Generic Name: lanthanum
carbonate
Dosage Form: tablet, chewable; oral powder
Indications and
Usage for Fosrenol
Fosrenol is a
phosphate binder indicated to reduce serum phosphate in patients with end stage
renal disease (ESRD).
Management of
elevated serum phosphorus levels in end stage renal disease patients usually
includes all of the following: reduction in dietary intake of phosphate,
removal of phosphate by dialysis and reduction of intestinal phosphate
absorption with phosphate binders.
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Fosrenol Dosage
and Administration
Divide the total
daily dose of Fosrenol and take with or immediately after meals. The
recommended initial total daily dose of Fosrenol is 1500 mg. Titrate the dose
every 2-3 weeks until an acceptable serum phosphate level is reached. Monitor
serum phosphate levels as needed during dose titration and on a regular basis
thereafter.
In clinical
studies of ESRD patients, Fosrenol doses up to 4500 mg were evaluated. Most
patients required a total daily dose between 1500 mg and 3000 mg to reduce
plasma phosphate levels to less than 6.0 mg/dL. Doses were generally titrated
in increments of 750 mg/day.
Information for
Fosrenol Chewable Tablets
Chew or crush
Fosrenol Chewable Tablets completely before swallowing. Do not swallow intact
Fosrenol Chewable Tablets.
Information for
Fosrenol Oral Powder
Sprinkle
Fosrenol Oral Powder on a small quantity of applesauce or other similar food
and consume immediately. Do not open until ready to use. Do not store Fosrenol
Oral Powder for future use once mixed with food. As Fosrenol Oral Powder is
insoluble, do not attempt to dissolve in liquid for administration.
Consider using
the oral powder formulation in patients with poor dentition or who have
difficulty chewing tablets.
Dosage Forms and
Strengths
Fosrenol
Chewable Tablets: 500 mg, 750 mg, and 1000 mg.
Fosrenol Oral
Powder: 750 mg and 1000 mg.
Contraindications
Contraindicated
in bowel obstruction, including ileus and fecal impaction.
Warnings and
Precautions
Gastrointestinal
Adverse Effects
Serious cases
of gastrointestinal obstruction, ileus, subileus, gastrointestinal perforation
and fecal impaction have been reported in patients taking lanthanum, some requiring
surgery or hospitalization.
Risk factors
for gastrointestinal obstruction and gastrointestinal perforation identified
from post-marketing reports in patients taking Fosrenol Chewable Tablets
include altered gastrointestinal anatomy (e.g., diverticular disease,
peritonitis, history of gastrointestinal surgery, gastrointestinal cancer,
gastrointestinal ulceration), hypomotility disorders (e.g., constipation,
ileus, subileus, diabetic gastroparesis) and concomitant medications (e.g.,
calcium channel blockers). Some cases were reported in patients with no history
of gastrointestinal disease.
Patients with
acute peptic ulcer, ulcerative colitis, Crohn's disease or bowel obstruction
were not included in Fosrenol clinical studies [see Contraindications
(4)].
Advise patients
who are prescribed Fosrenol Chewable Tablets to chew the tablet completely to
reduce the risk of serious adverse gastrointestinal events such as those
described above.
Diagnostic Tests
Fosrenol has
radio-opaque properties and therefore may give the appearance typical of an
imaging agent during abdominal X-ray procedures.
Adverse
Reactions
The following
adverse reactions are discussed in greater detail in other sections of the
labeling:
·
Gastrointestinal Adverse Effects [see Warnings and
Precautions (5.1)]
Overall, the
safety profile of Fosrenol has been studied in over 5200 subjects in completed
clinical trials. The most common adverse reactions for Fosrenol were
gastrointestinal events, such as nausea, vomiting, and abdominal pain and they
generally abated over time with continued dosing.
Clinical Trials
Experience
Because clinical
trials are conducted under widely varying conditions, adverse reaction rates
observed in clinical trials of a drug cannot be directly compared to rates in
the clinical trials of another drug and may not reflect the rates observed in
practice.
In double-blind,
placebo-controlled studies where a total of 180 and 95 ESRD patients were
randomized to Fosrenol chewable tablet and placebo, respectively, for 4-6 weeks
of treatment, the most common reactions that were more frequent (≥5%
difference) in the Fosrenol group were nausea, vomiting, and abdominal pain
(Table 1).
Table 1. Adverse Reactions* That Were More Common on Fosrenol in
Placebo-Controlled, Double-Blind Studies With Treatment Periods of 4-6 Weeks
|
|
|
Fosrenol
%
(N=180)
|
Placebo
%
(N=95)
|
|
*
expressed as the
event rate for each term
|
|
Nausea
|
11
|
5
|
|
Vomiting
|
9
|
4
|
|
Abdominal pain
|
5
|
0
|
In an open-label
long-term 2 year extension study in 93 patients who had transitioned from other
studies, resulting in a total of up to 6 years treatment, mean baseline values
and changes in transaminases were similar to those observed in the earlier comparative
studies, with little change during treatment.
The safety of
Fosrenol was studied in two long-term, open-labeled clinical trials, which
included 1215 patients treated with Fosrenol and 944 with alternative therapy.
Fourteen percent (14%) of Fosrenol treated patients discontinued treatment due
to adverse events. Gastrointestinal adverse reactions, such as nausea, diarrhea
and vomiting were the most common types of event leading to discontinuation.
