Tulip combo

Package leaflet: Information for the patient

Tulip Combo, 10 mg + 10 mg, film-coated tablets
Tulip Combo, 10 mg + 20 mg, film-coated tablets
Tulip Combo, 10 mg + 40 mg, film-coated tablets
Tulip Combo, 10 mg + 80 mg, film-coated tablets
Ezetimibe + Atorvastatin
Please read all of this leaflet carefully before 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 a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

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

1. What Tulip Combo is and what it is used for

Tulip Combo is a medicine that lowers high levels of cholesterol. Tulip Combo contains
ezetimibe and atorvastatin.
Tulip Combo is used in adults to lower levels of total cholesterol, "bad" cholesterol (LDL), and fat substances called triglycerides in the blood.
Additionally, Tulip Combo increases levels of "good" cholesterol (HDL).
Tulip Combo reduces cholesterol levels in two ways. It reduces cholesterol absorption in the gastrointestinal tract and decreases its production in the body.
Cholesterol is one of several fatty substances present in the blood. Total cholesterol consists mainly of "bad" (LDL) and "good" (HDL) cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can deposit in the walls of arteries and form atherosclerotic plaque. Over time, this buildup can lead to narrowing of the arteries. This narrowing may slow down or block blood flow to vital organs such as the heart and brain. Blocking blood flow may result in a heart attack or stroke.
HDL cholesterol is often called "good" cholesterol because it helps prevent "bad" cholesterol from depositing in artery walls and protects against heart disease.
Triglycerides are other fats present in the blood that may increase the risk of heart disease.
Your doctor may prescribe Tulip Combo if you are already taking atorvastatin and ezetimibe at the doses contained in this medicine, as an adjunct to a cholesterol-lowering diet in cases of:

• elevated blood cholesterol levels (primary heterozygous familial and non-familial hypercholesterolemia) or elevated blood fat levels (mixed hyperlipidemia).
• a hereditary disorder (homozygous familial hypercholesterolemia) causing high blood cholesterol levels.

Tulip Combo does not affect body weight reduction.

2. Important information before using Tulip Combo

When not to use Tulip Combo

• if the patient is allergic to atorvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6)
• if the patient currently has or has previously had liver disease;
• if the patient has unexplained abnormal results of liver function blood tests;
• if the patient is of childbearing age and is not using effective methods of contraception;
• if the patient is pregnant, planning to become pregnant, or breastfeeding;
• if the patient is currently taking glecaprevir with pibrentasvir for the treatment of hepatitis C virus infection.

Warnings and precautions
Before taking Tulip Combo, discuss with your doctor or pharmacist if:

• the patient has previously had a haemorrhagic stroke or if there are small fluid-filled cysts in the brain following previous strokes.
• the patient has kidney disease.
• the patient has hypothyroidism (underactive thyroid).
• the patient experiences recurrent or unexplained muscle pain, or has had muscle disease previously or in the family.
• the patient experienced muscle-related symptoms during previous treatment with other lipid-lowering medicines (e.g. other "statins" or "fibrates").
• the patient currently has or has previously had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), because statins may sometimes worsen symptoms of the disease or lead to the development of myasthenia (see section 4).
• the patient is currently taking or has taken within the last 7 days an oral or injectable medicine called fusidic acid (used to treat bacterial infections). Combining fusidic acid with a medicine containing ezetimibe and atorvastatin may lead to serious consequences involving muscle problems (rhabdomyolysis).
• the patient regularly consumes large amounts of alcohol.
• the patient has previously had liver disease.
• the patient is over 70 years of age.

Contact your doctor immediately if you experience unexplained
muscle pain, tenderness or weakness while taking Tulip Combo. In rare
cases, muscle-related symptoms may be serious, including breakdown of muscle tissue leading to kidney damage. It is known that atorvastatin can cause muscle-related problems. Cases of muscle-related problems have also been reported during treatment with ezetimibe.
If muscle weakness persists, inform your doctor or pharmacist. Additional tests may be required to diagnose these symptoms and appropriate treatment may be needed.
Before taking Tulip Combo, consult your doctor or pharmacist:

• if the patient has severe respiratory insufficiency.

