Gribero

Package leaflet: Information for the patient

Gribero, 110 mg, hard capsules
Dabigatranum etexilatum
Please read carefully the entire leaflet before taking the use of this 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 questions, 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 you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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. It works by blocking a substance in the body responsible for blood clot formation.
Gribero is used in adults to:

• prevent the formation of blood clots in veins after hip or knee replacement surgery.
• prevent the formation of blood clots in the brain (stroke) and other blood vessels in the body in patients with a type of irregular heartbeat called non-valvular atrial fibrillation and at least one additional risk factor.
• treat blood clots in the legs and lungs and prevent recurrence of blood clots in the legs and lungs.

Gribero is used in children to:

• treat blood clots and prevent recurrence of blood clots.

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

• if you are allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6).
• if you have severe kidney problems.
• if you are currently experiencing bleeding.
• if you have a disease of an internal organ that increases the risk of major bleeding (e.g. stomach ulcer, brain injury or intracranial bleeding, recent brain or eye surgery).
• if you have an increased tendency to bleed. This may be congenital, of unknown cause, or caused by other medicines.
• if you are 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 you have severe liver problems or liver disease that may lead to death.
• if you are taking oral ketoconazole or itraconazole, medicines used to treat fungal infections.
• if you are taking oral cyclosporine, a medicine used to prevent rejection of a transplanted organ.
• if you are taking dronedarone, a medicine used to treat heart rhythm disorders.
• if you are taking a fixed-dose combination medicine containing glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C virus infection.
• if you have an artificial heart valve implanted, which requires continuous use of blood-thinning medicines.

Warnings and precautions
Before starting treatment with Gribero, discuss it with your doctor. If symptoms occur or you need to undergo a surgical procedure during treatment, consult your doctor.
You should inform your doctor if you have or have previously had any medical conditions or diseases, especially those listed below:

• if you have an increased risk of bleeding, such as: if you have recently experienced bleeding; if you have undergone a surgical tissue biopsy (biopsy) within the last month; if you have suffered a serious injury (e.g. bone fracture, head injury, or any injury requiring surgical treatment); if you have oesophagitis or gastritis; if you have gastro-oesophageal reflux (acid reflux into the oesophagus); if you are taking medicines that may increase the risk of bleeding. See below "Gribero and other medicines"; if you are taking non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, ibuprofen, piroxicam; if you have an infection of the heart (bacterial endocarditis); if you have reduced kidney function or you are dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated) and/or foamy urine); if you are over 75 years of age; if you are an adult weighing 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 you have conditions diagnosed that increase the risk of myocardial infarction.
if you have liver disease affecting blood test results. In such a case, use of this medicine is not recommended.
When to exercise special caution when taking Gribero

• if you need to undergo surgery: in such cases, 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 your doctor before and after surgery.
• if surgery 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 your doctor before and after surgery. You must inform your doctor immediately if you experience numbness or weakness in the lower limbs or problems with the bowel or bladder after the anaesthetic wears off, as urgent medical care is required.
• if you fall or injure yourself during treatment, especially if you injure your head. Seek immediate medical attention. Your doctor will assess whether you may have an increased risk of bleeding.
• if you have a condition called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), you should inform your doctor, who will decide whether a change in treatment is needed.

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 must inform 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, tikagrelor, rivaroxaban, acetylsalicylic acid).
• Medicines used to treat fungal infections (e.g. ketoconazole, itraconazole), unless these medicines are applied topically to the skin only.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking medicines containing amiodarone, quinidine, or verapamil, your doctor may recommend a lower dose of Gribero depending on the condition for which the medicine has been prescribed. See also section 3.
• Medicines used to prevent rejection of transplanted organs (e.g. tacrolimus, cyclosporine).
• Fixed-dose 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).
• Certain medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, you should consult your doctor before using this medicine.
It is not known what effect Gribero has on pregnancy and the unborn child. Do not take this medicine during pregnancy unless your 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 using machines
Gribero has no effect or has a negligible effect on the ability to drive and operate machinery.
Gribero contains sodium
This 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 formulations are available for treating children under 12 years of age, provided they can swallow soft foods.

This medicine should always be taken exactly as prescribed by the doctor. In case of doubt, consult your doctor.

Gribero should be taken as follows:

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

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

If renal function is 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 each).

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 each).

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

In both types of surgery, treatment should not be initiated if there is bleeding at the surgical site. If treatment cannot be started within the next day after surgery, it should be initiated at a dose of 2 capsules once daily.

After knee joint replacement surgery

Gribero treatment should be started 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

Gribero treatment should be started 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.