In pooled active
comparator controlled clinical trials, hypocalcemia was noted with an incidence
of approximately 5% in both lanthanum and active comparator groups. A
nonclinical study and a phase 1 study have shown reduced absorption of calcium
in the intestine with lanthanum carbonate treatment.
In a crossover
study in 72 healthy individuals comparing Fosrenol chewable tablets to Fosrenol
oral powder, gastrointestinal adverse reactions such as nausea, diarrhea and
vomiting were more common for the oral powder formulation (18%) than for the
chewable tablets (7%).
Postmarketing
Experience
The following
adverse reactions have been identified during post-approval use of Fosrenol.
Because these reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or
establish a causal relationship to drug exposure: constipation, intestinal
perforation, intestinal obstruction, ileus, subileus, dyspepsia, allergic skin
reactions, hypophosphatemia, and tooth injury while chewing the tablet.
Drug
Interactions
Lanthanum in
Fosrenol has the potential to bind to drugs with anionic (e.g., carboxyl,
carbonyl and hydroxyl) groups. Fosrenol may decrease the bioavailability of
tetracyclines or fluoroquinolones via this mechanism.
There are no
empirical data on avoiding drug interactions between Fosrenol and most
concomitant oral drugs. For oral medications where a reduction in the
bioavailability of that medication would have a clinically significant effect
on its safety or efficacy, consider separation of the timing of the
administration of the two drugs. The duration of separation depends upon the
absorption characteristics of the medication concomitantly administered, such
as the time to reach peak systemic levels and whether the drug is an immediate
release or an extended release product. Consider monitoring clinical responses
or blood levels of concomitant medications that have a narrow therapeutic
range.
Drugs Binding to
Antacids
There is a
potential for Fosrenol to interact with compounds which bind to cationic
antacids (i.e., aluminum-, magnesium-, or calcium-based). Therefore, do not
administer such compounds within 2 hours of dosing with Fosrenol. Examples of
relevant classes of compounds where antacids have been demonstrated to reduce
bioavailability include antibiotics (such as quinolones, ampicillin and
tetracyclines), thyroid hormones, ACE-inhibitors, statin lipid regulators and
anti-malarials.
Quinolone
Antibiotics
Co-administration
of Fosrenol with quinolone antibiotics may reduce the extent of their
absorption. The bioavailability of oral ciprofloxacin was decreased by
approximately 50% when taken with Fosrenol in a single dose study in healthy
volunteers. Administer oral quinolone antibiotics at least 1 hour before or 4
hours after Fosrenol. When oral quinolones are given for short courses,
consider eliminating the doses of Fosrenol that would be normally scheduled near
the time of quinolone intake to improve quinolone absorption [see Clinical
Pharmacology (12.3)].
Levothyroxine
The
bioavailability of levothyroxine was decreased by approximately 40% when taken
together with Fosrenol. Administer thyroid hormone replacement therapy at least
2 hours before or 2 hours after dosing with Fosrenol and monitor thyroid
stimulating hormone (TSH) levels [see Clinical
Pharmacology (12.3)].
USE IN SPECIFIC
POPULATIONS
Pregnancy
Pregnancy
Category C. No adequate and well-controlled studies have been conducted in
pregnant women. The effect of Fosrenol on the absorption of vitamins and other
nutrients has not been studied in pregnant women. Fosrenol is not recommended
for use during pregnancy.
Studies in
pregnant rabbits showed that oral administration of lanthanum carbonate at 1500
mg/kg/day (5 times the maximum recommended daily human dose (MRHD) of 5725 mg,
on a mg/m2basis, assuming a 60 kg patient) was associated with
increased post-implantation loss, reduced fetal weights, and delayed fetal
ossification [see Nonclinical Toxicology (13.3)].
Labor and
Delivery
No Fosrenol
treatment-related effects on labor and delivery were seen in animal studies.
The effects of Fosrenol on labor and delivery in humans is unknown.
Nursing Mothers
It is not known
whether lanthanum carbonate is excreted in human milk. As many drugs are
excreted in human milk, consider the possibility of infant exposure when
Fosrenol is administered to a nursing woman.
Pediatric Use
The safety and
efficacy of Fosrenol in pediatric patients have not been established. While
growth abnormalities were not identified in long-term animal studies, lanthanum
was deposited into developing bone including growth plate. The consequences of
such deposition in developing bone in pediatric patients are unknown.
Therefore, the use of Fosrenol in this population is not recommended.
Geriatric Use
Of the total
number of patients in clinical studies of Fosrenol, 32% (538) were ≥65, while
9.3% (159) were ≥75. No overall differences in safety or effectiveness were
observed between patients ≥65 years of age and younger patients.
Overdosage
The symptoms
associated with overdose are adverse reactions such as headache, nausea and
vomiting. In clinical trials in healthy adults, GI symptoms were reported with
daily doses up to 6000 mg/day of lanthanum carbonate administered with food.
Given the topical activity of lanthanum in the gut, and the excretion in feces
of the majority of the dose, supportive therapy is recommended for overdosage.
Lanthanum carbonate was not acutely toxic in animals by the oral route. No
deaths and no adverse effects occurred in mice, rats or dogs after single oral
doses of 2000 mg/kg (1.7, 3.4, and 11.3 times the MRHD, respectively, on a mg/m2 basis).
