Renvela

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Sevelamer carbonate 2400 mg
Available from:
sanofi-aventis new zealand limited
INN (International Name):
Sevelamer carbonate 2400 mg
Dosage:
2.4 g
Pharmaceutical form:
Powder for oral suspension
Composition:
Active: Sevelamer carbonate 2400 mg Excipient: 'Natural and Artificial Citrus Cream' proprietary flavouring Iron oxide yellow Propylene glycol alginate Sodium chloride Sucralose
Prescription type:
Prescription
Manufactured by:
Genzyme Ltd
Therapeutic indications:
Renvela is indicated for the management of hyperphosphataemia in adult patients with stage 4 and 5 chronic kidney disease.
Product summary:
Package - Contents - Shelf Life: Sachet, Opaque, foil lined heat sealed - 15 dose units - 36 months from date of manufacture stored at or below 25°C protect from moisture. Do not refrigerate. - Sachet, Opaque, foil lined heat sealed - 60 dose units - 36 months from date of manufacture stored at or below 25°C protect from moisture. Do not refrigerate. - Sachet, Opaque, foil lined heat sealed - 90 dose units - 36 months from date of manufacture stored at or below 25°C protect from moisture. Do not refrigerate.
Authorization number:
TT50-9571/1a
Authorization date:
2014-06-05

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RENVELA

Renvela

Sevelamer carbonate

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about Renvela.

It does not contain all the available

information. It does not take the

place of talking to your doctor or

pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you taking Renvela

against the benefits this medicine is

expected to have for you.

If you have any concerns about

taking this medicine, ask your

doctor or pharmacist.

Keep this leaflet

. You may need to

read it again.

What Renvela is used

for

Renvela contains the active substance

sevelamer carbonate and is used to

treat hyperphosphatemia, a condition

caused by too much dietary

phosphorus being retained in your

body due to a diseased kidney.

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.

Renvela helps to remove excess

phosphorus that has built up in your

body by binding the phosphorus that

is in the food that you eat.

Your doctor, however, may have

prescribed Renvela for another

purpose.

Ask your doctor if you have any

questions about why it has been

prescribed for you

This medicine is only available with

a doctor's prescription.

Before you take

Renvela

When you must not take

Renvela

Do not take Renvela if you have an

allergy to:

any medicine containing

sevelamer carbonate (the active

ingredient)

any of the ingredients listed at

the end of this leaflet

any other similar medicine, such

as sevelamer hydrochloride.

Symptoms that may indicate an

allergic reaction include

shortness of breath

wheezing or difficulty breathing

swelling of the face, lips, tongue

or other parts of the body

rash, itching or hives on the skin.

Tell your doctor if you are

experiencing these symptoms.

Do not take Renvela if you have:

hypophosphatemia, a condition

where you do not have enough

phosphorus in your body

a bowel obstruction.

Renvela should not be used after

the expiry date (exp) printed on the

pack.

If you take this medicine after

the expiry date it may have no effect

at all, or worse, an unexpected effect.

Renvela should not be used if the

packaging is torn or shows signs of

tampering.

Do not give Renvela to children.

The safety and efficacy of Renvela in

children under the age of 18 years as

not been established.

If you are not sure whether you

should start taking this medicine,

talk to your doctor.

Before you start to take it

Tell your doctor or pharmacist if

you have:

allergies to any other medicines

or substances such as foods,

preservatives or dyes.

swallowing problems

severe constipation

problems with movement in

your stomach and bowel

active inflammation of the bowel

undergone major surgery on

your stomach or bowel

you have or have had any other

medical conditions, including a

bowel obstruction or

hypophosphatemia

RENVELA

thyroid problems.

If you are pregnant or breast-

feeding, think you may be

pregnant or are planning to have a

baby.

Tell your doctor about any of the

above before you take Renvela.

Renvela powder contains

sucralose.

Additional Information

Due to either your kidney

condition or your dialysis

treatment you may:

Develop low or high levels of

calcium in your blood. Since

Renvela 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.

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 tenderness,

constipation, fever, chills,

nausea or vomiting.

Taking other medicines

Tell your doctor or pharmacist if you

are taking, have recently taken, or

might take any other medicines

(including vaccinations), medicines

that you buy without a prescription

from your pharmacy, supermarket or

health food shop.

