Ketoplus

Package leaflet: Information for the patient

KETOPLUS

200 mg prolonged-release hard capsules
Ketoprofen
Equivalent medicine
Please read 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be dangerous.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What KETOPLUS is and what it is used for

KETOPLUS contains the active substance ketoprofen.
Ketoprofen belongs to a group of medicines called non-steroidal anti-inflammatory and anti-rheumatic drugs, used to relieve painful and inflammatory conditions of various origin, including rheumatic or traumatic conditions affecting the joints, muscles, tendons and ligaments (musculoskeletal system).
KETOPLUS is indicated for the treatment of:

• Rheumatoid arthritis, ankylosing spondylitis, acute gout; osteoarthritis at various sites
• Sciatica, radiculitis
• Myalgia, bursitis, tendinitis, tenosynovitis, synovitis, capsulitis, contusions, sprains, dislocations, muscle strains
• Phlebitis, superficial thrombophlebitis, lymphangitis
• Painful inflammatory conditions in dentistry, otorhinolaryngology, urology and pneumology.

2. What you need to know before taking KETOPLUS

Do not take KETOPLUS

• if you are allergic to ketoprofen or any of the other ingredients of this medicine (listed in section 6);

• if you have previously experienced an allergic reaction after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).
  There is a possibility that, if you are allergic to these substances, you may also be allergic to ketoprofen, and you could therefore experience breathing difficulties (bronchospasm, asthma attacks), rhinitis, urticaria, or other allergic-type reactions. Severe, sudden-onset allergic reactions (anaphylactic), rarely fatal, have been reported in such patients;

• if you are undergoing intensive treatment with drugs that stimulate diuresis (diuretics);

• if you have severe kidney problems;

• if you have severe liver problems (hepatic cirrhosis, severe hepatitis);

• if you have leukopenia or thrombocytopenia;

• if you have active bleeding;

• if you are predisposed to bleeding;

• if you have coagulation disorders;

• if you have severe heart problems;

• if you suffer or have previously suffered from bleeding, lesions (ulcers), or perforation in the stomach or intestine;

• if you are in the last 3 months of pregnancy (see section “Pregnancy and breastfeeding”);

• if the person taking this medicine is a child.

Warnings and precautions
Talk to your doctor or pharmacist before taking KETOPLUS:

• If you are taking other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors. During treatment with all NSAIDs, gastrointestinal bleeding, ulceration, and perforation may occur, which can be fatal, especially if you are elderly or have previously suffered from ulcers. If you experience gastrointestinal toxicity, particularly if you are an elderly patient. In this case, inform your doctor of any abdominal discomfort, especially during the initial stages of treatment.
• If you are taking other medicines that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants like warfarin, antidepressants (selective serotonin reuptake inhibitors), or antiplatelet agents such as aspirin (see section “Other medicines and KETOPLUS”).
• If you experience gastrointestinal bleeding or ulcers. In this case, stop treatment immediately.
• If you suffer from gastrointestinal diseases (ulcerative colitis, Crohn’s disease). The use of NSAIDs may worsen your condition (see section 4).
• If you are asthmatic or suffer from chronic rhinitis, chronic sinusitis, and/or nasal polyps. These conditions may increase your risk of developing allergic reactions to anti-inflammatory medicines and aspirin (acetylsalicylic acid) (see “Other medicines and KETOPLUS”).
• If you have severe kidney, heart, or liver problems. Renal function should be monitored at the start of treatment if you have heart failure, chronic renal failure, cirrhosis, or nephrosis, if you are taking diuretic medicines, or if you are elderly. In all these cases, the use of ketoprofen could reduce blood flow to the kidneys and lead to renal decompensation. Only your doctor can decide whether you may use KETOPLUS and, if so, will subject you to careful monitoring of renal function.
• If you suffer from heart conditions (uncontrolled hypertension, congestive heart failure, confirmed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease) or are affected by conditions that predispose you to cardiovascular disease (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking). The use of KETOPLUS must be evaluated by your doctor, who will determine whether the benefits outweigh any potential risks.
• If you have a heart rhythm disorder (atrial fibrillation).
• If you are an elderly patient. Your age increases your risk of experiencing adverse effects from anti-inflammatory drugs, especially stomach or intestinal bleeding and perforation, sometimes with fatal outcomes. The risk increases with high-dose use. Your doctor will advise you to start treatment with the lowest available dose and to take gastric-protective medicines.
• If you develop a skin rash, mucosal lesions, or any sign of hypersensitivity. In this case, stop treatment immediately, as you may develop severe skin reactions, some of which may be fatal, such as exfoliative dermatitis (skin peeling), Stevens-Johnson syndrome (severe skin reaction with skin peeling and swelling, skin blisters, affecting the mouth, eyes, genitals), and toxic epidermal necrolysis (severe skin reaction with skin peeling and swelling, skin blisters affecting the mouth, eyes, genitals, often accompanied by malaise, chills, myalgia, and fever). These adverse effects usually occur within the first month of treatment.
• If you develop hyperkalemia, which is especially likely if you have diabetes, renal failure, and/or are being treated with agents that promote hyperkalemia. In these cases, potassium levels should be monitored.
• If you have an infection, see section «Infections» below.
• If you experience visual disturbances (such as blurred vision). In this case, discontinue treatment.
• Immediately discontinue treatment with KETOPLUS at the first sign of skin rash, mucosal lesions, or any other sign of allergy (hypersensitivity).