Fosrenol
Description
Fosrenol
contains lanthanum carbonate with molecular formula La2(CO3)3 xH2O (on average
x=4-5 moles of water) and molecular weight 457.8 (anhydrous mass). Lanthanum
carbonate is described as white to almost white powder. Lanthanum carbonate is
practically insoluble in water and is insoluble in organic solvents; it
dissolves in dilute mineral acids with effervescence.
Each Fosrenol,
white to off-white, chewable tablet contains lanthanum carbonate hydrate
equivalent to 500, 750, or 1000 mg of elemental lanthanum and the following
inactive ingredients: colloidal silicon dioxide NF, dextrates (hydrated) NF,
magnesium stearate NF.
Fosrenol Oral
Powder is a white to off-white powder containing lanthanum carbonate hydrate
equivalent to 750 or 1000 mg of elemental lanthanum and the following inactive
ingredients: colloidal silicon dioxide NF, dextrates (hydrated) NF, magnesium
stearate NF.
Fosrenol -
Clinical Pharmacology
Mechanism of
Action
Fosrenol is a
phosphate binder that reduces absorption of phosphate by forming insoluble
lanthanum phosphate complexes that pass through the gastrointestinal (GI) tract
unabsorbed. Both serum phosphate and calcium phosphate product are reduced as a
consequence of the reduced dietary phosphate absorption.
Pharmacodynamics
In vitro studies
have shown that lanthanum binds phosphate in the physiologically relevant pH
range of 3 to 7. In simulated gastric fluid, lanthanum binds approximately 97%
of the available phosphate at pH 3-5 and 67% at pH 7, when lanthanum is present
in a two-fold molar excess to phosphate. Bile acids have not been shown to
affect the phosphate binding affinity of lanthanum. In order to bind dietary
phosphate, Fosrenol must be administered with or immediately after meals.
In five Phase I
pharmacodynamic studies comparing the reduction from baseline of urinary
phosphorus excretion in healthy volunteers (N=143 taking lanthanum carbonate),
it was shown that the mean intestinal phosphate binding capacity of lanthanum
ranged from 235 to 468 mg phosphorus/day when lanthanum was administered at a
dose of 3 g per day with food. By comparison, in one study with an untreated
control group (n=10) and another study with a placebo group (n=3), the
corresponding mean changes from baseline were 3 mg phosphorus/day and 87 mg
phosphorus/day, respectively.
In healthy
subjects Fosrenol Oral Powder was found to be similar to Fosrenol Chewable
Tablets, based on urinary phosphate excretion.
Pharmacokinetics
Absorption and
Distribution - Following single or multiple dose oral administration of Fosrenol
to healthy subjects, the concentration of lanthanum in plasma was very low
(bioavailability <0.002%). Following oral administration in patients, the
mean lanthanum Cmax was 1.0 ng/mL. During long-term administration (52
weeks) in ESRD patients, the mean lanthanum concentration in plasma was
approximately 0.6 ng/mL. There was minimal increase in plasma lanthanum
concentrations with increasing doses within the therapeutic dose range. The timing
of food intake relative to lanthanum administration (during and 30 minutes
after food intake) has a negligible effect on the systemic level of lanthanum.
Systemic
exposure to lanthanum was approximately 30% higher following administration of
Fosrenol Oral Powder when compared to Fosrenol Chewable Tablets. However,
systemic exposure to lanthanum from both formulations in this study was within
the range seen in previous pharmacokinetic studies of Chewable Tablets in
healthy individuals.
In vitro, lanthanum is
highly bound (>99%) to human plasma proteins, including human serum albumin,
α1-acid glycoprotein, and transferrin. Binding to erythrocytes in vivo is
negligible in rats.
In animal
studies, lanthanum concentrations in several tissues, particularly gastrointestinal
tract, mesenteric lymph nodes, bone and liver, increased over time to levels
several orders of magnitude higher than those in plasma. The level of lanthanum
in the liver was higher in renally impaired rats due to higher intestinal
absorption. Lanthanum was found in the lysosomes and the biliary canal
consistent with transcellular transport. Steady state tissue concentrations in
bone and liver were achieved in dogs between 4 and 26 weeks. Relatively high
levels of lanthanum remained in these tissues for longer than 6 months after
cessation of dosing in dogs. There is no evidence from animal studies that
lanthanum crosses the blood-brain barrier.
In 105 bone
biopsies from patients treated with Fosrenol for up to 4.5 years, rising levels
of lanthanum were noted over time. Estimates of elimination half-life from bone
ranged from 2.0 to 3.6 years. Steady state bone concentrations were not reached
during the period studied.
Metabolism and Elimination -
Lanthanum is not metabolized. Lanthanum was cleared from plasma of patients
undergoing dialysis with an elimination half-life of 53 hours following
discontinuation of therapy.
No information
is available regarding the mass balance of lanthanum in humans after oral
administration. In rats and dogs, the mean recovery of lanthanum after an oral
dose was about 99% and 94%, respectively, and was essentially all from feces.
Biliary excretion is the predominant route of elimination for circulating
lanthanum in rats. In healthy volunteers administered intravenous lanthanum as
the soluble chloride salt (120 µg), renal clearance was less than 2% of total
plasma clearance.
Drug
Interactions
Fosrenol has a
low potential for systemic drug-drug interactions because of the very low
bioavailability of lanthanum and because it is not a substrate or inhibitor of
major cytochrome P450 enzyme groups involved in drug metabolism (CYP1A2,
CYP2C9/10, CYP2C19, CYP2D6 and CYP3A4/5).
