Optinate Septimum 35 mg Enterotablett

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

26-02-2020

Produktens egenskaper Produktens egenskaper (SPC)

22-05-2019

Aktiva substanser:
risedronatnatrium
Tillgänglig från:
Theramex Ireland Limited
ATC-kod:
M05BA07
INN (International namn):
risedronate
Dos:
35 mg
Läkemedelsform:
Enterotablett
Sammansättning:
risedronatnatrium 35 mg Aktiv substans
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Blister, 4 tabletter; Blister, 1 tablett; Blister, 2 tabletter; Blister, 12 tabletter; Blister, 10 tabletter; Blister, 16 tabletter
Bemyndigande status:
Godkänd
Godkännandenummer:
53583
Tillstånd datum:
2016-11-28

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

14-04-2021

Produktens egenskaper Produktens egenskaper - engelska

14-04-2021

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

28-11-2016

Läs hela dokumentet

Package leaflet: Information for the patient

Optinate Septimum 35 mg gastro-resistant tablets

risedronate sodium

Read all of this leaflet carefully before you start taking this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What Optinate Septimum is and what it is used for

What you need to know before you take Optinate Septimum

How to take Optinate Septimum

Possible side effects

How to store Optinate Septimum

Contents of the pack and other information

1.

What Optinate Septimum is and what it is used for

What Optinate Septimum is

Optinate Septimum belongs to a group of non-hormonal medicines called bisphosphonates which are

used to treat bone diseases. It works directly on your bones to make them stronger and therefore less

likely to break.

Bone is a living tissue. Old bone is constantly removed from your skeleton and replaced with new

bone.

Postmenopausal osteoporosis is a condition occurring in women after the menopause where the bones

become weaker, more fragile and more likely to break after a fall or strain.

Osteoporosis can also occur in men due to a number of causes including ageing and/or a low level of

the male hormone, testosterone.

The spine, hip and wrist are the most likely bones to break, although this can happen to any bone in

your body. Osteoporosis–related fractures can also cause back pain, height loss and a curved back.

Many patients with osteoporosis have no symptoms and you may not even have known that you had it.

What Optinate Septimum is used for

Treatment of osteoporosis in postmenopausal women, even if osteoporosis is severe. It reduces the risk

of spinal and hip fractures.

2.

What you need to know before you take Optinate Septimum

Do not take Optinate Septimum:

If you are allergic to risedronate sodium or any of the other ingredients of this medicine (listed

in section 6)

If your doctor has told you that you have a condition called hypocalcaemia (a low blood calcium

level)

If you may be pregnant, are pregnant or planning to become pregnant

If you are breast-feeding

If you have severe kidney problems.

Warnings and precautions

Talk to your doctor or pharmacist before taking Optinate Septimum:

If you are unable to stay in an upright position (sitting or standing) for at least 30 minutes.

If you have abnormal bone and mineral metabolism (for example lack of vitamin D, parathyroid

hormone abnormalities, both leading to a low blood calcium level).

If you have or have had problems in the past with your oesophagus (the tube that connects your

mouth with your stomach). For instance you may have or have had pain or difficulty in

swallowing food or you have previously been told that you have Barrett's oesophagus (a

condition associated with changes in the cells that line the lower oesophagus).

If you have had or have pain, swelling or numbness of the jaw or a “heavy jaw feeling” or

loosening of a tooth.

If you are under dental treatment or will undergo dental surgery, tell your dentist that you are

being treated with Optinate Septimum.

Your doctor will advise you on what to do when taking Optinate Septimum if you have any of the

above.

Children and adolescents

Optinate Septimum is not recommended for use in children below 18 due to insufficient data on safety

and efficacy.

Other medicines and Optinate Septimum

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines.

Medicines containing one of the following lessen the effect of Optinate Septimum if taken at the same

time:

Calcium

Magnesium

Aluminium (for example some indigestion mixtures)

Iron

Take these medicines at a different time of day to your Optinate Septimum.

Optinate Septimum with food and drink

Optinate Septimum should be taken immediately after breakfast.

Pregnancy and breast-feeding

Do not take Optinate Septimum if you may be pregnant, are pregnant or planning to become pregnant

(see section 2, “Do not take Optinate Septimum”).

Do not take Optinate Septimum if you are breast-feeding (see section 2, “Do not take Optinate

Septimum”).

Optinate Septimum should only be used to treat postmenopausal women.

Driving and using machines

Optinate Septimum is not known to affect your ability to drive and use machines.

