ALIVIOSIN 100 mg Suppositories

Contents of the leaflet

1. Introduction
2. What Aliviosin is and what it is used for
3. What you need to know before starting to use Aliviosin
4. How to use Aliviosin
5. Possible Adverse Effects
6. Conservation of Aliviosin
7. Packaging Contents and Additional Information

Introduction

Leaflet: information for the patient

Aliviosin 100 mg suppositories

Indomethacin

Read the entire leaflet carefully before starting to use this medication, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed to 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 side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Aliviosin is and what it is used for
2. What you need to know before starting to use Aliviosin
3. How to use Aliviosin
4. Possible side effects
5. Storage of Aliviosin
6. Package contents and additional information

1. What Aliviosin is and what it is used for

Aliviosin contains indomethacin as the active ingredient, belonging to the group of medications called non-steroidal anti-inflammatory drugs (NSAIDs), used to treat pain and inflammation.

It is indicated for symptomatic treatment in patients suffering from:

• Rheumatoid arthritis, ankylosing spondylitis (inflammation affecting the joints of the spine) and osteoarthritis.
• Acute gout attack.
• Acute musculoskeletal processes.
• Post-traumatic inflammation, pain, and swelling situations.

2. What you need to know before starting to use Aliviosin

It is essential that you use the smallest dose that relieves/controls the pain and should not use this medication, Aliviosin, for longer than necessary to control your symptoms.

Do not use Aliviosin:

• if you are allergic to indomethacin, salicylates, and other non-steroidal anti-inflammatory drugs or to any of the other components of this medication (listed in section 6).
• if you have asthma, hives, or rhinitis after taking acetylsalicylic acid or other NSAIDs.
• if you have had a stomach or duodenal ulcer or have suffered a perforation of the digestive tract. History of recurrent stomach injuries.
• if you have an active gastrointestinal ulcer (two or more different episodes of ulceration or bleeding confirmed).
• if you have a recent history of rectal inflammation, hemorrhoids, or rectal bleeding (bleeding through the rectum).
• if you have severe heart failure.
• if you are in the third trimester of pregnancy or breastfeeding.
• children under 14 years of age.
• if you are taking other NSAIDs (e.g., naproxen) or COX II inhibitors (e.g., celecoxib).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Aliviosin:

• If you have had or developed an ulcer, bleeding, or perforation in the stomach or duodenum, which may be manifested by intense or persistent abdominal pain and/or black stools, even without previous warning symptoms. This risk is higher when using high doses and prolonged treatments, in patients with a history of stomach or duodenal ulcers, and in elderly patients. In these cases, your doctor will consider the possibility of associating a stomach-protecting medication. Your doctor should prescribe the lowest doses that provide sufficient pain relief. You should inform your doctor if you experience any unusual abdominal symptoms.
• If gastrointestinal bleeding or ulcer occurs, treatment should be discontinued immediately.

Tell your doctor:

• If you have bleeding or coagulation disorders.
• If you are taking medications that alter blood coagulation, such as corticosteroids, oral anticoagulants, or antiplatelet agents like acetylsalicylic acid. You should also inform your doctor about the use of other medications that may increase the risk of bleeding, such as corticosteroids and selective serotonin reuptake inhibitors (SSRIs).
• If you have Crohn's disease or ulcerative colitis, medications like Aliviosin may worsen these conditions.
• If you have a history of high blood pressure or congestive heart failure, kidney or liver failure.
• If you have fluid retention due to liver, kidney, or heart disease.
• If you have peripheral arterial disease (a problem with leg circulation).
• If you have diabetes mellitus, hyperlipidemia, or are a smoker.
• If you have systemic lupus erythematosus (SLE) or other connective tissue disorders.

The use of anti-inflammatory medications (indomethacin) may be associated with a moderate increase in the risk of suffering a heart attack (myocardial infarction) or stroke. This risk is more likely when using high doses and prolonged treatments. Your doctor should assess the suitability of the treatment. It is essential to take the lowest dose of Aliviosin that relieves/controls the symptoms for the minimum necessary time.

Similarly, this type of medication may cause fluid retention, especially in patients with heart failure and/or high blood pressure.

During prolonged treatments, periodic ophthalmological examinations are recommended, as corneal deposits and retinal alterations have been reported.

At the beginning of treatment, headache may appear, sometimes accompanied by dizziness. 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 dose reduction, the medication should be discontinued.

It will be used with caution in patients with psychiatric disorders, epilepsy, or Parkinson's disease, as the medication may worsen these conditions in certain cases.

Like all potent anti-inflammatory drugs, it can mask the symptoms of an infectious process. It should be used with caution in patients with a controlled existing infection.

Caution should be exercised 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 medication.

