ARTRINOVO 50 mg SUPPOSITORIES

2. What you need to know before you use Artrinovo

Do not use Artrinovo:

• if you are allergic to indomethacin, salicylates, and other non-steroidal anti-inflammatory drugs or to any of the other components of this medicine (listed in section 6).
• if you have had asthma, hives, rhinitis, or other allergic reactions after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).
• if you have had a history of stomach bleeding, intestinal bleeding, or perforation related to previous treatments with NSAIDs.
• if you have an active or recurrent gastrointestinal ulcer (two or more different episodes of ulceration or bleeding).
• if you have a serious heart condition.
• if you are in the third trimester of pregnancy or breastfeeding.
• if you are undergoing treatment for perioperative pain in the case of coronary artery bypass grafting (CABG), surgery to treat a blocked heart artery
• if you are under 14 years old.
• if you have a recent history of rectal inflammation, hemorrhoids, or rectal bleeding (bleeding through the rectum).

Warnings and precautions

Consult your doctor or pharmacist before starting to use this medicine.

You should avoid taking Artrinovo with other NSAIDs, including other anti-inflammatory medicines such as selective cyclo-oxygenase-2 (COX-2) inhibitors.

Tell your doctor if you suffer from or have suffered from any of the following conditions:

• Gastrointestinal bleeding, ulcers, or perforations in the stomach or intestine, which can be manifested by severe abdominal pain or persistent pain and/or black stools, or even without previous warning symptoms.
• Hypertension, heart problems, or having had a stroke.
• Severe skin disorders.
• Any serious liver disease or abnormal liver tests.
• Renal failure.
• Bleeding or other coagulation problems.
• Psychiatric disorders, epilepsy, or Parkinson's disease.
• Infections.
• Blood disorders, such as a decrease in white blood cells, red blood cells, or platelets.
• If you have a coagulation disorder or are receiving treatment with anticoagulants.

Consult your doctor before starting to use Artrinovo:

• If you are taking medicines that alter blood coagulation or increase the risk of ulcers, such as oral anticoagulants or antiplatelet agents of the acetylsalicylic acid type. You should also discuss the use of other medicines that may increase the risk of such bleeding, such as corticosteroids and selective serotonin reuptake inhibitors.
• If you suffer from Crohn's disease or ulcerative colitis, as medicines of the Artrinovo type may worsen these conditions. If you experience abdominal pain, diarrhea, or vomiting, stop taking Artrinovo and inform your doctor immediately.

Gastrointestinal risks

The most frequent adverse effects that occur with medicines like Artrinovo are gastrointestinal: peptic ulcers, gastrointestinal bleeding, perforations (in some cases fatal), especially in elderly people. Less frequently, gastritis has been observed. These can occur at any time during treatment with or without previous warning.

The risk of gastrointestinal bleeding is higher when high doses are used, if you have a history of peptic ulcers, or if you are elderly. In these cases, your doctor will consider the possibility of associating a stomach-protecting medicine.

If you experience abdominal pain, vomiting blood or material that looks like coffee grounds, or black stools, these can be symptoms of gastrointestinal bleeding. Stop taking Artrinovo and seek medical help immediately.

Cardiovascular precautions

Medicines like Artrinovo can be associated with a moderate increase in the risk of suffering heart attacks ("myocardial infarction") or strokes. This risk is more likely to occur when used in high doses and in prolonged treatments. Your doctor should assess the suitability of the treatment. It is important to use the lowest dose of Artrinovo that relieves/controls the symptoms for the minimum necessary time. Do not exceed the recommended dose or treatment duration.

If you have heart problems, a history of strokes, or think you may be at risk of suffering from these conditions (for example, if you have high blood pressure, suffer from diabetes, have high cholesterol, or are a smoker), you should consult your doctor or pharmacist about this treatment.

Similarly, this type of medicine can cause fluid retention, especially in patients with heart failure and/or high blood pressure (hypertension).

Risk of severe skin reactions

This medicine can be associated, in very rare cases, with severe adverse reactions in the skin, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The greatest risk of suffering these reactions is at the beginning of treatment (usually within the first month of treatment). If you experience skin rashes, possibly with blistering or mucosal ulcers (for example, in the mouth), or other symptoms of an allergic reaction, stop using Artrinovo and consult your doctor immediately.

