Package leaflet: Information for the user

OKi 80 mg granules for oral solution

ketoprofen lysine salt
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 others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What OKi is and what it is used for
What you need to know before taking OKi
How to take OKi
Possible side effects
How to store OKi
Contents of the pack and other information

1. What OKi is and what it is used for

OKi 80 mg granules for oral solution contains as the active substance ketoprofen lysine salt, which belongs to a group of medicines used against pain and inflammation called "Non-Steroidal Anti-Inflammatory Drugs" (NSAIDs).
This medicine is used for
Adults:
symptomatic treatment of inflammatory conditions associated with pain, including:

rheumatoid arthritis (an autoimmune disease causing joint pain and stiffness),
ankylosing spondylitis (a chronic inflammatory disease mainly affecting the spine and joints),
painful osteoarthritis (a disease affecting the joints),
extra-articular rheumatism (rheumatic diseases affecting structures outside the joints),
post-traumatic inflammation (inflammatory condition following trauma),
painful inflammatory conditions in dentistry, otorhinolaryngology, urology and pneumology;

Children and adolescents:
short-term symptomatic treatment of inflammatory conditions associated with pain, sometimes accompanied by pyrexia (fever), such as those affecting the osteoarticular system, post-operative pain and otitis.

2. What you need to know before taking OKi

Do not take OKi

if you are allergic to ketoprofen, to other non-steroidal anti-inflammatory drugs (NSAIDs), or to any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”);
if you have a history of hypersensitivity reactions (allergy) such as bronchospasm, asthma attacks, acute rhinitis, urticaria, nasal polyps, angioedema (swelling of deep dermis and subcutaneous tissue, which may also affect mucous membranes), or other allergic-type reactions to ketoprofen or substances with a similar mechanism of action (e.g. acetylsalicylic acid or other NSAIDs). Severe anaphylactic reactions, rarely fatal, have been observed in these patients (see section 4 “Possible side effects”);
if you suffer from pre-existing bronchial asthma;
if you have severe heart failure (inability of the heart to pump sufficient blood to meet the body’s needs);
if you currently have a peptic ulcer (in the stomach) or gastrointestinal bleeding, or if you have previously suffered from recurrent peptic ulcer or bleeding (two or more distinct, confirmed episodes of bleeding or ulceration);
if you have previously experienced gastrointestinal bleeding, ulceration, or perforation, or chronic dyspepsia;
if you have a history of gastrointestinal bleeding or perforation related to previous NSAID therapy;
if you have leukopenia (reduced number of white blood cells) or thrombocytopenia (reduced number of platelets in the blood);
if you suffer from Crohn’s disease or ulcerative colitis;
if you suffer from gastritis;
if you have severe liver (e.g. cirrhosis, severe hepatitis, reduced liver function) or kidney (reduced kidney function) insufficiency;
if you suffer from haemorrhagic diathesis (predisposition to develop bleeding) or other coagulation disorders, or if you have haemostatic disorders;
if you are undergoing intensive diuretic therapy;
if you are in the last three months of pregnancy.

Do not give this medicine to children under 6 years of age.
Warnings and precautions
Warnings
Side effects can be minimized by using the shortest duration of treatment necessary to control symptoms (see subsection “How to take OKi” and the sections below on gastrointestinal and cardiovascular risks).
Concomitant use of OKi with other NSAIDs should be avoided, including selective cyclooxygenase-2 inhibitors.
During treatment with all NSAIDs, including OKi, gastrointestinal bleeding, ulceration, and perforation have been reported at any time, with or without warning symptoms or previous history of serious gastrointestinal events, and may be fatal.
Your doctor may recommend concomitant use of gastroprotective agents (e.g. misoprostol or proton pump inhibitors), especially if you are elderly, have a history of ulcers, or are taking low-dose acetylsalicilic acid or other medicines that may increase the risk of gastrointestinal events (see subsection “Other medicines and OKi”).
Report any unusual abdominal signs or symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.
Exercise caution if you are taking medications that could increase the risk of ulceration or bleeding, such as oral corticosteroids (medicines used to treat inflammatory conditions), selective serotonin reuptake inhibitors (SSRIs, e.g. medicines used to treat depression), anticoagulants (medicines that thin the blood, such as warfarin), or antiplatelet agents such as acetylsalicylic acid (see subsection “Other medicines and OKi”).
Elderly patients are at higher risk of developing adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 3 “How to take OKi”). Elderly patients are also more prone to reduced kidney, heart, and liver function.
Children:
Gastrointestinal bleeding, occasionally severe, and ulcers have been observed in some pediatric patients treated with lysine ketoprofen salt (see section 4 “Possible side effects”); therefore, the product should be administered under strict medical supervision, with the dosing regimen individually assessed.
You should be closely monitored if you have or have previously had gastrointestinal disease, for the onset of digestive disturbances, especially gastrointestinal bleeding.
Immediately discontinue treatment with OKi at the first signs of gastrointestinal bleeding or ulceration.
Patients with active or past peptic ulcer:
Exercise caution if you have a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease), as these conditions may recur with NSAID use (see section 4 “Possible side effects”).
Ketoprofen, especially at high doses, may be associated with a higher risk of severe gastrointestinal toxicity compared to other NSAIDs.
Skin reactions:
Severe skin reactions (of the skin), some of which are fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have very rarely been reported in association with NSAID use (see section 4 “Possible side effects”). In the early stages of therapy, patients appear to be at higher risk: the reaction usually occurs within the first month of treatment. Discontinue use of OKi at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
If you have coeliac disease (gluten intolerance), you may take OKi as it does not contain gluten.
If you have diabetes, you may take OKi as it does not affect low-calorie or controlled diets.
Talk to your doctor or pharmacist before taking OKi:

If you have impaired kidney function, OKi should be administered with caution.
If you have heart failure (a condition in which the heart is weakened), liver function abnormalities such as cirrhosis (severe liver impairment), kidney function abnormalities such as nephrosis (degenerative kidney disease), or chronic renal insufficiency (impaired kidney function), if you are taking diuretics (medicines used to increase urine production), or if you may have low blood volume (hypovolemia), especially if you are elderly at the start of treatment, as kidney function must be closely monitored.
As with all NSAIDs, the medicine may increase certain laboratory test values, such as blood urea nitrogen and creatinine.
If you have liver disease or abnormal liver function tests, as liver enzyme (transaminase) levels should be periodically evaluated, particularly during long-term therapy.
As with other NSAIDs, the medicine may cause small transient increases in some liver parameters and even significant increases in GPT/ALT and GOT/AST transaminases (liver enzymes) (see section 4 “Possible side effects”). If such parameters increase markedly, treatment must be discontinued. Cases of jaundice (yellowing of the skin and eyes) and hepatitis (liver disease) have been rarely reported with ketoprofen use. During long-term therapy, liver and kidney function tests and blood counts should be performed.
If you have uncontrolled hypertension (high blood pressure), congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate cardiac pump function), confirmed ischemic heart disease (heart disease due to reduced blood flow caused by narrowing of the coronary arteries), peripheral artery disease, and/or cerebrovascular disease (disease of the brain’s blood vessels), as treatment with lysine ketoprofen, like all NSAIDs, should only occur after careful evaluation.
If you have heart problems, a history of stroke (cerebrovascular accident), or think you may be at risk for these conditions (e.g. if you have high blood pressure, diabetes, high cholesterol, or smoke).
If you have a history (even familial) of mild to moderate hypertension (high blood pressure) and/or congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate cardiac pump function), as adequate monitoring and appropriate instructions are required. Fluid retention and edema (swelling) have been observed during NSAID treatment.
Medicines such as OKi may be associated with a modest increase in the risk of heart attack (myocardial infarction) or stroke (cerebrovascular accident). Any risk is more likely with high doses and prolonged treatment.
An increased risk of atrial fibrillation (heart rhythm disturbance) has been reported with NSAID use.
Hyperkalemia may occur, especially if you have diabetes, renal insufficiency, and/or are taking agents that promote hyperkalemia (see subsection “Other medicines and OKi”). In these circumstances, potassium levels should be monitored.
If you have an infection – see section «Infections» below.
If you have allergic manifestations or a history of allergy, as the medicine should be administered with caution.
Like all non-steroidal drugs, the use of ketoprofen in patients with bronchial asthma or allergic diathesis (predisposition to develop allergy) may trigger an asthma attack. If you have asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis, you are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to the general population. Administration of this medicine may cause asthma attacks or bronchospasm, shock, and other allergic phenomena, especially in subjects allergic to acetylsalicylic acid and/or NSAIDs (see subsection “Do not take OKi”).
Consult your doctor if you experience visual disturbances, such as blurred vision, as treatment must be discontinued.
If you have hematopoietic disorders (altering blood cell formation and maturation), systemic lupus erythematosus (an immune system disease), or mixed connective tissue disorders, as OKi should be administered with caution.

Infections
OKi 80 mg granules for oral solution may mask symptoms of infections such as fever and pain.
Therefore, OKi 80 mg granules for oral solution may delay appropriate treatment of the infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to varicella. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Other medicines and OKi
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
It is not recommended that you take OKi in combination with:

Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates (over 3 g/day), as they may increase the risk of gastrointestinal ulcers and bleeding.
Medicines that thin the blood (anticoagulants such as heparin and warfarin, and platelet aggregation inhibitors such as ticlopidine and clopidogrel). NSAIDs may enhance the effects of these medicines (see subsection “Warnings and precautions”), thereby increasing the risk of bleeding. If co-administration cannot be avoided, you must be closely monitored.
Lithium (a medicine used to treat manic-depressive psychosis). NSAIDs may increase lithium blood levels to toxic values.
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and cancers), used at doses exceeding 15 mg/week: there may be an increased risk of methotrexate hematological toxicity. At least 12 hours should elapse between stopping or starting ketoprofen treatment and methotrexate administration.
Hydantoins (such as phenytoin) and sulfonamides (such as certain antibiotics and other medicines): the toxic effects of these substances may be increased.

Caution is required if you take OKi in combination with:

Medicines that may promote hyperkalemia, such as potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim.
Tenofovir (a medicine used in the treatment of certain viral infections): may increase the risk of renal failure.
Medicines used to treat high blood pressure, such as beta-blockers, diuretics, ACE inhibitors, and angiotensin II antagonists. You should be adequately hydrated before starting concomitant therapy, and renal function should be monitored after starting concomitant therapy (see subsection “Warnings and Precautions”). NSAIDs may reduce the effect of diuretics.
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and cancers), used at doses below 15 mg/week: there may be an increase in methotrexate hematological toxicity. During the first weeks of combination use, weekly complete blood count monitoring should be performed. If you are elderly or have impaired renal function, monitoring should be more frequent.
Corticosteroids (medicines used to treat inflammatory conditions): there may be an increased risk of gastrointestinal ulceration or bleeding (see subsection “Warnings and Precautions”).
Pentoxifylline (a medicine used to improve blood circulation in the limbs): there may be an increased risk of bleeding. More frequent clinical monitoring may be necessary.
Zidovudine (a medicine used to treat HIV): there may be an increase in hematological toxicity with possible severe anemia. Blood tests should be performed after starting NSAID treatment.
Sulfonylureas (diabetes medicines, such as gliclazide): NSAIDs may enhance the hypoglycemic effect of sulfonylureas.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase cardiac glycoside levels; however, a pharmacokinetic interaction between ketoprofen and cardiac glycosides has not been demonstrated.

Combinations with other medicines to consider:

Antihypertensive medicines (beta-blockers, ACE inhibitors, diuretics): NSAIDs may reduce the effect of antihypertensive medicines.
Mifepristone (a medicine used for medical termination of pregnancy): the effectiveness of the contraceptive method may theoretically decrease due to the properties of NSAIDs.
Intrauterine contraceptive devices: the effectiveness of the device may be reduced, leading to pregnancy.
Cyclosporine, tacrolimus (medicines used after transplantation or for treating immune system disorders): risk of additional toxic effects on the kidneys, especially in the elderly.
Thrombolytics (medicines that facilitate the dissolution of blood clots): increased risk of bleeding.
Antiplatelet agents (ticlopidine and clopidogrel) and selective serotonin reuptake inhibitors (SSRIs, such as certain antidepressants): increased risk of gastrointestinal bleeding.
Probenecid (a medicine used to treat gout): co-administration of probenecid may increase ketoprofen blood concentrations.
Quinolone antibiotics: possible increased risk of developing seizures.
Phenytoin and sulfonamides: dosage reduction may be necessary.
Gemeprost (a medicine used in gynecological procedures): reduced effectiveness.
Avoid alcohol consumption.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
The use of ketoprofen during the first and second trimesters of pregnancy should be avoided.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.
Epidemiological studies suggest an increased risk of miscarriage and cardiac malformations and gastroschisis (fetal abdominal wall defect) following the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is considered to increase with dose and duration of treatment.
During the first and second trimesters of pregnancy, take this medicine only if strictly necessary and on medical advice.
If ketoprofen is used by a woman wishing to become pregnant, or during the first and second trimesters of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:

cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension, i.e. increased pressure in the pulmonary circulation);
renal dysfunction, which may progress to renal failure with oligohydramnios (amniotic fluid volume below normal);

and the mother and newborn, at the end of pregnancy, to:

possible prolongation of bleeding time, and anti-aggregating effect, which may occur even at very low doses;
inhibition of uterine contractions resulting in delayed or prolonged labor.

