ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Renagel 400 mg film-coated tablets
2.
Each tablet contains 400 mg sevelamer hydrochloride.
For a full list of excipients, see section 6.1.
3.
Film-coated tablet (tablet)
The off-white, oval tablets are imprinted with “Renagel 400” on one side.
4.
Renagel is indicated for the control of hyperphosphataemia in adult patients receiving haemodialysis
or peritoneal dialysis. Renagel should be used within the context of a multiple therapeutic approach,
which could include calcium supplements, 1,25 – dihydroxy Vitamin D
3
or one of its analogues to
control the development of renal bone disease.
Posology
Starting dose
The recommended starting dose of Renagel is 2.4 g, 3.6 g or 4.8 g per day based on clinical needs and
serum phosphorus level. Renagel must be taken three times per day with meals.
Serum phosphate level in patients not on
phosphate binders
Starting dose of Renagel 400 mg
tablets
1.76 – 2.42 mmol/l (5.5-7.5 mg/dl)
2 tablets, 3 times per day
2.42- 2.91 mmol/l (7.5-9 mg/dl)
3 tablets, 3 times per day
> 2.91 mmol/l
4 tablets, 3 times per day
For patients previously on phosphate binders, Renagel should be given on a gram for gram basis with
monitoring of serum phosphorus levels to ensure optimal daily doses.
Titration and maintenance
Serum phosphate levels should be closely monitored and the dose of Renagel adjusted accordingly
with the goal of lowering serum phosphate to 1.76 mmol/l (5.5mg/dl)
or less. Serum phosphate should
be tested every two to three weeks until a stable serum phosphate level is reached and on a regular
basis thereafter.
The dose range may vary between 1 and 10 tablets per meal. The average actual daily dose used in the
chronic phase of a one year clinical study was 7 grams of sevelamer.
2
Paediatric population
The safety and efficacy of this product has not been established in patients below the age of 18 years.
Renagel is not recommended in children below the age of 18 years.
Renal impairment
The safety and efficacy of this product has not been established in predialysis patients. Renagel is not
recommended in these patients.
Method of administration
For oral use.
Patients should take Renagel with meals and adhere to their prescribed diets. The tablets must be
swallowed whole.
4.3 Contra-indications
•
Hypersensitivity to sevelamer or to any of the excipients..
•
Hypophosphataemia
•
Bowel obstruction.
Efficacy and safety of Renagel has not been studied in patients with :
•
swallowing disorders
•
active inflammatory bowel disease
•
gastrointestinal motility disorders including untreated or severe gastroparesis, diverticulosis
retention of gastric contents and abnormal or irregular bowel motion
•
patients with a history of major gastrointestinal surgery
Therefore caution should be exercised when Renagel is used in patients with these disorders.
Intestinal obstruction and ileus/subileus
In very rare cases, intestinal obstruction and ileus/subileus have been observed in patients during
treatment with Renagel. Constipation may be a preceding symptom. Patients who are constipated
should be monitored carefully while being treated with Renagel. Renagel treatment should be re-
evaluated in patients who develop severe constipation or other severe gastrointestinal symptoms.
Fat-soluble vitamins
Depending on diet intake and the nature of end stage renal failure, dialysis patients may develop low
vitamin A, D, E and K levels. It cannot be excluded that Renagel can bind fat-soluble vitamins
contained in ingested food. Therefore, in patients not taking these vitamins, monitoring vitamin A, D
and E levels and assessing vitamin K status through the measurement of thromboplastin time should
be considered and the vitamins should be supplemented if necessary. Additional monitoring of
vitamins and folic acid is recommended in patients receiving peritoneal dialysis, since in the clinical
study, vitamin A, D, E and K levels were not measured in these patients.
Folate deficiency
There is at present insufficient data to exclude the possibility of folate deficiency during long term
Renagel treatment.
Hypocalcaemia/hypercalcaemia
Patients with renal insufficiency may develop hypocalcaemia or hypercalcaemia. Renagel does not
contain calcium. Serum calcium levels should be monitored as is done in normal follow-up of a
dialysis patient. Elemental calcium should be given as a supplement in case of hypocalcaemia.
Metabolic acidosis
Patients with chronic renal failure are predisposed to developing metabolic acidosis. Worsening of
acidosis has been reported upon switching from other phosphate binders to sevelamer in a number of
3
studies where lower bicarbonate levels in the sevelamer-treated patients compared to patients treated
with calcium-based binders were observed. Closer monitoring of serum bicarbonate levels is therefore
recommended.
Peritonitis
Patients receiving dialysis are subject to certain risks for infection specific to the dialysis modality.
Peritonitis is a known complication in patients receiving peritoneal dialysis (PD) and in a clinical
study with Renagel, a number of peritonitis cases were reported. Therefore, patients on PD should be
closely monitored to ensure the reliable use of appropriate aseptic technique with the prompt
recognition and management of any signs and symptoms associated with peritonitis.
Anti-arrhythmic and anti-seizure medicinal products
Caution should be exercised when prescribing Renagel to patients also taking anti-arrhythmias and
anti-seizure medicinal products (see section 4.5).
Hypothyroidism
Closer monitoring of patients with hypothyroidism co-administered with sevelamer hydrochloride and
levothryroxine is recommended (see section 4.5).
Long term chronic treatment
As data on the chronic use of sevelamer for over one year are not yet available, potential absorption
and accumulation of sevelamer during long-term chronic treatment cannot be totally excluded (see
section 5.2 Pharmacokinetics).
Hyperparathyroidism
Renagel alone is not indicated for the control of hyperparathyroidism. In patients with secondary
hyperparathyroidism Renagel should be used within the context of a multiple therapeutic approach,
which could include calcium supplements, 1,25 - dihydroxy Vitamin D
3
or one of its analogues to
lower the intact parathyroid hormone (iPTH) levels.
Serum chloride
Serum chloride may increase during Renagel treatment as chloride may be exchanged for phosphorus
in the intestinal lumen. Although no clinically significant serum chloride increase has been observed
in the clinical studies, serum chloride should be monitored as is done in the routine follow-up of a
dialysis patient. One gram of Renagel contains approximately 180 mg (5.1mEq) chloride.
Interaction studies have not been conducted in patients on dialysis.
