Gribero

Package leaflet: Information for the patient

Gribero, 150 mg, hard capsules
Dabigatranum etexilatum
Please read carefully the entire leaflet before taking the use of the medicine, because
it contains important information 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 are the same.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What is Gribero and what is it 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 is Gribero and what is it used for

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

• prevent the formation of blood clots in the brain (stroke) and in other blood vessels in the patient's body, if the patient has a form of irregular heart rhythm called non-valvular atrial fibrillation and at least one additional risk factor.
• treat blood clots in the veins of the legs and lungs and to prevent recurrence of blood clots in the veins of the legs and lungs.

Gribero is used in children to:

• treat blood clots and to prevent 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 impairment of kidney function.

• if the patient currently has bleeding.

• if the patient has an internal organ disease that increases the risk of major bleeding (e.g. peptic 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 using a procedure called catheter ablation in atrial fibrillation.

• if the patient has severe impairment of liver function 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 had a mechanical heart valve implanted, 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 currently have or have had in the past any pathological 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 underwent surgical 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 inflammation of the esophagus or stomach. 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 in the heart (bacterial endocarditis). if the patient has reduced kidney function or the patient is dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated) and (or) foamy urine). if the patient is over 75 years of age. if the patient is an adult and weighs 50 kg or less. only when used in children: if the child has an infection around or within the brain. in case of previous myocardial infarction or if the patient has been diagnosed with conditions increasing the risk of myocardial infarction. if the patient has liver disease affecting blood test results. In such a case, use of this medicine is not recommended.

When to exercise particular caution when using Gribero

• if the patient needs to undergo surgery: in such a case, temporary discontinuation of Gribero is necessary due to the 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 anesthesia 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 anesthesia wears off, as urgent medical care is required.
• if the patient fell or injured themselves during treatment, especially if the head was injured. Immediate medical attention is required. 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 clotting), the patient should inform their doctor, who will decide on possible changes in treatment.

Gribero and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take. In particular, you should tell your doctor before taking Gribero if you are 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 topically on the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking medicines containing 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 selective 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 is planning 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 age should avoid becoming pregnant while taking Gribero.
Breastfeeding is not recommended during treatment with Gribero.
Driving and operating machinery
Gribero has no effect or has 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, meaning 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 formulations are available for treating children under 12 years of age, provided they are able to swallow soft foods.

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

Gribero should be taken according to the following recommendations:

Prevention of thromboembolic events in blood vessels of the brain and the rest of the body caused by blood clots forming due to abnormal heart function, and treatment of blood clots in the veins of the legs and lungs, as well as prevention of recurrence of such clots.

The recommended dose is 300 mg taken as one 150 mg capsule twice daily.

In patients aged 80 years or older, the recommended dose is 220 mg taken as one 110 mg capsule twice daily.

Patients taking medicines containing verapamil should receive a reduced dose of Gribero of 220 mg taken as one 110 mg capsule twice daily, due to a potentially increased risk of bleeding.

In patients with a potentially increased risk of bleeding, the doctor may recommend treatment with a dose of 220 mg taken as one 110 mg capsule twice daily.

Treatment with this medicine may be continued if the patient requires restoration of normal heart rhythm by a procedure called cardioversion or by a procedure called catheter ablation for atrial fibrillation. Gribero should be taken exactly as prescribed by the doctor.

In the case of implantation of a medical device (stent) into a blood vessel to maintain its patency, using a procedure called percutaneous coronary intervention with stent implantation, the patient may be treated with Gribero after the doctor has confirmed adequate control of blood coagulation. Gribero should be taken exactly as prescribed by the doctor.

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 ideally be 12 hours.

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

Table 1 shows the single and total daily doses of Gribero in milligrams (mg). 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: as two 110 mg capsules
185 mg: as one 75 mg capsule and one 110 mg capsule
150 mg: as 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 and taking a capsule, 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 recommended
Taking too high a dose of this medicine increases the risk of bleeding. If a patient takes too many
capsules, contact a doctor immediately. Specific treatment methods are available.
Missed dose of Gribero
A missed dose may be taken up to 6 hours before the next scheduled dose.
If less than 6 hours remain until the next scheduled dose, the missed dose should not be taken.
Do not take a double dose to make up for a missed dose.
Stopping Gribero treatment
Gribero should be taken as directed by the doctor. Do not stop taking this medicine without first consulting your doctor, as the risk of blood clots 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 effects