Optinate Septimum contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per gastro-resistant tablet, that is to say

essentially ‘sodium-free’.

3.

How to take Optinate Septimum

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor

or pharmacist if you are not sure.

The recommended dose is one Optinate Septimum (35 mg of risedronate sodium) once a week.

Choose one day of the week that best fits your schedule. Every week, take the Optinate Septimum on

your chosen day.

For your convenience, so that you take your tablet on the right day every week, there is a feature

included with Optinate Septimum pack:

There are boxes/spaces on the back of the blister card. Please mark the day of the week you have

chosen to take your Optinate Septimum. Also, write in the dates you will take the tablet.

When to take Optinate Septimum

Optinate Septimum should be taken immediately after breakfast. If taken on an empty stomach there is

an increased risk of abdominal pain.

How to take Optinate Septimum

Optinate Septimum is for oral use.

Take the tablet whilst you are in an upright position (you may sit or stand) to avoid heartburn.

Swallow the tablet with at least one glass (120 ml) of plain water.

The tablet must be swallowed whole. Do not suck or chew the tablet.

Do not lie down for 30 minutes after taking your tablet.

Your doctor will tell you if you need calcium and vitamin supplements, if you are not taking enough

from your diet.

If you take more Optinate Septimum than you should

If you or somebody else has accidentally taken more tablets than prescribed, drink one full glass of

milk and seek medical attention.

If you forget to take Optinate Septimum

If you have forgotten to take your tablet on your chosen day, take it on the day you remember. Return

to taking one tablet once a week on the day the tablet is normally taken. Do not take two tablets on the

same day.

If you stop taking Optinate Septimum

If you stop treatment you may begin to lose bone mass. Please talk to your doctor before you consider

stopping treatment.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Optinate Septimum and contact a doctor immediately

if you experience any of the

following:

Symptoms of a severe allergic reaction such as:

Swelling of face, tongue or throat

Difficulties in swallowing

Hives and difficulties in breathing

Severe skin reactions such as:

Blistering of the skin, mouth, eyes and other moist body surfaces (genitals) (Stevens

Johnson syndrome)

Palpable red spots on the skin (leukocytoclastic vasculitis)

Red rash over many parts of the body and/or loss of the outer layer of the skin (toxic

epidermal necrolysis).

Tell your doctor promptly

if you experience the following side effects:

Eye inflammation, usually with pain, redness and light sensitivity.

Bone necrosis of the jaw (osteonecrosis) associated with delayed healing and infection, often

following tooth extraction (see section 2, “Warnings and precautions”).

Symptoms from oesophagus such as pain when you swallow, difficulties in swallowing, chest

pain or new or worsened heartburn.

Unusual fracture of the thigh bone particularly in patients on long-term treatment for osteoporosis may

occur rarely. Contact your doctor if you experience pain, weakness or discomfort in your thigh, hip or

groin as this may be an early indication of a possible fracture of the thigh bone.

However in clinical studies the other side effects that were observed were usually mild and did not

cause the patient to stop taking their tablets.

Other possible side effects:

Common side effects

(may affect up to 1 in 10 people):

Indigestion, feeling sick, stomach ache, stomach cramps or discomfort, constipation, feelings of

fullness, bloating, diarrhoea, vomiting, abdominal pain

Pain in your bones, muscles or joints

Headache

Uncommon side effects

(may affect up to 1 in 100 people):

Decreased number of white blood cells

Depressed mood

Dizziness, numbness tingling or burning sensation, decreased sensitivity

Inflammation of the coloured part of the eye (iris) (red painful eyes with a possible change in

vision), inflammation of the outermost layer of the eye and the inner surface of the eyelids

(conjunctivitis), eye redness, vision blurred

Hot flush, low blood pressure

Coughing

Inflammation or ulcer of the oesophagus (the tube that connects your mouth with your stomach)

causing difficulty and pain in swallowing (see also section 2, “Warnings and precautions”),

inflammation of the stomach and duodenum (bowel draining the stomach), reflux from

oesophagus or from stomach, gastritis, increased acid in the stomach, stomach hernia, gut

inflammation, gut distension, belching, wind, blood in the stool, bleeding from your bowels,

heartburn, haemorrhoids, stool leakage

Numbness of mouth, swollen tongue, swollen lips, dry mouth, gum inflammation, mouth sores

Redness of the skin, rash, itching, purple spots on the skin, allergic dermatitis

Muscle weakness/tiredness, muscle spasm, back pain, pain in extremity, pain in jaw, joint pain,

neck pain

Kidney stones

Cyst in the ovary

Tiredness, chills, flu like illness, pain in the chest, fever, swelling of face or body, pain, fatigue

Increased activity of parathyroid gland

Blood calcium and phosphate level decreased, blood calcium level increased, platelet count

decreased, heart rate irregular, occult blood in the stools, urine analysis abnormal

Allergic reactions

Rare side effects

(may affect up to 1 in 1,000 people):

Narrowing of the oesophagus (the tube that connects your mouth with your stomach), tongue

inflammation.

