Israel - English - Ministry of Health
The format of this leaflet has been defined by the Ministry of Health and its content has been checked
and approved by it in 10.2012. The leaflet was updated according to the MoH guidelines in 10.2018.
Patient leaflet in accordance with the
Pharmacists’ Regulations (preparations), 1986
The dispensing of this medicine requires a
Read the entire leaflet carefully before you start taking this medicine.
FOSRENOL 500 MG, 750 MG, 1000 MG Chewable tablets
Each chewable tablet contains 500 mg; 750 mg;
1000 mg of the active ingredient Lanthanum (as lanthanum carbonate hydrate)
For Inactive ingredients, see section 6: “Additional information” in this leaflet.
Read this leaflet carefully and in its entirety before using this medicine.
This leaflet contains summarized information regarding the medicine. If you have additional questions
please refer to your physician or pharmacist.
This medicine has been prescribed for the treatment of your ailment. Do not pass it on to others. It may
harm them, even if it seems to you that their ailment is similar.
This medicine is not intended for patients below the age of 18 years
The safety and efficacy of
Fosrenol has not been established in children below the age of 18 years.
Attention: Do not swallow! It is imperative to chew the tablet completely.
It is important to take the medicine with or immediately after a meal.
Inform your physician if you are about to have an X-ray examination, since the use of Fosrenol may
affect the results.
1.What is this medicine intended for?
Fosrenol is indicated for reducing phosphate level in the blood, in chronic renal failure patients on
Fosrenol is also indicated in patients with chronic kidney disease not on dialysis with high serum
phosphate levels, in whom a low phosphate diet alone is insufficient to control serum phosphate levels.
Therapeutic activity: Fosrenol is bound in the intestine with dietary phosphorus. This binding prevents its
absorption by the body, and thus Fosrenol helps in lowering the phosphate level in the blood.
Therapeutic group: Drugs for treatment of hyperkalaemia and hyperphosphataemia.
2. Before using the medicine:
Do not use the medicine if:
if you are sensitive (allergic ) to the active ingredient lanthanum carbonate hydrate or to any of the
other ingredients of this medicine (listed in section 6).
if you suffer from hypophosphataemia (low levels of phosphates in the blood).
Special warnings regarding the use of the medicine:
Before using Fosrenol, tell your physician If you suffer or have suffered in the past from:
stomach or intestinal cancer
inflammatory bowel disease including ulcerative colitis or Crohn’s disease
abdominal surgery, or infection or inflammation of the abdomen/bowel (peritonitis)
stomach or intestinal ulcers
blockage of the intestine or slow motility (movement) in the intestine (e.g. constipation and
stomach complications due to diabetes)
reduced liver or kidney function
It is very important to chew completely Fosrenol tablets and not to swallow them whole or incompletely
chewed. This will reduce the risk of adverse gastrointestinal complications like rupture in the intestine
wall, blockage in the intestine, constipation (see section 4).
Test to perform before using this medicine
If you have reduced kidney function your doctor may decide to check the level of calcium in your blood
from time to time. If you have too little calcium, you may then be given extra calcium.
If you need to have an x-ray, please inform your doctor that you are taking Fosrenol as it may affect the
Other medicines and Fosrenol
If you are taking, or have taken recently, or might take any
other medicines including non-
prescription medicines and nutritional supplements, inform the physician or pharmacist.
Fosrenol can affect how certain drugs are absorbed from your digestive tract. If you are taking any of the
following medicines, you should take them at least two hours before or after taking Fosrenol:
chloroquine – for the treatment of rheumatism or malaria.
ketoconazole – for the treatment of fungal infections
antibiotics such as tetracycline or doxycycline
It is not recommended that you take oral floxacin antibiotics (including ciprofloxacin) within 2 hours
before or 4 hours after taking Fosrenol.
levothyroxine - for an under active thyroid – it should be taken 2 hours before or 2 hours after taking
Fosrenol. Your physician may want to monitor the levels of thyroid-stimulating hormone (TSH) in your
blood more closely.
Using the medicine and food:
Fosrenol should be taken with, or immediately after food. See Section 3 for instructions on how to take
Pregnancy and breast-feeding:
Fosrenol should not be taken during pregnancy. If you are pregnant or breast-feeding, think you may be
pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this
As it is not known whether the drug can be transferred to a child in breast-milk, you should not breast-
feed whilst taking Fosrenol. If you are breast-feeding, ask your doctor or pharmacist for advice before
taking any medicines.