In patients with blood disorders, such as a decrease in white blood cells, red blood cells, or platelets, its use should be avoided.

Women who are trying to become pregnant or are undergoing fertility research should inform their doctor of their intention to become pregnant and if they have had problems becoming pregnant.

In exceptional cases, hepatotoxicity (liver damage) has been associated with the use of indomethacin. As with many other NSAIDs, a transient elevation of liver-related parameters in blood tests can be expected. However, if abnormal values in blood tests persist over time, worsen, or if signs or symptoms of liver disease appear, or effects at other levels, such as eosinophilia (an increase in a type of white blood cell) or skin rashes, treatment should be discontinued. In chronic treatments, it is convenient to periodically monitor liver function.

This medication may be associated with rare but severe skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The highest risk is at the beginning of treatment; if skin rashes, blisters, oral ulcers, or any symptoms of an allergic reaction appear, stop using Aliviosin and consult your doctor.

Your doctor may ask you to perform tests to monitor your liver or kidney function, blood cell levels, and effects on your stomach and intestine, especially if you are an elderly patient. If you have a history of high blood pressure or heart failure, your doctor may request controls.

Children and adolescents

It is contraindicated in children under 14 years of age.

Elderly patients

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

Using Aliviosin with other medications

Tell your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

The use of acetylsalicylic acidmay decrease indomethacin plasma levels.

Concomitant administration with diflunisalmay increase indomethacin plasma levels by one-third, with decreased renal elimination. Concomitant use of both medications is not recommended.

Usual precautions will be taken in combined treatments of anticoagulants and anti-inflammatory drugs.

This medication may reduce the effect of diuretics and antihypertensives. It may reduce the antihypertensive action of beta-blockers (e.g., atenolol), alpha-blockers (e.g., prazosin), angiotensin-converting enzyme inhibitors (ACEIs) (e.g., captopril), angiotensin II receptor antagonists (e.g., valsartan), thiazide diuretics (e.g., hydrochlorothiazide), loop diuretics (e.g., furosemide), or medications like hydralazine, nifedipine. In case of concomitant administration, the antihypertensive treatment should be reevaluated.

It may also increase lithiumblood levels in patients on maintenance treatment with lithium carbonate, due to decreased renal elimination. Therefore, when starting combined treatment, frequent determinations of plasma lithium levels should be performed.

Probenecidmay also increase indomethacin plasma levels. It may be necessary to reduce the dose during combined treatment.

Tell your doctor or pharmacist if you are using:

• Other NSAIDs, including acetylsalicylic acid, naproxen, or COX II inhibitors (e.g., celecoxib) or diflunisal (for pain and inflammation).
• Medications used to thin the blood: oral anticoagulants like warfarin, antiplatelet agents like clopidogrel.
• Digoxin (for the treatment of heart failure and irregular heartbeat).
• Phenylpropanolamine (decongestant in cold medications).
• Quinolone antibiotics.
• Cyclosporine (immunosuppressant).
• Methotrexate (for the treatment of certain types of cancer, psoriasis, or rheumatoid arthritis).
• Corticosteroids.
• Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, citalopram, paroxetine.
• Haloperidol (antipsychotic).
• Sulfonylureas (oral antidiabetic).

Pregnancy, breastfeeding, and fertility

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

It should not be administered during pregnancy or breastfeeding. Indomethacin is excreted in breast milk.

Precautions during pregnancy and in women of childbearing age

Since the administration of medications like Aliviosin has been associated with an increased risk of congenital anomalies/abortions, its administration is not recommended during the first and second trimesters of pregnancy unless strictly necessary. In these cases, the dose and duration will be limited to the minimum possible.

In the third trimester of pregnancy, the administration of Aliviosin is contraindicated.

For women of childbearing age, it should be taken into account that medications like Aliviosin have been associated with a decrease in fertility.

Driving and using machines

Due to the risk of dizziness, drowsiness, or vision problems, precautions should be taken when driving or operating machinery.

3. How to use Aliviosin

Follow your doctor's instructions for administering this medication exactly. If you have any doubts, consult your doctor or pharmacist again.

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

The recommended dose is:

Adults

The usual dose is 100 mg to 200 mg of indomethacin (1 to 2 suppositories) per day.

It is recommended to administer a 100 mg suppository at night before bedtime and, if necessary, a second dose of 100 mg in the morning. The dose is determined according to the individual patient's response and how the patient tolerates the medication.

Maximum daily dose

Do not use more than 200 mg of indomethacin per day.

Elderly patients

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

Use in children and adolescents

Aliviosin should not be used in children under 14 years of age.

Patients with kidney problems

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

Method of administration:

Rectal route.