Fosrenol does
not alter gastric pH. Therefore, Fosrenol drug interactions based on altered
gastric pH are not expected.
In an in vitro investigation,
lanthanum did not form insoluble complexes when mixed in simulated gastric
fluid with warfarin, digoxin, furosemide, phenytoin, metoprolol and enalapril.
Clinical studies have shown that Fosrenol (three doses of 1000 mg on the day
prior to exposure and one dose of 1000 mg on the day of co-administration)
administered 30 minutes earlier did not alter the pharmacokinetics of oral
warfarin (10 mg), digoxin (0.5 mg), or metoprolol (100 mg). Potential
pharmacodynamic interactions between lanthanum and these drugs (e.g., bleeding
time or prothrombin time) were not evaluated. None of the drug interaction
studies were done with the maximum recommended therapeutic dose of lanthanum
carbonate. No drug interaction studies assessed the effects of drugs on
phosphate binding by lanthanum carbonate.
Ciprofloxacin
In a randomized,
two–way crossover study in healthy volunteers examining the interaction
potential of a single oral dose of ciprofloxacin (750 mg) alone and with lanthanum
carbonate (1 g TID), the maximum plasma concentration of ciprofloxacin was
reduced by 56% and the area under the ciprofloxacin plasma concentration-time
curve was reduced by 54%. The 24-h urinary recovery of ciprofloxacin was
reduced 52% by Fosrenol [see Drug Interactions (7.2)].
Levothyroxine
In a single-dose
crossover study of levothyroxine (1 mg) with or without simultaneous
administration of a single dose of Fosrenol (500 mg) in six euthyroid normal
healthy volunteers, the area under the serum T4 concentration-time curve was
decreased by 40% [see Drug Interactions (7.3)].
Fat Soluble
Vitamins
Fosrenol appears
not to affect the availability of fat soluble vitamins (A, D, E and K) or other
nutrients [see Clinical Studies (14.2)].
Citrate
Citrate did not
increase the absorption of lanthanum.
Nonclinical Toxicology
Carcinogenesis,
Mutagenesis, Impairment of Fertility
Oral
administration of lanthanum carbonate to rats for up to 104 weeks, at doses up
to 1500 mg of the salt per kg/day [2.5 times the MRHD of 5725 mg, on a mg/m2 basis,
assuming a 60-kg patient] revealed no evidence of carcinogenic potential. In
the mouse, oral administration of lanthanum carbonate for up to 99 weeks, at a
dose of 1500 mg/kg/day (1.3 times the MRHD) was associated with an increased
incidence of glandular stomach adenomas in male mice.
Lanthanum
carbonate tested negative for mutagenic activity in an in vitro Ames assay
using Salmonella typhimurium and Escherichia coli strains and in vitro HGPRT gene
mutation and chromosomal aberration assays in Chinese hamster ovary cells. Lanthanum
carbonate also tested negative in an oral mouse micronucleus assay at doses up
to 2000 mg/kg (1.7 times the MRHD), and in micronucleus and unscheduled DNA
synthesis assays in rats given IV lanthanum chloride at doses up to 0.1 mg/kg,
a dose that produced plasma lanthanum concentrations >2000 times the peak
human plasma concentration.
Lanthanum
carbonate, at doses up to 2000 mg/kg/day (3.4 times the MRHD), did not affect
fertility or mating performance of male or female rats.
Developmental
Toxicity
In pregnant
rats, oral administration of lanthanum carbonate at doses as high as 2000
mg/kg/day (3.4 times the MRHD) resulted in no evidence of harm to the fetus. In
pregnant rabbits, oral administration of lanthanum carbonate at 1500 mg/kg/day
(5 times the MRHD) was associated with a reduction in maternal body weight gain
and food consumption, increased post-implantation loss, reduced fetal weights,
and delayed fetal ossification. Lanthanum carbonate administered to rats from
implantation through lactation at 2000 mg/kg/day (3.4 times the MRHD) caused
delayed eye opening, reduction in body weight gain, and delayed sexual
development (preputial separation and vaginal opening) of the offspring.
Clinical Studies
The
effectiveness of Fosrenol in reducing serum phosphorus in ESRD patients was
demonstrated in one short-term, placebo-controlled, double-blind dose-ranging
study, two placebo-controlled randomized withdrawal studies and two long-term,
active-controlled, open-label studies in both hemodialysis and peritoneal
dialysis (PD) patients.
Double-Blind
Placebo-Controlled Studies
One hundred and
forty-four patients with chronic renal failure undergoing hemodialysis and with
elevated phosphate levels were randomized to double-blind treatment at a fixed
dose of lanthanum carbonate of 225 mg (n=27), 675 mg (n=29), 1350 mg (n=30) or
2250 mg (n=26) or placebo (n=32) in divided doses with meals. Fifty-five
percent of subjects were male, 71% black, 25% white and 4% of other races. The
mean age was 56 years and the duration of dialysis ranged from 0.5 to 15.3
years. Steady-state effects were achieved after two weeks. The effect after six
weeks of treatment is shown in Figure 1.
Figure 1.
Difference in Phosphate Reduction in the Fosrenol and Placebo Group in a
6-Week, Dose-Ranging, Double-Blind Study in ESRD Patients (with 95% Confidence
Intervals)
One-hundred and
eighty-five patients with end stage renal disease undergoing either
hemodialysis (n=146) or peritoneal dialysis (n=39) were enrolled in two
placebo-controlled, randomized withdrawal studies. Sixty-four percent of
subjects were male, 28% black, 62% white and 10% of other races. The mean age
was 58.4 years and the duration of dialysis ranged from 0.2 to 21.4 years.