The use of the medicine close to delivery may cause alterations in the hemodynamics of the newborn’s pulmonary circulation with serious consequences for respiration.
Therefore, DO NOT use OKi during the third trimester of pregnancy (see subsection “Do not take OKi”).
Breastfeeding
There is no available information on the excretion of ketoprofen in breast milk. Ketoprofen is not recommended during breastfeeding.
Fertility
The use of NSAIDs, including OKi, may reduce female fertility and is not recommended in women attempting to conceive.
Administration of NSAIDs, including OKi, should be suspended in women with fertility problems or undergoing fertility investigations.
Driving and using machines
If drowsiness, dizziness, or seizures occur after taking ketoprofen, avoid driving, operating machinery, or performing activities requiring special alertness.
OKi 80 mg granules for oral solution contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially 'sodium-free'.
OKi 80 mg granules for oral solution contains sucrose (contained in the mint flavor).
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take OKi

Recommended doses are:
Adults: one 80 mg sachet (full dose) three times daily with meals.
The maximum daily dose is 320 mg of ketoprofen lysine salt. Higher doses are not recommended (see subsection "Warnings and precautions").

Special populations
Use in children aged 6 to 14 years: half a sachet of 40 mg (half dose), three times daily with meals.
OKi 80 mg granules for oral solution are contraindicated in children under 6 years of age (see subsection "Do not take OKi").

Use in the elderly: the dose must be carefully determined by the doctor, who will consider whether a reduction of the above doses may be necessary (see subsection "Warnings and precautions").

Use in patients with hepatic impairment: it is recommended to initiate therapy at the lowest daily dosage (see subsection "Warnings and precautions").

Use in patients with mild to moderate renal impairment: it is recommended to reduce the initial dose and maintain therapy with the lowest effective dose. Individual dose adjustments may be considered only after good tolerability of the drug has been established. Monitor urine output and kidney function (see subsection "Warnings and precautions").
OKi 80 mg granules must not be used in patients with severe hepatic or renal dysfunction (see subsection "Do not take OKi").

Method of administration
By opening the sachet along the line marked "half dose", a 40 mg dose is obtained.
By opening the sachet along the line marked "full dose", an 80 mg dose is obtained.
Empty the contents of the sachet into half a glass of water and stir.

If you take more OKi than you should
In case of accidental ingestion/overdose of OKi, contact your doctor immediately or go to the nearest hospital.
Cases of overdose with doses up to 2.5 g of ketoprofen have been reported. In most cases, symptoms have been mild and limited to lethargy, drowsiness, nausea, vomiting, epigastric pain (in the upper abdomen), abdominal pain, headache, dizziness, and diarrhoea.
In cases of severe overdose, hypotension, respiratory depression, and gastrointestinal bleeding have been observed.
The patient should be immediately transferred to a specialist centre to initiate symptomatic treatment.
There are no specific antidotes in case of ketoprofen overdose. In case of suspected massive overdose, gastric lavage is recommended, along with symptomatic and supportive treatment.
In patients with renal impairment, haemodialysis may be useful in removing the drug from the body.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
The most commonly observed adverse events are gastrointestinal in nature.
The following adverse reactions have been observed with the use of ketoprofen in adults:

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

dyspepsia (indigestion), nausea, abdominal pain, vomiting

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

headache, dizziness, vertigo, somnolence
constipation, diarrhoea, flatulence (presence of gas in the intestine), gastritis, abdominal discomfort
skin rash, pruritus
oedema (fluid accumulation causing swelling), fatigue, peripheral oedema (swelling), chills

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

haemorrhagic anaemia (anaemia due to blood loss)
paraesthesia (abnormal skin sensation, tingling)
blurred vision (see section “Warnings and precautions”)
tinnitus (ringing in the ear)
asthma
stomatitis (mouth ulcer), peptic ulcer (gastric or duodenal ulcer), colitis
hepatitis, increased transaminases (liver enzymes), increased blood bilirubin (elevated serum bilirubin levels due to liver disorders), jaundice
weight increased

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

dyskinesia (movement disorder), syncope
hypotension (lowered blood pressure)
laryngeal oedema (swelling of the larynx)
haematuria (blood in urine)
asthenia (physical weakness), facial oedema

Not known (frequency cannot be estimated from the available data):

thrombocytopenia (reduced number of platelets in the blood), agranulocytosis (severe reduction in white blood cells), bone marrow failure (reduced production of blood cells), haemolytic anaemia (anaemia due to abnormal destruction of red blood cells), neutropenia (reduced number of neutrophil white blood cells); aplastic anaemia (anaemia due to insufficient production of blood cells in the bone marrow); leucocytosis (increased number of white blood cells), thrombocytopenic purpura; leucopenia (reduced number of white blood cells)
anaphylactic reactions (including shock); hypersensitivity
depression, hallucinations, confusion, mood alterations, excitability, insomnia. In a paediatric patient who had taken a double dose compared to that recommended in the SmPC, anxiety and behavioural disorder were also observed
convulsions
dysgeusia (altered taste)
tremor, hyperkinesia
cardiac failure (weak heart), atrial fibrillation (irregular heart rhythm), palpitations, tachycardia (increased heart rate)
hypertension (increased blood pressure), vasodilation (dilation of blood vessels), vasculitis (inflammation of blood or lymphatic vessels) (including leukocytoclastic vasculitis)
bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea (difficulty breathing), laryngospasm, acute respiratory failure (a single fatal case has been reported in an asthmatic and aspirin-sensitive patient)
gastralgia (stomach pain), exacerbation of colitis and Crohn’s disease, gastrointestinal haemorrhage, gastrointestinal perforation (sometimes fatal, particularly in the elderly), pyrosis (heartburn), gastric ulcer, duodenal ulcer, oedema (swelling) of the mouth, pancreatitis, erosive gastritis, haematemesis (vomiting blood) or melena (passing of digested blood in stools), hyperchlorhydria (excess hydrochloric acid in gastric juice), gastric pain (stomach pain), oedema of the tongue
photosensitisation (reaction to sunlight or UV lamps), alopecia (hair loss), urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome, Lyell’s syndrome and toxic epidermal necrolysis (serious skin reactions), erythema (skin redness), exanthema (skin rash), maculopapular exanthema, purpura, acute generalized exanthematous pustulosis (skin eruption with pustule formation), dermatitis
acute renal failure, tubulointerstitial nephritis, nephritis or nephritic syndrome, nephrotic syndrome, glomerular nephritis, fluid/sodium retention with possible oedema, acute tubular necrosis (damage to kidney tubular cells), renal papillary necrosis (damage to kidney papillae), oliguria (reduced urine output), abnormal kidney function tests
periorbital oedema (swelling around the eyes)
aseptic meningitis (inflammation of the membranes covering the brain not caused by bacteria)
lymphangitis (inflammation of lymphatic vessels)
hyperkalaemia (increased potassium levels in blood), hyponatraemia (decreased sodium levels in blood)

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

5. How to store OKi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month. The indicated expiry date applies to the product in its original, undamaged packaging, correctly stored.
This medicine does not require any special storage precautions.
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 OKi contains

The active substance is ketoprofen lysine salt. Each dual-chamber sachet contains 80 mg of ketoprofen lysine salt, equivalent to 50 mg of ketoprofen.
The other components are mannitol, sodium chloride, colloidal silica, ammonium glycyrrhizinate, povidone, sodium saccharin, extra mint flavor 125 (contains sucrose).