If you use more Aliviosin than you should

In case of accidental massive ingestion, the symptoms of overdose are: nausea, vomiting, pain in the upper abdomen, abdominal pain, intestinal bleeding, diarrhea, disorientation, excitement, coma, dizziness, fainting, occasional convulsions, feeling sick, loss of appetite, drowsiness, headache, ringing or noises in the ears, restlessness, and agitation.

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. The administration of antacids may be useful to minimize the risk.

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 medication and the amount ingested.

If you forget to use Aliviosin

Do not use a double dose to make up for forgotten doses.

If you interrupt treatment with Aliviosin

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

4. Possible Adverse Effects

Like all medicines, this medicine can have adverse effects, although not all people suffer from them.

If you experience any of these adverse effects, stop using this medicine and consult a doctor.

• 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-colored 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.

Very Common (may affect more than 1 in 10 people)

Lack of appetite, nausea, vomiting, gastric discomfort, abdominal pain, constipation, or diarrhea. Oral inflammation, stomach inflammation, bleeding from the large intestine, either hidden or caused by lesions of the intestinal wall, or by the perforation of pre-existing lesions of the large intestine.

Other described effects are ulcers (simple or multiple) in the esophagus or small intestine, sometimes with bleeding or perforation, gastrointestinal bleeding without evidence of ulcers, increased abdominal pain in patients with pre-existing ulcerative colitis.

Common (may affect up to 1 in 10 people)

Headache, dizziness, or dizziness.

Uncommon (may affect up to 1 in 100 people)

Very low levels of white blood cells in the blood, lack of production of blood cells in the bone marrow, decrease in white blood cell count in the blood.

Insomnia, hallucinations, psychotic episodes.

Blurred vision, double vision, eye pain, and surrounding areas. Corneal deposits and retinal disorders, including the appearance of dark spots in the visual field.

Tinnitus (ringing in the ears).

Itching, hives, inflammation of blood vessels, angioedema (skin swelling in areas such as the eyelids, lips, or genitals), erythema nodosum (skin inflammation in the form of painful nodules, usually on the front of the legs), skin rashes, skin peeling, hair loss, rapid drop in blood pressure resembling a state of "shock", bronchospasm, or acute respiratory failure.

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

Depression, anxiety, and nervousness, personality changes, mental confusion.

Somnolence, seizures, coma, syncope, nerve root disorders, involuntary muscle movements, or muscle weakness. Most of these effects are transient or disappear when the dose is reduced, but sometimes they require treatment to be suspended.

Swelling, fluid retention, high blood pressure, and heart failure associated with treatment with NSAIDs. Medicines like Aliviosin may be associated with a moderate increase in the risk of suffering a heart attack ("myocardial infarction") or stroke.

Acute kidney inflammation with blood in the urine, protein in the urine, and sometimes large amounts of protein loss in the urine. Renal failure in patients with pre-existing severe or moderate renal insufficiency or sodium retention.

Intestinal ulceration followed by abnormal narrowing and obstruction.

Liver damage.

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

Blood disorders, including a decrease in platelet count, skin spots due to rupture of blood vessels, decrease in red blood cell count due to altered production or increased destruction, and blood coagulation disorders.

In some patients, iron deficiency anemia may appear, associated with maintained blood loss or blood loss through the gastrointestinal tract.

Hearing loss.

Hepatitis or jaundice.

Medicines like Aliviosin may be associated with liver disorders that cause yellowing of the skin and eyes, sometimes with high fever or swelling and sensitivity or pain in the upper abdomen.

If any of the following reactions occur: yellowing of the skin or eyes, discontinue treatment and inform your doctor immediately.

Medicines like Aliviosin may be associated, in very rare cases, with severe blistering reactions on the skin and mucous membranes, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

Vaginal bleeding, high blood glucose levels, glucose in urine (glucosuria), nasal bleeding (epistaxis), oral mucosa ulcers (aphthae).

Adverse Reactions Reported Due to the Pharmaceutical Form of Aliviosin

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

Reporting of Adverse Effects

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

5. Conservation of Aliviosin

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

Do not use this medicine after the expiration date that appears on the packaging, after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be thrown down the drain or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Aliviosin

The active ingredient is indomethacin. Each suppository contains 100 mg of indomethacin.

The other components (excipients) are: Massa stearinum B.

Appearance of the Product and Packaging Contents

Aliviosin suppositories are presented in packages containing 20 suppositories (4 blisters with 5 suppositories each).

The suppository is slightly yellow in color.

Marketing Authorization Holder and Manufacturer

Especialidades Farmacéuticas Centrum, S.A.

C/ Sagitario, 14

03006, Alicante

Spain

Phone: +34 965 28 67 00

Fax: +34 965 28 64 34

Email: [email protected]

Date of the Last Revision of this Prospectus: June 2017

Detailed information about this prospectus can be found on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es