Some medicines may be affected by

Renvela or may affect how well

Renvela works. You may need

different amounts of your medicine,

or you may need to take different

medicines. Your doctor will advise

you.

The effects of medicines such as

ciclosporin, mycophenolate mofetil

and tacrolimus (medicines used to

suppress the immune system) may be

reduced by Renvela. Your doctor will

advise you if you are taking these

medicines.

Renvela should not be taken at the

same time as ciprofloxacin (an

antibiotic).

Thyroid hormone deficiency may

uncommonly be observed in certain

people taking levothyroxine (used to

treat low thyroid hormone levels) and

Renvela. Therefore your doctor may

monitor the levels of thyroid

stimulating hormone in your blood

more closely.

If you are taking medicines for heart

rhythm problems, stomach problems,

or for epilepsy, you should consult

your doctor before taking Renvela.

How to take Renvela

How much to take

The recommended starting dose of

Renvela is 2.4 g to 4.8 g per day to

be divided over 3 meals.

For tablets, this means one to two

800 mg tablets with each meal three

times a day. For powder this means

up to one full sachet (1.6 g) with

each meal, three times a day.

The dose will depend on your serum

phosphorus level.

Follow all directions given to you

by your doctor or pharmacist

carefully.

These directions may differ from the

information contained in this leaflet.

How to take it

Tablets

Swallow Renvela tablets whole with

a glass of water. Do not crush, chew

or break into pieces.

If you are having difficulty

swallowing Renvela tablets, speak to

you doctor. You may be prescribed

Renvela powder as an alternative.

Powder

The 1.6 g powder for oral suspension

should be dispersed in 40 ml of water

per sachet.

The 2.4 g powder for oral suspension

should be dispersed in 60 ml of water

per sachet.

The powder isn’t expected to fully

dissolve in water. When dispersed it

creates a cloudy white suspension in

which small particles are visible.

Drink within 30 minutes of being

prepared. It is important to drink all

of the dose and it may be necessary

to rinse the glass with water and

drink this as well to ensure that all of

the powder is swallowed.

How long to take it

Renvela helps lower your dietary

phosphate. It does not cure your

condition. Therefore, you must

continue to take it as directed by your

doctor.

You may have to take phosphate-

lowering medicines for the rest of

your life. If you stop taking Renvela,

your phosphate levels may rise again.

It is important to keep taking your

medicines even if you feel well.

Do not stop taking Renvela. Your

doctor may need to change the dose

of your other medicines if you stop

taking Renvela, so you should only

stop when your treating doctor tells

you to.

If you forget to take it

If you miss a dose, do not take an

extra dose to make up for the one you

missed. Take the next dose at the

usual time with your meal.

RENVELA

It is important to take Renvela as

prescribed by your doctor.

If you take too much

(overdose)

Immediately telephone your

treating doctor or Poisons

Information Centre telephone 0800

POISON or 0800 764 766, or go to

accident and emergency at your

nearest hospital, if you think that

you or anyone else may have taken

too much Renvela. Do this even if

there are no signs of discomfort or

poisoning.

You may need urgent

medical attention. Keep telephone

numbers of these places handy.

While you are taking

Renvela

Things you must do

If you become pregnant while you

are taking Renvela, tell your

doctor.

Tell your doctor or pharmacist if

you are taking any other

medicines, including any that you

get without a prescription from

your pharmacy, supermarket or

health food shop.

If you are about to be started on any

new medicine, tell your doctor and

pharmacist that you are taking

Renvela.

Be sure to keep all your doctor's

appointments so your progress can be

checked.

Your doctor will check your progress

and monitor your phosphorus levels

from time to time. This helps to

ensure you are getting the right dose

of Renvela.

Things you must not do

Do not give Renvela to anyone else,

even if they have the same condition

as you.

Do not use Renvela to treat any other

complaints unless your doctor tells

you to.

Do not stop taking your medicine or

lower the dosage without checking

with your doctor.

Side Effects

Tell your doctor, pharmacist or

nurse as soon as possible if you do

not feel well while you are taking

Renvela.

All medicines can have side effects.

Sometimes they are serious, most of

the time they are not. You may need

medical treatment if you get some of

the side effects.