Abnormal liver tests have been reported. These can only be diagnosed from a blood test.

Very rare side effects

(may affect up to 1 in 10,000 people):

Talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These

could be signs of bone damage in the ear.

During post-marketing experience, the following have been reported (unknown frequency):

Hair loss

Liver disorders, some cases were severe

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system

listed in Appendix V. By reporting side effects you can help provide more information on the safety of

this medicine.

5.

How to store Optinate Septimum

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The

expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Optinate Septimum contains

The active substance is risedronate sodium. Each tablet contains 35 mg risedronate sodium, equivalent

to 32.5 mg risedronic acid.

The other ingredients are:

Tablet core

Microcrystalline cellulose, silica (colloidal anhydrous), disodium edetate, sodium starch glycolate,

stearic acid, magnesium stearate.

Enteric coating:

Methacrylic acid - ethyl acrylate copolymer (1:1), triethyl citrate, talc, iron oxide yellow E172,

simeticone, polysorbate 80.

What Optinate Septimum looks like and contents of the pack

Optinate Septimum are oval, yellow tablets with “EC 35” engraved on one side.

The dimensions of the tablet are as follows: width 13 mm, length 6 mm.

Blister packs of 1, 2, 4, 10, 12 or 16 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

[To be completed nationally]

Manufacturer:

Balkanpharma-Dupnitsa AD

3, Samokovsko Shosse Str.

2600 Dupnitsa

Bulgaria

This medicinal product is authorised in the Member States of the EEA under the following

names:

Belgium:

Actonel 35 mg wekelijks maagsapresistente tabletten

France:

Actonel GR 35 mg comprimé gastro-résistant

Germany:

Actonel einmal wöchentlich 35 mg magensaftresistente Tabletten

Greece:

Actonel GR

Italy:

Actonel

The Netherlands:

Actonel Wekelijks MSR35 mg, maagsapresistente tabletten

Portugal:

Actonel 35 mg comprimido gastrorresistente

Romania:

Actonel 35 mg comprimate gastrorezistente

Spain:

Actonel semanal 35 mg comprimidos gastroresistentes

Sweden:

Optinate Septimum

This leaflet was last revised in 2021-03-31

Läs hela dokumentet

SUMMARY OF THE PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Optinate Septimum 35 mg gastro-resistant tablets

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gastro-resistant tablet contains 35 mg risedronate sodium (equivalent to 32.5 mg risedronic acid).

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Gastro-resistant tablet.

Oval, yellow, gastro-resistant tablet with “EC 35” engraved on one side.

The dimensions of the tablet are as follows: width 13 mm, length 6 mm.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Treatment of osteoporosis in postmenopausal women at increased risk of fractures (see section 5.1).

4.2

Posology and method of administration

Posology

The recommended dose in adults is one Optinate Septimum 35 mg gastro-resistant tablet orally once a

week. The tablet should be taken on the same day each week.

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need

for continued treatment should be re-evaluated periodically based on the benefits and potential risks of

risedronate on an individual patient basis, particularly after 5 or more years of use.

Special populations

Elderly

Of the patients receiving risedronate 35 mg gastro-resistant tablets in postmenopausal osteoporosis

studies, 59% were 65 and over, while 13 % were 75 and over. No overall differences in safety and

effectiveness were observed between these patients and younger patients.

Patients with renal impairment

No dosage adjustment is required for those patients with mild to moderate renal impairment. The use

of risedronate sodium is contraindicated in patients with severe renal impairment (creatinine clearance

lower than 30 ml/min) (see sections 4.3 and 5.2).

Paediatric population

Risedronate sodium is not recommended for use in children below age 18 due to insufficient data on

safety and efficacy (also see section 5.1).

Method of administration

Optinate Septimum 35 mg gastro-resistant tablets should be taken orally in the morning immediately

after breakfast. Administration under fasting conditions may lead to an increased risk of upper

abdominal pain (see section 4.8 and 5.2).