Description of the appearance of OKi and the contents of the pack
Granules for oral solution – pack containing 10, 20 or 30 dual-chamber sachets.
Marketing Authorization Holder
Dompé farmaceutici S.p.A. – Via San Martino, 12 – 20122 Milan
Manufacturer
Dompé farmaceutici S.p.A. - Via Campo di Pile - L'Aquila
or
Lamp San Prospero S.p.A. – Via della Pace 25/A – San Prospero (MO)

Package leaflet: information for the user

OKi 80 mg/ml oral drops, solution

ketoprofen lysine salt
Please read this leaflet carefully before taking this medicine, as 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 others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What OKi is and what it is used for
What you need to know before taking OKi
How to take OKi
Possible side effects
How to store OKi
Contents of the pack and other information

1. What OKi is and what it is used for

OKi 80 mg/ml oral drops, solution contains the active substance ketoprofen lysine salt, which
belongs to a group of medicines used against pain and inflammation called "Non-Steroidal Anti-Inflammatory Drugs" (NSAIDs).
This medicine is used for the short-term symptomatic treatment of inflammatory conditions
associated with pain, even when accompanied by pyrexia (fever).

2. What you need to know before taking OKi

Do not take OKi

if you are allergic to ketoprofen, to other non-steroidal anti-inflammatory drugs (NSAIDs), or to any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”);
if you have a history of hypersensitivity reactions (allergy) such as bronchospasm, asthma attacks, acute rhinitis, urticaria, nasal polyps, angioedema (swelling of the deep dermis and subcutaneous tissue, which may also affect mucous membranes), or other allergic-type reactions to ketoprofen or substances with a similar mechanism of action (e.g. acetylsalicylic acid or other NSAIDs). Severe anaphylactic reactions, rarely fatal, have been observed in these patients
(see section 4 “Possible side effects”);
if you have pre-existing bronchial asthma;
if you have severe heart failure (inability of the heart to pump adequate blood flow to meet the body’s needs);
if you currently have a peptic ulcer (in the stomach) or gastrointestinal bleeding, or if you have previously suffered from recurrent peptic ulcer or bleeding (two or more distinct, confirmed episodes of bleeding or ulceration);
if you have previously experienced gastrointestinal bleeding, ulceration, or perforation, or chronic dyspepsia;
if you have a history of gastrointestinal bleeding or perforation related to previous NSAID therapy;
if you have leukopenia (reduced number of white blood cells) or thrombocytopenia (reduced number of platelets in the blood);
if you suffer from Crohn’s disease or ulcerative colitis;
if you suffer from gastritis;
if you have severe hepatic (liver cirrhosis, severe hepatitis, reduced liver function) or renal (reduced kidney function) impairment;
if you have hemorrhagic diathesis (predisposition to develop bleeding) or other coagulation disorders, or if you have hemostatic disorders;
if you are undergoing intensive diuretic therapy;
if you are in the last three months of pregnancy.

Do not give this medicine to children under 6 years of age.
Warnings and precautions
Warnings
Undesirable effects can be minimized by using the shortest possible duration of treatment needed to control symptoms (see section “How to take OKi” and the subsections below regarding gastrointestinal and cardiovascular risks).
Concomitant use of OKi with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
During treatment with all NSAIDs, including OKi, gastrointestinal bleeding, ulceration, and perforation—sometimes fatal—have been reported at any time, with or without warning symptoms or previous history of serious gastrointestinal events.
Your doctor may recommend concomitant use of gastroprotective agents (e.g. misoprostol or proton pump inhibitors), especially if you are elderly, have a history of ulcers, or are taking low-dose acetylsalicylic acid or other medicines that may increase the risk of gastrointestinal events (see subsection “Other medicines and OKi”).
Report any unusual abdominal signs or symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.
Exercise caution if you are taking medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids (medicines used to treat inflammatory conditions), selective serotonin reuptake inhibitors (SSRIs, e.g. medicines used to treat depression), anticoagulants (medicines that thin the blood, such as warfarin), or antiplatelet agents such as acetylsalicic acid (see subsection “Other medicines and OKi”).
Elderly patients are at higher risk of developing adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal (see section 3 “How to take OKi”). Elderly patients are also more prone to reduced kidney, heart, and liver function.
Children:
Gastrointestinal bleeding, occasionally severe, and ulcers have been observed in some pediatric patients treated with lysine ketoprofen salt (see section 4 “Possible side effects”); therefore, the product should be administered under strict medical supervision, with the physician evaluating the appropriate dosage regimen on a case-by-case basis.
You should be closely monitored if you have or have previously had gastrointestinal disorders, particularly for the onset of digestive disturbances, especially gastrointestinal bleeding.
Discontinue treatment with OKi immediately at the first signs of gastrointestinal bleeding or ulceration.
Patients with active or previous peptic ulcer:
Exercise caution if you have a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease), as these conditions may recur with NSAID use (see section 4 “Possible side effects”).
Ketoprofen, especially at high doses, may be associated with a higher risk of severe gastrointestinal toxicity compared to other NSAIDs.
Skin reactions:
Severe skin reactions (of the skin), some of which have been fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have very rarely been reported in association with NSAID use (see section 4 “Possible side effects”). In the early stages of therapy, patients appear to be at higher risk: the reaction usually occurs within the first month of treatment. Discontinue use of OKi at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
If you have celiac disease (gluten intolerance), you may take OKi as it does not contain gluten.
If you have diabetes, you may take OKi as it does not affect low-calorie or controlled diets.
Talk to your doctor or pharmacist before taking OKi:

If you have impaired kidney function, OKi should be administered with caution.
If you have heart failure (a condition in which the heart is weakened), liver function disorders such as cirrhosis (severe liver impairment), kidney function disorders such as nephrosis (degenerative kidney disease), chronic renal failure (impaired kidney function), if you are taking diuretics (medicines used to increase urine production), or if you may have low blood volume (hypovolemia), especially if you are elderly at the start of treatment, as kidney function must be closely monitored.
As with all NSAIDs, the medicine may increase the values of certain laboratory tests, such as blood urea nitrogen and creatinine.
If you have liver disease or abnormal liver function tests, as liver transaminase levels (liver enzymes) should be periodically assessed, particularly during long-term therapy.
As with other NSAIDs, the medicine may cause slight transient increases in some liver parameters and also significant increases in liver transaminases GPT/ALT and GOT/AST (liver enzymes) (see section 4 “Possible side effects”). If such parameters increase significantly, treatment must be discontinued. Rare cases of jaundice (yellowing of the skin and eyes) and hepatitis (liver disease) have been reported with ketoprofen use. Liver and kidney function tests and blood counts should be monitored during long-term therapy.
If you have uncontrolled hypertension (high blood pressure), congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate cardiac pumping function), confirmed ischemic heart disease (heart disease due to reduced blood flow caused by narrowing of the coronary arteries), peripheral arterial disease, and/or cerebrovascular disease (disease of the brain’s blood vessels), as treatment with lysine ketoprofen salt, like all NSAIDs, should only be initiated after careful evaluation.
If you have heart problems, a history of stroke (cerebrovascular accident), or think you may be at risk for these conditions (e.g. if you have high blood pressure, diabetes, high cholesterol, or smoke).
If you have a history (even familial) of mild to moderate hypertension (high blood pressure) and/or congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate cardiac pumping function), as adequate monitoring and appropriate instructions are required. Fluid retention and edema (swelling) have been observed during NSAID treatment.
Medicines such as OKi may be associated with a modest increase in the risk of heart attack (myocardial infarction) or stroke (cerebrovascular accident). Any risk is more likely with high doses and prolonged treatment.
An increased risk of atrial fibrillation (disturbance of heart rhythm) has been reported with NSAID use.
Hyperkalemia may occur, especially if you have diabetes, renal failure, and/or are taking agents that promote hyperkalemia (see subsection “Other medicines and OKi”). In these cases, potassium levels should be monitored.
If you have an infection – see section “Infections” below.
If you have allergic manifestations or a history of allergy, as the medicine should be administered with caution.
As with all non-steroidal drugs, the use of ketoprofen in patients with bronchial asthma or allergic diathesis (predisposition to allergy) may trigger an asthma attack. If you have asthma associated with chronic rhinitis, chronic sinusitis, and/or nasal polyposis, you are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to the general population. Administration of this medicine may cause asthma attacks or bronchospasm, shock, and other allergic phenomena, especially in individuals allergic to acetylsalicylic acid and/or NSAIDs (see subsection “Do not take OKi”).
Consult your doctor if you experience visual disturbances, such as blurred vision, as treatment must be discontinued.
If you have hematopoietic disorders (affecting blood cell formation and maturation), systemic lupus erythematosus (an immune system disease), or mixed connective tissue disorders, as OKi should be administered with caution.

Infections
OKi 80 mg/ml oral drops may mask symptoms of infections such as fever and pain. Therefore, OKi 80 mg/ml oral drops may delay appropriate treatment of the infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to varicella. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Other medicines and OKi
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
It is not recommended that you take OKi in combination with:

Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates (over 3 g/day), as they may increase the risk of gastrointestinal ulcers and bleeding.
Medicines that thin the blood (anticoagulants such as heparin and warfarin, and platelet aggregation inhibitors such as ticlopidine and clopidogrel). NSAIDs may enhance the effects of these medicines (see subsection “Warnings and precautions”), thereby increasing the risk of bleeding. If coadministration cannot be avoided, you must be closely monitored.
Lithium (a medicine used to treat manic-depressive psychosis). NSAIDs may increase lithium blood levels to toxic levels.
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and some cancers), used at doses exceeding 15 mg/week: there may be an increased risk of methotrexate hematological toxicity. Allow at least 12 hours between discontinuation or initiation of ketoprofen treatment and methotrexate administration.
Hydantoins (such as phenytoin) and sulfonamides (such as certain antibiotics and other medicines): the toxic effects of these substances may be increased.

Caution is required if you take OKi in combination with:

Medicines that may promote hyperkalemia, such as potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim.
Tenofovir (a medicine used in the treatment of certain viral infections): may increase the risk of renal failure.
Medicines used to treat high blood pressure, such as beta-blockers, diuretics, ACE inhibitors, and angiotensin II antagonists.
You should be adequately hydrated before starting concomitant therapy, and renal function should be monitored after starting concomitant therapy (see subsection “Warnings and Precautions”). NSAIDs may reduce the effect of diuretics.
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and some cancers), used at doses below 15 mg/week: there may be an increased risk of methotrexate hematological toxicity. During the first weeks of combination therapy, weekly monitoring of complete blood count is recommended. If you are elderly or have impaired renal function, monitoring should be more frequent.
Corticosteroids (medicines used to treat inflammatory conditions): there may be an increased risk of gastrointestinal ulceration or bleeding (see subsection “Warnings and Precautions”).
Pentoxifylline (a medicine used to improve blood circulation in the limbs): there may be an increased risk of bleeding. More frequent clinical monitoring may be necessary.
Zidovudine (a medicine used for the treatment of HIV): there may be an increased risk of hematological toxicity with possible severe anemia. Blood tests should be performed after starting treatment with the NSAID.
Sulfonylureas (anti-diabetic medicines such as gliclazide): NSAIDs may enhance the hypoglycemic effect of sulfonylureas.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase cardiac glycoside levels; however, a pharmacokinetic interaction between ketoprofen and cardiac glycosides has not been demonstrated.