Tell your doctor or pharmacist if

you notice any of the following and

they worry you:

allergic reaction

vomiting

nausea

constipation

diarrhoea

flatulence

indigestion

abdominal pain

pain in hand and/or foot

fatigue

loss of appetite

muscle spasms

headache

urinary tract infection

cough.

Tell your doctor immediately if

you notice any of the following

symptoms:

rash, itching or hives on the skin

severe

constipation

dizziness.

If any of the following happen, tell

your doctor immediately or go to

the Accident and Emergency at

your nearest hospital:

shortness of breath

wheezing or difficulty in

breathing

swelling of the face, lips, tongue

or other parts of the body

severe abdominal pain, stomach

or intestine disorders, or blood in

the stool (gastrointestinal

bleeding). These symptoms can

be due to serious inflammatory

bowel disease caused by

sevelamer crystal deposit in your

bowel.

Other side effects not listed above

may occur in some patients. Tell

your doctor if you notice anything

making you feel unwell when you

are taking, or soon after you have

finished taking Renvela.

After using Renvela

Storage

Keep Renvela in a cool dry place

where the temperature stays below

25°C. Do not put Renvela in the

refrigerator. Do not put it in the

bathroom or near the sink. Do not

leave it in the car or on window sills.

Heat and dampness can destroy some

medicines.

Keep Renvela where young children

cannot reach it. A locked cupboard at

least one and a half meters above the

ground is a good place to store

medicines.

Disposal

If your doctor tells you to stop taking

Renvela or your Renvela tablets or

powder have passed their expiry date,

ask your pharmacist what to do with

any tablet or powder that is left over.

Product description

What Renvela looks like

Renvela is available as tablets or

powder.

Renvela tablets are white oval film-

coated tablets imprinted with

RENVELA

‘RENVELA 800’ on one side and are

blank on the other side.

Renvela powder is pale yellow in

colour.

Ingredients

Tablet

Active ingredients:

Sevelamer carbonate

Other ingredients:

Acetylated monoglycerides

Hypromellose E-15

Hypromellose E-5

Isopropyl alcohol

Microcrystalline cellulose

Opacode

Propylene glycol

Sodium chloride

Zinc stearate.

Powder

Active ingredients:

Sevelamer carbonate

Other ingredients:

'Natural and Artificial Citrus

Cream' proprietary flavouring

Iron oxide yellow

Propylene glycol alginate

Sodium chloride

Sucralose.

Supplied by

Renvela is supplied in New Zealand

sanofi-aventis new zealand ltd

56 Cawley St

Ellerslie, Auckland,

New Zealand

Toll Free Number (medical

information): 0800 283 684

Email:

medinfo.australia@sanofi.com

This leaflet was prepared on April

2020

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Read the complete document

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NEW ZEALAND DATA SHEET

1

PRODUCT NAME

Renvela 800mg film coated tablet

Renvela 1.6g powder for oral suspension

Renvela 2.4g powder for oral suspension

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Renvela film-coated tablet contains 800 mg of sevelamer carbonate on an anhydrous basis.

Each Renvela sachet contains 1.6 g or 2.4 g of sevelamer carbonate for oral suspension on an

anhydrous basis.

For the full list of excipients, see Section 6.1 List of excipients.

3

PHARMACEUTICAL FORM

Renvela film-coated tablets: white oval film-coated tablets imprinted with “RENVELA 800” on

one side and are blank on the other side.

Renvela powder for oral suspension: pale yellow powder free from foreign particles in a sachet.

4

CLINICAL PARTICULARS

4.1

THERAPEUTIC INDICATIONS

Renvela is indicated for the management of hyperphosphataemia in adult patients with stage 4 and

5 chronic kidney disease.

4.2

DOSE AND METHOD OF ADMINISTRATION

Renvela is available as tablets or powder for oral suspension.

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Renvela

should

taken

conjunction

with

prescribed

diet

management

hyperphosphatemia.

Renvela 800 mg tablets must be taken three times per day with meals at a dosage based on

individual patient requirements to control phosphate levels. Tablets should be swallowed intact

and should not be crushed, chewed, or broken into pieces prior to administration. Patients should

swallow the tablets whole with water.