The tablet must be swallowed whole and not sucked or chewed. To aid delivery of the tablet to the

stomach, it is to be taken while in an upright position with a glass of plain water (≥120 ml). Patients

should not lie down for 30 minutes after taking the tablet (see section 4.4).

Supplemental calcium and vitamin D should be considered if the dietary intake is inadequate.

Patients should be instructed that if a dose is missed, it should be taken on the day that the tablet is

remembered. Patients should then return to taking one tablet once a week on the day the tablet is

normally taken. Two tablets should not be taken on the same day.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Hypocalcaemia (see section 4.4).

Pregnancy and lactation.

Severe renal impairment (creatinine clearance <30 ml/min).

4.4

Special warnings and precautions for use

Medicinal products containing polyvalent cations (such as calcium, magnesium, iron and aluminium)

interfere with the absorption of bisphosphonates and should be taken at a different time of day to

risedronate tablets (see section 4.5). In order to achieve the intended efficacy, strict adherence to

dosing recommendations is necessary (see section 4.2).

Efficacy of bisphosphonates in the treatment of osteoporosis is related to the presence of low bone

mineral density and/or prevalent fracture.

High age or clinical risk factors for fracture alone are not sufficient reasons to initiate treatment of

osteoporosis with a bisphosphonate.

The evidence to support efficacy of bisphosphonates including risedronate in the very elderly

(>80 years) is limited (see section 5.1).

Hypocalcaemia should be treated before starting risedronate therapy. Other disturbances of bone and

mineral metabolism (i.e. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of

starting risedronate therapy.

Upper gastrointestinal adverse reactions

Bisphosphonates have been associated with oesophagitis, gastritis, oesophageal ulcerations and

gastroduodenal ulcerations. Thus, caution should be used:

In patients who have a history of oesophageal disorders which delay oesophageal transit or

emptying e.g. stricture or achalasia.

In patients who are unable to stay in the upright position for at least 30 minutes after taking the

tablet.

If risedronate is given to patients with active or recent oesophageal or upper gastrointestinal

problems (including known Barrett’s oesophagus).

Prescribers should emphasise to patients the importance of paying attention to the dosing instructions

and be alert to any signs and symptoms of possible oesophageal reaction. The patients should be

instructed to seek timely medical attention if they develop symptoms of oesophageal irritation such as

dysphagia, pain on swallowing, retrosternal pain or new/worsened heartburn.

Osteonecrosis of the jaw

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including

osteomyelitis) has been reported in patients with cancer receiving treatment regimens including

primarily intravenously administered bisphosphonates. Many of these patients were also receiving

chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with

osteoporosis receiving oral bisphosphonates.

A dental examination with appropriate preventive dentistry should be considered prior to treatment

with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy,

radiotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients

who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate

the condition. For patients requiring dental procedures, there are no data available to suggest whether

discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw.

Clinical judgement of the treating physician should guide the management plan of each patient based

on individual benefit /risk assessment.

Osteonecrosis of the external auditory canal

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in

association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory

canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The

possibility of osteonecrosis of the external auditory canal should be considered in patients receiving

bisphosphonates who present with ear symptoms including chronic ear infections.

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate

therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short

oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just

above the supracondylar flare. These fractures occur after minimal or no trauma and some patients

experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to

months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the

contralateral femur should be examined in bisphosphonate-treated patients who have sustained a

femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of

bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered

pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and

any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

This medicinal product contains less than 1 mmol sodium (23 mg) per gastro-resistant tablet, that is to

say essentially ‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

Medicinal products containing polyvalent cations (such as calcium, magnesium, iron and aluminium)

interfere with the absorption of bisphosphonates and should be taken at a different time of day to

risedronate tablets (see section 4.4).

Risedronate sodium is not systemically metabolised, does not induce cytochrome P450 enzymes, and

has low protein binding.

Co-administration of risedronate 35 mg gastro-resistant tablets with the proton pump inhibitor

esomeprazole increased the risedronate bioavailability. The maximum plasma concentration (Cmax)

and the area under the plasma concentration time curve (AUC) were increased by 60% and 22%

respectively, but the clinical implications measured by body mass density changes were not

statistically significant.

If considered appropriate risedronate sodium may be used concomitantly with oestrogen

supplementation.

4.6

Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of risedronate sodium in pregnant women. Studies in animals

have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.

Breast-feeding

Studies in animal indicate that a small amount of risedronate sodium pass into breast milk.