In interaction studies in healthy volunteers, Renagel decreased the bioavailability of ciprofloxacin by
approximately 50% when co-administered with Renagel in a single dose study. Consequently, Renagel
should not be taken simultaneously with ciprofloxacin.
Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications
for the control of seizure disorders were excluded from clinical trials. Caution should be exercised
when prescribing Renagel to patients also taking these medications.
During post marketing experience, very rare cases of increased TSH levels have been reported in
patients co-administered Renagel and levothyroxine. Closer monitoring of TSH levels is therefore
recommended in patients receiving both medications.
Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant
patients when coadministered with Renagel without any clinical consequences (i.e graft rejection). The
possibility of an interaction cannot be excluded and a close monitoring of blood concentrations of
4
mycophenolate mofetil, ciclosporin and tacrolimus should be considered during the use of
combination and after its withdrawal.
In interaction studies in healthy volunteers, Renagel had no effect on the bioavailability of digoxin,
warfarin, enalapril or metoprolol.
Renagel is not absorbed and may affect the bioavailbility of other medicinal products. When
administering any medicinal product where a reduction in the bioavailability could have a clinically
significant effect on safety or efficacy, the medicinal product should be administered at least one hour
before or three hours after Renagel, or the physician should consider monitoring blood levels.
Pregnancy:
The safety of Renagel has not been established in pregnant women. In animal studies there was no
evidence that sevelamer induced embryo-foetal toxicity. Renagel should only be given to pregnant
women if clearly needed and after a careful risk/benefit analysis has been conducted for both the
mother and the foetus (See 5.3 Preclinical safety data).
Lactation:
The safety of Renagel has not been established in lactating women. Renagel should only be given to
lactating women if clearly needed and after a careful risk/benefit analysis has been conducted for both
the mother and the infant (See 5.3 Preclinical safety data).
No studies on the effects on ability to drive and use machines have been performed.
In parallel design studies involving 244 haemodialysis patients with treatment duration of up to 54
weeks and 97 peritoneal dialysis patients with treatment duration of 12 weeks, the most frequently
occurring (≥ 5% of patients) adverse reactions possibly or probably related to Renagel were all in the
gastrointestinal disorders system organ class. Adverse reactions from these studies (299 patients) and
from uncontrolled clinical trials (384 patients) are listed by frequency in the table below. The reporting
rate is classified as very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100),
rare (≥1/10,000, <1/1,000), very rare (<1/10,000), not known (cannot be estimated form the available
data).
Gastrointestinal disorders
Very common
(≥1/10)
:
Nausea, vomiting
Common
(≥1/100 to <1/10)
:
Diarrhoea
,
dyspepsia, flatulence, upper abdominal pain,
constipation
Post-marketing experience
: During post-approval use of Renagel, cases of pruritus, rash, abdominal
pain, intestinal obstruction, ileus/subileus, diverticulitis and intestinal perforation have been reported.
No case of overdose has been reported.
Renagel has been given to normal healthy volunteers in doses up to 14 grams, the equivalent of thirty-
five 400 mg tablets, per day for eight days with no undesirable effects.
5
5
5.1 Pharmacodynamic properties
Treatment of hyperphosphatemia. ATC code: V03AE02.
Renagel contains sevelamer, a non-absorbed phosphate binding poly(allylamine hydrochloride)
polymer, free of metal and calcium. It contains multiple amines separated by one carbon from the
polymer backbone. These amines become partially protonated in the intestine and interact with
phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the
gastrointestinal tract, sevelamer lowers the phosphate concentration in the serum.
In clinical trials, selevamer has been shown to be effective in reducing serum phosphorus in patients
receiving haemodialysis or peritoneal dialysis.
Sevelamer decreases the incidence of hypercalcaemic episodes as compared to patients using calcium
based phosphate binders alone, probably because the product itself does not contain calcium. The
effects on phosphate and calcium were proven to be maintained throughout a study with one year
follow-up.
Sevelamer has been shown to bind bile acids
in vitro
and
in vivo
in experimental animal models. Bile
acid binding by ion exchange resins is a well-established method of lowering blood cholesterol. In
clinical trials mean total and LDL cholesterol declined by 15-31%. This effect is observed after 2
weeks is maintained with long-term treatment. Triglycerides, HDL cholesterol and albumin did not
change.
In the clinical studies in haemodialysis patients, sevelamer alone did not have a consistent and
clinically significant effect on serum intact parathyroid hormone (iPTH). In the 12 week study
involving peritoneal dialysis patients however, similar iPTH reductions were seen compared with
patients receiving calcium acetate. In patients with secondary hyperparathyroidism Renagel should be
used within the context of a multiple therapeutic approach, which could include calcium supplements,
1,25 – dihydroxy Vitamin D
3
or one of its analogues to lower the intact parathyroid hormone (iPTH)
levels.
In a clinical trial of one-year duration, Renagel had no adverse effect on bone turnover or
mineralisation compared to calcium carbonate.
5.2 Pharmacokinetic properties
Renagel is not absorbed from the gastrointestinal tract according to a single dose pharmacokinetic
study in healthy volunteers. Pharmacokinetic studies have not been carried out in renal failure patients
(see section 4.4 Special warnings and special precautions for use).
5.3 Preclinical safety data
In preclinical studies in rats and dogs, Renagel at a dose of 10 times the maximum human doses
reduced absorption of fat soluble vitamins D, E and K, and folic acid.
In a study in rats, administering sevelamer in 15-30 x the human dose, an increase in serum copper
was detected. This was not confirmed in a dog study or in clinical trials.
Currently, no formal carcinogenicity data are available. However, in vitro and in vivo studies have
indicated that Renagel does not have genotoxic potential. Also the medicinal product is not absorbed
in the gastrointestinal tract.
In reproduction studies there was no evidence that sevelamer induced embryolethality, foetotoxicity or
teratogenicity at the doses tested (up to 1 g/kg/day in rabbits and up to 4.5 g/kg/day in rats). Deficits in
6
skeletal ossification were observed in several locations in fetuses of female rats dosed with sevelamer
at 8-20 times the maximum human dose of 200 mg/kg. The effects may be secondary to vitamin D
and/or vitamin K depletion at these high doses.