Driving and using machines:
This medicine may sometimes lead to a feeling of vertigo or dizziness. If you experience these side
effects, be careful while driving or operating machinery.
3. How to use the medicine?
Always use according to the physician's instructions. Check with the physician or pharmacist if you are
You should take Fosrenol with, or immediately after food.
Side effects such as nausea and vomiting are more likely if you take Fosrenol before your meal.
The tablets must be chewed completely and not swallowed whole. To aid with chewing, the tablets may
be crushed. Additional fluid is not necessary.
The dosage and manner of treatment will be decided by the physician only.
Your physician will tell you how many tablets you must take with each meal (your daily dose will be
divided between meals). The number of tablets that you take will depend on the amount of phosphate in
the food you eat and your blood phosphate levels.
The usual acceptable dose is 3 tablets a day, divided between the different meals.
Fosrenol works by binding phosphate from the food in your gut. It is very important to take Fosrenol at
every meal. If you change your diet, contact your physician as you may need to take extra Fosrenol.
Your physician will tell you what to do in this case.
Do not exceed the recommended dose.
Tests and follow up
Every 2-3 weeks your doctor will check the level of phosphate in your blood and may increase your dose
until the level of phosphate in your blood is acceptable.
If you have accidently taken a higher dose
If you have taken a higher dose, consult your physician. Symptoms of overdose may include nausea
If you have taken an overdose, or if a child swallowed the medicine by mistake, refer immediately to the
physician or to a hospital emergency room and bring the package of the medicine with you.
If you forgot to take Fosrenol
It is important to take Fosrenol with every meal.
If you forgot to take this medicine at the proper time, take the next dose with your next meal.
Do not take a double dose to make up for a forgotten dose.
If you stop taking the medicine
Follow the treatment as recommended by the physician. Do not discontinue treatment with the medicine,
even if there is an improvement in your condition, without consulting the physician.
Do not take medications in the dark! Check the label and dose every time you take a medicine. Use
glasses if you need them for reading.
If you have further question about the use of this medicine, consult the physician or pharmacist.
4. Side Effects:
Like with any medicine, using Fosrenol can cause side effects in some of the users. Do not be alarmed
when reading the list of side effects. You may experience none of them.
Some side effects could be serious. If you get any of the following side effects, seek immediate
Rupture in the intestinal wall (signs include: severe stomach pain, chills, fever, nausea,
vomiting, or a tender abdomen). This is a rare side effect (may affect up to 1 in 1,000
Blockage in the intestine (signs include: severe bloating; abdominal pain, swelling or
cramps; severe constipation). This is an uncommon side effect (may affect up to 1 in 100
Contact your doctor if you have new or severe constipation, it could be an early sign of
blockage in your intestine. Constipation is a common side effect (may affect 1 in 10
Other less serious side effects include the following:
Very common side effects (may affect more than 1 in 10 people):
Nausea, vomiting, diarrhoea, abdomen pain, headache, itching, rash.
Common side effects (may affect up to 1 in 10 people):
Hypocalcaemia (too little calcium in your blood) is also a common side effect; the
symptoms of which can include tingling in the hands and feet, muscle and abdominal
cramps or spasms of the facial and feet muscles.
Uncommon side effects (may affect up to 1 in 100 people):
Tiredness; feeling of discomfort; chest pain, weakness; swelling of hands and feet; body pain; dizziness;
vertigo; belching; inflammation of the stomach and intestines (gastroenteritis); indigestion; irritable bowel
syndrome; dry mouth; tooth disorders; inflammation of the gullet or mouth; loose stools; increase in
certain liver enzymes, parathyroid hormone; increase in blood aluminium, calcium and glucose; increase
or decrease in blood phosphates; thirst; weight loss; joint pain; muscle pain; weakness and thinning of
the bones (osteoporosis); lack of and increased appetite; inflammation of the larynx; loss of hair;
sweating increased; taste disturbance and increase in white blood cells count.
If any side effect appears, If any side effect gets worse, or if you suffer from a side effect not
mentioned in the leaflet, you should consult the physician.
Side effects can be reported to the Ministry of Health by clicking on the link “Adverse Drug Reactions
Report” that appears on the home page of the Ministry of Health web site (www.health.gov.il), which
leads to an online form for reporting side effects.
Alternatively you can use the following link:
5. How to Store the Medicine?
Avoid poisoning! This medicine and all other medicines should be kept in a closed place out of the
sight and reach of children and/or infants to avoid poisoning.
Do not induce vomiting unless explicitly instructed to do so by the physician.