Infections
KETOPLUS may mask symptoms of infections such as fever and pain. Therefore, KETOPLUS may delay appropriate treatment of the infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you take this medicine while having an infection and the symptoms persist or worsen, contact your doctor immediately.
Elderly
Elderly patients have a higher frequency of developing adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 3). Your doctor will advise you on the appropriate dose and whether you need to take medicines that protect against ulcers (misoprostol or proton pump inhibitors). Your doctor should monitor you closely during treatment with ketoprofen.
Children
The safety and efficacy of ketoprofen have not been studied in children.
Other medicines and KETOPLUS
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Some medicines may alter the effect of KETOPLUS, or their effects may be altered by KETOPLUS. This type of interaction may reduce the effect of one or both medicines. Alternatively, it may increase the risk or severity of adverse effects.
KETOPLUS is not recommended with:

• Other non-steroidal anti-inflammatory drugs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates, due to increased risk of ulcers and gastrointestinal bleeding (see “Warnings and precautions”).
• Anticoagulants (such as heparin and warfarin): NSAIDs may enhance the effects of anticoagulants.
• Antiplatelet agents (such as ticlopidine, clopidogrel): increased risk of gastrointestinal bleeding (see “Warnings and precautions”).
• Lithium: risk of increased lithium blood levels.
• Methotrexate at doses exceeding 15 mg/week: increased risk of blood toxicity caused by methotrexate. There should be a 12-hour interval between discontinuation or initiation of ketoprofen treatment and methotrexate administration.

Pay particular attention when using KETOPLUS if you are taking the following medicines:

• Medicines or therapeutic classes that may promote hyperkalemia (e.g., potassium salts, potassium-sparing diuretics, ACE inhibitors and angiotensin II antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim).
• Corticosteroids (used for allergies and inflammation): concomitant use may increase the risk of gastrointestinal ulceration or bleeding (see “Warnings and precautions”).
• Diuretics: NSAIDs may reduce the effect of diuretics and other medicines used to lower blood pressure (antihypertensives). In patients, especially dehydrated patients taking diuretics, there may be a high risk of developing renal dysfunction. These patients should be adequately rehydrated before starting concomitant treatment with NSAIDs, and their renal function should be monitored when treatment begins (see “Warnings and precautions”).
• Pentoxifylline (used to inhibit blood clot formation in vessels): these medicines increase the risk of bleeding when taken together with ketoprofen. Your doctor will perform more frequent clinical checks and monitor bleeding time.
• Medicines that lower blood pressure (ACE inhibitors and angiotensin II antagonists): in patients with impaired renal function (e.g., if dehydrated or elderly), concomitant administration of a blood pressure-lowering medicine such as an ACE inhibitor or angiotensin II antagonist with an NSAID may lead to further worsening of renal function. You should be adequately hydrated and your renal function adequately monitored.
• Methotrexate (used in the treatment of neoplasms and autoimmune diseases) at doses below 15 mg/week. During the first weeks of combination therapy, a complete blood count should be performed weekly.
• Tenofovir: concomitant administration with NSAIDs may increase the risk of renal failure.
• Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase cardiac glycoside levels.