6.
6.1 List of excipients
Tablet core
:
Silica, colloidal anhydrous
Stearic acid
Film-coating
:
Hypromellose
Diacetylated monoglycerides
Printing ink
:
Iron oxide black (E172)
Propylene glycol
Hypromellose
6.2 Incompatibilities
Not applicable
6.3 Shelf-life
2 years.
6.4 Special precautions for storage
Do not store above 25ºC.
Keep the bottle tightly closed in order to protect from moisture.
6.5 Nature and contents of container
HDPE bottles, with a child resistant polypropylene cap and a foil induction seal.
Package sizes are:
1 bottle of 360 tablets
2 bottles of 360 tablets
3 bottles of 360 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Genzyme Europe B.V., Gooimeer 10, 1411 DD Naarden, The Netherlands
7
8.
EU/1/99/123/005
EU/1/99/123/006
EU/1/99/123/007
9.
Date of first authorisation: 28/01/2000
Renewal date: 02/02/2010
{MM/YYYY}
Detailed information on this medicinal product is available on the website of the European Medicines
Agency
HTTP://WWW.EMA.EUROPA.EU/
.
8
1.
Renagel 800 mg film-coated tablets
2.
Each tablet contains 800 mg sevelamer hydrochloride.
For a full list of
excipients, see section 6.1.
3.
Film-coated tablet (tablet)
The off-white, oval tablets are imprinted with “Renagel 800” on one side.
4.
Renagel is indicated for the control of hyperphosphataemia in adult patients receiving haemodialysis
or peritoneal dialysis. Renagel should be used within the context of a multiple therapeutic approach,
which could include calcium supplements, 1,25 – dihydroxy Vitamin D
3
or one of its analogues to
control the development of renal bone disease.
Posology
Starting dose
The recommended starting dose of Renagel is 2.4 g or 4.8 g per day based on clinical needs and serum
phosphorus level. Renagel must be taken three times per day with meals.
Serum phosphate level in patients not on
phosphate binders
Starting dose of Renagel 800
mg tablets
1.76 – 2.42 mmol/l (5.5-7.5 mg/dl)
1 tablet, 3 times per day
> 2.42 mmol/l (>7.5 mg/dl)
2 tablets, 3 times per day
For patients previously on phosphate binders, Renagel should be given on a gram for gram basis with
monitoring of serum phosphorus levels to ensure optimal daily doses.
Titration and maintenance
Serum phosphate levels should be closely monitored and the dose of Renagel adjusted accordingly
with the goal of lowering serum phosphate to 1.76 mmol/l (5.5 mg/dl)
or less. Serum phosphate should
be tested every two to three weeks until a stable serum phosphate level is reached and on a regular
basis thereafter.
The dose range may vary between 1 and 5 tablets of 800 mg per meal. The average actual daily dose
used in the chronic phase of a one year clinical study was 7 grams of sevelamer.
Paediatric population
The safety and efficacy of this product has not been established in patients below the age of 18 years.
Renagel is not recommended in children below the age of 18 years.
9
Renal impairment
The safety and efficacy of this product has not been established in predialysis patients. Renagel is not
recommended in these patients.
Method of administration
For oral use
Patients should take Renagel with meals and adhere to their prescribed diets. The tablets must be
swallowed whole. Do not chew.
4.3 Contra-indications
•
Hypersensitivity to sevelamer or to any of the excipients..
•
Hypophosphataemia
•
Bowel obstruction.
Efficacy and safety of Renagel has not been studied in patients with:
•
swallowing disorders
•
active inflammatory bowel disease
•
gastrointestinal motility disorders including untreated or severe gastroparesis, diverticulosis,
retention of gastric contents and abnormal or irregular bowel motion
•
patients with a history of major gastrointestinal surgery
Therefore caution should be exercised when Renagel is used in patients with these disorders.
Intestinal obstruction and ileus/subileus
In very rare cases, intestinal obstruction and ileus/subileus have been observed in patients during
treatment with Renagel. Constipation may be a preceding symptom. Patients who are constipated
should be monitored carefully while being treated with Renagel. Renagel treatment should be re-
evaluated in patients who develop severe constipation or other severe gastrointestinal symptoms.
Fat-soluble vitamins
Depending on diet intake and the nature of end stage renal failure, dialysis patients may develop low
vitamin A, D, E and K levels. It cannot be excluded that Renagel can bind fat-soluble vitamins
contained in ingested food. Therefore, in patients not taking these vitamins, monitoring vitamin A, D
and E levels and assessing vitamin K status through the measurement of thromboplastin time should
be considered and the vitamins should be supplemented if necessary. Additional monitoring of
vitamins and folic acid is recommended in patients receiving peritoneal dialysis, since in the clinical
study, vitamin A, D, E and K levels were not measured in these patients.
Folate deficiency
There is at present insufficient data to exclude the possibility of folate deficiency during long term
Renagel treatment.
Hypocalcaemia/hypercalcaemia
Patients with renal insufficiency may develop hypocalcaemia or hypercalcaemia. Renagel does not
contain calcium. Serum calcium levels should be monitored as is done in normal follow-up of a
dialysis patient. Elemental calcium should be given as a supplement in case of hypocalcaemia.
Metabolic acidosis
Patients with chronic renal failure are predisposed to developing metabolic acidosis. Worsening of
acidosis has been reported upon switching from other phosphate binders to sevelamer in a number of
studies where lower bicarbonate levels in the sevelamer-treated patients compared to patients treated
with calcium-based binders were observed. Closer monitoring of serum bicarbonate levels is therefore
recommended.
10
Peritonitis
Patients receiving dialysis are subject to certain risks for infection specific to the dialysis modality.
Peritonitis is a known complication in patients receiving peritoneal dialysis (PD) and in a clinical
study with Renagel, a number of peritonitis cases were reported. Therefore, patients on PD should be
closely monitored to ensure the reliable use of appropriate aseptic technique with the prompt
recognition and management of any signs and symptoms associated with peritonitis.
Anti-arrhythmic and anti-seizure medicinal products
Caution should be exercised when prescribing Renagel to patients also taking anti-arrhythmias and
anti-seizure medicinal products (see section 4.5).