Do not use this medicine after the expiry date (exp. date) stated on the package. The expiry date
relates to the last day of that month.
Store at a temperature below 30°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
throw away medicines you no longer use. These measures will help protect the environment.
6. Additional information:
In addition to the active ingredient the medicine also contains:
Dextrates (hydrated), colloidal anhydrous silica, magnesium stearate.
Fosrenol contains Glucose If you have been told by your doctor that you have an intolerance to
some sugars, contact your doctor before taking this medicinal product.
What does the medicine look like and what are the contents of the package?
White, round, flat tablets debossed with ‘S405/500’, ‘S405/750' and 'S405/1000’ on one side, for
Fosrenol 500, 750 and 1000 respectively.
Carton packs containing bottles of the following quantities:
Fosrenol 500 – 45, 90 chewable tablets
Fosrenol 750 – 15, 90 chewable tablets
Fosrenol 1000 – 90 chewable tablets
It is possible that not all packs are marketed.
Takeda Israel Ltd.,25 Efal st.,
Petach Tikva 4951125
Manufacturer: Shire Pharmaceutical Contracts Ltd,
1 Kingdom Street, London, W2 6BD, UK
Registration number of the medicine in the National Drug Registry of the Ministry of Health:
Fosrenol 500 mg chewable tablets: 140 50 31968 00
Fosrenol 750 mg chewable tablets: 140 51 31998 00
Fosrenol 1000 mg chewable tablets: 140 52 31969 00
This leaflet was checked and approved by the Ministry of Health in October 2012, and was updated
according to the MoH guidelines in October 2018
The format of this leaflet was determined by the Ministry of Health and its content was checked and
approved by the Ministry of Health in 10.2012, and updated according to the MoH instructions in
SUMMARY OF THE PRODUCT CHARACTERISTICS
AME OF THE
Fosrenol 500 mg; 750 mg ; 1000 mg chewable tablets.
Each chewable tablet contains lanthanum carbonate hydrate corresponding to 500, 750, and 1000 mg
Excipient(s) with known effect
500, 750, and 1000
mg chewable tablets also contain on average
1066, 1599 and 2132
of dextrates, containing glucose.
For the full list of excipients, see section 6.1.
Fosrenol 500 mg chewable tablets:
White, round, 18mm, bevelled-edge flat tablets debossed
with ‘S405/500’ on one side.
Fosrenol 750 mg chewable tablets:
White, round, 20mm, bevelled-edge flat tablets debossed
with ‘S405/750’ on one side.
Fosrenol 1000 mg chewable tablets:
White, round, 22mm, bevelled-edge flat tablets debossed
with ‘S405/1000’ on one side.
Fosrenol is indicated as a phosphate binding agent for use in the control of hyperphosphataemia in
chronic renal failure patients on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
Fosrenol is also indicated in adult patients with chronic kidney disease not on dialysis with serum
1.78 mmol/L in whom a low phosphate diet alone is insufficient to control serum
Posology and method of administration
Fosrenol is for oral administration.
The tablets must be chewed completely and not swallowed whole. To aid with chewing the tablets
may be crushed.
Adults, including elderly (> 65 years)
Fosrenol should be taken with or immediately after food, with the daily dose divided between meals.
Patients should adhere to recommended diets in order to control phosphate and fluid intake. Fosrenol
is presented as a chewable tablet therefore avoiding the need to take additional fluid. Serum phosphate
levels should be monitored and the dose of Fosrenol titrated every 2-3 weeks until an acceptable serum
phosphate levels is reached, with regular monitoring thereafter.
Control of serum phosphate level has been demonstrated at doses starting from 750 mg per day. The
maximum dose studied in clinical trials, in a limited number of patients, is 3750 mg. Patients who
respond to lanthanum therapy, usually achieve acceptable serum phosphate levels at doses of 1500 –
3000 mg lanthanum per day.
Children and Adolescents
The safety and efficacy of Fosrenol has not been established in patients below the age of 18 years (see
The effect of hepatic impairment on Fosrenol pharmacokinetics has not been assessed. Due to its
mechanism of action and the lack of liver metabolism doses in hepatic impairment should not be
modified, but patients should be monitored carefully (see sections 4.4 and 5.2).
the active substance
or to any of the excipients
listed in section 6.1
Special warnings and precautions for use
Tissue deposition of lanthanum has been shown with Fosrenol in animal studies. In 105 bone
biopsies from patients treated with Fosrenol, some for up to 4.5 years, rising levels of lanthanum
were noted over time (see section 5.1
).Cases of lanthanum deposition in gastrointestinal
mucosa, mainly after long term use, have been reported. The clinical significance of this
finding is yet unknown.
