydrochloride-treated patients and 8.9% to 43% in the calcium-treated patients.
Lanthanum Carbonate
Lanthanum is a trivalent cation with a high affinity for phosphorus. In vitro studies indicate that lanthanum carbonate binds phosphorus as effectively as aluminum hydroxide at clinically relevant pH levels.[33] It is worthwhile to note that the magnitude of the forces involved in binding are commonly described in terms of the so-called "affinity constant" or " k 1." Because the binding affinity for lanthanum is pH-independent through a range of 3-7, the k 1 remains unchanged at a pH of 6.1,[34] indicating a very high affinity of lanthanum for phosphorus. By comparison, the binding affinity for sevelamer is pH-dependent and the k 1 varies from a low of .025 at a pH of 3 and a high of 1.45 at a pH of 5.7. This is consistent with data of others who found a k 1 of .08 at a pH of 4 to a high of 1.4 at a pH of 7.[35] In that study, the differences in the affinity constants at pH 4 compared with pH 7 were related to the fact that at pH 4, the monobasic ion is predominantly bound and at pH 7 the dibasic ion is predominantly bound. This also indicates that lanthanum has greater than a 200-fold higher binding affinity at the gastric ph of 3 and a 4-fold higher binding affinity at the intestinal pH 5-7.
Preclinical studies have used a rat model of chronic renal failure (5 of 6 nephrectomized rats) in which the urinary excretion of phosphorus was used as a marker of dietary binding. It was found that when lanthanum carbonate, aluminum hydroxide, calcium carbonate, and sevelamer hydrochloride were given daily over 6 weeks, lanthanum carbonate reduced the urinary phosphorus levels more effectively than either calcium carbonate or sevelamer hydrochloride and to the same extent as aluminum hydroxide.[36]
There are 2 published studies comparing lanthanum carbonate with calcium carbonate. Of note, neither was primarily designed to establish the relative efficacy of one binder vs the other. In the first study,[36] 98 patients were titrated to a lanthanum dose of 3750 mg/day or calcium up to 9000 mg/day (3600 mg of elemental calcium). In the 68 patients who finished the study, the median dose of lanthanum was 1250 mg/day, whereas the median dose of calcium carbonate was 2000 mg/day (800 mg of elemental calcium). In both treatment groups, the phosphorus levels throughout the trial were described as "well-controlled." The incidence of hypercalcemia was 6% with lanthanum and 49% with calcium.
In the second study,[37] 800 hemodialysis patients completed a 3-week screening and washout period and were randomized 2:1 to either lanthanum carbonate or calcium carbonate with a reduction in the serum phosphorus level to ≤ 5.58 mg/dL (1.80 mmol/L), the primary efficacy end point; 54.2% of the patients randomized to lanthanum carbonate and 57.7% of the patients randomized to calcium carbonate completed a 5-week titration phase and a 24-week maintenance phase. At the end of the 5-week titration phase, the serum phosphorus level decreased from a mean value of 8.28 to 5.79 mg/dL (2.67- 1.87 mmol/L) in patients receiving lanthanum and from 8.34 to 5.15 mg/dL (2.69-1.66 mmol/L) in those receiving calcium. These reductions were sustained, and at week 25, 65.8% of the lanthanum-treated patients and 63.9% of the calcium carbonate-treated patients had phosphorus levels ≤ 5.58 mg/dL (1.8 mmol/L). Overall, the most frequently administered dose of lanthanum was 1500 mg, with a range of 375-3000 mg/day. The most frequently administered dose of calcium carbonate was 3000 mg (1200 mg of elemental calcium), with a range of 1500-9000 mg/day (600-3600 mg of elemental calcium). The incidence of hypercalcemia was .4% with lanthanum and 20.2% with calcium.
Conclusion
Aluminum compounds are effective phosphorus-binding agents that are still used when rapid reduction of the serum phosphorus is necessary and/or other agents have failed. Unfortunately, significant toxicity prevents their long-term use. A number of studies have demonstrated the superiority of calcium acetate over calcium carbonate. However, the use of both agents is accompanied by a significant incidence of hypercalcemia. To achieve satisfactory phosphorus control, the doses often exceed the limits set by the K/DOQI guidelines. Sevelamer hydrochloride is also an effective binding agent, particularly at high doses. Based on the data from comparative studies, a dose in the range of 7 g/day may be necessary to consistently achieve serum phosphorus levels at or below 5.5 mg/dL. Lanthanum carbonate in doses up to 3750 mg/day is as effective as calcium carbonate, even at doses of elemental calcium that far exceed the upper limit suggested by the K/DOQI guidelines. Even at doses limited by the study protocols, 2 of 3 of lanthanum carbonate treated-patients in comparative studies achieved serum phosphorus levels at or below 5.5 mg/dL.
| REVLAMER | sevelamer hydrochloride | 800mg | sun | 10 | 800 mg x 10's (108.7 INR) | 30 | 90 |
| brand name | Ingredient | Best strength | Manufacturer | Each tablet | available prep1 | available prep2 | daily low cost | daily high cost | |
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