Risk of liver reactions

Medicines like Artrinovo can be associated with liver problems that cause yellowing of the skin and eyes, sometimes with high fever or swelling and sensitivity of the upper abdomen.

Vision

If you have blurred vision while taking Artrinovo, stop taking Artrinovo and inform your doctor.

Other precautions

Tell your doctor if you have a headache, possibly with dizziness and drowsiness after taking Artrinovo. The incidence is minimized by starting with low doses that will be progressively increased. These symptoms usually disappear as treatment continues or when the dose is reduced, but if they persist after reducing the dose, the medication should be discontinued.

In some cases, Artrinovo can worsen psychiatric disorders, epilepsy, and Parkinson's disease. Therefore, if you suffer from any of these disorders and notice a worsening, you should consult your doctor about this treatment.

Like other non-steroidal anti-inflammatory drugs, Artrinovo can mask the symptoms of an infection.

Care should be taken in post-operative patients, as bleeding time is prolonged. If you have undergone surgery or are about to undergo surgery, contact your doctor before using this medicine.

Your doctor may indicate the need for blood tests during treatment with Artrinovo to monitor your blood cells, liver function, kidney function, or blood levels of other medicines.

Children and adolescents

This medicine is contraindicated in children under 14 years old.

Patients over 65 years old

Elderly patients suffer from a higher incidence of adverse reactions, such as bleeding and gastrointestinal perforation.

Other medicines and Artrinovo

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicine.

Certain medicines can interact with Artrinovo. In these cases, it may be necessary to change the dose or interrupt treatment with one of the other medicines.

This is especially important if you are taking:

• Anticoagulants, platelet aggregation inhibitors (to prevent blood coagulation).
• Corticosteroids (e.g., cortisone, prednisone) (used to treat various types of inflammation or autoimmune diseases).
• Selective serotonin reuptake inhibitors (SSRIs) (to treat depression).
• Acetylsalicylic acid (aspirin) or other NSAIDs, including selective COX-2 inhibitors.
• Diflunisal (used to treat fever, pain, or inflammation).
• Probenecid (used to treat gout).
• Methotrexate (to treat certain types of cancer, psoriasis, or rheumatic diseases).
• Cyclosporin (used to suppress the immune system).
• Lithium (used to treat a certain type of depression).
• Diuretics, angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, renin inhibitors (medicines to treat high blood pressure).
• Digoxin (for the treatment of heart conditions).
• Phenylpropanolamine (decongestant in cold medicines).
• Sulfonylureas (oral antidiabetic)

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy and breastfeeding:

Indomethacin is not recommended during pregnancy or breastfeeding. The use of medicines during pregnancy can be hazardous for the embryo or fetus and should be monitored by your doctor. Indomethacin is excreted in breast milk.

Precautions during pregnancy and in women of childbearing age

Because the administration of medicines of the Artrinovo type has been associated with an increased risk of congenital anomalies/abortions, it is not recommended to administer it during the first and second trimester of pregnancy unless it is strictly necessary. In these cases, the dose and duration will be limited to the minimum possible.

In the third trimester, the administration of this medicine is contraindicated (see "Do not take Artrinovo").

Fertility:

For patients of childbearing age, it should be taken into account that Artrinovo can decrease the ability to become pregnant.

Driving and using machines

This medicine can cause drowsiness, dizziness, and blurred vision. In these cases, do not drive or use any tool or machinery that requires you to be alert.

3. How to use Artrinovo

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

Your doctor will indicate the dose you should use and the duration of the treatment. It is important that you use the lowest dose that controls your pain and do not use Artrinovo for longer than necessary to control the symptoms.

The recommended dose is:

Adults

The recommended dose is one suppository (50 mg) at night, when going to bed. If necessary, a second dose of 50 mg (one suppository) in the morning. The dose is determined according to the individual response of the patient and how the patient tolerates the medicine.

Maximum daily dose:

Do not use more than 4 suppositories (200 mg of indomethacin) per day.

Use in children and adolescents

This medicine should not be used in children under 14 years old.

Patients over 65 years old

Elderly patients may be more sensitive to the effects of this medicine. Therefore, it is especially important that elderly patients immediately inform their doctor of any adverse reactions that occur.