The use of Fosrenol in clinical studies beyond 2 years is currently limited. However, treatment of
subjects with Fosrenol for up to 6 years has not demonstrated a change in the benefit/risk profile.
There have been cases of gastrointestinal obstruction, ileus, subileus, and gastrointestinal
perforation reported in association with lanthanum, some requiring surgery or
hospitalisation (see section 4.8).
Exercise caution in all patients predisposed to gastrointestinal obstruction, ileus, subileus
and perforation; for example those with altered gastrointestinal anatomy (e.g., diverticular
disease, peritonitis, history of gastrointestinal surgery, gastrointestinal cancer and
gastrointestinal ulceration), hypomotility disorders (e.g., constipation, diabetic
gastroparesis) and when used with medications known to potentiate these effects.
During treatment with lanthanum carbonate, physicians and patients should remain alert for
signs and symptoms of gastrointestinal disorders, especially constipation and abdominal
pain/distension which may indicate bowel obstruction, ileus or subileus.
Treatment with lanthanum carbonate should be re-evaluated in patients who develop severe
constipation or other severe gastrointestinal signs and symptoms.
Patients with acute peptic ulcer, ulcerative colitis, Crohn’s disease or bowel obstruction were not
included in clinical studies with Fosrenol.
Fosrenol tablets must be chewed completely and not swallowed whole
(see section 4.2)
Serious gastrointestinal complications have been reported in association with unchewed
or incompletely chewed Fosrenol tablets.
Patients with renal insufficiency may develop hypocalcaemia. Fosrenol does not contain calcium.
Serum calcium levels should therefore be monitored at regular time intervals for this patient
population and appropriate supplements given.
Lanthanum is not metabolised by liver enzymes but it is most likely excreted in the bile. Conditions
resulting in a marked reduction of bile flow may be associated with incrementally slower elimination
of lanthanum, which may result in higher plasma levels and increased tissue deposition of lanthanum
(see sections 5.2 and 5.3).
As the liver is the principle organ of elimination of absorbed lanthanum monitoring of liver function
tests is recommended.
Safety and efficacy of Fosrenol have not been established in children and adolescents; use in children
and adolescents is not recommended (see section 4.2).
Fosrenol should be discontinued if hypophosphataemia develops.
Abdominal x-rays of patients taking lanthanum carbonate may have a radio-opaque appearance typical
of an imaging agent.
Patients with rare glucose-galactose malabsorption should not take this medicine.
Interaction with other medicinal products and other forms of interaction
hydrate may increase gastric pH
It is recommended that compounds, which are
known to interact with antacids, should not be taken within 2 hours of dosing with Fosrenol
chloroquine, hydroxychloroquine and ketoconazole).
In healthy subjects, the absorption and pharmacokinetics of lanthanum were not affected by co-
administration of citrate.
Serum levels of fat-soluble vitamins A, D, E and K, were not affected by Fosrenol administration in
Human volunteer studies have shown that co-administration of Fosrenol with digoxin, warfarin or
metoprolol does not produce clinically-relevant changes in the pharmacokinetic profiles of these
In simulated gastric juice, lanthanum carbonate hydrate did not form insoluble complexes with
, phenytoin, metoprolol or enalapril, suggesting a low potential to affect
the absorption of these drugs.
However, interactions with drugs such as tetracycline, and doxycycline are
theoretically possible and if these compounds are to be co-administered, it is recommended
that they are not to be taken within 2 hours of dosing with Fosrenol.
The bioavailability of oral ciprofloxacin was decreased by approximately 50% when taken with
Fosrenol in a single dose study in healthy volunteers. It is recommended that oral floxacin
formulations are taken at least 2 hours before or 4 hours after Fosrenol.
Phosphate binders (including Fosrenol) have been shown to reduce the absorption of levothyroxine.
Consequently, thyroid hormone replacement therapy should not be taken within 2 hours of dosing with
Fosrenol and closer monitoring of TSH levels is recommended in patients receiving both medicinal
Lanthanum carbonate hydrate is not a substrate for cytochrome P450 and does not significantly inhibit
the activities of the major human cytochrome P450 isoenzymes, CYP1A2, CYP2D6, CYP3A4,
CYP2C9 or CYP2C19 in vitro.
pregnancy and lactation
There are no adequate data from the use of Fosrenol in pregnant women.