Inform your doctor if you are taking the following medicines. Only your doctor can determine whether you may take KETOPLUS together with the following medicines:

• Antihypertensives (beta-blockers, angiotensin-converting enzyme inhibitors, diuretics). Administration together with NSAIDs may reduce antihypertensive efficacy.
• Thrombolytics (used to induce thrombus breakdown): increase the risk of bleeding.
• Several substances are involved in interactions due to their antiplatelet effect: tirofiban, eptifibatide, abciximab, and iloprost. The use of multiple antiplatelet agents increases the risk of bleeding.
• Antidepressants (Selective Serotonin Reuptake Inhibitors (SSRIs)): risk of increased gastrointestinal bleeding.
• Probenecid (used in the treatment of hyperuricemia and gout): concomitant administration of probenecid may significantly reduce the plasma clearance of ketoprofen.
• Gemeprost (used in obstetric-gynecological treatments): concurrent use with ketoprofen may reduce the efficacy of gemeprost.
• Intrauterine contraceptive devices (IUDs): concurrent use may reduce device effectiveness, potentially resulting in pregnancy.
• Mifepristone: efficacy of the method may theoretically decrease due to the anti-prostaglandin properties of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin (acetylsalicylic acid).
• Cyclosporine, tacrolimus (immunosuppressive drugs): when used with ketoprofen, increase the risk of nephrotoxic effects, especially in the elderly.
• Quinolone antibiotics: possible increased risk of seizures.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not use KETOPLUS during the first and second trimesters of pregnancy. Ketoprofen may be administered only if strictly necessary and only under medical supervision. If ketoprofen is used during this period or while planning a pregnancy, the dose should be the lowest possible and the treatment duration as short as possible.
From week 20 of pregnancy onwards, if taken for more than a few days, KETOPLUS may cause kidney problems in the fetus, leading to low levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is required for more than a few days, your doctor may recommend additional monitoring.
Do not take KETOPLUS during the last trimester of pregnancy, as it may cause problems for your baby and during childbirth (see section 2 “Do not take KETOPLUS”). It may cause kidney and heart problems in the fetus. It may affect your and your baby’s tendency to bleed and delay or prolong labor beyond expectations.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose:

• the fetus to:
• cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with oligo- or anhydramnios;
• the mother and newborn, at the end of pregnancy, to:
• possible prolongation of bleeding time, and antiplatelet effects that may occur even at very low doses;
• inhibition of uterine contractions, resulting in delayed or prolonged labor;
• alterations in the newborn’s pulmonary circulation hemodynamics with serious consequences for respiration, if used close to delivery. Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding
There are no data available on the excretion of ketoprofen in breast milk. Ketoprofen is not recommended for breastfeeding women.
Fertility
The use of NSAIDs may impair female fertility and is not recommended for women intending to become pregnant. In women with fertility problems or undergoing fertility investigations, discontinuation of treatment should be considered.
Driving and use of machinery
KETOPLUS may cause dizziness, drowsiness, vertigo, seizures, or visual disturbances. If these symptoms occur, do not drive or operate machinery and avoid activities requiring special vigilance.
KETOPLUS contains sucrose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take KETOPLUS

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
This medicine is intended for adults only.
The recommended oral dose of ketoprofen is:
1 capsule of 200 mg daily, to be taken after a meal.
The dose should be adjusted according to the severity of symptoms.
It is recommended to take the capsule with a glass of water during a meal.
The maximum daily dose is 200 mg. Doses higher than 200 mg per day are not recommended.
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary.
The lowest effective dose for the shortest duration needed to relieve symptoms should be used. If you have an infection, contact your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Patients with renal impairment and elderly patients
If you suffer from renal impairment or are an elderly patient, the initial dose should be reduced and maintenance therapy should be carried out using the lowest effective dose, followed by individual dose adjustments as needed.