Hypothyroidism
Closer monitoring of patients with hypothyroidism co-administered with sevelamer hydrochloride and
levothryroxine is recommended (see section 4.5).
Long term chronic treatment
As data on the chronic use of sevelamer for over one year are not yet available, potential absorption
and accumulation of sevelamer during long-term chronic treatment cannot be totally excluded (see
section 5.2 Pharmacokinetics).
Hyperparathyroidism
Renagel alone is not indicated for the control of hyperparathyroidism. In patients with secondary
hyperparathyroidism Renagel should be used within the context of a multiple therapeutic approach,
which could include calcium supplements, 1,25 - dihydroxy Vitamin D
3
or one of its analogues to
lower the intact parathyroid hormone (iPTH) levels.
Serum chloride
Serum chloride may increase during Renagel treatment as chloride may be exchanged for phosphorus
in the intestinal lumen. Although no clinically significant serum chloride increase has been observed
in the clinical studies, serum chloride should be monitored as is done in the routine follow-up of a
dialysis patient. One gram of Renagel contains approximately 180 mg (5.1mEq) chloride.
Interaction studies have not been conducted in patients on dialysis.
In interaction studies in healthy volunteers, Renagel decreased the bioavailability of ciprofloxacin by
approximately 50% when co-administered with Renagel in a single dose study. Consequently, Renagel
should not be taken simultaneously with ciprofloxacin.
Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications
for the control of seizure disorders were excluded from clinical trials. Caution should be exercised
when prescribing Renagel to patients also taking these medications.
During post marketing experience, very rare cases of increased TSH levels have been reported in
patients co-administered Renagel and levothyroxine. Closer monitoring of TSH levels is therefore
recommended in patients receiving both medications.
Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant
patients when coadministered with Renagel without any clinical consequences (i.e graft rejection). The
possibility of an interaction cannot be excluded and a close monitoring of blood concentrations of
mycophenolate mofetil, ciclosporin and tacrolimus should be considered during the use of
combination and after its withdrawal.
11
In interaction studies in healthy volunteers, Renagel had no effect on the bioavailability of digoxin,
warfarin, enalapril or metoprolol.
Renagel is not absorbed and may affect the bioavailability of other medicinal products. When
administering any medicinal product where a reduction in the bioavailability could have a clinically
significant effect on safety or efficacy, the medicinal product should be administered at least one hour
before or three hours after Renagel, or the physician should consider monitoring blood levels.
Pregnancy:
The safety of Renagel has not been established in pregnant women. In animal studies there was no
evidence that sevelamer induced embryo-foetal toxicity. Renagel should only be given to pregnant
women if clearly needed and after a careful risk/benefit analysis has been conducted for both the
mother and the foetus (See 5.3 Preclinical safety data).
Lactation:
The safety of Renagel has not been established in lactating women. Renagel should only be given to
lactating women if clearly needed and after a careful risk/benefit analysis has been conducted for both
the mother and the infant (See 5.3 Preclinical safety data).
No studies on the effects on ability to drive and use machines have been performed.
In parallel design studies involving 244 haemodialysis patients with treatment duration of up to 54
weeks and 97 peritoneal dialysis patients with treatment duration of 12 weeks, the most frequently
occurring (≥ 5% of patients) adverse reactions possibly or probably related to Renagel were all in the
gastrointestinal disorders system organ class. Adverse reactions from these studies (299 patients) and
from uncontrolled clinical trials (384 patients) are listed by frequency in the table below. The reporting
rate is classified as very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100),
rare (≥1/10,000, <1/1,000), very rare (<1/10,000), not known (cannot be estimated form the available
data).
Gastrointestinal disorders
Very common (≥1/10) : Nausea, vomiting
Common (≥1/100 to <1/10): Diarrhoea, dyspepsia, flatulence, upper abdominal pain,
constipation
Post-marketing experience
: During post-approval use of Renagel, cases of pruritus, rash, abdominal
pain, intestinal obstruction, ileus/subileus, diverticulitis and intestinal perforation have been reported.
No case of overdose has been reported.
Renagel has been given to normal healthy volunteers in doses up to 14 grams, the equivalent of
seventeen 800 mg tablets, per day for eight days with no undesirable effects.
5
5.1 Pharmacodynamic properties
12
Treatment of hyperphosphatemia. ATC code: V03AE02.
Renagel contains sevelamer, a non-absorbed phosphate binding poly(allylamine hydrochloride)
polymer, free of metal and calcium. It contains multiple amines separated by one carbon from the
polymer backbone. These amines become partially protonated in the intestine and interact with
phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the
gastrointestinal tract, sevelamer lowers the phosphate concentration in the serum.
In clinical trials, selevamer has been shown to be effective in reducing serum phosphorus in patients
receiving haemodialysis or peritoneal dialysis.
Sevelamer decreases the incidence of hypercalcaemic episodes as compared to patients using calcium
based phosphate binders alone, probably because the product itself does not contain calcium. The
effects on phosphate and calcium were proven to be maintained throughout a study with one year
follow-up.
Sevelamer has been shown to bind bile acids
in vitro
and
in vivo
in experimental animal models. Bile
acid binding by ion exchange resins is a well-established method of lowering blood cholesterol. In
clinical trials mean total and LDL cholesterol declined by 15-31%. This effect is observed after 2
weeks is maintained with long-term treatment. Triglycerides, HDL cholesterol and albumin did not
change.
In the clinical studies in haemodialysis patients, sevelamer alone did not have a consistent and
clinically significant effect on serum intact parathyroid hormone (iPTH). In the 12 week study
involving peritoneal dialysis patients however, similar iPTH reductions were seen compared with
patients receiving calcium acetate. In patients with secondary hyperparathyroidism Renagel should be
used within the context of a multiple therapeutic approach, which could include calcium supplements,
1,25 – dihydroxy Vitamin D
3
or one of its analogues to lower the intact parathyroid hormone (iPTH)
levels.
In a clinical trial of one-year duration, Renagel had no adverse effect on bone turnover or
mineralisation compared to calcium carbonate.
5.2 Pharmacokinetic properties
Renagel is not absorbed from the gastrointestinal tract according to a single dose pharmacokinetic
study in healthy volunteers. Pharmacokinetic studies have not been carried out in renal failure patients
(see section 4.4 Special warnings and special precautions for use).