Prevention of thromboembolic events in blood vessels of the brain and the rest of the body caused by clots forming due to irregular heart function, and treatment of blood clots in the veins of the legs and lungs, as well as prevention of recurrent venous thromboembolism

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 potential increased risk of bleeding.

In patients with potentially increased risk of bleeding, the doctor may recommend treatment with Gribero at 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 through a procedure called cardioversion. Gribero should be taken according to the doctor's instructions.

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 receive treatment with Gribero after the doctor confirms adequate control of blood coagulation. Gribero should be taken according to the doctor's instructions.

Treatment 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 medications unless the 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: 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 blister foil.
Instructions for the bottle
Press and turn to open the bottle.
After removing a capsule and taking the dose, immediately close the bottle tightly with the cap.
Changing anticoagulant therapy
Do not change anticoagulant medication without receiving specific instructions from your doctor.
Accidental overdose of Gribero
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 usual time on the following day. Do not take a double dose to make up for a missed dose.
Use in adults: Prevention of thromboembolic events in the brain and other parts 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
Use in children: Treatment of blood clots and prevention of recurrent blood clots
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, 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 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Gribero affects the blood clotting system; therefore, 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 location, it may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.
If bleeding that does not stop spontaneously occurs, 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 observation 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 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, rectum, under the skin, into joints, due to injury, after injury, or after a surgical procedure
• 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 oozing from the surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorder

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

• Bleeding
• Bleeding into the brain, from the surgical incision site, injection site, or site of intravenous catheter insertion
• Blood-tinged discharge from the intravenous catheter insertion site
• Coughing up blood or blood-tinged 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 due to 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 discharge from the wound
• Fluid discharge 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

Prevention of blood clots in the brain and other parts of 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, stomach or intestines, penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decreased 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 from haemorrhoids, rectum, or brain
• Formation of haematomas
• Coughing up blood or blood-tinged sputum
• Decreased platelet count in the blood
• Decreased haemoglobin levels in the blood (a 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 joints, from the surgical incision site, wound, injection site, or 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 consisting of dark red, raised, itchy bumps due to an allergic reaction
• Decreased proportion of blood cells
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorder

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

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.
Treatment 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, stomach or intestines, rectum, 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 into joints or due to injury
• Bleeding from haemorrhoids
• Decreased number of red blood cells in the blood
• Formation of haematomas
• Coughing up blood or blood-tinged 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 the surgical incision site, injection site, intravenous catheter insertion site, or bleeding from the brain
• Decreased platelet count in the blood
• 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 due to an allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decreased haemoglobin levels in the blood (a substance in red blood cells)
• Decreased proportion of blood cells
• Decreased number or even absence of white blood cells (which help fight infections)
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorder
• 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 and prevention of recurrence of 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 due to 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 may occur from the stomach or intestines, brain, rectum, penis or vagina or urinary tract (including pink or red urine due to presence of blood), or 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-tinged 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 disease or blood disorder

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, surgical incision sites, injection sites, or intravenous catheter insertion sites
• Bleeding from haemorrhoids
• 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 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 4921301; Fax: +48 22 4921309; 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

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 required. Such measures help protect the environment.

6. Contents of the pack and other information

What does Gribero contain?

• The active substance is dabigatran etexilate. Each capsule contains 110 mg of dabigatran etexilate (as mesylate).
• Other components are:
  • 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 1 capsule with a white, opaque cap printed with "MD" and a white, opaque body printed with "110" in black ink. The capsule contains a mixture of white to pale yellow pellets and pale yellow granules.
Gribero is available as:
OPA/Aluminum/PE blisters + moisture-absorbing agent/Aluminum/PE containing 10, 30, 60, 100, 180 and 200 hard capsules, in a cardboard box.
Perforated OPA/Aluminum/PE blisters + moisture-absorbing agent/Aluminum/PE 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 moisture-absorbing agent and 60 hard capsules, in a cardboard box.
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 about this medicine, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
Poland
Tel: 22 209 70 00

This medicine is authorised for marketing in the European Economic Area under the following names:
Austria Gribero 110 mg – Hartkapseln
Bulgaria Gribero 110 mg hard capsules
Czech Republic Gribero
Estonia Gribero
Greece Gribero
Croatia Gribero 110 mg tvrde kapsule
Lithuania Gribero 110 mg kietosios kapsulės
Latvia Gribero 110 mg cietās kapsulas
Poland Gribero
Romania Gribero 110 mg capsule
Slovenia Gribero 110 mg trde kapsule
Slovakia Gribero 110 mg tvrdé kapsuly