Renvela 1.6 or 2.4 g powder sachet must be taken three times per day with meals individually or

in combination at a dosage based on individual patient requirements to control phosphate levels.

The powder should be dispersed in water (40 ml for 1.6 g powder sachet and 60 ml for 2.4 g

powder sachet) prior to administration. Multiple sachets may be mixed together, as long as the

appropriate amount of water is used. Patients should drink the preparation within 30 minutes.

Starting dose

The recommended starting dose of Renvela is 2.4 to 4.8 g per day based on clinical needs and

phosphorus level (Table 1). Renvela must be taken three times per day with meals.

Table 1 - Starting dose for patients not taking a phosphate binder

Serum Phosphorus

Total daily dose taken over three meals per day

> 1.78 and < 2.42 mmol/L

2.4 g

2.42

4.8 g

For patients previously on calcium based phosphate binders, Table 2 below provides guidance on

switching to Renvela. Serum phosphorus levels should be monitored to ensure optimal daily

doses.

Table 2 - Starting dose for patients switching from calcium carbonate to Renvela

Calcium Carbonate (500mg*)

(tablets per meal)

Renvela 800mg tablet

(tablets per meal)

Renvela Powder

(g per meal)

1 tablet

2 tablets

3 tablets

* elemental calcium of 200mg

It is recommended to continue monitoring serum phosphorus levels in patients when switching

between sevelamer carbonate tablets and powder.

Titration and Maintenance

Serum phosphorus levels must be monitored and the dose of sevelamer carbonate titrated every 2-

4 weeks until an acceptable serum phosphorus level is reached, with regular monitoring thereafter.

renvela-ccdsv8-dsv4-09apr20

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The dose may be increased or decreased by one tablet per meal at two week intervals as necessary

(Table 3). Patients taking Renvela should adhere to their prescribed diets.

Table 3 - Dose titration guideline 800mg tablets

Serum Phosphorus

Renvela Dose

> 1.78 mmol/L

Increase 1 tablet per meal at 2 week intervals

1.13 – 1.78 mmol/L

Maintain current dose

< 1.13 mmol/L

Decrease 1 tablet per meal

In clinical practice, treatment will be continuous based on the need to control serum phosphorus

levels and the daily dose is expected to be an average of approximately 6 g per day.

4.3

CONTRAINDICATION

Renvela is contraindicated in patients:

known to be hypersensitive to sevelamer carbonate or any of the other components of the

tablet

with hypophosphataemia

with bowel obstruction

4.4

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

General

The safety and efficacy of Renvela have not been established in adult patients with chronic kidney

disease not on dialysis with serum phosphorus < 1.78 mmol/L.

The safety and efficacy of Renvela in patients with dysphagia, swallowing disorders, severe

gastrointestinal (GI) motility disorders, severe constipation or major GI tract surgery have not

been established. Consequently, caution should be exercised when Renvela is used in patients

with these GI disorders.

Cases

serious

inflammatory

disorders

tract

(with

complications

including

haemorrhage,

perforation,

ulceration,

necrosis

colitis/cecal

mass)

with

presence

sevelamer crystals have been reported (Section 4.8 Undesirable Effects). Inflammatory disorders

may resolve upon Renvela discontinuation. Treatment with Renvela should be re-evaluated in

patients who develop severe gastrointestinal symptoms.

Intestinal obstruction and ileus/subileus

In very rare cases, intestinal obstruction and ileus/subileus have been observed in patients during

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treatment with sevelamer hydrochloride, which contains the same active moiety as sevelamer

carbonate. Constipation may be a preceding symptom. Patients who are constipated should be

monitored carefully while being treated with Renvela. Renvela treatment should be re-evaluated

in patients who develop severe constipation or other severe gastrointestinal symptoms.

Fat-soluble vitamins

Depending on dietary intake and the nature of chronic kidney disease, dialysis patients may

develop low vitamin A, D, E and K levels. It

cannot be excluded that Renvela can bind fat-soluble

vitamins contained in ingested food

.

Therefore, in patients not taking these vitamins, monitoring

vitamin

levels

assessing

vitamin

status

through

measurement

thromboplastin

time

should

considered

these

vitamins

should

supplemented

necessary. In patients undergoing peritoneal dialysis additional monitoring of fat-soluble vitamins

and folic acid is recommended, since vitamin A, D, E and K levels were not measured in a clinical

study in these patients.