Patients with hepatic impairment
If you suffer from hepatic impairment, you must be closely monitored and treated with the lowest effective daily dose (see "Warnings and precautions").

Children
The use of this medicine in children has not been studied.

If you take more KETOPLUS than you should
In case of accidental ingestion of an excessive dose of ketoprofen, stop taking the medicine immediately and contact your doctor or go to the nearest hospital.
Symptoms of overdose may include: lethargy, drowsiness, stomach pain, nausea, and vomiting. Headache, dizziness, diarrhoea, and abdominal pain may also occur.
In cases of severe overdose, low blood pressure, breathing problems (respiratory depression), and gastrointestinal bleeding may also occur.
If you experience any of the symptoms listed above, your doctor or the hospital physician will provide the most appropriate treatment based on your symptoms. There are no specific antidotes.
In case of renal impairment, haemodialysis may be useful to remove circulating drug.

If you forget to take KETOPLUS
If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose.
Do not take a double dose to make up for the forgotten dose.
Inform your doctor, who will advise you on how to continue the treatment.

If you stop taking KETOPLUS
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following side effects have been reported in adults, according to the following frequencies:

Common: affects up to 1 in 10 people

• nausea
• vomiting
• abdominal pain
• dyspepsia (indigestion)

Uncommon: affects up to 1 in 100 people

• headache
• dizziness
• vertigo
• somnolence (drowsiness)
• constipation
• diarrhoea
• gastritis
• flatulence
• skin rash
• pruritus (itching)
• oedema (swelling)
• fatigue

Rare: affects up to 1 in 1,000 people

• anaemia due to bleeding, leucopenia
• blurred vision
• paraesthesia
• tinnitus (ringing in the ears)
• asthma
• ulcerative stomatitis, peptic ulcers, colitis
• increased liver enzymes, increased serum bilirubin due to liver disease
• weight gain
• hepatitis
• jaundice

Frequency not known: cannot be estimated from the available data

• acute renal failure, tubulo-interstitial nephritis, nephrotic syndrome, abnormal kidney function tests
• skin rash, erythema, angioedema, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis, generalized acute exanthematous pustulosis
• exacerbation of colitis and Crohn’s disease, gastrointestinal perforation or bleeding (sometimes fatal), particularly in elderly patients (see section 2 “Warnings and precautions”), melaena and haematemesis, pancreatitis
• changes in blood cell levels (thrombocytopenia, agranulocytosis), bone marrow aplasia, haemolytic anaemia
• mood alterations, depression, hallucinations, confusion
• taste disturbances
• heart failure, atrial fibrillation, palpitations and tachycardia
• hypertension
• vasodilation
• vasculitis (including leukocytoclastic vasculitis)
• bronchospasm
• nasal congestion (rhinitis)
• dyspnoea (shortness of breath)
• urticaria, worsening of chronic urticaria
• photosensitivity reactions
• alopecia (hair loss)
• aseptic meningitis, seizures
• hyponatraemia and hyperkalaemia
• anaphylactic reactions (including shock)

Please note that
The use of products such as KETOPLUS (especially at high doses and for long-term treatment) may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store KETOPLUS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after "Exp.".
The expiry date refers to the last day of that month and applies to the product in its original packaging,
stored correctly.
Store below 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What KETOPLUS contains
The active substance is ketoprofen. One prolonged-release capsule contains 200 mg of ketoprofen.
The other components are: sucrose and starch microgranules, Povidone K30, poly(methyl) methacrylates (Eudragit RS), talc.
Capsule constituents: gelatin, titanium dioxide (E171).
Description of the appearance of KETOPLUS and the contents of the pack
The cardboard box contains 28 prolonged-release hard capsules, packaged in blisters.
Marketing Authorization Holder and Manufacturer
S.F. Group srl
Via Tiburtina, 1143 – 00156 Rome
Manufacturer
SPECIAL PRODUCT’S LINE Srl
Via Fratta Rotonda Vado Largo, 1
03012 Anagni (FR)
Italy