After titration of lanthanum carbonate to achieve a phosphate level between 4.0
and 5.6 mg/dL in one study (doses up to 2250 mg/day) or ≤5.9 mg/dL in the
second study (doses up to 3000 mg/day) and maintenance through 6 weeks, patients
were randomized to lanthanum or placebo. During the placebo-controlled,
randomized withdrawal phase (four weeks), the phosphorus concentration rose in
the placebo group by 1.7 mg/dL in one study and 1.9 mg/dL in the other study
relative to patients who remained on lanthanum carbonate therapy.
Open-Label
Active-Controlled Studies
Two long-term
open-label studies were conducted, involving a total of 2028 patients with ESRD
undergoing hemodialysis. Patients were randomized to receive Fosrenol or alternative
phosphate binders for up to six months in one study and two years in the other.
The daily Fosrenol doses, divided and taken with meals, ranged from 375 mg to
3000 mg. Doses were titrated to reduce serum phosphate levels to a target
level. The daily doses of the alternative therapy were based on current
prescribing information or those commonly utilized. Both treatment groups had
similar reductions in serum phosphate of about 1.8 mg/dL. Maintenance of
reduction was observed for up to three years in patients treated with Fosrenol
in long-term, open-label extensions.
No effects of
Fosrenol on serum levels of 25-dihydroxy vitamin D3, vitamin A, vitamin B12,
vitamin E and vitamin K were observed in patients who were monitored for 6
months.
Paired bone biopsies
(at baseline and at one or two years) in 69 patients randomized to either
Fosrenol or calcium carbonate in one study and 99 patients randomized to either
Fosrenol or alternative therapy in a second study showed no differences in the
development of mineralization defects between the groups.
Vital status was
known for over 2000 patients, 97% of those participating in the clinical
program during and after receiving treatment. The adjusted yearly mortality
rate (rate/years of observation) for patients treated with Fosrenol or
alternative therapy was 6.6%.
How
Supplied/Storage and Handling
Fosrenol
Chewable Tablets
Fosrenol is
supplied as a chewable tablet in three dosage strengths for oral
administration: 500 mg tablets, 750 mg tablets, and 1000 mg tablets. Each
chewable tablet is white to off-white round, flat with a bevelled edge, and
debossed on one side with 'S405' and the dosage strength corresponding to the
content of elemental lanthanum.
500 mg Patient
Pack (2 bottles of 45 tablets, NDC 54092-252-45, per each patient pack) NDC
54092-252-90.
750 mg Patient
Pack (6 bottles of 15 tablets, NDC 54092-253-15, per each patient pack) NDC
54092-253-90.
1000 mg Patient
Pack (9 bottles of 10 tablets, NDC 54092-254-10, per each patient pack) NDC
54092-254-90.
Fosrenol Oral
Powder
Fosrenol Oral
Powder is supplied in two dosage strengths for oral administration: 750 mg and
1000 mg. Each 750 mg and 1000 mg stick pack contains 2.1 g and 2.8 g oral
powder, respectively, packed in a polyethylene
terephthalate/aluminium/polyethylene laminate.
|
Strength
|
Carton of 10 Stick Packs
|
Patient Pack of 9 Cartons
|
|
750 mg
|
NDC 54092-256-01
|
NDC 54092-256-02
|
|
1000 mg
|
NDC 54092-257-01
|
NDC 54092-257-02
|
Storage - Store
at 25°C (77°F): excursions permitted to 15-30°C (59-86°F).
[See USP
controlled room temperature].
Patient
Counseling Information
Advise the
patient to read the FDA-approved patient labelling (Medication Guide).
Advise patients
to take Fosrenol with or immediately after meals [see Dosage and
Administration (2)].
Instruct
patients on concomitant medications that should be dosed apart from
Fosrenol [see Drug Interactions (7)]
Instruct
patients who are prescribed Fosrenol Chewable Tablets to chew or crush tablets
completely before swallowing. Emphasize that Fosrenol Chewable Tablets should not be
swallowed intact. Consider crushing Fosrenol Chewable Tablets completely or
prescribing the oral powder formulation for patients with poor dentition or who
have difficulty chewing tablets [see Dosage and
Administration (2)].
Instruct
patients who are prescribed Fosrenol Oral Powder to sprinkle powder on a small
quantity of applesauce or other similar food. Patients should be instructed to
consume the entire dose immediately. Fosrenol Oral Powder is insoluble so no
attempt should be made to dissolve the powder in liquid for
administration [see Dosage and Administration (2)].
Advise patients
who are taking an oral medication where a reduction in the bioavailability of
that medication would have a clinically significant effect on its safety or
efficacy to separate the dosing of Fosrenol from the dosing of the affected
drug by several hours [see Drug Interactions (7)].
Advise patients
to notify their physician that they are taking Fosrenol prior to an abdominal
X-ray or if they have a history of gastrointestinal disease [see Warnings and
Precautions (5.1,5.2)].
Fosrenol
Chewable Tablets manufactured by Patheon Manufacturing Services LLC,
5900 Martin Luther King Jr. Highway,
Greenville, NC 27834
Fosrenol Oral
Powder manufactured by Catalent Germany Schorndorf GmbH,
Steinbeisstrasse 1-2
D-73614 Schorndorf
Germany
Manufactured for
Shire US Inc., 300 Shire Way, Lexington, MA 02421.