In clinical trials, there was no evidence of reduction in serum levels of vitamins with the

exception of a one year clinical trial in which Renagel treatment was associated with reduction of

25 - hydroxyvitamin D (normal range 10 to 55 µg/mL) from 39± 22 µg/mL to 34± 22 μg/mL

(p<0.01). Most patients in Renagel clinical trials received vitamin supplements, which is typical

of patients on haemodialysis. Indirect evidence of a reduction in vitamin K levels (an increase in

haemorrhage corrected by vitamin K supplementation) was also seen in animals.

Folate deficiency

There is at present insufficient data to exclude the possibility of folate deficiency during long term

Renvela treatment.

Swallowing and choking difficulties

Uncommon case reports of difficulty swallowing the Renvela tablet have been reported. Many of

these cases involved patients with contributing co-morbid conditions affecting the ability to

swallow including swallowing disorders or oro-esophageal abnormalities. Caution should be

exercised when Renvela tablets are used in these patients. Consider using Renvela powder for

oral suspension in patients with a history of difficulty swallowing.

Hypocalcaemia/hypercalcaemia

Patients with CKD may develop hypocalcaemia or hypercalcaemia. Renvela does not contain

calcium. Serum calcium levels should be monitored and elemental calcium should be given as a

supplement in case of hypocalcaemia.

Metabolic acidosis

Patients with chronic kidney disease are predisposed to metabolic acidosis. As part of good

clinical practice, monitoring of serum bicarbonate levels is therefore recommended.

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Peritonitis

Patients receiving dialysis are subject to certain risks for infection specific to dialysis modality.

Peritonitis is a known complication in patients receiving peritoneal dialysis and in a clinical study

with

sevelamer

hydrochloride,

greater

number

peritonitis

cases

were

reported

sevelamer group than in the control group. Patients on peritoneal dialysis should be closely

monitored to ensure the correct 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 Renvela to patients also taking antiarrhythmic and

anti-seizure medicinal products (see Section 4.5 Interactions with other medicines and other forms

of interactions).

Hypothyroidism

Closer monitoring of patients with hypothyroidism co-administered with sevelamer carbonate and

levothyroxine is recommended (see Section 4.5 Interactions with other medicines and other forms

of interactions).

Hyperparathyroidism

Renvela is not indicated for the control of hyperparathyroidism. In patients with secondary

hyperparathyroidism

Renvela

should

used

within

context

multiple

therapeutic

approach, which could include calcium as supplements, 1,25 - dihydroxy Vitamin D3 or one of its

analogues to lower the intact parathyroid hormone (iPTH) levels.

Instructions to Patients

The contents of Renvela expand in water thus tablets should be swallowed intact and should not

be crushed, chewed or broken into pieces prior to administration (see Section 4.2 Dose and

method of administration).

Use in the elderly

No data available

Paediatric use

The safety and effectiveness of Renvela in patients below the age of 18 years have not been

established.

Effect on Laboratory Tests

No information available.

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4.5

INTERACTION WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTION

Interaction studies have not been conducted in patients on dialysis.

In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same

active moiety as Renvela, decreased the bioavailability of ciprofloxacin by approximately 50%

when

co-administered

with

sevelamer

hydrochloride

single

dose

study.

Consequently,

Renvela should not be taken simultaneously with ciprofloxacin.

Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in

transplant patients when co-administered with sevelamer hydrochloride without any clinical

consequences (i.e graft rejection). The possibility of an interaction cannot be excluded and a close

monitoring of blood concentrations of ciclosporin, mycophenolate mofetil and tacrolimus should

be considered during the use of combination and after its withdrawal.

During post-marketing experience, very rare cases of increased TSH levels have been reported in

patients co-administered sevelamer hydrochloride, which contains the same active moiety as

sevelamer

carbonate

levothyroxine.

Closer

monitoring

levels

therefore

recommended in patients receiving both medications.

During post-marketing experience, very rare cases of increased phosphate levels have been

reported in patients taking proton pump inhibitors co-administered with sevelamer carbonate.

Patients

taking

anti-arrhythmic

medications

control

arrhythmias

anti-seizure

medications for the control of seizure disorders were excluded from clinical trials. Special

precautions should be taken when prescribing Renvela to patients also taking these medications.