If any of the above situations apply to the patient (or if the patient is unsure), consult a doctor or pharmacist before taking Tulip Combo, as the doctor may need to perform a blood test before starting treatment and periodically during therapy to assess the risk of muscle-related adverse effects. The risk of muscle-related adverse effects, such as rhabdomyolysis (breakdown of skeletal muscle), increases when certain medicines are taken concomitantly (see section 2 "Tulip Combo with other medicines").
Your doctor will closely monitor your health status during treatment if you have diabetes or are at risk of developing diabetes. The likelihood of developing diabetes is higher in people who have high blood sugar and fat levels, are overweight, and have high blood pressure.
Inform your doctor about all medical conditions, including allergies.
Children and adolescents
Tulip Combo is not recommended for use in children and adolescents.
Tulip Combo and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
Avoid taking Tulip Combo together with fibrates (medicines that lower cholesterol levels).
There are several medicines that may alter the effect of Tulip Combo, or whose effect may be altered by Tulip Combo (see section 3). This type of interaction may reduce the effectiveness of one or both medicines. It may also increase the risk or severity of adverse effects, including a serious condition damaging muscles known as "rhabdomyolysis", described in section 4:

• cyclosporine (a medicine commonly used in organ transplant patients).
• erythromycin, clarithromycin, telithromycin, fusidic acid, rifampicin (medicines used to treat bacterial infections).
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medicines used to treat fungal infections).
• gemfibrozil, other fibrates and fibric acid derivatives, nicotinic acid, colestipol, cholestyramine (medicines used to regulate fat levels).
• certain calcium channel blockers used for angina and high blood pressure, e.g. amlodipine, diltiazem.
• digoxin, verapamil, amiodarone (medicines regulating heart rhythm).
• letermovir, a medicine used to prevent cytomegalovirus infection.
• medicines used in the treatment of HIV, e.g. ritonavir, lopinavir, atazanavir, indinavir, darunavir, combination of tipranavir with ritonavir (used in the treatment of AIDS).
• certain medicines used to treat hepatitis C virus infection, such as telaprevir, boceprevir, and the combination of elbasvir with grazoprevir.
• daptomycin (a medicine used to treat complicated skin and skin structure infections and bloodstream infections).
• if oral fusidic acid is required to treat a bacterial infection, temporary discontinuation of this medicine is necessary. Your doctor will advise when it is safe to resume taking Tulip Combo. Taking Tulip Combo together with fusidic acid may rarely lead to muscle weakness, tenderness or pain (rhabdomyolysis). For additional information on rhabdomyolysis, see section 4.

Other medicines interacting with the combination product:

• oral contraceptives (medicines preventing pregnancy).
• stiripentol (an anticonvulsant used in the treatment of epilepsy).
• cimetidine (a medicine used to treat heartburn and stomach ulcers).
• phenazone (a pain-relieving medicine).
• antacids (products containing aluminium or magnesium).
• warfarin, phenprocoumon, acenocoumarol or fluindione (medicines used to prevent blood clots).
• colchicine (used in the treatment of gout).
• St John's wort Hypericum perforatum (a herbal remedy used to treat depression).

Tulip Combo with food and alcohol
See section 3 for instructions on how to take Tulip Combo. Pay attention to the following points:
Grapefruit juice
Do not exceed one or two small glasses of grapefruit juice per day, as larger quantities may alter the effect of the combination medicine.
Alcohol
Avoid drinking excessive amounts of alcohol while being treated with this medicine. See section 2 "Warnings and precautions".
Pregnancy, breastfeeding and fertility
Do not take Tulip Combo if the patient is pregnant, planning to become pregnant, or suspects she may be pregnant.
Women of childbearing potential should not use Tulip Combo unless they are using effective methods of contraception. If a patient becomes pregnant while taking Tulip Combo, she must stop taking the medicine immediately and inform her doctor without delay.
Do not take Tulip Combo while breastfeeding.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before taking this medicine.
Driving and operating machinery
Tulip Combo is not expected to affect the ability to drive or operate machinery. However, consider that dizziness may occur in some individuals after taking Tulip Combo. If dizziness occurs after taking this medicine, do not drive or operate machinery.
Tulip Combo contains lactose
If the patient has previously been diagnosed with an intolerance to certain sugars, the patient should contact their doctor before taking this medicine.
Tulip Combo contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Tulip Combo

This medicine should always be taken as directed by the physician. The doctor will determine the appropriate dose for each individual patient, depending on the current treatment and individual risk factors.
If in doubt, consult a doctor or pharmacist.

• Before starting treatment with Tulip Combo, a cholesterol-lowering diet should be initiated.
• During treatment with Tulip Combo, a cholesterol-lowering diet should be maintained.