Fosrenol® is
registered in the U.S. Patent and Trademark Office.
© 2016 Shire US Inc.
This product is
covered by US patents 5,968,976, 7,465,465, 8,980,327 and 9,023,397.
MEDICATION GUIDE
Fosrenol® (foss-wren-all)
(lanthanum carbonate)
Read this
Medication Guide before you start taking Fosrenol and each time you get a
refill. There may be new information. This information does not take the place
of talking to your healthcare provider about your medical condition or
treatment.
What is the most
important information I should know about Fosrenol?
Fosrenol may
cause a bowel blockage, a hole in the bowel or severe constipation, which can
be serious, and sometimes lead to surgery or treatment in a hospital.
·
You may have a higher risk of bowel blockage, a hole in
the bowel or severe constipation if you take Fosrenol and have:
o a history of
surgery, ulcers or cancer in the stomach or bowel
o a history of
bowel blockage, or problems resulting in a decreased movement of food through
your stomach and bowel (e.g. feeling full quickly after eating or constipation)
o an infection or
inflammation of the stomach/bowel (peritonitis)
Do not swallow
Fosrenol Chewable Tablets whole. Chew tablets completely before swallowing. If
you can not chew tablets completely, you may crush the tablets thoroughly
before swallowing or discuss the oral powder formulation with your healthcare
provider.
What is
Fosrenol?
Fosrenol is a
prescription medicine used in people with end stage renal disease (ESRD) to
lower the amount of phosphate in the blood.
Who should not
take Fosrenol?
Do not take
Fosrenol if you:
·
have blocked bowels
·
have severe constipation
Fosrenol has not
been studied in children and adolescents under 18 years of age.
What should I
tell my healthcare provider before taking Fosrenol?
Fosrenol may not
be right for you. Before starting Fosrenol, tell your healthcare provider if
you:
·
have a history of surgery, ulcers or cancer in the
stomach or bowel
·
have a history of a bowel blockage, constipation, or
problems resulting in a decreased movement of food through your stomach and
bowel especially if you also have diabetes
·
have ulcerative colitis, Crohn's disease or an infection
or inflammation of the stomach/bowel (peritonitis)
·
plan to have an X-ray of your stomach (abdomen)
·
have any other medical conditions
·
are pregnant, plan to become pregnant, or plan to
breastfeed. It is not known if Fosrenol will harm your unborn baby
Tell your
healthcare provider about all of the medicines you take, including
prescription and non-prescription medicines, vitamins, and herbal supplements.
Especially tell
your healthcare provider if you take:
·
antacids
·
antibiotics
·
thyroid medicine
Know the medicines
you take. Keep a list of them and show it to your healthcare provider and
pharmacist when you get a new medicine.
How should I
take Fosrenol?
·
Take Fosrenol exactly as prescribed by your healthcare
provider
·
Your healthcare provider will tell you how much Fosrenol
to take
·
Your healthcare provider may change your dose if needed
·
Chewable Tablets - Do not swallow
tablets whole. Chew tablets completely before swallowing. If you cannot chew
tablets completely, or if you have tooth disease, you may crush the tablets
thoroughly before swallowing or discuss the oral powder formulation with your
healthcare provider.
·
Oral Powder – Sprinkle powder on a small
quantity of applesauce or other similar food. Consume the entire dose
immediately. Fosrenol Oral Powder will not dissolve in liquid.
·
Take Fosrenol with or right after meals
·
If you take an antacid medicine, take the antacid 2 hours
before or 2 hours after you take Fosrenol
·
If you take medicine for your thyroid (levothyroxine),
take the thyroid medicine 2 hours before or 2 hours after you take Fosrenol
·
If you take an antibiotic medicine, take the antibiotic 1
hour before or 4 hours after you take Fosrenol
What are
possible or reasonably likely side effects of Fosrenol?
See "What is the most
important information I should know about Fosrenol?"
The most common
side effects of Fosrenol include:
·
nausea
·
vomiting
·
diarrhea
·
stomach pain
Tell your
healthcare provider if you have any side effect that bothers you or that does
not go away.
These are not
all the side effects of Fosrenol. For more information, ask your healthcare
provider or pharmacist.
Call your doctor
for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I
store Fosrenol?
·
Store Fosrenol between 59°F to 86°F (15°C to 30°C).
Keep Fosrenol
and all medicines out of the reach of children.
General
information about Fosrenol
Medicines are
sometimes prescribed for purposes other than those listed in a Medication
Guide. Do not use Fosrenol for a condition for which it was not prescribed. Do
not give Fosrenol to other people, even if they have the same condition. It may
harm them.
This Medication
Guide summarizes the most important information about Fosrenol. If you would
like more information, talk with your healthcare provider. You can ask your
pharmacist or healthcare provider for information about Fosrenol that is
written for healthcare professionals.
For more
information go to www.Fosrenol.com or call 1-800-828-2088.
What are the
ingredients in Fosrenol?
Active
ingredient: lanthanum
carbonate
Inactive
ingredients: colloidal silicon dioxide NF, dextrates (hydrated) NF, and magnesium
stearate NF.
This Medication
Guide has been approved by the US Food and Drug Administration.
© 2016 Shire US
Inc.