Combinations with other medicines to consider:

Antihypertensive medicines (beta-blockers, ACE inhibitors, diuretics): NSAIDs may reduce the effect of antihypertensive medicines.
Mifepristone (a medicine used for medical termination of pregnancy): the effectiveness of the contraceptive method may theoretically be reduced due to the properties of NSAIDs.
Intrauterine contraceptive devices: device effectiveness may be reduced, leading to pregnancy.
Cyclosporine, tacrolimus (medicines used after transplantation or for the treatment of immune system disorders): risk of additional nephrotoxic effects, especially in the elderly.
Thrombolytics (medicines that facilitate the dissolution of blood clots): increased risk of bleeding.
Antiplatelet agents (ticlopidine and clopidogrel) and selective serotonin reuptake inhibitors (SSRIs, such as certain antidepressants): increased risk of gastrointestinal bleeding.
Probenecid (a medicine used for the treatment of gout): coadministration of probenecid may increase ketoprofen blood concentrations.
Quinolone antibiotics: possible increased risk of seizures.
Phenytoin and sulfonamides: dosage reduction may be necessary.
Gemeprost (a medicine used in gynecological procedures): reduced effectiveness.
Avoid alcohol consumption.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
The use of ketoprofen during the first and second trimesters of pregnancy should be avoided.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.
Epidemiological studies suggest an increased risk of miscarriage and cardiac malformations and gastroschisis (fetal abdominal wall defect) following the use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with dose and duration of treatment.
During the first and second trimesters of pregnancy, take this medicine only if clearly necessary and under medical advice.
If ketoprofen is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:

cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension, i.e. increased pressure in the pulmonary circulation);
renal dysfunction, which may progress to renal failure with oligoamnios (reduced amniotic fluid volume);

and the mother and newborn, at the end of pregnancy, to:

possible prolongation of bleeding time, and anti-aggregating effect, which may occur even at very low doses;
inhibition of uterine contractions, resulting in delayed or prolonged labor.

The use of this medicine close to delivery may cause alterations in the hemodynamics of the newborn’s pulmonary circulation, with serious consequences for respiration.
Therefore, DO NOT use OKi during the third trimester of pregnancy (see subsection “Do not take OKi”).
Breastfeeding
There is no available information on the excretion of ketoprofen in breast milk. Ketoprofen is not recommended during breastfeeding.
Fertility
The use of NSAIDs, including OKi, may reduce female fertility and is not recommended in women attempting to conceive.
Administration of NSAIDs, including OKi, should be discontinued in women experiencing fertility problems or undergoing fertility investigations.
Driving and using machines
If drowsiness, dizziness, or seizures occur after taking ketoprofen, avoid driving, operating machinery, or performing activities requiring special alertness.
OKi 80 mg/ml oral drops, solution contains sorbitol.
One pack of OKi 80 mg/ml oral drops contains 5.25 g of sorbitol. When taken according to the recommended dosage, each dose provides up to 0.17 g of sorbitol.
Sorbitol is a source of fructose. If your doctor has informed you (or the child) that you are intolerant to certain sugars, or if you have a diagnosis of hereditary fructose intolerance, a rare genetic disorder in which patients cannot metabolize fructose, consult your doctor before you (or the child) take this medicine.
OKi 80 mg/ml oral drops, solution contains methyl parahydroxybenzoate.
It may cause allergic reactions (including delayed reactions).
OKi 80 mg/ml oral drops, solution contains propylene glycol (also contained in the mint flavor).
This medicine contains 202.93 mg of propylene glycol per dose (20 drops).
OKi 80 mg/ml oral drops, solution contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per dose (20 drops), i.e. essentially 'sodium-free'.
OKi 80 mg/ml oral drops, solution contains ethanol (contained in the mint flavor).
This medicine contains 29.6 mg of alcohol (ethanol) per dose (20 drops). The amount in 20 drops of this medicine is equivalent to less than 1 ml of beer or 1 ml of wine.
The small amount of alcohol in this medicine will not produce significant effects.

3. How to take OKi

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The lowest effective dose for the shortest duration necessary 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).
Recommended doses are:
Adults: 20 (twenty) drops equal to 80 mg of ketoprofen lysine salt three times daily.
The maximum daily dose is 320 mg of ketoprofen lysine salt. Higher doses are not recommended (see subsection “Warnings and precautions”).
Special populations
Use in children aged between 6 and 14 years: 1 drop per 3 kg of body weight, three times daily, or as prescribed by the doctor. However, do not exceed 20 drops per single dose.
OKi 80 mg/ml oral drops, solution is contraindicated in children under 6 years of age (see subsection “Do not take OKi”).
Use in elderly patients: The dose must be carefully determined by the doctor, who should consider reducing the above-mentioned doses (see subsection “Warnings and precautions”).
Use in patients with hepatic impairment: It is recommended to start therapy at the lowest daily dosage (see subsection “Warnings and precautions”).
Use in patients with mild or moderate renal impairment: It is recommended to reduce the initial dose and maintain therapy using the lowest effective dose. Individual dose adjustments may be considered only after good tolerability of the drug has been established. Monitor urine output and kidney function (see subsection “Warnings and precautions”).
OKi 80 mg/ml oral drops, solution must not be used in patients with severe hepatic or renal dysfunction (see subsection “Do not take OKi”).

Instructions for use

Technical drawing showing a hand applying a device to the skin and a hand pouring the contents of a vial into a glass

The bottle has a child-resistant cap. To dispense the drops:
To open, press lightly on the container while turning the cap counterclockwise until it opens.
Dilute the drops in half a glass of still (non-carbonated) water, mix and take, preferably during meals.

If you take more OKi than you should
In case of accidental ingestion/overdose of OKi, contact your doctor immediately or go to the nearest hospital.
In cases of severe overdose, hypotension, respiratory depression, and gastrointestinal bleeding have been observed.
The patient should be immediately transferred to a specialist center to begin symptomatic treatment.
There are no specific antidotes in case of ketoprofen overdose. In case of suspected massive overdose, gastric lavage is recommended, along with symptomatic and supportive treatment.
In case of renal failure, hemodialysis may be useful to remove the drug from the body.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The most commonly observed adverse events are gastrointestinal in nature.
The following adverse reactions have been observed with the use of ketoprofen in adults:

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

Dyspepsia (indigestion), nausea, abdominal pain, vomiting.

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

Headache, dizziness, vertigo, somnolence
Constipation, diarrhoea, flatulence (intestinal gas), gastritis, abdominal discomfort
Rash, pruritus (itching)
Oedema (fluid accumulation causing swelling), fatigue, peripheral oedema (peripheral swelling), chills.

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

Haemorrhagic anaemia (anaemia due to blood loss)
Paraesthesiae (abnormal skin sensations, tingling)
Blurred vision (see section “Warnings and precautions”)
Tinnitus (ringing in the ears)
Asthma
Stomatitis (mouth ulcer), peptic ulcer (gastric or duodenal ulcer), colitis
Hepatitis, increased transaminases (liver enzymes), increased blood bilirubin (elevated serum bilirubin levels due to liver disorders), jaundice
Weight gain.

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

Dyskinesia (movement disorder), syncope
Hypotension (low blood pressure)
Oedema (swelling) of the larynx
Haematuria (blood in urine)
Asthenia (physical weakness), facial oedema.

