Package Insert: Information for the Patient

Aspifox 5 mg/100 mg Hard Capsules

Aspifox 10 mg/100 mg Hard Capsules

Aspifox 20 mg/100 mg Hard Capsules

Rosuvastatin/Acetylsalicylic Acid

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Aspifox contains two active substances – rosuvastatina and acetylsalicylic acid.

• Rosuvastatina belongs to a group of substances called statins, which are medications that regulate the level of lipids (fats), reducing the levels of cholesterol and triglycerides in the blood, when a low-fat diet and lifestyle changes on their own have failed. Cholesterol is a fatty substance (lipid) that can cause the narrowing of blood vessels in the heart, causing coronary heart disease. If you are at risk of having a heart attack, rosuvastatina can also be used to reduce this risk even if your cholesterol levels are normal. You must maintain a low-cholesterol diet during treatment.

• Acetylsalicylic acid in low doses belongs to a group of medications called antiplatelet agents. Platelets are small blood cells that produce blood clotting and are involved in thrombosis. When a blood clot forms in an artery, it stops blood flow and cuts off oxygen supply. When this happens in the heart, it can cause a heart attack or angina.

These two active substances, taken together, reduce the likelihood of having another heart attack if you have had one previously or if you suffer from unstable chest pain (angina pectoris).

Aspifox is indicated in patients who are already taking rosuvastatina and acetylsalicylic acid at these doses. Instead of taking rosuvastatina and acetylsalicylic acid as separate tablets, you will receive an Aspifox capsule that contains both components with the same dose as before.

Do not take Aspifox

• If you are allergic to rosuvastatin, acetylsalicylic acid, or any other salicylate or nonsteroidal anti-inflammatory drugs (NSAIDs) or to any of the other components of this medication (listed in section 6).
• If you are pregnant or breastfeeding or if you become pregnant while taking Aspifox, stop taking this medication immediately and inform your doctor. Women should avoid becoming pregnant while taking Aspifox using appropriate contraceptive methods.
• If you have liver disease.
• If you have severe kidney problems.
• If you have repeated or unexplained muscle pain.
• If you are taking a combination of sofosbuvir/velpatasvir/voxilaprevir (used for hepatitis C infection).
• If you are taking a medication called ciclosporin (used, for example, after an organ transplant).
• If you have had an asthma attack or inflammation of some parts of the body, for example face, lips, throat, or tongue (angioedema) after taking salicylates or NSAIDs.
• If you have ever developed a severe skin rash or skin peeling, blisters, and/or mouth sores after taking rosuvastatin or other related medications.
• If you currently have or have ever had a stomach ulcer or intestinal ulcer or any other type of bleeding, such as a cerebral hemorrhage.
• If you have ever had a problem with your blood not clotting properly.
• If you have gout.
• If you have uncompensated heart failure.
• If you are taking a medication called metotrexato (for example, for cancer or rheumatoid arthritis) in doses above 15 mg per week.
• If you are allergic to peanuts or soy.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Aspifox.

• If you have kidney problems.
• If you have liver problems.
• If you have had repeated or unexplained muscle pain, personal or family history of muscle problems, or previous history of muscle problems when taking other cholesterol-lowering medications. Inform your doctor immediately if you have unexplained muscle pain, especially if you feel unwell or have a fever. Also inform your doctor or pharmacist if you have persistent muscle weakness.
• If you have or have had myasthenia (a disease that causes generalized muscle weakness that, in some cases, affects the muscles used for breathing) or myasthenia gravis (a disease that causes eye muscle weakness), as statins may sometimes worsen the disease or cause myasthenia (see section 4).
• If you regularly drink large amounts of alcohol.
• If your thyroid gland does not function correctly.
• If you are taking other medications called fibrates for cholesterol reduction. Read this leaflet carefully, even if you have already taken other cholesterol-lowering medications.
• If you are taking medications used to treat HIV infection, for example ritonavir with lopinavir and/or atazanavir, consult "Other medications and Aspifox".
• If you are taking or have taken within the last 7 days medications containing fusidic acid (used to treat bacterial infections) administered orally or by injection; taking Aspifox with fusidic acid may cause severe muscle pain (rhabdomyolysis); consult "Other medications and Aspifox".
• If you have severe respiratory failure.
• If you are over 70 years old.
• If you are of Asian origin, that is, Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian. Your doctor should choose the correct initial dose of Aspifox that suits you.
• If you have or have had stomach or intestinal problems (ulcers or gastrointestinal bleeding).
• If you have high blood pressure.
• If you are asthmatic, have hay fever, nasal polyps, or other chronic respiratory diseases; acetylsalicylic acid may induce an asthma attack.
• In case of hypersensitivity (allergy) to other pain medications and anti-inflammatory medications, other rheumatism medications, or other factors that cause allergy.
• If you have other allergies (for example, skin reactions, itching).
• If you are taking other medications called anticoagulants (for example, derivatives of coumarin, heparin, except for low-dose heparin).
• With renal insufficiency or reduced cardiac and vascular blood flow (for example, renal vascular disease, heart muscle weakness, reduced blood volume, major surgery, poisoning, or increased bleeding): acetylsalicylic acid may further increase the risk of renal dysfunction and acute renal insufficiency.
• If you have heavy menstrual periods.