Risedronate sodium must not be used during pregnancy or by breast-feeding women.

Fertility

There are no adequate data on the effects of risedronate on human fertility. Animal studies showed

adverse effects at exposures considerably above that in humans (see section 5.3).

4.7

Effects on ability to drive and use machines

Risedronate sodium has no or negligible influence on the ability to drive and use machines.

4.8

Undesirable effects

Summary of the safety profile

The most commonly reported side effects with risedronate tablets are gastrointestinal disorders

including abdominal pain, diarrhoea, dyspepsia, nausea, constipation; musculoskeletal pain and

headache.

Tabulated list of adverse reactions from clinical studies

Risedronate sodium has been studied in phase III clinical studies involving more than 15,000 patients.

The majority of undesirable effects observed in clinical studies was mild to moderate in severity and

usually did not require cessation of therapy.

Adverse experiences reported in phase III clinical studies in postmenopausal women with osteoporosis

and considered possibly or probably related to risedronate sodium are listed below using the following

convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare

(≥1/10,000 to <1/1,000); very rare (<1/10,000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1

MedDRA

System Organ Class

Common

Uncommon

Rare

Infections and

infestations

Influenza

Blood and lymphatic

system disorders

Leukopenia,

neutropenia

Immune system

disorders

Hypersensitivity

Endocrine disorders

Hyperparathyroidism

secondary

Metabolism and

nutrition disorders

Hypercalcaemia

Psychiatric disorders

Depression

Nervous system

disorders

Headache

Dizziness, paresthesia,

hypoaestesia

Eye disorders

Iritis*, ocular

hyperaemia,

conjunctivitis, vision

blurred

Ear and labyrinth

disorders

Vertigo

Vascular disorders

Hot flush, hypotension

Respiratory, thoracic

and mediastinal

disorders

Cough

Gastrointestinal

disorders

Abdominal pain

including abdominal

pain upper and

abdominal pain

lower, constipation,

dyspepsia, nausea,

diarrhoea, vomiting

Gastritis, Helicobacter

gastritis, oesophagitis,

dysphagia, duodenitis,

oesophageal ulcer,

abdominal discomfort,

abdominal distension,

erosive esophagitis,

gastritis erosive,

haematochezia,

hyperchlorhydria,

eructation, flatulence,

gastritis atrophic,

gastroesophageal

reflux disease,

gingivitis,

haemorrhoids, hiatus

hernia, melaena,

abdominal tenderness,

aphtous stomatitis,

colitis, dry mouth,

faecal incontinence,

gastric mucosal

hypertrophy,

gastrointestinal

inflammation,

gastrointestinal pain,

hypoaesthesia oral, lip

swelling, odynophagia,

swollen tongue

Oesophageal stricture,

glossitis

Hepatobiliary

disorders

Abnormal liver function

tests*

Skin and subcutaneous

tissue disorders

Erythema, Henoch-

Schonlein

purpura,

urticarial, dermatitis

allergic, pruritus, rash

Musculoskeletal and

connective tissues

disorders

Musculoskeletal pain

Arthralgia, back pain,

muscle spasm,

myalgia, pain in

extremity, bone pain,

muscle fatigue,

muscular weakness,

neck pain, pain in jaw

Renal and Urinary

disorders

Nephrolithiasis

Reproductive system

and breast disorders

Ovarian cyst

General disorders and

Asthenia, chills,

administration site

conditions

fatigue, influenza like

illness, chest

discomfort, chest pain,

face oedema, oedema,

oedema peripheral,

pain, pyrexia

Investigations

Blood calcium

andphosphate

decreased, heart rate

irregular, urine

analysis abnormal,

transaminases

increased blood

alkaline phosphatase

increased, blood

parathyroid hormone

increased, occult

blood, platelet count

decreased

* No relevant incidences from Phase III osteoporosis studies; frequency based on adverse

event/laboratory/rechallenge findings in earlier clinical studies.

Description of selected adverse events

Gastrointestinal disorders

In the Phase III study, comparing risedronate 35 mg gastro-resistant tablets and risedronate sodium 5

mg daily (immediate-release) more patients that used NSAID/aspirin reported upper gastrointestinal

treatment-emergent adverse events than non-users.