5.3 Preclinical safety data
In preclinical studies in rats and dogs, Renagel at a dose of 10 times the maximum human doses
reduced absorption of fat soluble vitamins D, E and K, and folic acid.
In a study in rats, administering sevelamer in 15-30 x the human dose, an increase in serum copper
was detected. This was not confirmed in a dog study or in clinical trials.
Currently, no formal carcinogenicity data are available. However, in vitro and in vivo studies have
indicated that Renagel does not have genotoxic potential. Also the medicinal product is not absorbed
in the gastrointestinal tract.
In reproduction studies there was no evidence that sevelamer induced embryolethality, foetotoxicity or
teratogenicity at the doses tested (up to 1 g/kg/day in rabbits and up to 4.5 g/kg/day in rats). Deficits in
skeletal ossification were observed in several locations in fetuses of female rats dosed with sevelamer
at 8-20 times the maximum human dose of 200 mg/kg. The effects may be secondary to vitamin D
and/or vitamin K depletion at these high doses.
13
6.
6.1 List of excipients
Tablet core
:
Silica, colloidal anhydrous
Stearic acid
Film-coating
:
Hypromellose
Diacetylated monoglycerides
Printing ink
:
Iron oxide black (E172)
Propylene glycol
Hypromellose
6.2 Incompatibilities
Not applicable
6.3 Shelf-life
3 years
6.4 Special precautions for storage
Do not store above25ºC.
Keep the bottle tightly closed in order to protect from moisture.
6.5 Nature and contents of container
HDPE bottles, with a child resistant polypropylene cap and a foil induction seal.
Package sizes are:
6 bottles of 30 tablets
1bottle of 100 tablets
1 bottle of 180 tablets
2 bottles of 180 tablets
3 bottles of 180 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Genzyme Europe B.V., Gooimeer 10, 1411 DD Naarden, The Netherlands
8.
14
EU/1/99/123/008
EU/1/99/123/009
EU/1/99/123/010
EU/1/99/123/011
EU/1/99/123/012
EU/1/99/123/013
9.
Date of first authorisation: 28/01/2000
Renewal date: 02/02/2010
{MM/YYYY}
Detailed information on this medicinal product is available on the website of the European Medicines
Agency
http://www.ema.europa.eu/
.
15
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
16
A
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR
BATCH RELEASE
Name and address of the manufacturer responsible for batch release
Genzyme Limited, 37 Hollands Road, Haverhill, Suffolk CB9 8PU, United Kingdom
Genzyme Ireland Ltd., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland
The printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
B
CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
The MAH commits to performing a registry study and additional pharmacovigilance activities detailed
in the Pharmacovigilance Plan.
An updated Risk Management Plan should be provided as per the CHMP Guideline on Risk
Management Systems .for medicinal products for Human Use.
The MAH will submit 6-montly PSURs unless otherwise specified by the CHMP
17
ANNEX III
LABELLING AND PACKAGE LEAFLET
18
A. LABELLING
19
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON – 1 BOTTLE OF 360 TABLETS 400 mg
1.
Renagel 400 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 400 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
360 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
20
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/005
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
400 mg
21
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON - 2 BOTTLES OF 360 TABLETS 400 mg
1.
Renagel 400 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 400 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
2 bottles of 360 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
22
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/006
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
400 mg
23
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON - 3 BOTTLES OF 360 TABLETS 400 mg
1.
Renagel 400 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 400 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
3 bottles of 360 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
24
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/007
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
400 mg
25
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
LABEL - 1 BOTTLE OF 360 TABLETS 400 mg
1.
Renagel 400 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 400 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
360 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
26
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/005
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
400 mg
27
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON - 6 BOTTLES OF 30 TABLETS 800 mg
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
6 bottles of 30 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
28
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/013
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
29
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON – 1 BOTTLE OF 100 TABLETS 800 mg
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
100 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
30
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/011
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
31
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON – 1 BOTTLE OF 180 TABLETS 800 mg
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
180 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use. Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
32
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/008
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
33
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON - 2 BOTTLES OF 180 TABLETS 800 mg
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
2 bottles of 180 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
34
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/009
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
35
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON - 3 BOTTLES OF 180 TABLETS 800 mg
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
3 bottles of 180 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
36
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/010
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
37
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
LABEL - 1 BOTTLE OF 30 TABLETS 800 mg
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
30 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
38
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/013
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
39
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
LABEL – 1 BOTTLE OF 100 TABLETS 800 mg
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
100 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
40
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/011
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
41
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
LABEL - 1 BOTTLE OF 180 TABLETS 800 mg WITH OUTER CARTON
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
180 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
42
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/008
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
43
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
LABEL – 1 BOTTLE OF 180 TABLETS 800 mg WITHOUT OUTER CARTON
1.
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 800 mg of the sevelamer hydrochloride.
3.
LIST OF EXCIPIENTS
4.
180 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For oral use.
Tablets must be swallowed whole. Do not chew.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the bottle tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
44
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
EU/1/99/123/012
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Renagel
800 mg
45
B. PACKAGE LEAFLET
46
PACKAGE LEAFLET: INFORMATION FOR THE USER
Renagel 400 mg film-coated tablets
sevelamer hydrochloride
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have further questions, ask your doctor or your pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if
their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
1. What Renagel is and what it is used for.
2. Before you take Renagel.
3. How to take Renagel.
4. Possible side effects.
5. How to store Renagel.
6. Further information.
1.
WHAT RENAGEL IS AND WHAT IT IS USED FOR
Renagel contains sevelamer as the active ingredient. It binds phosphate from food in the digestive tract
and so reduces serum phosphate levels in the blood.
Adult patients whose kidneys have failed and who are receiving haemodialysis or peritoneal dialysis
are not able to control the level of serum phosphate in their blood. The amount of phosphate then rises
(your doctor will call this hyperphosphataemia). Increased levels of serum phosphorus can lead to hard
deposits in your body called calcification. These deposits can stiffen your blood vessels and make it
harder for blood to be pumped around the body. Increased serum phosphorus can also lead to itchy
skin, red eyes, bone pain and fractures.