You must seek medical attention immediately if your symptoms worsen or if you experience severe or unexpected side effects, for example unusual bleeding symptoms, severe skin reactions, or any other sign of severe allergy (see section "Possible side effects").

Severe skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported associated with rosuvastatin treatment. Stop using Aspifox and seek medical attention immediately if you notice any of the symptoms described in section 4.

In a small number of people, statins can affect the liver. This is identified by a simple test that detects elevated levels of liver enzymes in the blood. For this reason, your doctor will usually perform this blood test (liver function test) before and during treatment with Aspifox.

While taking this medication, your doctor will monitor you for diabetes or risk of developing it. You are likely to be at risk of developing diabetes if you have high blood sugar and fat levels, are overweight, or have high blood pressure.

You must be careful not to become dehydrated (you may feel thirsty with a dry mouth) as the use of acetylsalicylic acid at the same time may cause a deterioration in renal function.

Inform your doctor if you are planning to undergo surgery (even a small one, such as tooth extraction), as acetylsalicylic acid thins the blood, so it may increase the risk of bleeding.

Acetylsalicylic acid may cause Reye's syndrome when administered to children. Reye's syndrome is a rare disease that affects the brain and liver and can be potentially fatal. For this reason, Aspifox should not be administered to children and adolescents under 18 years old.

In patients with severe glucose-6-phosphate dehydrogenase deficiency: acetylsalicylic acid may cause rapid collapse, red blood cell collapse, or a certain type of anemia. This risk may be caused by factors such as high doses, fever, or acute infections.

Acetylsalicylic acid reduces the excretion of uric acid at low doses. This may trigger a gout attack in patients at risk.

If you cut or injure yourself, bleeding may take a little longer than usual. This is related to the effect of acetylsalicylic acid. Small cuts and injuries (for example, when shaving) are usually not significant. If you have unusual bleeding (in an unusual place or of unusual duration), contact your doctor.

Children and adolescents

Aspifox should not be used in children or adolescents.

Other medications and Aspifox

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medication.

Aspifox may affect or be affected by other medications, such as:

• fibrates (such as gemfibrozil, fenofibrate) or any other medication used to reduce cholesterol (such as ezetimiba)
• medications for indigestion (used to neutralize acid in the stomach)
• oral contraceptives (the pill)
• hormone replacement therapy.
• regorafenib, darolutamida, capmatinib (used to treat cancer)
• fostamatinib (used to treat low platelet counts)
• febuxostat (used to treat and prevent high levels of uric acid in the blood)
• teriflunomida (used to treat multiple sclerosis)
• any of the following medications used to treat viral infections, including HIV or hepatitis C, alone or in combination (see "Warnings and precautions"): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, gelcaprevir, pibrentasvir

ketoconazol, itraconazol (antifungal medications)