300 Shire Way,
Lexington, MA 02421.
Issued [02/2016]
PRINCIPAL
DISPLAY PANEL - 500 mg Tablet Bottle Label
NDC 54092-252-45
Fosrenol®
(lanthanum carbonate)
chewable tablets
500 mg
Do not swallow tablets
whole.
Chew or crush tablets completely
before swallowing.
Take with or immediately after meals.
ATTENTION
PHARMACIST: Each patient is required
to receive the enclosed Medication Guide.
45 TABLETS
Rx only
Shire
PRINCIPAL
DISPLAY PANEL - 500 mg Tablet Bottle Carton
NDC 54092-252-90
Fosrenol®
(lanthanum carbonate)
chewable tablets
500 mg
Do not swallow
tablets whole.
Chew or crush tablets completely
before swallowing.
Take with or immediately after
meals.
2 bottles/45
chewable tablets each
Rx only
Shire
Active
Ingredient: Each
tablet contains 500 mg
of lanthanum as lanthanum
carbonate hydrate
Inactive
Ingredients:
Colloidal silicon dioxide,
dextrates, and magnesium
stearate.
See package
insert for full
prescribing information.
Store at 25°C (77°F)
excursions permitted to
15-30°C (59-86°F)
[see USP Controlled Room
Temperature]
PRINCIPAL
DISPLAY PANEL - 750 mg Tablet Bottle Label
NDC 54092-253-15
Fosrenol®
(lanthanum carbonate)
chewable tablets
750 mg
Do not swallow
tablets whole.
Chew or crush tablets completely
before swallowing.
Take with or immediately after meals.
ATTENTION
PHARMACIST: Each patient is required
to receive the enclosed Medication Guide.
15 TABLETS
Rx only
Shire
PRINCIPAL
DISPLAY PANEL - 750 mg Tablet Bottle Carton
NDC 54092-253-90
Fosrenol®
(lanthanum carbonate)
chewable tablets
750 mg
Do not swallow
tablets whole.
Chew or crush tablets completely
before swallowing.
Take with or immediately after meals.
6 bottles/15
chewable tablets each
Rx only
Shire
Active
Ingredient: Each
tablet contains 750 mg
of lanthanum as lanthanum
carbonate hydrate
Inactive
Ingredients:
Colloidal silicon dioxide,
dextrates, and magnesium
stearate.
See package
insert for full
prescribing information.
Store at 25°C (77°F)
excursions permitted to
15-30°C (59-86°F)
[see USP Controlled Room
Temperature]
PRINCIPAL
DISPLAY PANEL - 1000 mg Tablet Bottle Label
NDC 54092-254-10
Fosrenol®
(lanthanum carbonate)
chewable tablets
1000 mg
Do not swallow
tablets whole.
Chew or crush tablets completely
before swallowing.
Take with or immediately after meals.
ATTENTION
PHARMACIST: Each patient is required
to receive the enclosed Medication Guide.
10 TABLETS
Rx only
Shire
PRINCIPAL
DISPLAY PANEL - 1000 mg Tablet Bottle Carton
NDC 54092-254-90
Fosrenol®
(lanthanum carbonate)
chewable tablets
1000 mg
Do not swallow
tablets whole.
Chew or crush tablets completely
before swallowing.
Take with or immediately after meals.
9 bottles/10
chewable tablets each
Rx only
Shire
Active
Ingredient: Each
tablet contains 1000 mg
of lanthanum as lanthanum
carbonate hydrate
Inactive
Ingredients:
Colloidal silicon dioxide,
dextrates, and magnesium
stearate.
See package
insert for full
prescribing information.
Store at 25° C (77°F)
excursions permitted to
15-30°C (59-86°F)
[see USP Controlled Room
Temperature]
PRINCIPAL
DISPLAY PANEL - 750 mg Packet Carton - 10 Stick Pack
NDC 54092-256-01
Fosrenol®
(lanthanum carbonate)
oral powder
750 mg
Mix with small
quantity of soft food
and take immediately
Shire
10 stick packs
Rx only
PRINCIPAL
DISPLAY PANEL - 750 mg Packet Carton - 90 Stick Pack
NDC 54092-256-02
Fosrenol®
(lanthanum carbonate)
oral powder
750 mg
Mix with small
quantity of soft food
and take immediately
Shire
9 cartons, each
carton contains 10 stick packs
Rx only
PRINCIPAL
DISPLAY PANEL - 1000 mg Packet Carton - 10 Stick Pack
NDC 54092-257-01
Fosrenol®
(lanthanum carbonate)
oral powder
1000 mg
Mix with small
quantity of soft food
and take immediately
Shire
10 stick packs
Rx only
PRINCIPAL
DISPLAY PANEL - 1000 mg Packet Carton - 90 Stick Pack
NDC 54092-257-02
Fosrenol®
(lanthanum carbonate)
oral powder
1000 mg
Mix with small
quantity of soft food
and take immediately
Shire
9 cartons, each
carton contains 10 stick packs
Rx only
|
Fosrenol lanthanum
carbonate tablet, chewable
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:54092-252
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
LANTHANUM CARBONATE (LANTHANUM CATION (3+))
|
LANTHANUM CATION (3+)
|
500 mg
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
DEXTRATES
|
|
|
SILICON DIOXIDE
|
|
|
MAGNESIUM STEARATE
|
|
|
|
Product Characteristics
|
|
Color
|
WHITE (white)
|
Score
|
no score
|
|
Shape
|
ROUND (ROUND)
|
Size
|
18mm
|
|
Flavor
|
|
Imprint Code
|
S405;500
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:54092-252-90
|
2 BOTTLE in 1 PACKAGE
|
|
|
1
|
NDC:54092-252-45
|
45 TABLET, CHEWABLE in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA021468