One study in rats showed reproductive foetotoxicity (delayed eye opening and sexual maturation) and
reduced pup weights at high doses (see section 5.3). The potential risk for humans is unknown.
Fosrenol is not recommended for use during pregnancy.
It is unknown whether lanthanum is excreted in human breast milk. The excretion of lanthanum in
milk has not been studied in animals. Caution should be used in taking a decision whether to
continue/discontinue breast feeding or to continue/discontinue therapy with Fosrenol, taking into
account the potential benefit of breast feeding to the child and the potential benefit of Fosrenol therapy
to the nursing mother.
There are no fertility data available on lanthanum carbonate in humans. In rat toxicology studies,
lanthanum carbonate had no adverse effects on fertility.
Effects on ability to drive and use machines
Fosrenol may induce dizziness and vertigo, which may impair the ability to drive and use machinery.
The most commonly reported adverse drug reactions, with the exception of headache and allergic skin
reactions, are gastrointestinal in nature; these are minimised by taking Fosrenol with food and generally
abated with time with continued dosing (see section 4.2).
The following convention was used for frequency of adverse drug reactions: Very common (≥1/10);
Common (≥1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥1/10,000 to < 1/1,000); Very rare
(< 1/10,000), not known (cannot be estimated from the available data).
Infections and Infestations
Blood and lymphatic system disorders
Metabolism and nutrition disorders
Hypercalcaemia, hyperglycaemia, hyperphosphataemia,
hypophosphataemia, anorexia, appetite increased
Nervous system disorders
Dizziness, taste alteration
Ear and Labyrinth disorders
Abdominal pain, diarrhoea, nausea, vomiting
Constipation, dyspepsia, flatulence
Ileus, ,Subileus, intestinal obstruction , irritable bowel
syndrome, oesophagitis, stomatitis, loose stools,
indigestion , gastrointestinal disorder ( Not otherwise
specified) , dry mouth, tooth disorder , eructation
Skin and subcutaneous tissue disorders
Alopecia, sweating increased
Musculoskeletal and connective tissue
Arthralgia, myalgia, osteoporosis
General disorders and administration site
Asthenia, chest pain, fatigue, malaise, peripheral
oedema, pain, thirst
Blood aluminium increased, increase in GGT, increases
in hepatic transaminases, alkaline phosphatase
increased, weight decrease.
Post marketing experience:
During post-approval use of Fosrenol, cases of allergic skin reactions
(including skin rashes, urticaria and pruritus) have been reported which show a close temporal
relationship to lanthanum carbonate therapy. In clinical trials, allergic skin reactions were seen in both
Fosrenol and placebo/active comparator groups at a frequency of very common (≥1/10)
Although there have been a number of additional isolated reactions reported, none of these reactions are
considered unexpected in this patient population.
Transient QT changes have been observed but these were not associated with an increase of cardiac
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows
continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events
should be reported to the Ministry of Health according to the National Regulation by using an online form
No case of overdose has been reported. The highest daily dose of lanthanum
administered to healthy
volunteers during Phase I studies was 4718 mg given for 3 days. The adverse events seen were mild to
moderate and included nausea and headache.
Pharmacotherapeutic group: Drugs for treatment of hyperkalaemia and hyperphosphataemia.
ATC code: V03A E03
Fosrenol contains lanthanum carbonate hydrate. The activity of lanthanum carbonate hydrate
as a phosphate binder is dependent on the high affinity of lanthanum ions, which are released
from the carbonate salt in the acid environment of the stomach, for dietary
Insoluble lanthanum phosphate is formed which reduces the absorption of phosphate from the
A total of 1130 patients with chronic renal failure treated with maintenance haemodialysis or
CAPD were studied in two phase II and two phase III studies. Three studies were placebo
controlled (1 fixed dose and 2 titrated dose designs) and one included calcium carbonate as an
active comparator. During these studies, 1016 patients received lanthanum carbonate, 267
received calcium carbonate and 176 received placebo.
Two placebo-controlled, randomised studies enrolled patients on dialysis after a washout from
previous phosphate binders. After titration of lanthanum carbonate to achieve a serum
phosphate level between 1.3 and 1.8 mmol/L in one study (doses up to 2250 mg/day), or ≤1.8
mmol/L in a second study (doses up to 3000mg/day), patients were randomised to lanthanum
carbonate or placebo as maintenance treatment. After the 4-week randomised placebo-
controlled phase, the serum phosphate concentration rose between 0.5 and 0.6 mmol/L in the
placebo group, in both studies, relative to patients who remained on lanthanum carbonate
therapy. There were 61% patients on lanthanum carbonate who maintained their response,
compared to 23% on placebo.