Renagel is used to control the levels of phosphate in the blood of adult kidney failure patients on
haemodialysis or peritoneal dialysis treatment.
It may be necessary to use other medicines with Renagel, which could include calcium or vitamin D
supplements, to control the development of renal bone disease.
2.
BEFORE YOU TAKE RENAGEL
Do not take Renagel if:
•
you have low levels of phosphate in your blood
•
you have bowel obstruction.
•
you are allergic (hypersensitive) to sevelamer or to any of the other ingredients of the product
(see Section 6: Further information)
.
47
Take special care with Renagel
If any of the following applies to you, please consult your doctor before taking Renagel
:
•
you are not on dialysis
•
swallowing problems
•
problems with motility (movement) in your stomach and bowel
•
retention of stomach contents
•
active inflammation of the bowel
•
have undergone major surgery on your stomach or bowel.
The safety and efficacy in children (below the age of 18 years) has not been established. Therefore
Renagel is not recommended for use in this population.
Additional treatments
:
Due to either your kidney condition or your dialysis treatment you may:
•
develop a low or high level of calcium in your blood. Since Renagel does not contain calcium
your doctor might prescribe additional calcium tablets.
•
have a low amount of vitamin D in your blood. Therefore, your doctor may monitor the levels
of vitamin D in your blood and prescribe additional vitamin D as necessary. If you do not take
multivitamin supplements you may also develop low levels of vitamins A, E, K and folic acid
in your blood and therefore your doctor may monitor these levels and prescribe supplemental
vitamins as necessary.
Changing treatment
:
When you switch from another phosphate binder to Renagel, your doctor might consider monitoring
the levels of bicarbonate in your blood more closely because Renagel may decrease the levels of
bicarbonate.
Special note for patients on peritoneal dialysis
You may develop peritonitis (infection of your abdominal fluid) associated with your peritoneal
dialysis. This risk can be reduced by careful adherence to sterile techniques during bag changes. You
should tell your doctor immediately if you experience any new signs or symptoms of abdominal
distress,
abdominal swelling, abdominal pain, abdominal tenderness, or abdominal rigidity,
constipation, fever, chills, nausea or vomiting.
You should expect to be monitored more carefully for problems with low levels of vitamins A, D, E, K
and folic acid.
Taking other medicines
Please tell your doctor all if you are taking or have recently taken other medicines, including
medicines obtained without a prescription.
Renagel should not be taken at the same time as ciprofloxacin (an antibiotic).
If you are taking medicines for heart rhythm problems or for epilepsy, you should consult your doctor
when taking Renagel.
The effects of medicines such as ciclosporin, mycophenolate mofetil and tacrolimus (medicines used
in transplant patients) may be reduced by Renagel. Your doctor will advise you if you are taking these
medicines.
Increased levels of thyroid stimulating hormone (TSH, a substance in your blood which stimulates the
thyroid gland to make thyroid hormone which helps control your body’s metabolism) may very rarely
be observed in certain people taking levothyroxine (a thyroid hormone) and Renagel. Therefore your
doctor may monitor the levels of TSH in your blood more closely.
Your doctor will check for interactions between Renagel and other medicines on a regular basis.
48
Taking Renagel with food and drink
You should take Renagel tablets with meals. However, you should adhere to your prescribed diet and
liquid intake.
Do not chew. The tablets must be swallowed whole.
Pregnancy and breast-feeding
The safety of Renagel has not been established in pregnant or lactating women. Renagel should only
be given to pregnant or lactating women if clearly needed.
Driving and using machines
No studies on the effects on the ability to drive and use machines has been performed. If you are
affected, do not drive and do not use any tools or machines.
3.
HOW TO TAKE RENAGEL
You should take Renagel as prescribed by your doctor. He/she will base the dose on your serum
phosphate level. The recommended starting dose of Renagel for adults and the elderly (> 65 years) is
two to four tablets with each meal 3 times a day.
Your doctor will check the levels of phosphate in your blood periodically and he/she may adjust the
dose of Renagel when necessary (between 1 and 10 tablets of 400 mg per meal) to reach an adequate
phosphate level.
In some cases where Renagel should be administered at the same time as another medicine. Your
doctor may advise you to take this medicine 1 hour before or 3 hours after Renagel intake, or he/she
may consider monitoring the blood levels of that medicine.
If you take more Renagel than you should
There are no reported overdoses in patients.
In the event of a possible overdose you should contact your doctor immediately.
If you forget to take Renagel
If you have missed one dose, this dose should be omitted and the next dose should be taken at the
usual time with a meal. Do not take a double dose to make up for a forgotten dose
.
4
.
POSSIBLE SIDE EFFECTS
Like all medicines, Renagel
can cause side effects, although not everybody gets them.
The following side effects have been reported in patients taking Renagel:
Very common
(affects more than 1 user in 10): nausea, vomiting.
Common
(affects 1 to 10 users in 100): diarrhoea, indigestion, abdominal pain, constipation, flatulence
In clinical use of Renagel, cases of itching, rash, abdominal pain, slow intestine motility (movement),
blockages in the intestine, inflammation of abnormal small pouches (called diverticula) in the large
intestine and perforation in the intestine wall have been reported.
Since constipation may be a preceding symptom in very rare cases of blockages in your intestine,
please inform your doctor or pharmacist.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
49
5.
HOW TO STORE RENAGEL
Keep out of the reach and sight of children.
Do not store above 25 °C. Keep the bottle tightly closed in order to protect from moisture.
Do not use Renagel after the expiry date stated on the carton and/or bottle after the letters “EXP”.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Renagel contains
- The active substance is sevelamer.
- The other ingredients are silica colloidal anhydrous and stearic acid. The tablet coating contains
hypromellose and diacetylated monoglycerides. The printing ink contains iron oxide black (E172),
hypromellose and propylene glycol.
What Renagel looks like and contents of the pack
Renagel tablets are film coated, off white, oval tablets with Renagel 400 imprinted on one side.
The tablets are packed in high density polyethylene bottles with a child resistant polypropylene cap
and an induction seal.