Your doctor may prescribe a lower dose and reduce the duration of the treatment.

Patients withkidney problems

If you have any kidney disease, consult your doctor before using this medicine.

Method of administration:

Rectal route.

If you use more Artrinovo than you should

In case of accidental massive ingestion, the symptoms of overdose are nausea, vomiting, severe headache, dizziness, confusion, disorientation, drowsiness, paresthesia, fainting, and convulsions.

Treatment in these cases will consist of stomach lavage and supportive treatment. The patient should be kept under surveillance for several days considering the possibility of a delayed reaction of ulceration or gastrointestinal bleeding.

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

If you forget to use Artrinovo

Do not use a double dose to make up for forgotten doses. Put the suppository in as soon as you remember and continue with the next one at the usual time.

If you stop using Artrinovo

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any of these side effects, stop using this medicine and go to your doctor immediately:

• Severe allergic reaction, such as swelling of the face, lips, or throat, wheezing, or difficulty breathing, sudden drop in blood pressure, skin rashes.
• Severe abdominal pain (stomach pain) or other abdominal symptoms.
• Blood in stools.
• Black stools.
• Vomiting blood or dark material that looks like coffee grounds.
• Jaundice (yellowing of the skin and the white part of the eyes).
• Blisters or peeling of the skin.
• Red, irregular spots on the skin of the hands and arms.

The following side effects have been reported:

Very common (may affect more than 1 in 10 people):

Headache, dizziness, fainting, vertigo.

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

Depression, fatigue or tiredness, nausea, loss of appetite, vomiting, indigestion, stomach pain, constipation, diarrhea.

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

Ringing in the ears, hearing disorders, changes in liver enzyme test results, abdominal pain, bleeding or perforation of the intestine, inflammation of the mouth, stomach irritation, flatulence, swelling due to fluid retention, hair loss.

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

Itching of the skin, hives, inflammation of blood vessels, skin rash, sudden difficulty breathing, asthma, fluid in the lungs, psychological disorders, delirium, confusion, anxiety, fainting, drowsiness, tingling or numbness in the limbs, speech problems, insomnia, worsening of epilepsy or Parkinson's disease, involuntary muscle movements, muscle weakness, convulsions, coma, blurred vision, double vision, eye pain, hearing loss, rapid heart rate, irregular heartbeat, heart failure, chest pain, high blood pressure, low blood pressure, hepatitis, liver disorders, gastrointestinal ulcers in the esophagus, stomach, or small or large intestine, blood in the urine, vaginal bleeding, breast enlargement (also in men), breast tenderness, flushing, sweating, nosebleeds, high levels of potassium or glucose in the blood, glucose in the urine, high levels of urea in the blood.

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

Decrease in white blood cells, deficiency of a type of white blood cells, deficiency of red blood cells, decrease in platelets, bleeding in the skin, coagulation disorders, deposits in the cornea of the eye, alterations of the retina, abnormal amounts of protein in the urine, kidney disorders, kidney failure.

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

Pancreatitis.

Adverse reactions reported due to the pharmaceutical form

In the specific case of indomethacin suppositories, the following have been described: feeling of needing to defecate (tenesmus), inflammation of the rectum (proctitis), vaginal bleeding or feeling of discomfort, pain, burning, or itching.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Artrinovo

Do not store at a temperature above 30°C.

Do not use this medication after the expiration date shown on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or waste. Deposit the packaging and medications you no longer need at the pharmacy's SIGRE point. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Artrinovo

• The active ingredient is indomethacin. Each suppository contains 50 mg of indomethacin.
• The other components are lactose monohydrate and semi-synthetic solid glycerides.

Appearance of the Product and Package Contents

Artrinovo 50 mg suppositories are presented in the form of white, torpedo-shaped suppositories.

They are available in packages of 12 suppositories and 100 suppositories (clinical packaging).

Marketing Authorization Holder

Laboratorios Llorens, S.L.

Ciudad de Balaguer, 7-11

08022 Barcelona, Spain

Manufacturer

Laboratorios Llorens, S.L.

C/ Llacuna, 19-21

08005 Barcelona, Spain

Date of the Last Revision of this Leaflet: July 2020

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)