The frequency of patients that reported such events were:

22.0% in NSAID/aspirin users vs 15.7% in the NSAID/aspirin non-users in the 35 mg

immediately-following-breakfast group

29.8% in NSAID/aspirin users vs 15.3% in the NSAID/aspirin non-users in the 35 mg 30

minutes- before-breakfast group

22.4% in NSAID/aspirin users vs 13.4% in the NSAID/aspirin non-users in the 5 mg

immediate-release before-breakfast group

A higher incidence of upper abdominal pain was seen when risedronate 35 mg gastro-resistant tablets

were taken in a fasted state 30 minutes before breakfast.

The frequency of lower gastrointestinal treatment-emergent adverse events were 22.1% in the 35 mg

immediately-following-breakfast group, 20.1% in the 35 mg 30 minutes- before-breakfast group and

15.6% in the 5 mg immediate-release group.

During post marketing experience the following reactions have been reported

Rare: Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse

reaction).

Very rare: Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction).

Frequency not known (cannot be estimated from available data)

Eye disorders

Uveitis

Musculoskeletal and connective tissues disorders

Osteonecrosis of the jaw

Skin and subcutaneous tissue disorders

Hypersensitivity and skin reactions, including angioedema, and bullous skin reactions, some severe

including isolated reports of Stevens Johnson syndrome, toxic epidermal necrolysis and

leukocytoclastic vasculitis.

Hair loss

Immune system disorders

Anaphylactic reaction

Hepatobiliary disorders

Serious hepatic disorders. In most of the reported cases the patients were also treated with other

products known to cause hepatic disorders.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare

professionals are asked to report any suspected adverse reactions via the national reporting system

listed in Appendix V.

4.9

Overdose

No specific information is available on the treatment of overdose with risedronate sodium.

Decreases in serum calcium following substantial overdose may be expected. Signs and symptoms of

hypocalcaemia may also occur in some of these patients.

Milk or antacids containing magnesium, calcium or aluminium should be given to bind risedronate

and reduce absorption of the drug.

The impact of this intervention for Optinate Septimum 35 mg gastro-resistant tablets has not been

evaluated. The Optinate Septimum 35 mg gastro-resistant formulation is less sensitive to the binding

effects of divalent cations. Standard procedures that are effective for treating hypocalcaemia, including

the administration of calcium intravenously, would be expected to restore physiologic amounts of

ionised calcium and to relieve signs and symptoms of hypocalcaemia.

In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed drug if

performed within 30 minutes of ingestion.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for treatment of bone diseases, Drugs affecting bone structure and

mineralization, Bisphosphonates, ATC Code: M05BA07.

Mechanism of action

Risedronate sodium is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits

osteoclast-mediated bone resorption. The bone turnover is reduced while the osteoblast activity and

bone mineralisation is preserved.

Pharmacodynamic effects

In preclinical studies risedronate sodium demonstrated potent anti-osteoclast and anti-resorptive

activity, and dose dependently increased bone mass and biomechanical skeletal strength. The activity

of risedronate sodium was confirmed by measuring biochemical markers for bone turnover during

pharmacodynamic and clinical studies. In studies of postmenopausal women, decreases in biochemical

markers of bone turnover were observed at month 3 and at subsequent timepoints. Decreases in

biochemical markers of bone turnover were similar with risedronate 35 mg gastro-resistant weekly

tablets and risedronate 5 mg daily at all-time points.

Clinical efficacy and safety

Treatment of Postmenopausal Osteoporosis

Based on effects on mean change in lumbar spine BMD, risedronate 35 mg gastro-resistant tablets

(n=307 following breakfast and n=308 before breakfast) was shown to be equivalent to risedronate

5 mg daily tablets (n=307) in a two-year, double-blind, multicentre study of postmenopausal women

with osteoporosis.

Risedronate 35 mg gastro-resistant tablets administered either before or after breakfast was shown to

be therapeutically equivalent to risedronate 5 mg daily (immediate-release formulation) in a 2-year,

double-blind, multicentre study of postmenopausal women with osteoporosis. The primary efficacy

endpoint of percent change from baseline in lumbar spine BMD (LS) at week 52 was met. Secondary

efficacy endpoints included percent change from baseline in lumbar spine BMD at week 104; non-

vertebral fractures at week 104 which were consistent with the primary outcome measure; and change

in bone turnover markers. Table 2 presents the primary efficacy analysis at 1 year (Primary Analysis

Population), as well as the 2 year results (Week 104 Endpoint Population).