• rifampicina, eritromicina, claritromicina (antibiotics)
• blood thinners/bleeding prevention medications (for example, warfarin, heparin, coumarin, clopidogrel, ticlopidina, ticagrelor): acetylsalicylic acid may increase the risk of bleeding if taken before clotting blood or before treatment to thin the blood. Therefore, if you are about to undergo such treatment, be aware of signs of external or internal bleeding (for example, hematomas)
• medications to prevent organ rejection after transplant (ciclosporina, tacrolimus)
• medications to treat high blood pressure (for example, diuretics and ACE inhibitors)
• medications to regulate heart rhythm (digoxina)
• medications to treat manic-depressive disorder (litio)
• medications to treat pain and inflammation (for example, NSAIDs, such as ibuprofen, naproxen, or steroids)
• medications to treat gout (for example, probenecid, benzbromarona)
• medications to treat glaucoma (acetazolamida)
• medications for cancer or rheumatoid arthritis (metotrexato; in doses below 15 mg per week)
• medications to reduce blood sugar (antidiabetic medications) (for example, glibenclamida): blood sugar levels may decrease
• medications to treat depression (selective serotonin reuptake inhibitors (SSRIs) such as sertralina or paroxetina)
• medications such as hormone replacement therapy when the adrenal glands or the pituitary gland have been destroyed or removed (except for products applied to the skin or corticosteroid replacement therapy for Addison's disease), or to treat inflammation, including rheumatic diseases and intestinal inflammation (corticosteroids). Concomitant use increases the risk of gastrointestinal side effects.
• anticonvulsant medications for the brain [epilepsy] (ácido valproico)
• medications that cause an increase in urine excretion (diuretics: the so-called aldosterone antagonists, such as spironolactone and canrenone, diuretics of the loop, for example, furosemida)
• metamizol (substance to reduce pain and fever) may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells stick together and form a blood clot), when taken concomitantly. Therefore, this combination should be used with caution in patients taking low doses of acetylsalicylic acid for cardioprotection.
• alcohol: the risk of gastrointestinal ulcers and bleeding increases.

If you need to take fusidic acid orally to treat a bacterial infection, you should temporarily stop using Aspifox. Your doctor will tell you when it is safe to restart the treatment with this medication. Taking Aspifox with fusidic acid may cause muscle weakness, sensitivity, or pain (rhabdomyolysis). See more information about rhabdomyolysis in section 4.

Aspifox may further lower your blood pressure if you are already taking other medications to treat your high blood pressure.

Taking Aspifox with food and drinks

You must take Aspifox with food. Do not take grapefruit juice during treatment with Aspifox.

The consumption of alcohol may increase the risk of gastrointestinal bleeding and prolong bleeding time.

Pregnancy and breastfeeding

Do not take Aspifox if you are pregnant or breastfeeding. If you become pregnant while taking Aspifox, stop taking the medication immediately and consult your doctor. Women should avoid becoming pregnant using appropriate contraceptive methods.

Driving and using machines

Most people can drive a car and use machines during treatment with Aspifox; this will not affect your ability. However, some people may feel sick, dizzy, or tired, or have a headache during treatment, so do not drive or use machines and contact your doctor immediately.

Aspifox contains lactose

If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medication.

Aspifox contains soy lecithin

This medication contains traces of soy lecithin, which may contain soy oil. It should not be used in case of allergy to peanuts or soy.

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Adults

Your doctor will determine the appropriate dose for you depending on your disease, current treatment, and risk level.

This medication is not suitable for starting treatment. Treatment initiation should only be done by administering active principles separately and after establishing the appropriate doses, it is possible to switch to Aspifox with the appropriate concentration.

The recommended dose is one capsule per day.

This medication should be taken with food. You should take your medication at the same time every day. Capsules should be swallowed with plenty of liquid and should not be crushed or chewed.

Do not take Aspifox with grapefruit juice.

If you are admitted to a hospital or receive treatment for another disease, inform the medical staff that you are taking Aspifox.

Use in elderly patients

No dose adjustment is necessary in elderly patients.

Use in children and adolescents

Aspifox should not be used in children and adolescents.

Patients with renal insufficiency

No dose adjustment is necessary if you have mild or moderate renal insufficiency.

The use of Aspifox in patients with severe renal insufficiency is contraindicated.

Patients with hepatic insufficiency

No dose adjustment is necessary if you have mild or moderate hepatic insufficiency.

The use of Aspifox in patients with severe hepatic insufficiency is contraindicated.

If you take more Aspifox than you should

Contact your doctor or nearest hospital for advice.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Aspifox

Do not worry. If you forget to take a capsule, omit that dose completely. Take your next dose at the usual time. Do not take a double dose to compensate for the missed doses.

If you stop taking Aspifox

Your doctor will advise you for how long you should take your medication. Your cholesterol levels may increase again if you stop taking Aspifox. Your disease may reappear if you stop using your medication before it is indicated.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Stop taking Aspifox and seek medical attentionimmediatelyif you experience any of the following rare and serious side effects after taking this medicine:

• Abrupt onset of wheezing, chest pain, shortness of breath, or difficulty breathing.
• Swelling of the eyelids, face, or lips.

• Swelling of the tongue and throat that causes severe difficulty breathing and/or swallowing.
• Intense itching on the skin (with raised bumps).
• Reddish patches on the trunk, flat, in the shape of a target or circles, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
• Generalized rash, high body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).
• If you experience black stools or vomiting with blood (signs of severe stomach bleeding).

