Gribero

Package leaflet: Information for the patient

Gribero, 75 mg, hard capsules
Dabigatranum etexilatum
Please read this leaflet carefully before taking using the medicine, because
it contains information important for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms of illness are the same.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform the doctor or pharmacist. See section 4.

Leaflet contents

1. What Gribero is and what it is used for
2. Important information before taking Gribero
3. How to take Gribero
4. Possible side effects
5. How to store Gribero
6. Contents of the pack and other information

1. What Gribero is and what it is used for

Gribero contains dabigatran etexilate as the active substance and belongs to a group of medicines called anticoagulants. Its action is based on blocking in the body a substance responsible for blood clot formation.
Gribero is used in adults for:

• prevention of blood clots in veins after hip or knee replacement surgery.

Gribero is used in children for:

• treatment of blood clots and prevention of recurrence of blood clots.

2. Important information before taking Gribero
When not to take Gribero

• if the patient is allergic to dabigatran etexilate or to any of the other ingredients of this medicine (listed in section 6).
• if the patient has severe kidney function impairment.
• if the patient is currently experiencing bleeding.
• if the patient has an internal organ disease that increases the risk of major bleeding (e.g. gastric ulcer, brain injury or intracranial hemorrhage, recent brain or eye surgery).
• if the patient has an increased tendency to bleed. This may be congenital, of unknown cause, or caused by taking other medicines.
• if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, apixaban or heparin), except when switching anticoagulant therapy, inserting a venous or arterial catheter through which heparin is administered to maintain its patency, or restoring normal heart rhythm by a procedure called catheter ablation in atrial fibrillation.
• if the patient has severe liver function impairment or liver disease that may lead to death.
• if the patient is taking oral ketoconazole or itraconazole, medicines used for fungal infections.
• if the patient is taking oral cyclosporine, a medicine used to prevent rejection of a transplanted organ.
• if the patient is taking dronedarone, a medicine used to treat heart rhythm disorders.
• if the patient is taking a combination medicine containing glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C virus infection.
• if the patient has a mechanical heart valve implant, which requires continuous use of blood-thinning medicines.

Warnings and precautions
Before starting to take Gribero, discuss this with your doctor. If symptoms occur or the patient needs to undergo a surgical procedure during treatment with this medicine, consult your doctor.
The patient should inform the doctor if they have or have had any medical conditions or diseases, especially those listed below:

• if the patient has an increased risk of bleeding, such as: if the patient has recently experienced bleeding; if the patient has undergone a surgical tissue biopsy within the last month; if the patient has suffered a serious injury (e.g. bone fracture, head injury or any injury requiring surgical treatment); if the patient has esophagitis or gastritis; if the patient has gastroesophageal reflux; if the patient is taking medicines that may increase the risk of bleeding. See below "Gribero and other medicines"; if the patient is taking non-steroidal anti-inflammatory drugs such as diclofenac, ibuprofen, piroxicam; if the patient has an infection of the heart (bacterial endocarditis); if the patient has reduced kidney function or is dehydrated (feeling thirsty and passing reduced amounts of dark [concentrated] and/or frothy urine); if the patient is over 75 years old; if the patient is an adult weighing 50 kg or less; only when used in children: if the child has an infection around or within the brain; if the patient has had a heart attack or has conditions diagnosed as increasing the risk of heart attack; if the patient has liver disease affecting blood test results. In such a case, use of this medicine is not recommended.

When to exercise special caution when using Gribero

• if the patient needs to undergo a surgical procedure: in such a case, temporary discontinuation of Gribero is necessary due to increased risk of bleeding during and immediately after surgery. It is very important to take Gribero exactly as directed by the doctor before and after surgery.
• if the surgical procedure requires insertion of a catheter or injection into the spine (e.g. for epidural or spinal anaesthesia or for pain relief):

it is very important to take Gribero exactly as directed by the doctor before and after surgery.
the patient should immediately inform the doctor if numbness or weakness of the lower limbs or problems with the intestines or bladder occur after the anaesthesia wears off, as urgent medical care is required.

• if the patient has fallen or injured themselves during treatment, especially if the head was injured. The patient should immediately seek medical attention. The doctor will assess whether the patient may have an increased risk of bleeding.
• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether a change in treatment is necessary.

Gribero and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. In particular, tell the doctor before taking Gribero if the patient is taking any of the following
medicines:

• Medicines that reduce blood clotting (e.g. warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid).
• Medicines used for fungal infections (e.g. ketoconazole, itraconazole), unless these medicines are used only on the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking medicines containing amiodarone, quinidine or verapamil, the doctor may recommend a lower dose of Gribero depending on the condition for which the medicine was prescribed. See also section 3.
• Medicines used to prevent rejection of a transplanted organ (e.g. tacrolimus, cyclosporine).
• A combination medicine containing glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C virus infection).
• Anti-inflammatory and pain-relieving medicines (e.g. acetylsalicylic acid, ibuprofen, diclofenac).
• St. John's wort, a herbal medicine used to treat depression.
• Antidepressant medicines called selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.
• Rifampicin or clarithromycin (both are antibiotics).
• Antiviral medicines used to treat AIDS (e.g. ritonavir).
• Some medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor before using this medicine.
It is not known what effect Gribero has on pregnancy and the unborn child. This medicine should not be taken during pregnancy unless the doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Gribero.
Breastfeeding is not recommended during treatment with Gribero.
Driving and operating machinery
Gribero has no effect or a negligible effect on the ability to drive and operate machinery.
Gribero contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, i.e. the medicine is considered "sodium-free".