In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same

active moiety as Renvela, had no effect on the bioavailability of digoxin, warfarin, enalapril or

metoprolol.

In 14 healthy subjects receiving 2.4 g of sevelamer hydrochloride three times a day with meals for

two days sevelamer did not alter the pharmacokinetics of a single dose of warfarin. In 14 healthy

subjects receiving 9.6 grams of sevelamer carbonate once daily with a meal, sevelamer did not

alter the pharmacokinetics of a single dose of warfarin.

In 19 healthy subjects receiving 2.4 grams of sevelamer hydrochloride three times a day with

meals for 2 days, sevelamer did not alter the pharmacokinetics of a single dose of digoxin. In 18

healthy subjects receiving 9.6 grams of sevelamer carbonate once daily with a meal, sevelamer

did not alter the pharmacokinetics of a single dose of digoxin.

Renvela 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 Renvela, or the physician should consider monitoring

blood levels.

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4.6

FERTILITY, PREGNANCY AND LACTATION

Pregnancy (Category B3)

The safety of Renvela has not been established in pregnant or lactating women. Renvela should

only be given to pregnant or lactating women if clearly needed and after careful risk/benefit

analysis has been conducted for both the mother and foetus or infant.

Studies in animals have shown minimal reproductive toxicity when sevelamer was administered

to rats at high doses.

There was no evidence of teratogenicity in rabbits or rats following oral administration of

sevelamer hydrochloride during the period of organogenesis at respective doses 1.5 and 4.5

g/kg/day (5 and 15 times respectively on a mg/kg basis for a 50 kg human). In rats receiving

doses of 1.5 and 4.5 g/kg/day during organogenesis, there was reduced or irregular ossification of

foetal bones at exposures of 5 and 15 times the maximum tested human dose. In rabbits receiving

1 g/kg/day during organogenesis, there was an increase in early resorptions leading to a reduction

in the number of live foetuses per liter at an exposure 3.3 times the maximum recommended

human dose.

Oral administration of sevelamer hydrochloride to female rats throughout gestation and lactation

at doses of 0.1 - 1 g/kg/day (exposure 0.3 - 3.3 times the maximum recommended human dose)

did not affect the birth or growth of their offspring or their postnatal development.

In pregnant rats given dietary doses of 0.5, 1.5 or 4.5 g/kg/day of sevelamer hydrochloride during

organogenesis, reduced or irregular ossification of foetal bones, probably due to a reduced

absorption of fat-soluble vitamin D, occurred in mid - and high - dose groups (human equivalent

doses less than the maximum clinical trial dose of 13 g). In pregnant rabbits given oral doses of

100, 500 or 1000 mg/kg/day of sevelamer hydrochloride by gavage during organogenesis, an

increase of early resorptions occurred in the high - dose group (human equivalent dose twice the

maximum clinical trial dose).

Breast-feeding

Oral administration of sevelamer hydrochloride to female rats throughout gestation and lactation

did not have any adverse effects on offspring (see Pregnancy).

No adequate and controlled studies have been conducted using sevelamer in nursing mothers. It is

unknown whether sevelamer is excreted in human breast milk. The non absorbed nature of

sevelamer indicates that excretion of sevelamer in breast milk is unlikely. Renvela tablets should

be used during breastfeeding only if the potential benefit justifies the potential risks.

Fertility

There are no data from the effect of sevelamer on fertility in humans. Sevelamer hydrochloride

administered orally to male and female rats prior to and throughout mating, at doses up to 4.5

renvela-ccdsv8-dsv4-09apr20

Page 8

g/kg/day (more than 15 times the maximum tested human dose on a mg/kg basis for a 50 kg

person) did not alter mating or fertility.

4.7

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

No studies on the effects on ability to drive and use machines have been performed.

4.8

UNDESIRABLE EFFECTS

The safety of sevelamer (as either carbonate and hydrochloride salts) has been investigated in

numerous clinical trials involving a total of 969 haemodialysis patients with treatment duration of

4 to 50 weeks (724 patients treated with sevelamer hydrochloride and 245 with sevelamer

carbonate), 97 peritoneal dialysis patients with treatment duration of 12 weeks (all treated with

sevelamer hydrochloride) and 128 patients with CKD not on dialysis with treatment duration of 8

weeks

patients

treatment

with

sevelamer

hydrochloride

with

sevelamer

carbonate). The safety profile of sevelamer carbonate in patients not on dialysis was similar to the

safety profile of the drug in patients on dialysis.