Table 2 Lumbar Spine BMD (LS) - Percent Change from Baseline at 1 yr and 2 yr Endpoints

[a]

Risedronate 5 mg

Daily immediate-

release

N=307

Risedronate 35 mg

Once a Week gastro-

resistant Following

Breakfast

N=307

Risedronate 35 mg

Once a Week

gastro-resistant

Before Breakfast

N=308

Primary Efficacy (LOCF), at 1

year [c]

LS Mean (95% CI)

3.1* (2.7, 3.5)

3.3* (2.9, 3.7)

3.4* (3.0, 3.8)

LS Mean Difference [b] (95% CI)

-0.2 (-0.8, 0.3)

-0.3 (-0.9, 0.3)

2 year-endpoint [d]

LS Mean (95% CI)

4.1 (3.7, 4.6)

5.2 (4.7, 5.7)

5.1 (4.6,5.6)

LS Mean Difference[b] (95% CI)

-1.1 (-1.8, -0.4)

-0.9 (-1.6, -0.2)

N = number of intent-to-treat patients within specified treatment; n = number of patients with values

at baseline and at the visit.

* Indicates a statistically significant difference from baseline determined from 95% CI unadjusted for

multiple comparisons.

at 1 year and 2 year LOCF

LS Mean Difference is 5 mg daily minus 35 mg weekly treatment.

Based on PE Population (all ITT patients who had analyzable lumbar spine BMD data at both

baseline and Week 52 LOCF Endpoint)

Based on

Week 104-Endpoint population(

all ITT patients who had analyzable lumbar spine

BMD data at both baseline and Week 104 LOCF Endpoint)

The clinical programme for risedronate sodium administered once daily studied the effect of

risedronate sodium on the risk of hip and vertebral fractures and contained early and late

postmenopausal women with and without fracture. Daily doses of 2.5 mg and 5 mg were studied and

all groups, including the control groups, received calcium and vitamin D (if baseline levels were low).

The absolute and relative risk of new vertebral and hip fractures was estimated by use of a time-to-first

event analysis.

Two placebo-controlled studies (n=3661) enrolled postmenopausal women under 85 years with

vertebral fractures at baseline. Risedronate sodium 5 mg daily given for 3 years reduced the risk

of new vertebral fractures relative to the control group. In women with respectively at least 2 or

at least 1 vertebral fractures, the relative risk reduction was 49% and 41% respectively

(incidence of new vertebral fractures with risedronate sodium 18.1% and 11.3%, with placebo

29.0% and 16.3%, respectively).

Two further placebo controlled studies enrolled postmenopausal women above 70 years with or

without vertebral fractures at baseline. Women 70-79 years were enrolled with femoral neck

BMD T-score <-3 SD (manufacturer’s range, i.e. -2.5 SD using NHANES III (National Health

and Nutrition Examination Survey)) and at least one additional risk factor. Women >80 years

could be enrolled on the basis of at least one non-skeletal risk factor for hip fracture or low bone

mineral density at the femoral neck. Statistical significance of the efficacy of risedronate versus

placebo is only reached when the two treatment groups 2.5 mg and 5 mg are pooled. The

following results are only based on

a-posteriori

analysis of subgroups defined by clinical

practise and current definitions of osteoporosis:

In the subgroup of patients with femoral neck BMD T-score ≤-2.5 SD (NHANES III) and

at least one vertebral fracture at baseline, risedronate sodium given for 3 years reduced

the risk of hip fractures by 46% relative to the control group (incidence of hip fractures in

combined risedronate sodium 2.5 mg and 5 mg groups 3.8%, placebo 7.4%);

Paediatric population

The safety and efficacy of risedronate sodium has been investigated in a 3-year study (a randomized,

double-blind, placebo-controlled, multicenter, parallel group study of one year duration followed by 2

years of open-label treatment) in paediatric patients aged 4 to less than 16 years with mild to moderate

osteogenesis imperfecta. In this study, patients weighing 10-30 kg received risedronate 2.5 mg daily

and patients weighing more than 30 kg received risedronate 5 mg daily.

After completion of its one-year randomized, double-blind, placebo-controlled phase, a statistically

significant increase in lumbar spine BMD in the risedronate group versus placebo group was

demonstrated; however an increased number of patients with at least 1 new morphometric (identified

by x-ray) vertebral fracture was found in the risedronate group compared to placebo. During the one-

year double-blind period, the percentage of patients who reported clinical fractures was 30.9% in the

risedronate group and 49.0% in the placebo group. In the open-label period when all patients received

risedronate (month 12 to month 36), clinical fractures were reported by 65.3% of patients initially

randomized to the placebo group and by 52.9% of patients initially randomized to the risedronate

group.