3. How to take Gribero

Gribero capsules can be used in adults and children aged 8 years or older who are able to swallow capsules whole. Other age-appropriate pharmaceutical forms are available for treating children under 12 years of age, provided they can swallow soft foods.

This medicine should always be taken as prescribed by your doctor. If in doubt, consult your doctor.

Take Gribero exactly as directed below:

Prevention of blood clots after surgery (joint replacement) of the hip or knee joint

The recommended dose of Gribero is 220 mg once daily (taken as 2 capsules of 110 mg).

In patients with renal function reduced by more than half, or in patients aged 75 years or older, the recommended dose is 150 mg once daily (taken as 2 capsules of 75 mg).

In patients taking medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Gribero is 150 mg once daily (taken as 2 capsules of 75 mg).

Patients taking medicines containing verapamil, who also have renal function reduced by more than half, should take a reduced dose of Gribero of 75 mg due to an increased risk of bleeding.

Treatment with Gribero should not be initiated if there is bleeding at the surgical site. If treatment cannot be started until the day after surgery, it should be initiated with a dose of 2 capsules once daily.

After knee joint replacement surgery

Start treatment with Gribero by taking one capsule within 1 to 4 hours after completion of the surgical procedure. Then take 2 capsules once daily for a total of 10 days.

After hip joint replacement surgery

Start treatment with Gribero by taking one capsule within 1 to 4 hours after completion of the surgical procedure. Then take 2 capsules once daily for a total of 28 to 35 days.

Treatment of blood clots and prevention of recurrent blood clots in children

Gribero should be taken twice daily, one dose in the morning and one in the evening, approximately at the same time each day. The interval between doses should be as close as possible to 12 hours.

The recommended dose depends on body weight and age. Your doctor will determine the correct dose and may adjust it during treatment. Continue taking all other medications unless your doctor advises otherwise.

Table 1 shows the single and total daily doses of Gribero in milligrams (mg). The doses depend on the patient's body weight in kilograms (kg) and age in years.

Table 1 Dosing table for Gribero capsules

Single doses requiring a combination of more than one
capsule: 300 mg: two 150 mg capsules or
four 75 mg capsules
260 mg: one 110 mg capsule and one 150 mg capsule or one 110 mg capsule and
two 75 mg capsules
220 mg: two 110 mg capsules
185 mg: one 75 mg capsule and one 110 mg capsule
150 mg: one 150 mg capsule or two 75 mg capsules
How to take Gribero
Gribero can be taken with or without food. The capsules should be swallowed whole,
with a glass of water, to facilitate passage into the stomach. Do not break, chew or empty the pellets from the capsule, as this may increase the risk of bleeding.
Instructions for blister packs
Push the capsules through the foil blister.
Instructions for the bottle
Press and twist to open the bottle.
After removing a capsule and taking the dose, immediately close the bottle tightly with the cap.
Switching anticoagulant medication
Do not switch anticoagulant medication without receiving detailed instructions from your doctor.
Taking more Gribero than prescribed
Taking too high a dose of this medicine increases the risk of bleeding. If a patient has taken too many
capsules, contact a doctor immediately. Specific treatment methods are available.
Missed dose of Gribero
Prevention of blood clots after hip or knee replacement surgery
Continue taking the missed daily dose of Gribero at the same time on the following day.
Do not take a double dose to make up for a missed dose.
Treatment and prevention of recurrence of blood clots in children
A missed dose may be taken up to 6 hours before the next scheduled dose.
If less than 6 hours remain before the next scheduled dose, do not take the missed dose.
Do not take a double dose to make up for a missed dose.
Stopping Gribero treatment
Gribero should be taken exactly as prescribed by the doctor. Do not stop taking this medicine without first consulting your doctor, as the risk of developing a blood clot may be higher if treatment is stopped prematurely. Contact your doctor if gastrointestinal discomfort occurs after taking Gribero.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Gribero affects the blood clotting system; therefore, most adverse reactions involve symptoms such as bruising or bleeding. Severe or major bleeding may occur, which is the most serious adverse reaction. Regardless of location, it may lead to disability, be life-threatening, or even result in death. In some cases, such bleeding may not be visible.
If you experience bleeding that does not stop spontaneously, or symptoms of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), contact your doctor immediately. Your doctor may decide to place you under close monitoring or change your treatment.
In case of a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

The possible adverse reactions listed below are grouped according to their frequency of occurrence.