Not known (frequency cannot be estimated from the available data):

Thrombocytopenia (reduced number of platelets in the blood), agranulocytosis (severe reduction in white blood cells), bone marrow failure (reduced production of blood cells), haemolytic anaemia (anaemia due to abnormal destruction of red blood cells), neutropenia (decrease in neutrophil white blood cells), aplastic anaemia (anaemia due to insufficient production of blood cells in the bone marrow), leukocytosis (increased number of white blood cells), thrombocytopenic purpura, leukopenia (reduced number of white blood cells)
Anaphylactic reactions (including shock), hypersensitivity
Depression, hallucinations, confusion, mood alterations, excitability, insomnia
Seizures
Dysgeusia (altered taste)
Tremor, hyperkinesia
Heart failure (weakened heart), atrial fibrillation (irregular heart rhythm), palpitations, tachycardia (increased heart rate)
Hypertension (increased blood pressure), vasodilation (dilation of blood vessels), vasculitis (inflammation of blood or lymphatic vessels) (including leukocytoclastic vasculitis)
Bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea (difficulty breathing), laryngospasm, acute respiratory failure (a single fatal case has been reported in an aspirin-sensitive asthmatic patient)
Gastralgia (stomach pain), exacerbation of colitis and Crohn’s disease, gastrointestinal haemorrhage, gastrointestinal perforation (sometimes fatal, particularly in the elderly), pyrosis (heartburn), gastric ulcer, duodenal ulcer, oedema (swelling) of the mouth, pancreatitis, gastritis, erosive gastritis, haematemesis (vomiting blood) or melaena (passage of digested blood in stools), hyperchlorhydria (excess hydrochloric acid in gastric juice), gastric pain (stomach pain), tongue oedema
Photosensitisation (reaction to sunlight or UV lamps), alopecia (hair loss), urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome, Lyell’s syndrome and toxic epidermal necrolysis (serious skin reactions), erythema (redness of the skin), exanthema (skin rash), maculopapular exanthema, purpura, acute generalised exanthematous pustulosis (skin eruption with pustule formation), dermatitis
Acute renal failure, tubulointerstitial nephritis, nephritis or nephritic syndrome, nephrotic syndrome, glomerulonephritis, fluid/sodium retention with possible oedema, acute tubular necrosis (damage to renal tubular cells), renal papillary necrosis (damage to renal papillae), oliguria (reduced urine output), abnormal renal function tests
Periorbital oedema (swelling around the eyes)
Aseptic meningitis (inflammation of the membranes covering the brain not caused by bacteria)
Lymphangitis (inflammation of lymphatic vessels)
Hyperkalaemia (increased potassium levels in blood), hyponatraemia (decreased sodium levels in blood).

Medicines such as OKi may be associated (particularly at high doses and with long-term use) with an increased risk of arterial thrombotic events (formation of blood clots in blood vessels), such as heart attack (myocardial infarction) or stroke (cerebrovascular accident) (see section 2 “What you need to know before taking OKi”).
Following the instructions provided in this leaflet reduces the risk of side effects.

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

5. How to store OKi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month. The stated expiry date applies to the product stored in its original, undamaged packaging and kept under proper storage conditions.
This medicine does not require any special storage precautions.
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 OKi contains

The active substance is ketoprofen lysine salt. 100 ml of solution contain 8 g of ketoprofen lysine salt (1 drop contains 4 mg), equivalent to 5 g of ketoprofen.
The other ingredients are sodium alginate, sorbitol 70%, propylene glycol, sodium saccharin, methyl parahydroxybenzoate, peppermint flavour (containing ethanol and propylene glycol), purified water.

Description of the appearance of OKi and contents of the pack
Oral drops, solution – 1 bottle of 30 ml.
Marketing Authorization Holder
Dompé farmaceutici S.p.A. - Via San Martino, 12 – 20122 Milan
Manufacturer
Dompé farmaceutici S.p.A. - Via Campo di Pile - L’Aquila
Package leaflet: information for the user

OKi 160 mg/2 ml intramuscular injection solution

ketoprofen lysine salt
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What OKi is and what it is used for
What you need to know before using OKi
How to use OKi
Possible side effects
How to store OKi
Package contents and other information

1. What OKi is and what it is used for

OKi 160 mg/2 ml injectable solution for intramuscular use contains as the active substance ketoprofen lysine salt, which belongs to a group of medicines used against pain and inflammation called non-steroidal anti-inflammatory drugs (NSAIDs).

This medicine is used for:

the symptomatic treatment of acute exacerbations (worsening) of:
- rheumatoid arthritis (an autoimmune disease causing joint pain and stiffness)
- osteoarthritis (such as coxarthrosis and gonarthrosis)
- ankylosing spondylitis (a chronic inflammatory disease mainly affecting the spine and joints)
- periarticular conditions such as scapulohumeral periarthritis, tendinitis and tenosynovitis, capsulitis and bursitis
- lumbar pain of musculoskeletal origin
- sciatica
- acute gout.
postoperative pain control.
the treatment of neoplastic pain.

2. What you should know before using OKi

Do not use OKi

if you are allergic to ketoprofen, to other non-steroidal anti-inflammatory drugs (NSAIDs), or to any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”);
if you have a history of hypersensitivity reactions (allergy) such as bronchospasm, asthma attacks, rhinitis, nasal polyps, angioedema (swelling of deep dermis and subcutaneous tissue, which may also affect mucous membranes), urticaria, or other allergic reactions to ketoprofen, acetylsalicylic acid, or other NSAIDs. Severe anaphylactic reactions, rarely fatal, have been observed in these patients (see section 4 “Possible side effects”);
if you are currently undergoing intensive diuretic therapy;
if you have leukopenia (reduced number of white blood cells) or thrombocytopenia (reduced number of platelets in the blood);
if you have gastritis;
if you are suffering from gastrointestinal bleeding or have an active peptic ulcer, or have previously experienced recurrent peptic ulcer or bleeding (two or more confirmed episodes of bleeding or ulceration);
if you have previously experienced gastrointestinal bleeding, ulceration, or perforation, or chronic dyspepsia;
if you suffer from Crohn’s disease or ulcerative colitis;
if you have a history of bronchial asthma;
if you suffer from severe heart failure (inability of the heart to pump adequate blood to meet the body’s needs);
if you suffer from severe liver failure (liver cirrhosis, severe hepatitis, reduced liver function);
if you suffer from severe renal failure (reduced kidney function);
if you have hemorrhagic diathesis (predisposition to bleeding) or other coagulation disorders and are being treated with anticoagulants (medicines that thin the blood);
if you are experiencing a cerebrovascular hemorrhage or any active bleeding;
if you are in the last three months of pregnancy;
if you are of pediatric age.