Overall, results do not support the use of risedronate sodium in paediatric patients with mild to

moderate osteogenesis imperfecta.

5.2

Pharmacokinetic properties

Absorption

The time to peak concentration (Tmax) for risedronate 35 mg gastro-resistant tablet is ~3 hours when

administered in the morning 4 hours prior to a meal. The relative bioavailability of the risedronate

35 mg gastro-resistant tablets administered after a high-fat breakfast was 2 to 4-fold higher than the

corresponding immediate-release formulation administered 30 minutes prior to a high-fat breakfast.

Food Effect

The presence of food did not appreciably affect the bioavailability of the gastro-resistant tablets.

Distribution

The mean steady state volume of distribution is 6.3 L/kg in humans. Plasma protein binding is about

24%.

Biotransformation

There is no evidence of systemic metabolism of risedronate sodium.

Elimination

Approximately half of the absorbed dose is excreted in urine within 24 hours, and 85% of an

intravenous dose is recovered in the urine after 28 days. Mean renal clearance is 105 ml/min and mean

total clearance is 122 ml/min, with the difference probably attributed to clearance due to adsorption to

bone. The renal clearance is not concentration dependent, and there is a linear relationship between

renal clearance and creatinine clearance. Unabsorbed risedronate sodium is eliminated unchanged in

faeces. After oral administration the concentration-time profile shows three elimination phases with a

terminal half-life of 480 hours.

Special Populations

Elderly

No dosage adjustment is necessary.

Acetyl salicylic acid/NSAID users

Among regular acetyl salicylic acid or NSAID users (3 or more days per week) the incidence of upper

gastrointestinal adverse events in risedronate sodium treated patients was similar to that in control

patients (see section 4.5).

5.3

Preclinical safety data

Repeat-dose toxicity

In toxicological studies in rat and dog, dose dependent liver toxic effects of risedronate sodium were

seen, primarily as enzyme increases with histological changes in rat. The clinical relevance of these

observations is unknown. Testicular toxicity occurred in rat and dog at exposures considered in excess

of the human therapeutic exposure. Dose related incidences of upper airway irritation were frequently

noted in rodents. Similar effects have been seen with other bisphosphonates. Lower respiratory tract

effects were also seen in longer term studies in rodents, although the clinical significance of these

findings is unclear.

The results of a 13-week repeat-dose toxicity study in dogs comparing the gastro-resistant risedronate

formulation with conventional risedronate showed a similar toxicity profile for the two formulations.

Reproductive toxicity

A fertility study in male and female rats showed no adverse effects at oral doses up to 16 mg/kg/day,

corresponding to systemic exposure (serum AUC 0-24h) about 30 times higher than that in humans

dosed at 30 mg/day. At higher dose levels, systemic toxicity, testicular atrophy and reduced fertility

were seen in male rats, but these effects are unlikely to have clinical relevance.

In reproduction toxicity studies at exposures close to clinical exposure ossification changes were seen

in sternum and/or skull of foetuses from treated rats and hypocalcemia and mortality in pregnant

females allowed to deliver. There was no evidence of teratogenesis at 3.2 mg/kg/day in rat and

10 mg/kg/day in rabbit, although data are only available on a small number of rabbits. Maternal

toxicity prevented testing of higher doses.

Studies on genotoxicity and carcinogenesis did not show any particular risks for humans.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Tablet core:

Microcrystalline cellulose (E460)

Silica, colloidal anhydrous

Disodium edetate

Sodium starch glycolate

Stearic acid

Magnesium stearate (E470b)

Enteric coating:

Methacrylic acid – ethyl acrylate copolymer (1:1)

Triethyl citrate (E1505)

Talc (E553b)

Iron oxide yellow E172

Simeticone

Polysorbate 80 (E433)

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

5 years.

6.4

Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container

Clear PVC/aluminium foil blisters in a cardboard carton.

Blisters in packs containing 1, 2, 4, 10, 12, or 16 tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local

requirements.

7.

MARKETING AUTHORISATION HOLDER

<[To be completed nationally]>

{Name and address}

<{tel}>

<{fax}>

<{e-mail}>

8.

MARKETING AUTHORISATION NUMBER(S)

<[To be completed nationally]>

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

<Date of first authorisation: {DD month YYYY}>

<Date of latest renewal: {DD month YYYY}>

<[To be completed nationally]>

10.

DATE OF REVISION OF THE TEXT

2021-03-31

Liknande Produkter

Sök varningar relaterade till denna produkt

Visa dokumenthistorik

Dela den här informationen