Prevention of blood clots after hip or knee replacement surgery
Common (may occur in up to 1 in 10 people):

• Decreased haemoglobin levels in the blood (a substance in red blood cells)
• Abnormal liver function test results

Uncommon (may occur in up to 1 in 100 people):

• Bleeding from the nose, stomach or intestines, penis or vagina or urinary tract (including pink or red urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into joints, due to injury or after injury or surgery
• Formation of haematomas or bruising occurring after surgery
• Blood in stool detected in laboratory tests
• Decreased number of red blood cells in the blood
• Decreased proportion of blood cells
• Allergic reaction
• Vomiting
• Frequent passage of loose or watery stools
• Nausea
• Presence of discharge from the wound (fluid leaking from the surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver or blood disease

Rare (may occur in up to 1 in 1,000 people):

• Bleeding
• Bleeding into the brain, from the surgical incision site, from the injection site or from the site where a venous catheter was inserted
• Blood-tinged discharge from the site where a venous catheter was inserted
• Coughing up blood or blood-stained sputum
• Decreased platelet count in the blood
• Decreased number of red blood cells in the blood after surgery
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash consisting of dark red, raised, itchy bumps occurring as a result of an allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Fluid leaking from the wound
• Fluid leaking from the surgical wound

Frequency not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decreased number or even absence of white blood cells (which help fight infections)
• Hair loss

Treatment of blood clots and prevention of recurrent blood clots in children
Common (may occur in up to 1 in 10 people):

• Decreased number of red blood cells in the blood
• Decreased platelet count in the blood
• Skin rash consisting of dark red, raised, itchy bumps occurring as a result of an allergic reaction
• Sudden change in skin colour and appearance
• Formation of haematomas
• Nosebleeds
• Regurgitation of stomach contents into the oesophagus (reflux)
• Vomiting
• Nausea
• Frequent passage of loose or watery stools
• Indigestion
• Hair loss
• Increased liver enzyme activity

Uncommon (may occur in up to 1 in 100 people):

• Decreased number of white blood cells (which help fight infections)
• Bleeding into the stomach or intestines, brain, rectum, penis or vagina or urinary tract (including pink or red urine due to presence of blood), or bleeding under the skin
• Decreased haemoglobin levels in the blood (a substance in red blood cells)
• Decreased proportion of blood cells
• Itching
• Coughing up blood or blood-stained sputum
• Abdominal pain or stomach pain
• Inflammation of the oesophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowing of the skin or whites of the eyes caused by liver or blood disease

Frequency not known (frequency cannot be estimated from available data):

• Absence of white blood cells (which help fight infections)
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Difficulty breathing or wheezing
• Bleeding
• Bleeding into joints, from wounds, from surgical incision sites, injection sites or sites where a venous catheter was inserted
• Bleeding from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 49 21 301; Fax: +48 22 49 21 309; Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Gribero

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister, or bottle
after: EXP. The expiry date refers to the last day of the stated month.
Blister packs and bottle:
Store below 30°C.
Bottle:
After opening, the medicine should be used within 60 days.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Gribero contains

• The active substance is dabigatran etexilate. Each capsule contains 75 mg of dabigatran etexilate (as mesylate).
• Other ingredients are:
• Capsule contents: tartaric acid (in the form of pellets), hypromellose (2910), talc, hydroxypropyl cellulose (353 cps – 658 cps), sodium croscarmellose, magnesium stearate.
• Capsule shell: titanium dioxide (E 171), hypromellose.
• Black printing ink: shellac, propylene glycol (E 1520), potassium hydroxide, iron oxide black (E 172).

What Gribero looks like and contents of the pack
Hard capsule.
Size 2 hard capsule with a white, opaque cap printed with "MD" and a white, opaque body printed with "75" in black ink. The capsule contains a mixture of pellets ranging in colour from white to pale yellow and pale yellow granules.
Gribero is available as:
OPA/Aluminium/PE + desiccant/Aluminium/PE blisters containing 10, 30, 60, 100, 180 and 200 hard capsules, in a cardboard carton.
Perforated OPA/Aluminium/PE + desiccant/Aluminium/PE blisters divided into single doses, containing 10 x 1, 20 x 1, 30 x 1, 50 x 1, 60 x 1, 100 x 1, 180 x 1 and 200 x 1 hard capsules, in a cardboard carton.
Polypropylene bottle with a child-resistant polypropylene cap, containing a desiccant and 60 hard capsules, in a cardboard carton.
Do not swallow the desiccant.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
Poland

Manufacturer/Importer
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben
Germany
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
Lek Pharmaceuticals, d.d.
Verovskova Ulica 57
Ljubljana, 1526
Slovenia

For further information on this medicinal product, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
Poland
Tel: +48 22 209 70 00

This medicinal product is authorised for marketing in the European Economic Area under the following names:
Austria Gribero 75 mg – Hartkapseln
Bulgaria Gribero 75 mg hard capsules
Czech Republic Gribero
Estonia Gribero
Greece Gribero
Croatia Gribero 75 mg tvrde kapsule
Lithuania Gribero 75 mg kietosios kapsulės
Latvia Gribero 75 mg cietās kapsulas
Poland Gribero
Romania Gribero 75 mg capsule
Slovenia Gribero 75 mg trde kapsule
Slovakia Gribero 75 mg tvrdé kapsuly