There are limited data on the safety of sevelamer carbonate powder, however based on the fact

that it contains the same active ingredient as the sevelamer carbonate tablet, the adverse event

profiles of the two formulations should be similar.

Data possibly or probably related to sevelamer from these studies are listed below by frequency.

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, <0.1/1,000), very rare (<1/10,000), not known (cannot be

estimated from the available data).

Table 4 below provides a tabulated list of adverse reactions in CKD patients on haemodialysis

(Study

GD3-163-201).

atients

received

sevelamer

carbonate

tablets

sevelamer

hydrochloride 800 mg tablets for eight weeks each

with meals. Adverse reactions occurring in ≥5%

of patients are listed by Medical Dictionary for Regulatory Activities (MedDRA) System Organ

Class (SOC) and Preferred Term (PT).

renvela-ccdsv8-dsv4-09apr20

Page 9

Table 4 - Treatment Emergent AEs (All Causality) Occurring in

5% of Patients during Either

Treatment Regimen in Study GD3-163-201

System Organ Class

Preferred Term

Sevelamer Carbonate

Tablets TID (N=73)

Patients %

Sevelamer Hydrochloride

Tablets TID (N=78)

Patients %

Gastrointestinal Disorders

Nausea

12.8

Vomiting

10.3

Diarrhoea

Gastro-oesophageal reflux disease

General Disorders and Administration Site

Conditions

Fatigue

Infections and Infestations

Urinary tract infection

Injury, Poisoning and Procedural Complications

Arteriovenous fistula site complication

Arteriovenous fistula site haemorrhage

Arteriovenous fistula thrombosis

11.5

Investigations

Carbon dioxide decreased

Metabolism and Nutrition Disorders

Hypercalcaemia

Musculoskeletal and Connective Tissue

Disorders

Muscle spasms

Pain in extremity

Nervous System Disorders

Dizziness

Headache

Respiratory, Thoracic and Mediastinal Disorders

Cough

The most frequently occurring (≥ 2% of patients) undesirable effects possibly or probably related

to sevelamer were mainly in the gastrointestinal disorders system organ class (Table 5). Most of

these adverse reactions were mild to moderate in intensity.

renvela-ccdsv8-dsv4-09apr20

Page 10

Table 5 - Adverse Reactions in Studies GD3-163-201 (N=73), SVCARB00205 (N=31), and

SVCARB00105 (N=49) in CIOMS format

System Organ Class

Common

(≥ 1/100 to <1/10 )

Nausea

Constipation

Vomiting

Gastrointestinal Disorders

Abdominal pain upper

Diarrhoea

Dyspepsia

Flatulence

Investigations

Carbon dioxide decreased

Post-marketing experience

Because these events are reported voluntarily from a population of uncertain size, it is not always

possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

During post- marketing experience, the following adverse events have been reported in patients

receiving Renvela: Hypersensitivity, pruritus, rash, abdominal pain and uncommon cases of ileus,

intestinal obstruction and intestinal perforation.

Cases of serious inflammatory disorders of the gastrointestinal tract (with complications including

haemorrhage, perforation, ulceration, necrosis, colitis, and intestinal mass) associated with the

presence of sevelamer crystals have been reported (see Section 4.4 Special Warnings and

Precautions for Use).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are

asked to report any suspected adverse reactions at https://nzphvc.otago.ac.nz/reporting/

4.9

OVERDOSE

In CKD patients on dialysis, the maximum dose studied was 14.4 grams of sevelamer carbonate

and 13 grams of sevelamer hydrochloride. Sevelamer hydrochloride, which contains the same

active moiety as sevelamer carbonate, has been given to normal healthy volunteers in doses of up

to 14.4 grams per day for 8 days with no adverse effects.

There are no reported cases of overdose with sevelamer carbonate or sevelamer hydrochloride in

patients. Since sevelamer is not absorbed, the risk of systemic toxicity is low.

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