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

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

Prevention of blood vessel blockages in the brain and elsewhere in the body caused by clots forming due to irregular heart function

Common (may occur in up to 1 in 10 people):

• Bleeding may occur from the nose, into the stomach or intestines, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in the number of red blood cells in the blood
• Abdominal pain or stomach pain
• Indigestion
• Frequent passage of loose or watery stools
• Nausea

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

• Bleeding
• Bleeding may occur from haemorrhoids, rectum, or into the brain
• Formation of bruises (haematomas)
• Coughing up blood or bloody sputum
• Decrease in the number of platelets in the blood
• Decrease in haemoglobin levels in the blood (the substance in red blood cells)
• 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)
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results

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

• Bleeding into a joint, from a surgical incision site, from a wound, from an injection site, or from the site of intravenous catheter insertion
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash appearing as dark red, raised, itchy bumps due to an allergic reaction
• Decrease in blood cell count
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver or blood disease

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

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

In clinical trials, the number of heart attacks observed with dabigatran etexilate was numerically higher than with warfarin. The overall number of events was small.

Treatment of blood clots in the legs and lungs, and prevention of recurrence of blood clots in the legs and lungs

Common (may occur in up to 1 in 10 people):

• Bleeding may occur from the nose, into the stomach or intestines, from the anus, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Indigestion

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

• Bleeding
• Bleeding may occur into a joint or following injury
• Bleeding from haemorrhoids may occur
• Decrease in the number of red blood cells in the blood
• Formation of bruises (haematomas)
• Coughing up blood or bloody sputum
• 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)
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent passage of loose or watery stools
• Abnormal liver function test results
• Increased liver enzyme activity

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

• Bleeding from a surgical incision site, injection site, or site of intravenous catheter insertion, or bleeding from the brain
• Decrease in the number of platelets in the blood
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash appearing as dark red, raised, itchy bumps due to an allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decrease in haemoglobin levels in the blood (the substance in red blood cells)
• Decrease in blood cell count
• Decrease in number or even absence of white blood cells (which help fight infections)
• Yellowing of the skin or whites of the eyes due to liver or blood disease
• Hair loss

In clinical trials, the number of heart attacks observed with dabigatran etexilate was numerically higher than with warfarin. The overall number of events was low. No difference in the number of heart attacks was observed between patients treated with dabigatran and those receiving placebo.

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

Common (may occur in up to 1 in 10 people):

• Decrease in the number of red blood cells in the blood
• Decrease in the number of platelets in the blood
• Skin rash appearing as dark red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin colour and appearance
• Formation of bruises (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):

• Decrease in the number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, from the brain, from the rectum, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in haemoglobin levels in the blood (the substance in red blood cells)
• Decrease in blood cell count
• Itching
• Coughing up blood or bloody 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 due to 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 may occur into a joint, from a wound, from a surgical incision site, from an injection site, or from the site of intravenous catheter insertion
• Bleeding from haemorrhoids may occur
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Gribero medicine

Keep the medicine out of the 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 in use. This will help protect
the environment.

6. Contents of the package and other information

What does Gribero contain?

• The active substance is dabigatran etexilate. Each capsule contains 150 mg of dabigatran etexilate (as mesilate).
• Other components:
• Capsule contents: tartaric acid (in the form of pellets), hypromellose (2910), talc, hydroxypropylcellulose (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 0 capsule with a white, opaque cap printed with "MD" and a white, opaque body printed with "150" 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 box.
Perforated OPA/Aluminium/PE + desiccant/Aluminium/PE blister packs 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 box.
Polypropylene bottle with a child-resistant polypropylene cap, containing a desiccant and 60 hard capsules, in a cardboard box.
Do not swallow the drying agent.
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 about this medicine, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
Poland
Tel: +48 22 209 70 00

This medicine is authorised for sale in the European Economic Area under the following names:
Austria Gribero 150 mg – Hartkapseln
Bulgaria Gribero 150 mg hard capsules
Czech Republic Gribero
Estonia Gribero
Greece Gribero
Croatia Gribero 150 mg tvrde kapsule
Lithuania Gribero 150 mg kietosios kapsulės
Latvia Gribero 150 mg cietās kapsulas
Poland Gribero
Romania Gribero 150 mg capsule
Slovenia Gribero 150 mg trde kapsule
Slovakia Gribero 150 mg tvrdé kapsuly