The active comparator study demonstrated that serum phosphate levels were reduced to target
levels of 1.8 mmol/l at the end of the 5 week titration period, in 51% of the lanthanum group
compared with 57% of the calcium carbonate group. At week 25 the percentage of
randomised patients showing controlled serum phosphate levels was similar in the two
treatment groups, 29% on lanthanum and 30% on calcium carbonate (using a missing=failure
approach). Mean serum phosphate levels were reduced by a similar amount in both treatment
Further long-term extension studies have demonstrated maintenance of phosphate reduction
for some patients following continued administration of at least 2 years of lanthanum
Hypercalcaemia was reported in 0.4% of patients with Fosrenol compared with 20.2% on
calcium-based binders in comparative studies. Serum PTH concentrations may fluctuate
depending on a patient’s serum calcium, phosphate and vitamin D status. Fosrenol has not
been shown to have any direct effects on serum PTH concentrations.
In the long-term bone studies a trend towards increasing bone lanthanum concentrations with
time in the control population was observed from the averaged data, the median rising 3-fold
from a baseline of 53
g/kg at 24 months. In patients treated with lanthanum carbonate, the
bone lanthanum concentration increased during the first 12 months of lanthanum carbonate
treatment up to a median of 1328
g/kg (range 122-5513
g/kg). Median and range
concentrations at 18 and 24 months were similar to 12 months. The median at 54 months was
g/kg (range 1673-9792
Paired bone biopsies (at baseline and at one or two years) in patients randomised to either
Fosrenol or calcium carbonate in one study and patients randomised to either Fosrenol or
alternative therapy in a second study, showed no differences in the development of
mineralization defects between the groups.
As binding between lanthanum and dietary phosphorus occurs in the lumen of the stomach
and upper small intestine, the therapeutic effectiveness of Fosrenol is not dependent on levels
of lanthanum in the plasma.
Lanthanum is present in the environment. Measurement of background levels in
non-lanthanum carbonate hydrate-treated chronic renal failure patients during Phase III
clinical trials revealed concentrations of <0.05 to 0.90 ng/mL in plasma, and <0.006 to 1.0
g/g in bone biopsy samples.
Lanthanum carbonate hydrate has low aqueous solubility (<0.01 mg/mL at pH 7.5) and is
minimally absorbed following oral administration. Absolute oral bioavailability is estimated
to be <0.002% in humans.
In healthy subjects, plasma AUC and C
increased as a function of dose, but in a less than
proportional manner, after single oral doses of 250 to 1000 mg lanthanum, consistent with
dissolution-limited absorption. The apparent plasma elimination half-life in healthy subjects
was 36 hours.
In renal dialysis patients dosed for 10 days with 1000 mg lanthanum 3 times daily, the mean
sd) peak plasma concentration was 1.06 (
1.04) ng/mL, and mean AUC
40.5) ng.h/mL. Regular blood level monitoring in 1707 renal dialysis patients taking
lanthanum carbonate hydrate for up to 2 years showed no increase in plasma lanthanum
concentrations over this time period.
Lanthanum does not accumulate in plasma in patients or in animals after repeated oral
administration of lanthanum carbonate hydrate. The small fraction of orally administered
lanthanum absorbed is extensively bound to plasma proteins (>99.7%) and in animal studies,
was widely distributed to systemic tissues, predominantly bone, liver and the gastrointestinal
tract, including the mesenteric lymph nodes. In long-term animal studies, lanthanum
concentrations in several tissues, including the gastrointestinal tract, bone and liver increased
over time to levels several orders of magnitude above those in plasma. An apparent steady-
state level of lanthanum was attained in some tissues, e.g. the liver whereas levels in
gastrointestinal tract increased with duration of treatment. Changes in tissue lanthanum levels
after withdrawal of treatment varied between tissues. A relatively high proportion of
lanthanum was retained in tissues for longer than 6 months after cessation of dosing (median
% retained in bone
100% (rat) and
87% (dog), and in the liver
6% (rat) and
82 % (dog).
No adverse effects were associated with the tissue deposition of lanthanum seen in long-term
animal studies with high oral doses of lanthanum carbonate (see 5.3) (See section 5.1 for
information regarding changes in lanthanum concentrations in bone biopsies taken from renal
dialysis patients after one year of treatment with lanthanum containing versus calcium
containing phosphate binders).
Lanthanum is not metabolised.