How to dose the medicine
The recommended dose of Tulip Combo is one tablet taken orally once daily, preferably at the same time each day. The tablet should be swallowed with an adequate amount of fluid (e.g. one glass of water).
When to take the medicine
Tulip Combo can be taken at any time of day, regardless of meals.
If your doctor has prescribed Tulip Combo together with another cholesterol-lowering medicine containing cholestyramine or another bile acid sequestrant (cholesterol-lowering agents), Tulip Combo should be taken at least 2 hours before or 4 hours after taking the bile acid sequestrant.

Taking more Tulip Combo than recommended
Contact a doctor or pharmacist.
If you forget to take a dose of Tulip Combo
Do not take a double dose to make up for the missed dose. Take the next tablet at the usual time.
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.
If the patient experiences any of the following serious adverse reactions, they should
stop taking the medicine immediately and contact their doctor or go to the emergency department of the nearest hospital, taking the medicine packaging with them.

• Severe allergic reaction causing swelling of the face, tongue and throat, which may cause severe breathing difficulties.
• Severe illness characterized by skin peeling and swelling, skin blisters, lesions in the mouth, eyes, genital areas, and fever; skin rash with pink-red spots, particularly on the palms or soles of the feet, possibly with blisters.
• Muscle weakness, tenderness, pain, muscle rupture or red-brown discoloration of urine, especially if accompanied by malaise or high fever; this may be due to muscle breakdown. This condition may be life-threatening and lead to kidney disease.
• Lupus-like syndrome (including skin rash, joint disorders and effects on blood cells).

Seek medical advice immediately if unexpected or unusual bleeding or bruising occurs, as this may indicate liver disorders.
Other possible adverse reactions associated with the use of Tulip Combo:

Common (may occur in less than 1 in 10 patients):

• Nasopharyngitis, sore throat, nosebleeds,
• Allergic reactions,
• Increased blood glucose levels; in diabetic patients, blood glucose levels should be carefully monitored,
• Headache,
• Nausea, constipation, flatulence, diarrhoea, indigestion, abdominal pain,
• Sore throat and (or) larynx,
• Joint pain and (or) pain in hands or feet, back pain, muscle pain, muscle cramps, joint swelling,
• Increased laboratory test values for muscle function (creatine kinase activity) in blood,
• Abnormal liver function test results, increased laboratory test values for liver function (aminotransferase activity) in blood,
• Feeling of fatigue.

Uncommon (may occur in less than 1 in 100 patients):

• Swelling due to allergic reaction,
• Decreased blood glucose levels (diabetic patients should carefully monitor blood glucose levels),
• Loss of appetite, weight gain,
• Cough,
• Muscle weakness, neck pain, chest pain,
• Hot flushes, high blood pressure, decreased heart rate,
• Vomiting, regurgitation, pancreatitis and hepatitis, heartburn, gastritis, dry mouth, bloating.
• Skin redness, urticaria, skin rash and itching, hair loss,
• Nightmares, difficulty falling asleep,
• Dizziness, numbness, taste disturbances, memory loss (amnesia), sensory disturbances,
• Blurred vision,
• Tinnitus,
• Feeling of general discomfort, uneasiness or pain,
• Weakness,
• Increased activity of the liver enzyme gamma-glutamyltransferase,
• Presence of white blood cells in urine analysis.

Rare (may occur in less than 1 in 1,000 patients):

• Decreased platelet count,
• Swelling of deeper skin layers of the face, tongue, throat, abdomen, hands or feet (angioedema),
• Widespread rash forming sharply demarcated red patches or rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genital organs due to allergic reaction,
• Inflammation of skeletal muscles, tendon inflammation sometimes with tendon rupture, muscle weakness as a symptom of muscle fiber loss,
• Vision disorders,
• Yellowing of the skin and whites of the eyes (jaundice).

Very rare (may occur in less than 1 in 10,000 patients):

• Anaphylactic shock due to allergic reaction,
• Hearing loss,
• Liver failure,
• Breast enlargement in men.

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

• Allergic reactions, including rash and swelling of deeper skin layers,
• Dyspnoea, cholecystitis, gallstones,
• Physical weakness, loss of strength, loss of muscle tissue due to antibody action,
• Depression,
• Myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing),
• Ocular myasthenia (a disease causing weakness of eye muscles).