Also, stop taking Aspifox and talk to your doctor immediately

• if you have unexplained muscle painsthat last longer than expected. Like other statins, a very small number of people have experienced unpleasant muscle side effects and rarely have become a potentially fatal muscle damage known asrabdomiolysis.
• if you experience muscle rupture
• if you have a syndrome similar to lupus (including skin rash, joint disorders, and blood cell abnormalities).

The following side effects have been reported. If the presence of any of them causes you problems orif they last more than a week, you shouldcontact your doctor.

ROSUVASTATIN

Frequent(can affect up to 1 in 10 people):

• Headache.
• Stomach pain.

• Constipation.

• Feeling sick.
• Muscle pain.
• Weakness.
• Dizziness.
• Diabetes. It is more common to occur if you have high blood sugar and fat levels, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine.

Less frequent(can affect up to 1 in 100 people):

• Hives, itching, urticaria, or other skin reactions.
• Increased protein in the urine: this usually returns to normal on its own without having to stop taking your Aspifox capsules (only at doses of 5-20 mg).

Rare(can affect up to 1 in 1,000 people):

• Severe allergic reaction: symptoms include swelling of the face, lips, tongue, and/or throat, difficulty swallowing and breathing, severe itching on the skin (with raised bumps).If you think you are having an allergic reaction, stop taking Aspifoxand seek medical help immediately.
• Adult muscle damage: as a precaution,stop taking Aspifox and talk to your doctor immediately if you have unexplained muscle painsthat last longer than expected.
• Intense stomach pain (pancreatitis).
• Increased liver enzymes in the blood.
• Reduced platelets, which increases the risk of bleeding or bruising (thrombocytopenia).
• A syndrome similar to lupus (includes rash, joint disorders, and blood cell abnormalities)

Very rare(can affect up to 1 in 10,000 people):

• Jaundice (yellowing of the skin and eyes).
• Hepatitis (liver inflammation).
• Presence of blood in the urine.
• Nerve damage in the legs and arms (such as numbness).
• Joint pain.
• Memory loss.
• Gynecomastia (breast enlargement in men).

Frequency unknown(the frequency cannot be estimated from the available data):

• Diarrhea (soft stools).
• Cough.
• Difficulty breathing.
• Swelling.
• Sleep disorders, including insomnia and nightmares.
• Sexual difficulties.
• Depression.
• Respiratory problems, including persistent cough and/or shortness of breath or fever.
• Tendon damage.
• A nerve disorder that can cause weakness, tingling, or numbness.
• Constant muscle weakness.
• Myasthenia gravis (a disease that causes generalized muscle weakness, which in some cases affects the muscles used for breathing).
• Myasthenia ocular (a disease that causes weakness of the eye muscles).

Consult your doctor if you experience weakness in your arms or legs that worsens after periods of activity, double vision, eyelid drooping, difficulty swallowing, or difficulty breathing.

ACID ACETYSALICYLIC

Frequent(can affect up to 1 in 10 people):

• Gastrointestinal discomfort such as heartburn, nausea, vomiting, abdominal pain, and diarrhea.
• Minor bleeding from the gastrointestinal tract (micro-bleeding).
• Bleeding such as nasal bleeding, bleeding gums, skin bleeding, or bleeding from the urinary tract and genital organs, with a possible extension of bleeding time. This effect can last from 4 to 8 days after ingestion.

Less frequent(can affect up to 1 in 100 people):

• Stomach or intestinal bleeding. After long-term use of acetylsalicylic acid, anemia (iron deficiency anemia) may occur due to hidden bleeding from the stomach or intestines.
• Subdural hemorrhage, blood in the urine.
• Stomach ulcers or intestinal ulcers, which very rarely may cause perforation.
• Gastrointestinal inflammation.
• Skin reactions.

Rare(can affect up to 1 in 1,000 people):

• Severe skin hypersensitivity reactions, respiratory tract, gastrointestinal system, and cardiovascular system, especially in asthmatics. The following characteristics of the disease may be present: hypotension, asthma attacks, nasal mucosa inflammation, nasal congestion, anaphylactic shock, facial swelling, tongue, and laryngeal edema (Quincke's edema).
• Severe bleeding, such as cerebral hemorrhage, especially in patients with uncontrolled high blood pressure and/or concomitant treatment with anticoagulants (anticoagulant medications) that may put individual lives at risk.
• Confusion
• Headache, dizziness
• Impaired hearing or tinnitus, especially in children and the elderly, may be signs of an overdose (see also "If you take more Aspifox than you should").