Pack sizes are:
1 bottle of 360 tablets
2 bottles of 360 tablets
3 bottles of 360 tablets
Marketing Authorisation Holder and Manufacturer
Marketing authorisation holder:
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
Manufacturing authorisation holders responsible for batch release:
Genzyme Ltd
37 Hollands Road
Haverhill, Suffolk
CB9 8PU
United Kingdom
Genzyme Ireland Ltd.
IDA Industrial Park
Old Kilmeaden Road
Waterford
Ireland
50
For any information about this medicine, please contact the local representative of the Marketing
Authorisation holder.
België/Belgique/Belgien/
Luxembourg/Luxemburg
Genzyme Belgium nv/sa (Belgique/Belgien),
Tél/Tel: + 32 2 714 17 11
Ísland
Vistor hf.
Tel: +354 535 7000
България
Търговско представителство на Genzyme CEE
GmbH
Тел. +359 2 971 1001
Magyarország
Genzyme Europe B.V. Képviselet,
Tel: +36 1 310 7440
Česká republika/Slovenská republika
Genzyme Czech s.r.o.
Tel: +420 227 133 665
Nederland
Genzyme Europe BV,
Tel: +31 35 6991200
Danmark/Norge/Sverige/Suomi/Finland
Genzyme A/S, (Danmark/Tanska),
Tlf/Puh.: + 45 32712600
Österreich
Genzyme Austria GmbH,
Tel: + 43 1 774 65 38
Deutschland
Genzyme GmbH,
Tel: +49 610236740
Polska/Eesti/Latvija/Lietuva
Genzyme Polska sp. z o.o. (Poola/Polija/Lenkija),
Tel: +48 22 516 24 32
Ελλάδα/Κύπρος
Genzyme Hellas Ltd. (Ελλάδα),
Τηλ: +30 210 99 49 270
Portugal
Genzyme Portugal,
Tel: +351 21 422 0100
España
Genzyme, S.L.,
Tel: +34 91 6591670
România
Genzyme CEE GmbH- Reprezentanta pentru
Romania
Tel: +40 21 243 42 28
France
Genzyme S.A.S,
Tél: + 33 (0) 825 825 863
Slovenija
Genzyme Europe B.V. Predstavništvo za Hrvaško
in Slovenijo (Hrvaška),
Tel: +385 1 6386 250
Italia/ Malta
Genzyme Srl (Italia/Italja),
Tel: +39 059 349811
United Kingdom/Ireland
Genzyme Therapeutics (United Kingdom),
Tel: +44 1865 405200
This leaflet was last approved in
{MM/YYYY}
Detailed information on this medicine is available on the European Medicines Agency (EMA) web
site:
http://www.ema.europa.eu
51
PACKAGE LEAFLET: INFORMATION FOR THE USER
Renagel 800 mg film-coated tablets
sevelamer hydrochloride
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have further questions, ask your doctor or your pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if
their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
1. What Renagel is and what it is used for.
2. Before you take Renagel.
3. How to take Renagel.
4. Possible side effects.
5. How to store Renagel.
6. Further information.
1.
WHAT RENAGEL IS AND WHAT IT IS USED FOR
Renagel contains sevelamer as the active ingredient. It binds phosphate from food in the digestive tract
and so reduces serum phosphate levels in the blood.
Adult patients whose kidneys have failed and who are receiving haemodialysis or peritoneal dialysis
are not able to control the level of serum phosphate in their blood. The amount of phosphate then rises
(your doctor will call this hyperphosphataemia). Increased levels of serum phosphorus can lead to hard
deposits in your body called calcification. These deposits can stiffen your blood vessels and make it
harder for blood to be pumped around the body. Increased serum phosphorus can also lead to itchy
skin, red eyes, bone pain and fractures.
Renagel is used to control the levels of phosphate in the blood of adult kidney failure patients on
haemodialysis or peritoneal dialysis treatment.
It may be necessary to use other medicines with Renagel, which could include calcium or vitamin D
supplements, to control the development of renal bone disease.
2.
BEFORE YOU TAKE RENAGEL
Do not take Renagel if:
•
you have low levels of phosphate in your blood
•
you have bowel obstruction.
•
you are allergic (hypersensitive) to sevelamer or to any of the other ingredients of the product
(
see Section 6: Further information
).
52
Take special care with Renagel
If any of the following applies to you, please consult your doctor before taking Renagel
:
•
you are not on dialysis
•
swallowing problems
•
problems with motility (movement) in your stomach and bowel
•
retention of stomach contents
•
active inflammation of the bowel
•
have undergone major surgery on your stomach or bowel.
The safety and efficacy in children (below the age of 18 years) has not been established. Therefore
Renagel is not recommended for use in this population.
Additional treatments
:
Due to either your kidney condition or your dialysis treatment you may:
•
develop a low or high level of calcium in your blood. Since Renagel does not contain calcium
your doctor might prescribe additional calcium tablets.
•
have a low amount of vitamin D in your blood. Therefore, your doctor may monitor the levels
of vitamin D in your blood and prescribe additional vitamin D as necessary. If you do not take
multivitamin supplements you may also develop low levels of vitamins A, E, K and folic acid
in your blood and therefore your doctor may monitor these levels and prescribe supplemental
vitamins as necessary.
Changing treatment
:
When you switch from another phosphate binder to Renagel, your doctor might consider monitoring
the levels of bicarbonate in your blood more closely because Renagel may decrease the levels of
bicarbonate.
Special note for patients on peritoneal dialysis
You may develop peritonitis (infection of your abdominal fluid) associated with your peritoneal
dialysis. This risk can be reduced by careful adherence to sterile techniques during bag changes. You
should tell your doctor immediately if you experience any new signs or symptoms of abdominal
distress,
abdominal swelling, abdominal pain, abdominal tenderness, or abdominal rigidity,
constipation, fever, chills, nausea or vomiting
.
You should expect to be monitored more carefully for problems with low levels of vitamins A, D, E, K
and folic acid.
Taking other medicines
Please tell your doctor if you are taking or have recently taken other medicines, including medicines
obtained without a prescription.
Renagel should not be taken at the same time as ciprofloxacin (an antibiotic).
If you are taking medicines for heart rhythm problems or for epilepsy, you should consult your doctor
when taking Renagel.
The effects of medicines such as ciclosporin, mycophenolate mofetil and tacrolimus (medicines used
in transplant patients) may be reduced by Renagel. Your doctor will advise you if you are taking these
medicines.