Talk to your doctor if the patient experiences weakness in the arms or legs, worsening after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.
Additionally, after market introduction, the following adverse reactions have been reported during the use of certain statins (cholesterol-lowering medicines):

• Breathing difficulties, including chronic cough and (or) dyspnoea or fever,
• Diabetes: likelihood of occurrence is higher in patients with high blood sugar and fat levels, obesity and hypertension,
• Sexual dysfunction.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products 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 authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Tulip Combo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the stated month.
This medicine should be stored in its original packaging. There are no special requirements regarding storage temperature.
Medicines must not be disposed of via the sewage system or in household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Tulip Combo contains
Tulip Combo, 10 mg + 10 mg
Each coated tablet contains 10 mg of ezetimibe (Ezetimibum) and 10 mg of atorvastatin (Atorvastatinum) in the form of atorvastatin calcium trihydrate.
Tulip Combo, 10 mg + 20 mg
Each tablet contains 10 mg of ezetimibe (Ezetimibum) and 20 mg of atorvastatin (Atorvastatinum) in the form of atorvastatin calcium trihydrate.
Tulip Combo, 10 mg + 40 mg
Each coated tablet contains 10 mg of ezetimibe (Ezetimibum) and 40 mg of atorvastatin (Atorvastatinum) in the form of atorvastatin calcium trihydrate.
Tulip Combo, 10 mg + 80 mg
Each coated tablet contains 10 mg of ezetimibe (Ezetimibum) and 80 mg of atorvastatin (Atorvastatinum) in the form of atorvastatin calcium trihydrate.

The other ingredients are: microcrystalline cellulose, mannitol, calcium carbonate, sodium croscarmellose, hydroxypropylcellulose, polysorbate 80, yellow iron oxide (E 172), magnesium stearate, povidone K29/32, sodium lauryl sulfate.

Tablet coating
Tulip Combo 10 mg + 10 mg, Tulip Combo 10 mg + 20 mg, Tulip Combo 10 mg + 40 mg, coated tablets
Opadry White OY-L28900:
Lactose monohydrate
Hypromellose 2910
Titanium dioxide (E 171)
Macrogol 4000

Tulip Combo 10 mg + 80 mg coated tablets
DrCoat FCU:
Hypromellose 2910
Titanium dioxide (E 171)
Talc (E553b)
Macrogol 400
Yellow iron oxide (E 172)

What Tulip Combo looks like and contents of the pack
Tulip Combo, 10 mg + 10 mg
White, round, biconvex coated tablets with a diameter of approximately 8.1 mm.
Tulip Combo, 10 mg + 20 mg
White, oval, biconvex coated tablets measuring approximately 11.6 mm x 7.1 mm.
Tulip Combo, 10 mg + 40 mg
White, biconvex, capsule-shaped coated tablets measuring approximately 16.1 mm x 6.1 mm.
Tulip Combo, 10 mg + 80 mg
Yellow, elongated, biconvex coated tablets measuring approximately 19.1 mm x 7.6 mm.

Blister packs made of OPA/Aluminium/PVC/Aluminium foil containing 30 coated tablets.
Perforated single-dose blister packs made of OPA/Aluminium/PVC/Aluminium foil containing 30 x 1 coated tablet.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl,
Austria

Manufacturer
Lek Pharmaceuticals d.d.
Verovškova 57
1526 Ljubljana, Slovenia
ELPEN Pharmaceutical Co. Inc.,
Marathonos Ave. 95, Pikermi Attiki,
19009, Greece

This medicinal product is authorised in the European Economic Area under the following names:
Hungary Ezetimibe/Atorvastatin Sandoz 10 mg/40 mg filmtabletta
Ezetimibe/Atorvastatin Sandoz 10 mg/80 mg filmtabletta
Ezetimibe/Atorvastatin Sandoz 10 mg/10 mg filmtabletta
Ezetimibe/Atorvastatin Sandoz 10 mg/20 mg filmtabletta
Spain Ezetimiba/Atorvastatina Sandoz 10 mg/10 mg comprimidos recubiertos con película
Ezetimiba/Atorvastatina Sandoz 10 mg/20 mg comprimidos recubiertos con película
Ezetimiba/Atorvastatina Sandoz 10 mg/40 mg comprimidos recubiertos con película
Ezetimiba/Atorvastatina Sandoz 10 mg/80 mg comprimidos recubiertos con película
Poland Tulip Combo
Slovakia Tulip Plus 10 mg/20 mg
Tulip Plus 10 mg/40 mg

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00