|
10/26/2004
|
|
|
|
Fosrenol lanthanum
carbonate tablet, chewable
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:54092-253
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
LANTHANUM CARBONATE (LANTHANUM CATION (3+))
|
LANTHANUM CATION (3+)
|
750 mg
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
DEXTRATES
|
|
|
SILICON DIOXIDE
|
|
|
MAGNESIUM STEARATE
|
|
|
|
Product Characteristics
|
|
Color
|
WHITE (white)
|
Score
|
no score
|
|
Shape
|
ROUND (ROUND)
|
Size
|
20mm
|
|
Flavor
|
|
Imprint Code
|
S405;750
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:54092-253-90
|
6 BOTTLE in 1 PACKAGE
|
|
|
1
|
NDC:54092-253-15
|
15 TABLET, CHEWABLE in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA021468
|
11/23/2005
|
|
|
|
Fosrenol lanthanum carbonate
tablet, chewable
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:54092-254
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
LANTHANUM CARBONATE (LANTHANUM CATION (3+))
|
LANTHANUM CATION (3+)
|
1000 mg
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
DEXTRATES
|
|
|
SILICON DIOXIDE
|
|
|
MAGNESIUM STEARATE
|
|
|
|
Product Characteristics
|
|
Color
|
WHITE (white)
|
Score
|
no score
|
|
Shape
|
ROUND (ROUND)
|
Size
|
22mm
|
|
Flavor
|
|
Imprint Code
|
S405;1000
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:54092-254-90
|
9 BOTTLE in 1 PACKAGE
|
|
|
1
|
NDC:54092-254-10
|
10 TABLET, CHEWABLE in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA021468
|
11/23/2005
|
|
|
|
Fosrenol lanthanum
carbonate powder
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:54092-256
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
LANTHANUM CARBONATE (LANTHANUM CATION (3+))
|
LANTHANUM CATION (3+)
|
750 mg
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
DEXTRATES
|
|
|
SILICON DIOXIDE
|
|
|
MAGNESIUM STEARATE
|
|
|
|
Product Characteristics
|
|
Color
|
WHITE
|
Score
|
|
|
Shape
|
|
Size
|
|
|
Flavor
|
|
Imprint Code
|
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:54092-256-02
|
9 CARTON in 1 PACKAGE
|
|
|
1
|
NDC:54092-256-01
|
10 POWDER in 1 CARTON
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA204734
|
09/24/2014
|
|
|
|
Fosrenol lanthanum
carbonate powder
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:54092-257
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
LANTHANUM CARBONATE (LANTHANUM CATION (3+))
|
LANTHANUM CATION (3+)
|
1000 mg
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
DEXTRATES
|
|
|
SILICON DIOXIDE
|
|
|
MAGNESIUM STEARATE
|
|
|
|
Product Characteristics
|
|
Color
|
WHITE
|
Score
|
|
|
Shape
|
|
Size
|
|
|
Flavor
|
|
Imprint Code
|
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:54092-257-02
|
9 CARTON in 1 CARTON
|
|
|
1
|
NDC:54092-257-01
|
10 POWDER in 1 CARTON
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA204734
|
09/24/2014
|
|
|
|
Labeler - Shire US Manufacturing Inc. (964907406)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Patheon Manufacturing Services LLC
|
|
079415560
|
ANALYSIS(54092-252, 54092-253, 54092-254),
LABEL(54092-252, 54092-253, 54092-254), MANUFACTURE(54092-252, 54092-253,
54092-254), PACK(54092-252, 54092-253, 54092-254)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Corden Pharma Bergamo, S.p.A.
|
|
438743601
|
ANALYSIS(54092-252, 54092-253, 54092-254, 54092-256,
54092-257), API MANUFACTURE(54092-252, 54092-253, 54092-254, 54092-256,
54092-257)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Exova Inc.
|
|
029170432
|
ANALYSIS(54092-252, 54092-253, 54092-254, 54092-256,
54092-257)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Reading Scientific Services Ltd (RSSL)
|
|
293610085
|
ANALYSIS(54092-252, 54092-253, 54092-254, 54092-256,
54092-257)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
SSCI Inc. (Aptuit)
|
|
020593403
|
ANALYSIS(54092-252, 54092-253, 54092-254, 54092-256,
54092-257)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Microbac Laboratories, Inc.
|
|
178463126
|
ANALYSIS(54092-252, 54092-253, 54092-254, 54092-256,
54092-257)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Catalent Germany Schorndorf GmbH
|
|
315732628
|
ANALYSIS(54092-256, 54092-257), LABEL(54092-256,
54092-257), MANUFACTURE(54092-256, 54092-257), PACK(54092-256, 54092-257)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
BCM Ltd
|
|
230780322
|
ANALYSIS(54092-256, 54092-257)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Reckitt Benckiser Healthcare International Ltd.
|
|
230780363
|
ANALYSIS(54092-252, 54092-253, 54092-254),
MANUFACTURE(54092-252, 54092-253, 54092-254)
|
Revised: 11/2017
Shire US
Manufacturing Inc.
