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 D3 or one of its analogues to
control the development of renal bone disease.

Children
The safety and efficacy of this product has not been established in patients below the age of 18 years.
Adults and elderly (> 65 years)
For patients who are not on phosphate binders, dosage is determined individually based on serum
phosphate concentration as indicated in the table below:
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
If Renagel is prescribed as an alternative phosphate binder, Renagel should be given in equivalent
doses on a mg weight basis compared to the patient’s previous calcium based phosphate binder. 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 5 800 mg tablets per meal. The average actual daily dose
used in the chronic phase of a one year clinical study was 7 grams of sevelamer.
Patients should take Renagel with meals and adhere to their prescribed diets. The tablets must be
swallowed whole. Do not chew.
8
Proprietary and Confidential Renvela / June 2009 / 0005 / 1.8.2 riskmgtsystem-annex7 / Page 55
Proprietary and Confidential Renvela® / November 2010 / SA / Product Registration Application / Page
890

Efficacy and safety of Renagel has not been studied in children or in predialysis patients.
The safety and efficacy of Renagel has not been studied in patients with swallowing disorders,

untreated or severe gastroparesis, and retention of gastric contents. Renagel should only be used in
these patients following careful assessment of benefit and risks.
Efficacy and safety of Renagel has not been studied in patients with active inflammatory bowel
disease, gastrointestinal motility disorders, abnormal or irregular bowel motion and patients with a
history of major gastrointestinal surgery. Consequently, caution should be exercised when Renagel is
used in patients with these disorders.
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 reevaluated
in patients who develop severe constipation or other severe gastrointestinal symptoms.
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 D3 or one of its analogues to
lower the intact parathyroid hormone (iPTH) levels.
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.
Depending on diet intake and the nature of end stage renal failure, dialysis patients may develop low
vitamin A, D, E and K levels. In preclinical studies, sevelamer at the equivalent of 10 times the
maximal human dose has been shown to reduce the absorption of vitamins D, E and K, and folic acid
(see also 5.3 Preclinical safety data). 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.
There is at present insufficient data to exclude the possibility of folate deficiency during long term
Renagel treatment.
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.
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.
9
Proprietary and Confidential Renvela / June 2009 / 0005 / 1.8.2 riskmgtsystem-annex7 / Page 56
Proprietary and Confidential Renvela® / November 2010 / SA / Product Registration Application / Page
891
Very rare cases of hypothyroidism have been reported in patients co-administered Renagel and
Levothyroxine. Closer monitoring of TSH levels is therefore recommended in patients receiving both
medicinal products.
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.
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.

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).

Interaction studies have not been conducted in patients on dialysis.
In interaction studies in healthy volunteers, Renagel had no effect on the bioavailability of digoxin,
warfarin, enalapril or metoprolol. However, the bioavailability of ciprofloxacin was decreased by
approximately 50% when co-administered with Renagel in a single dose study. Consequently, Renagel
should not be taken simultaneously with ciprofloxacin.
Renagel may affect the bioavailability of other medicinal products. 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. 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.

The safety of Renagel has not been established in pregnant or lactating women. In animal studies there
was no evidence that sevelamer induced embryo-foetal toxicity. Renagel should only be given to
pregnant or lactating women if clearly needed and after a careful risk/benefit analysis has been
conducted for both the mother and the foetus or 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) undesirable effects possibly or probably related to Renagel were all in the
gastrointestinal disorders system organ class. Data possibly or probably related to Renagel from these
studies (299 patients) and from uncontrolled clinical trials (384 patients) are listed by frequency in the
10
Proprietary and Confidential Renvela / June 2009 / 0005 / 1.8.2 riskmgtsystem-annex7 / Page 57
Proprietary and Confidential Renvela® / November 2010 / SA / Product Registration Application / Page
892
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), including isolated.
Gastrointestinal disorders

Very common (≥1/10) : Nausea, vomiting
Common (≥1/100 to <1/10): Diarrhoea, dyspepsia, flatulence, upper abdominal pain,
constipation
Most of these events are commonly observed in patients Stage 5 Chronic Kidney Disease and are not
necessarily attributable to Renagel.
Post-marketing experience: In very rare cases, intestinal obstruction and ileus/subileus have been
observed in patients during treatment with Renagel.

No case of overdose has been reported.
Renagel has been given to normal healthy volunteers in doses up to 14 grams, the equivalent of thirtyfive
403 mg capsules (equivalent to seventeen 800 mg tablets), per day for eight days with no
undesirable effects.

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 D3 or one of its analogues to lower the intact parathyroid hormone (iPTH)
levels.
11
Proprietary and Confidential Renvela / June 2009 / 0005 / 1.8.2 riskmgtsystem-annex7 / Page 58
Proprietary and Confidential Renvela® / November 2010 / SA / Product Registration Application / Page
893
In a clinical trial of one-year duration, Renagel had no adverse effect on bone turnover or
mineralisation compared to calcium carbonate.

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).

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.

Each tablet contains:

Silica, colloidal anhydrous
Stearic acid
The tablet coating contains:
Hypromellose
Diacetylated monoglycerides
The printing ink contains:
Iron oxide black (E172)
Propylene glycol
Hypromellose

Not applicable

Do not store above25ºC.
12
Proprietary and Confidential Renvela / June 2009 / 0005 / 1.8.2 riskmgtsystem-annex7 / Page 59
Proprietary and Confidential Renvela® / November 2010 / SA / Product Registration Application / Page
894
Keep the container tightly closed.

High density polyethylene bottles, with a child resistant polypropylene cap and an induction seal.
Package sizes are:
800 mg tablets 6 x 30 tablets
1 x 100 tablets
1 x 180 tablets
2 x 180 tablets
3 x 180 tablets
Not all pack sizes may be marketed.

No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.