Very rare(can affect up to 1 in 10,000 people):

• Abnormal liver function tests.
• Renal dysfunction and acute renal failure.
• Low blood sugar (hypoglycemia).
• Acetylsalicylic acid reduces the excretion of uric acid at low doses. This may trigger a gout attack in patients at risk.
• Febrile eruptions with mucous membrane involvement (erythema multiforme).

Frequency unknown(the frequency cannot be estimated from the available data):

• Rapid hemolysis or hemolysis of red blood cells and a certain form of anemia in patients with severe glucose-6-phosphate dehydrogenase deficiency.

If any of the side effects worsen or if you notice any side effect that is not listed in this leaflet, inform your doctor or pharmacist.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor orpharmacist, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificarames. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthe packagingafter CAD/EXP.The expiration date is the last day of the month indicated.

Store below 30 °C. Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE point of your pharmacy. In case of doubt (Not applicable in Hospital Use) ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition ofAspifox

The active principles are rosuvastatina (as rosuvastatina calcium) and acetic acid salicylic.

Aspifox 5 mg/100 mg hard capsules

Each hard capsule contains 5 mg of rosuvastatina (as rosuvastatina calcium) and 100 mg of acetic acid salicylic.

Aspifox 10 mg/100 mg hard capsules

Each hard capsule contains 10 mg of rosuvastatina (as rosuvastatina calcium) and 100 mg of acetic acid salicylic.

Aspifox 20 mg/100 mg hard capsules

Each hard capsule contains 20 mg of rosuvastatina (as rosuvastatina calcium) and 100 mg of acetic acid salicylic.

The other components are:

Coated rosuvastatina tablet

Tablet core

Lactose monohydrate (see section 2 “Aspifox contains lactose”)

Microcrystalline cellulose

Heavy magnesium oxide

Crospovidone (type IA)

Anhydrous colloidal silica

Magnesium stearate

Capsule coating system

Polivinyl alcohol

Titanium dioxide (E171)

Talc

Yellow iron oxide (E172)

Soja lecithin (see section 2 “Aspifox contains soja lecithin”)

Red iron oxide (E172)

Xanthan gum

Black iron oxide (E172)

Acetylsalicylic acid tablet

Microcrystalline cellulose

Maize starch

Anhydrous colloidal silica

Stearic acid

Capsule coating:

Gelatine

Titanium dioxide (E 171)

Indigotin (E 132)

Yellow iron oxide (E 172)

Black ink:

Shellac

Propylene glycol

Strong ammonia solution

Black iron oxide (E172)

Potassium hydroxide

Appearance of the product and contents of the pack

Aspifox 5 mg/100 mg hard capsules: hard gelatine capsules of size 2, opaque white body and opaque dark green cap. Each capsule contains a white or almost white uncoated tablet of acetylsalicylic acid and a brown coated tablet of 5 mg rosuvatatina.

Aspifox 10 mg/100 mg hard capsules: hard gelatine capsules of size 1 and with opaque white body with black overprint (ASA 100) and opaque light green cap with overprint “RSV 10”. Each capsule contains a white or almost white uncoated tablet of acetylsalicylic acid and a brown coated tablet with film of 10 mg rosuvatatina.

Aspifox 20 mg/100 mg hard capsules: hard gelatine capsules of size 0, with opaque white body with black overprint (ASA 100) and opaque green cap with overprint “RSV 20”. Each capsule contains a white or almost white uncoated tablet of acetylsalicylic acid and two brown coated tablets with film of 10 mg rosuvatatina.

Aspifox is available in blisters containing 20, 28, 30, 56, 60, 90 and 100 hard capsules.

Not all pack sizes may be marketed.

Marketing authorisation holder and responsible for manufacturing

Marketing authorisation holder

Teva B.V.

Swensweg 5

2031GA Haarlem

Netherlands

Responsible for manufacturing

Adamed Pharma S.A.

Pienków, ul. M. Adamkiewicza 6A

05-152 Czosnów

Poland

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorisation holder:

Teva Pharma, S.L.U.

C/ Anabel Segura, 11, Edifício Albatros B, 1ª planta,

Alcobendas, 28108, Madrid (Spain)

Last revision date of this leaflet: February 2025

Further detailed information on this medicinal product is available on the website of theSpanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es