Increased levels of thyroid stimulating hormone (TSH, a substance in your blood which stimulates the
thyroid gland to make thyroid hormone which helps control your body’s metabolism) may very rarely
be observed in certain people taking levothyroxine (a thyroid hormone) and Renagel. Therefore your
doctor may monitor the levels of TSH in your blood more closely.
Your doctor will check for interactions between Renagel and other medicines on a regular basis.
53
Taking Renagel with food and drink
You should take Renagel tablets with meals. However, you should adhere to your prescribed diet and
liquid intake.
Do not chew. The tablets must be swallowed whole.
Pregnancy and breast-feeding
The safety of Renagel has not been established in pregnant or lactating women. Renagel should only
be given to pregnant or lactating women if clearly needed.
Driving and using machines
No studies on the effects on the ability to drive and use machines have been performed. If you are
affected, do not drive and do not use any tools or machines.
3.
HOW TO TAKE RENAGEL
You should take Renagel as prescribed by your doctor. He/she will base the dose on your serum
phosphate level. The recommended starting dose of Renagel for adults and the elderly (> 65 years) is
one or two tablets with each meal 3 times a day.
Your doctor will check the levels of phosphate in your blood periodically and he/she may adjust the
dose of Renagel when necessary (between 1 and 5 tablets of 800 mg per meal) to reach an adequate
phosphate level.
In some cases where Renagel should be administered at the same time as another medicine. Your
doctor may advise you to take this medicine 1 hour before or 3 hours after Renagel intake, or he/she
may consider monitoring the blood levels of that medicine.
If you take more Renagel than you should
There are no reported overdoses in patients.
In the event of a possible overdose you should contact your doctor immediately.
If you forget to take Renagel
If you have missed one dose, this dose should be omitted and the next dose should be taken at the
usual time with a meal. Do not take a double dose to make up for a forgotten dose
.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Renagel
can cause side effects, although not everybody gets them.
The following side effects have been reported in patients taking Renagel:
Very common
(affects more than 1 user in 10): nausea, vomiting
Common
(affects 1 to 10 users in 100): diarrhoea, indigestion, abdominal pain, constipation,
flatulence.
In clinical use of Renagel, cases of itching, rash, abdominal pain, slow intestine motility (movement),
blockages in the intestine, inflammation of abnormal small pouches (called diverticula) in the large
intestine and perforation in the intestine wall have been reported.
Since constipation may be a preceding symptom in very rare cases of blockages in the intestine, please
inform your doctor or pharmacist.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
54
5.
HOW TO STORE RENAGEL
Keep out of the reach and sight of children.
Do not store above 25 °C. Keep the bottle tightly closed in order to protect from moisture.
Do not use Renagel after the expiry date stated on the carton and/or bottle after the letters “EXP”.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Renagel contains
- The active substance is sevelamer.
- The other ingredients are
silica colloidal anhydrous and stearic acid. The tablet coating contains
hypromellose and diacetylated monoglycerides. The printing ink contains iron oxide black (E172),
hypromellose and propylene glycol.
What Renagel looks like and contents of the pack
Renagel tablets are film coated, off white, oval tablets with Renagel 800 imprinted on one side. The
tablets are packed in high density polyethylene bottles with a child resistant polypropylene cap and an
induction seal.
Pack sizes are:
6 bottles of 30 tablets
1 bottle of 100 tablets
1 bottle of 180 tablets
2 bottles of 180 tablets
3 bottles of 180 tablets
Marketing Authorisation Holder and Manufacturer
Marketing authorisation holder:
Genzyme Europe B.V.
Gooimeer 10
1411 DD Naarden
The Netherlands
Manufacturing authorisation holders responsible for batch release:
Genzyme Ltd.
37 Hollands Road
Haverhill, Suffolk
CB9 8PU
United Kingdom
Genzyme Ireland Ltd.
IDA Industrial Park
Old Kilmeaden Road
Waterford
Ireland
55
For any information about this medicine, please contact the local representative of the Marketing
Authorisation holder.
België/Belgique/Belgien/
Luxembourg/Luxemburg
Genzyme Belgium nv/sa (Belgique/Belgien),
Tél/Tel: + 32 2 714 17 11
Ísland
Vistor hf.
Tel: +354 535 7000
България
Търговско представителство на Genzyme CEE
GmbH
Тел. +359 2 971 1001
Magyarország
Genzyme Europe B.V. Képviselet,
Tel: +36 1 310 7440
Česká republika/Slovenská republika
Genzyme Czech s.r.o.
Tel: +420 227 133 665
Nederland
Genzyme Europe BV,
Tel: +31 35 6991200
Danmark/Norge/Sverige/Suomi/Finland
Genzyme A/S, (Danmark/Tanska),
Tlf/Puh.: + 45 32712600
Österreich
Genzyme Austria GmbH,
Tel: + 43 1 774 65 38
Deutschland
Genzyme GmbH,
Tel: +49 610236740
Polska/Eesti/Latvija/Lietuva
Genzyme Polska sp. z o.o. (Poola/Polija/Lenkija),
Tel: +48 22 516 24 32
Ελλάδα/Κύπρος
Genzyme Hellas Ltd. (Ελλάδα),
Τηλ: +30 210 99 49 270
Portugal
Genzyme Portugal,
Tel: +351 21 422 0100
España
Genzyme, S.L.,
Tel: +34 91 6591670
România
Genzyme CEE GmbH- Reprezentanta pentru
Romania
Tel: +40 21 243 42 28
France
Genzyme S.A.S,
Tél: + 33 (0) 825 825 863
Slovenija
Genzyme Europe B.V. Predstavništvo za Hrvaško
in Slovenijo (Hrvaška),
Tel: +385 1 6386 250
Italia/ Malta
Genzyme Srl (Italia/Italja),
Tel: +39 059 349811
United Kingdom/Ireland
Genzyme Therapeutics (United Kingdom),
Tel: +44 1865 405200
This leaflet was last approved in
{MM/YYYY}
.
Detailed information on this medicine is available on the European Medicines Agency (EMA) web
site:
http://www.ema.europa.eu
.
56
Source: European Medicines Agency
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