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 | |
|
| LANTHONATE | lanthanum carbonate | 500mg | Micro (forcee) | 16 | 250 mg x 10's (80 INR) | 500 mg x 10's (160 INR) | 24 | 96 |
|
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