linaclotide: package leaflet

What Constella is used for
Constella contains the active substance linaclotide. It is used to treat the symptoms of moderate to severe irritable bowel syndrome (often just called “IBS”) with constipation in adult patients.

IBS is a common gut disorder. The main symptoms of IBS with constipation include:
- stomach or abdominal pain,
- feeling bloated,
- infrequent, hard, small or pellet-like stools (faeces).

These symptoms may vary from person to person.

How Constella works
Constella acts locally in your gut, helping you to feel less pain and less bloated, and to restore the normal functioning of your bowels. It is not absorbed into the body, but attaches to receptor called guanylate cyclase C on the surface of your gut. By attaching to this receptor, it blocks the sensation of pain and allows liquid to enter from the body into the gut, thereby loosening the stools and increasing your bowel movements.

Do not take Constella
- if you are allergic to linaclotide or any of the other ingredients of this medicine (listed in section 6).
- if you or your doctor know that you have a blockage in your stomach or bowels.

Warnings and precautions
Your doctor has given this medicine to you after excluding other diseases, especially of your bowels and concluding that you suffer from IBS with constipation. Because these other diseases may have the same symptoms as IBS, it is important that you report any change or irregularity in symptoms to your doctor promptly.

If you experience severe or prolonged diarrhoea (passing of frequent watery stools for 7 days or more), stop taking Constella and contact your doctor (see section 4). Make sure you drink plenty of fluids to replace the water and electrolytes like potassium lost from the diarrhoea.

If you have severe stomach symptoms which continue or get worse, stop taking Constella and contact your doctor immediately because these could be symptoms of a hole developing in the bowel wall (gastrointestinal perforation). See section 4.

Talk to your doctor if you experience bleeding from the bowel or rectum.

Take special care if you are older than 65 years, as there is a higher risk you experience diarrhoea.

Take also special care if you have severe or prolonged diarrhoea and an additional disease, such as high blood pressure, previous disease of the heart and blood vessels (e.g. such as previous heart attacks) or diabetes.

Talk to your doctor if you suffer from inflammatory diseases of the guts such as Crohn’s disease or ulcerative colitis as Constella is not recommended in these patients.

Children and adolescents
Do not give this medicine to children and adolescents under the age of 18 years because the safety and efficacy of Constella in this age group has not been established.

Other medicines and Constella
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines:
▪ Some medicines may not work as effectively if you have severe or prolonged diarrhoea, such as:
- Oral contraceptives. If you have very bad diarrhoea, the contraceptive pill may not work properly and the use of an extra method of contraception is recommended. See the instructions in the patient leaflet of the contraceptive pill you are taking.
- Medicines that need careful and exact dosing, such as levothyroxine (a hormone to treat reduced function of the thyroid gland).
▪ Some medicines may increase the risk of diarrhoea when taken with Constella, such as:
- Medicines to treat stomach ulcers or excessive production of stomach acid called Proton Pump Inhibitors.
- Medicines to treat pain and inflammation called NSAIDs.
- Laxatives.

Constella with food
Constella produces more frequent bowel movements and diarrhoea (looser stools) when it is taken with food than when it is taken on an empty stomach (see section 3).

Pregnancy and breast-feeding
Limited information is available on the effects of Constella in pregnant and breast-feeding women.

Do not take this medicine if you are pregnant, think you may be pregnant or are planning to have a baby, unless your doctor advises you to do so.

In a milk-only lactation study in seven lactating women, who were already taking linaclotide therapeutically, neither linaclotide nor its active metabolite were detected in the milk. Therefore breastfeeding is not expected to result in exposure of the infant to linaclotide and Constella can be used during breast-feeding.

Driving and using machines
Constella will not affect your ability to drive or use machines

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is one capsule (i.e. 290 micrograms of linaclotide) taken orally once a day. The capsule should be taken at least 30 minutes before a meal.

If you have not experienced improvement in your symptoms after 4 weeks of treatment, you should contact your doctor.

If you take more Constella than you should
The most likely effect of taking too much Constella is diarrhoea. Contact your doctor or pharmacist if you have taken too much of this medicine.

If you forget to take Constella
Do not take a double dose to make up for a forgotten dose. Just take the next dose at the scheduled time and continue as normal.

If you stop taking Constella
It is preferable to discuss stopping treatment with your doctor before actually doing so. However, treatment with Constella can be safely stopped at any time.

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

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

Serious side effects:
Stop using Constella and seek medical attention immediately if you experience any of the following symptoms: difficulty breathing, light-headedness, fainting, fast heartbeat, swelling of the face, throat, or other parts of the body and sweating. These could be signs of an anaphylactic reaction (sudden, severe allergic reaction) (not known: frequency cannot be estimated from the available data).

Very common (may affect more than 1 in 10 people):
- diarrhoea

Diarrhoea is normally short lived; however, if you experience severe or prolonged diarrhoea (passing of frequent watery stools for 7 days or more) and feel lightheaded, dizzy or faint, stop taking Constella and contact your doctor.