Studies in chronic renal failure patients with hepatic impairment have not been conducted. In
patients with co-existing hepatic disorders at the time of entry into Phase III clinical studies,
there was no evidence of increased plasma exposure to lanthanum or worsening hepatic
function after treatment with Fosrenol for periods up to 2 years.
Lanthanum is excreted mainly in the faeces with only around 0.000031% of an oral dose
excreted via the urine in healthy subjects (renal clearance approximately 1mL/min,
representing <2% of total plasma clearance).
After intravenous administration to animals, lanthanum is excreted mainly in the faeces (74%
of the dose), both via the bile and direct transfer across the gut wall. Renal excretion was a
Preclinical safety data
Preclinical data reveal no special hazards for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, fertility or genotoxicity.
Lanthanum carbonate hydrate reduced gastric acidity in the rat in a safety pharmacology
In rats administered high doses of lanthanum carbonate hydrate from day 6 of gestation to day
20 post partum there were no maternal effects, but reduced pup weight and delays in some
developmental markers (eye and vaginal opening) were seen. In rabbits given high daily doses
of lanthanum carbonate hydrate during gestation, maternal toxicity with reduced maternal
food intake and body weight gain, increased pre- and post-implantation losses and decreased
pup weight were seen.
Lanthanum carbonate hydrate was not carcinogenic in mice or rats. In mice, an increase in
gastric glandular adenomas was seen in the high-dose group (1500 mg/kg/day). The
neoplastic response in the mouse is considered to be related to an exacerbation of spontaneous
pathological stomach changes and to be of little clinical significance.
Studies in animals have shown deposition of lanthanum in tissues, mainly the gastrointestinal
tract, mesenteric lymph nodes, liver and bone (see section 5.2). However, life-time studies in
healthy animals do not indicate a hazard for man from the use of Fosrenol. Specific
immunotoxicity studies have not been performed.
List of excipients
Colloidal anhydrous silica
The expiry date of the product is indicated on the packaging materials
Special precautions for storage
Store below 30ºC
Nature and contents of container
White cylindrical HDPE bottles containing a rayon coil fitted with a tamper evident, child
resistant polypropylene screw cap.
Fosrenol 500 mg
: 45, 90 tablets
Fosrenol 750 mg
: 15, 90 tablets
Fosrenol 1000 mg
: 90 tablets
Not all pack sizes may be marketed.
Special precautions for disposal
No special requirements.
Shire Pharmaceutical Contracts Ltd, 1 Kingdom Street, London, W2 6BD, UK
Takeda Israel Ltd.,25 Efal st., Petach Tikva 4951125
Fosrenol 500 mg
: 140 50 31968 00
Fosrenol 750 mg
: 140 51 31998 00
Fosrenol 1000 mg
: 140 52 31969 00
,מ"עב לארשי תויטבצמרפ רייש לדגמ
Shire Pharmaceutical Israel Ltd, Electra Tower, Yigal Alon 98, Tel Aviv
FOSRENOL ( LANTHANUM CARBONATE ) 500 MG CHEWABLE TABLETS
FOSRENOL ( LANTHANUM CARBONATE ) 750 MG CHEWABLE TABLETS
FOSRENOL ( LANTHANUM CARBONATE ) 1000 MG CHEWABLE TABLETS
ןכרצלו אפורל םינולעב םינוכדע לע ךעידוהל תשקבמ ,םושירה תלעב ,מ"עב לארשי תויטבצמרפ רייש לונרסופ ירישכתל הסיעלל תוילבט
.דבלב םייתועמשמה םייונישהו תורמחהה םיטרופמ וז העדוהב
( םודאב ןמוסמ ףסוהש טסקט
( הצוח וק , טסקט קיחמ ןייצמ ) טסקט ת עקרב תנמוסמ הרמחה , ( בוהצ טסקט
:אפורל ןולעב םייוניש
Special warnings and precautions for use
No clinical data are available on deposition of lanthanum in other human
tissues.Cases of lanthanum deposition in gastrointestinal mucosa, mainly after
long term use, have been reported. The clinical significance of this finding is yet
There have been cases of gastrointestinal obstruction, ileus, subileus, and
requiring surgery or hospitalisation (see section 4.8).
Exercise caution in all patients predisposed to gastrointestinal obstruction, ileus,
subileus and perforation; for example those with altered gastrointestinal anatomy
gastrointestinal cancer and gastrointestinal ulceration), hypomotility disorders
(e.g., constipation, diabetic gastroparesis) and when used with medications
known to potentiate these effects.