Common (may affect up to 1 in 10 people):
- stomach or abdominal pain
- feeling bloated
- wind
- stomach flu (viral gastroenteritis)
- feeling dizzy

Uncommon (may affect up to 1 in 100 people):
- lack of control over passing stools (faecal incontinence)
- urgency to pass stools
- feeling lightheaded after standing up quickly
- dehydration
- low level of potassium in your blood
- decreased appetite

• rectal bleeding
• bleeding from the bowel or rectum including bleeding from piles/haemorrhoids
• nausea
• vomiting
• hives (urticaria)

Rare (may affect up to 1 in 1 000 people):
- bicarbonate decrease in your blood
- a hole developing in the bowel wall (gastrointestinal perforation)

Not known (frequency cannot be estimated from the available data):
- rash

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.

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 the bottle after ¨EXP¨. The expiry date refers to the last day of that month.
Once the bottle is opened, the capsules should be used within 18-weeks.

Do not store above 30 ºC. Keep the bottle tightly closed in order to protect from moisture.

Warning: The bottle contains one or more sealed canisters containing silica gel to keep the capsules dry.
Keep the canisters in the bottle. Do not swallow them.

Do not use this medicine if you notice any signs of damage to the bottle or any change in the appearance of the capsules.

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.

What Constella contains

• The active substance is linaclotide. Each capsule contains 290 micrograms of linaclotide.

• The other ingredients are :

Capsule content: microcrystalline cellulose, hypromellose, calcium chloride dihydrate and leucine.

Capsule shell: red iron oxide (E172), titanium dioxide (E171), yellow iron oxide (E172), gelatin and polyethylene glycol

Capsule ink: shellac, propylene glycol, concentrated ammonia solution, potassium hydroxide, titanium dioxide (E171) and black iron oxide (E172).

What Constella looks like and contents of the pack

The capsules are white to off-white-orange opaque hard capsules marked “290” with grey ink.

They are packaged in a white, high density polyethylene (HDPE) bottle with a tamper evident seal and a child-resistant screw cap, together with one or more desiccant canisters containing silica gel.

Constella is available in packs containing 10, 28 or 90 capsules and in multipacks of 112 capsules comprising 4 cartons, each containing 28 capsules. Not all pack-sizes may be marketed.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer

Forest Laboratories Ireland Limited
Clonshaugh Business and Technology Park
Clonshaugh
Dublin 17, D17 E400
Ireland

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: + 370 5 205 3023

България
АбВи ЕООД
Тел:+359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel.: +420 233 098 111

Magyarország
AbbVie Kft.
Tel:+36 1 455 8600
Danmark
AbbVie A/S
Tlf: +45 72 30 20 28

Malta
Vivian Corporation Ltd.
Tel: +356 27780331
Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel.: 00800 222843 33 (gebührenfrei)
Tel.: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel. +372 6231011

Norge
AbbVie AS
Tlf: +47 67 81 80 00

Ελλάδα
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

España
AbbVie Spain, S.L.U.
Tel: +34 913840910

Polska
AbbVie Sp. z o.o.
Tel.: +48 22 372 78 00

France
AbbVie
Tél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel.: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: + 385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35
Ireland
AbbVie Limited
Tel: +353 (0)1 4287900

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777
Italia
AbbVie S.r.l.
Tel: +39 06 928921
Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200

Κύπρος
Lifepharma (Z.A.M.) Ltd
Τηλ: +357 22 34 74 40
Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.

To listen to or request a copy of this leaflet in Braille, large print or audio, please contact the local representative of the Marketing Authorisation Holder.

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE
MARKETING AUTHORISATION(S)

Scientific conclusions
Taking into account the PRAC Assessment Report on the PSUR(s) for linaclotide, the scientific conclusions of PRAC are as follows:
In view of available data on anaphylactic reaction from spontaneous reports including cases with a close temporal relationship, typical symptoms, typical treatment and a positive de-challenge, the PRAC considers a causal relationship between linaclotide and anaphylactic reaction is at least a reasonable possibility. The PRAC concluded that the product information of products containing linaclotide should be amended accordingly.
Having reviewed the PRAC recommendation, the CHMP agrees with the PRAC overall conclusions and grounds for recommendation.
Grounds for the variation to the terms of the marketing authorisation(s)
On the basis of the scientific conclusions for linaclotide the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing linaclotide is unchanged subject to the proposed changes to the product information.
The CHMP recommends that the terms of the marketing authorisation(s) should be varied.
Update of section 4.8 of the SmPC to add anaphylactic reaction with a frequency not known. The Package leaflet is updated accordingly.
Summary of Product Characteristics
Section 4.8
The following adverse reaction(s) should be added under the SOC Immune system disorders with a frequency of ‘‘not known”:
Anaphylactic reaction
Package Leaflet
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects:
Stop using < product name > and seek medical attention immediately if you experience any of the following symptoms: difficulty breathing, light-headedness, fainting, fast heartbeat, swelling of the face, throat, or other parts of the body and sweating. These could be signs of an anaphylactic reaction (sudden, severe allergic reaction) (not known: frequency cannot be estimated from the available data).