During treatment with lanthanum carbonate, physicians and patients should
remain alert for signs and symptoms of gastrointestinal disorders, especially
obstruction, ileus or subileus.
,מ"עב לארשי תויטבצמרפ רייש לדגמ
Shire Pharmaceutical Israel Ltd, Electra Tower, Yigal Alon 98, Tel Aviv
Treatment with lanthanum carbonate should be re-evaluated in patients who
Patients with acute peptic ulcer, ulcerative colitis, Crohn’s disease or bowel
obstruction were not included in clinical studies with Fosrenol. Fosrenol should
be used in these patients following careful assessment of benefit and risk.
Fosrenol is known to cause constipation (see section 4.8) and therefore caution
should be exercised in patients predisposed to bowel obstruction (e.g. previous
abdominal surgery, peritonitis).
Fosrenol tablets must be chewed completely and not swallowed whole (see
association with unchewed or incompletely chewed Fosrenol tablets.
תועפות ופסוה :תואבה יאוולה
Uncommon: Ileus, subileus, intestinal obstruction
Rare : Intestinal perforation
:ןכרצל ןולעב םייוניש
"הפורתב שומיש ינפל .
שומישל תועגונה תודחוימ תורהזא הפורתב
:םא אפורל רפס ,לונרסופב לופיטה ינפל
:מ רבעב תלבס וא לבוס ךנה
יעמב וא הביקב ןטרס
הביק יביכ םייעמ וא
תיטיא תויתעונת וא
הביקב םיכוביסו תוריצע :אמגודל( תרכס תובקעב
לונרסופ תוילבט תא סועלל דואמ בושח
וסעלנש רחאל וא תומלש ןהשכ ןתוא עולבל אלו ןפוס דע ,יעמה ריק לש ערק ןוגכ לוכיעה תכרעמב םיקיזמ םיכוביסל ןוכיסה תא דירוי הז רבד .תיקלח הרוצב ףיעס האר( תוריצע ,יעמ תמיסח
תויתפורת ןיב תובוגת ,מ"עב לארשי תויטבצמרפ רייש לדגמ
Shire Pharmaceutical Israel Ltd, Electra Tower, Yigal Alon 98, Tel Aviv
)ןיצסקולפורפיצ ללוכ( ןיצסקולפה תחפשממ העילבל הקיטויביטנא
ינפל םייתעש ןיתמהל שי וא
.לונרסופ תליטנ ירחא תועש
,הקינמ וא ןוירהב ךנה םא .ןויריהה ךלהמב הפורתב שמתשהל ןיא תננכתמ וא ןוירהב ךנהש תבשוח .הפורתה תחיקל ינפל חקורב וא אפורב ץעוויהל ךיילע ןוירהל סנכיהל
תונפל ךיילע ,תועיפומ תואבה יאוולה תועפות םא .תורומח תויהל תולולע יאוולה תועפותמ קלח :תיאופר הרזע תלבקל תידימ
וא תואקה ,הליחב ,םוח ,תורומרמצ ,םירומח ןטב יבאכ :םיללוכ םינמיסה( יעמה ריקב ערק תוחיכשב עיפוהל הלולע( הרידנ יאוול תעפות וז .)ןטבה לש תושיגר לפוטמל דע לש
תוריצע ;תותיווע וא תוחפנתה ,ןטב יבאכ ;תורומח תוחיפנ :םיללוכ םינמיסה( םייעמ תמיסח לפוטמל דע לש תוחיכשב עיפוהל הלולע( החיכש הניא וז יאוול תעפות .)הרומח
יצעמ לבוס התאש וא ןכל םדוק תמייק התיה אל רשא תוריצע ךלצא העיפוה םא ,הרומח תור יעמה תמיסחל םדקומ ןמיס הניה תוריצעהו ןכתיו תויה אפורל תונפל ךיילע
הניה תוריצע לש תוחיכשב עיפוהל הלולע( החיכש יאוול תעפות
םילק םינוכדע םינולעב ושענ ףסונב
.הפוריאב םירשואמה םינולעה לע םיססובמ םינוכדעה בור
צלו אפורל םינולעה ןתינו ,תואירבה דרשמ רתאבש תופורתה רגאמב םוסרפל וחלשנ םינכדועמה ןכר ןולא לאגי ,מ"עב לארשי תויטבצמרפ רייש : תבותכב םושירה לעבל הינפ ידי לע םג םלבקל
לת , .ביבא
םינולס הקבר הנוממ תחקור