Warnings and precautions
Warnings
Undesirable effects can be minimized by using the shortest possible duration of treatment necessary to control symptoms (see subsection “How to take OKi” and the sections below on gastrointestinal and cardiovascular risks).
Concomitant use of OKi with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
During treatment with all NSAIDs, including OKi, cases of gastrointestinal ulceration, perforation, or bleeding have been reported at any time, with or without warning symptoms or previous history of serious gastrointestinal events, and may be fatal.
Your doctor may recommend concomitant use of gastroprotective agents (e.g., misoprostol or proton pump inhibitors), especially if you are elderly, have a history of ulcers, or are taking low-dose acetylsalicylic acid or other medicines that may increase the risk of gastrointestinal events (see subsection “Other medicines and OKi”).
Report any unusual abdominal signs or symptoms (especially gastrointestinal bleeding), particularly during the initial stages of treatment.
Exercise caution if you are taking medications that could increase the risk of ulceration or gastrointestinal bleeding, such as oral corticosteroids (medicines used to treat inflammatory conditions), selective serotonin reuptake inhibitors (e.g., medicines used to treat depression), anticoagulants (medicines that thin the blood, such as warfarin), or antiplatelet agents such as acetylsalicylic acid (see subsection “Other medicines and OKi”).
The risk of gastrointestinal bleeding is increased in patients with low body weight.
Immediately discontinue treatment with OKi at the first signs of gastrointestinal bleeding or ulceration.
Due to the severity of gastrointestinal side effects, gastric symptoms must be carefully monitored.
Patients with active or previous peptic ulcer:
Exercise caution if you have a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease), as these conditions may recur with NSAID use (see section 4 “Possible side effects”).
Ketoprofen, especially at high doses, may be associated with a higher risk of severe gastrointestinal toxicity compared to other NSAIDs.
Elderly patients are at greater risk of developing adverse reactions to NSAIDs, particularly gastrointestinal bleeding or perforation, which may be fatal (see section 3 “How to use OKi”). Elderly patients are also more prone to reduced kidney, heart, and liver function.
Skin reactions:
Severe skin reactions (of the skin), some of which are fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely reported in association with NSAID use (see section 4 “Possible side effects”). In the early stages of therapy, patients appear to be at higher risk: the reaction usually occurs within the first month of treatment.
Discontinue use of OKi at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
The safety of using OKi 160 mg/2 ml injectable solution for intramuscular use in children has not been established.
Consult your doctor or pharmacist before using OKi:

If you have impaired kidney function, OKi should be administered with caution.
If you suffer from heart failure (a condition in which the heart is weakened), liver dysfunction such as cirrhosis (severe liver impairment), kidney dysfunction such as nephrosis (a degenerative kidney disease), or chronic renal failure (impaired kidney function), if you are taking diuretics (medicines used to increase urine production), or if you may have low blood volume (hypovolemia), especially if you are elderly at the start of treatment, as kidney function must be closely monitored.
As with all NSAIDs, the medicine may increase the values of certain laboratory tests, such as blood urea nitrogen and creatinine.
If you have liver disease or abnormal liver function tests, as transaminase levels (liver enzymes) should be periodically evaluated, especially during long-term therapy.
As with other NSAIDs, the medicine may cause slight transient increases in some liver parameters and even significant increases in GPT/ALT and GOT/AST transaminases (liver enzymes) (see section 4 “Possible side effects”). If such parameters increase significantly, treatment should be discontinued. Cases of jaundice (yellowing of the skin and eyes) and hepatitis (liver disease) have been rarely reported with ketoprofen use. Liver and kidney function tests and blood counts should be monitored during long-term therapy.
If you suffer from uncontrolled hypertension (high blood pressure), congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate heart pumping function), established ischemic heart disease (heart disease due to reduced blood flow from coronary artery narrowing), peripheral artery disease, and/or cerebrovascular disease (disease of blood vessels in the brain), as treatment with ketoprofen lysine salt, like all NSAIDs, should only be initiated after careful evaluation.
If you have heart problems, a history of stroke (cerebrovascular accident), or think you may be at risk for these conditions (e.g., if you have high blood pressure, diabetes, high cholesterol, or smoke).
If you have a history (even familial) of mild to moderate hypertension (high blood pressure) and/or congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate heart pumping function), as adequate monitoring and appropriate instructions are required. Fluid retention and edema (swelling) have been observed during treatment with NSAIDs.
Medicines like OKi may be associated with a modest increase in the risk of heart attack (myocardial infarction) or stroke (cerebrovascular accident). Any risk is more likely with high doses and prolonged treatment.
An increased risk of atrial fibrillation (abnormal heart rhythm) has been reported with NSAID use.
Hyperkalemia may occur, especially if you have diabetes, renal failure, and/or are taking agents that promote hyperkalemia (see subsection “Other medicines and OKi”). In these cases, potassium levels should be monitored.
If you have an infection – see section “Infections” below.
If you have allergic manifestations or a history of allergy, as the medicine should be administered with caution.
Like all non-steroidal drugs, ketoprofen use in patients with bronchial asthma or allergic diathesis (predisposition to allergy) may trigger an asthma attack. If you have asthma associated with chronic rhinitis, chronic sinusitis, and/or nasal polyposis (nasal polyps), you are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to the general population. Administration of this medicine may cause asthma attacks or bronchospasm, shock, and other allergic phenomena, especially in individuals allergic to acetylsalicylic acid or NSAIDs (see subsection “Do not use OKi”).
Consult your doctor if you experience visual disturbances, such as blurred vision, as treatment must be discontinued.
If you have hematopoietic disorders (affecting blood cell formation and maturation), systemic lupus erythematosus (an immune system disease), or mixed connective tissue disease, as OKi should be administered with caution.

Infections
OKi 160 mg/2 ml injectable solution for intramuscular use may mask symptoms of infections such as fever and pain. Therefore, OKi 160 mg/2 ml injectable solution for intramuscular use may delay appropriate treatment of infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to varicella. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Other medicines and OKi
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
It is not recommended that you take OKi in combination with:

Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates (over 3 g/day), as they may increase the risk of gastrointestinal ulcers and bleeding.
Medicines that thin the blood (anticoagulants such as heparin and warfarin, and antiplatelet agents such as ticlopidine and clopidogrel); NSAIDs may enhance the effects of anticoagulants like warfarin (see subsection “Warnings and precautions”), thereby increasing the risk of bleeding (see subsection “Warnings and precautions”). If co-administration cannot be avoided, close monitoring is required.
Lithium (a medicine used to treat manic-depressive psychosis). NSAIDs may increase lithium blood levels to toxic levels.
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and some cancers) at doses exceeding 15 mg/week: there may be an increased risk of methotrexate toxicity. Allow at least 12 hours between discontinuation or initiation of ketoprofen treatment and methotrexate administration.
Hydantoins (such as phenytoin) and sulfonamides (such as certain antibiotics and other medicines): the toxic effects of these substances may be increased.

Caution is required if you take OKi in combination with:

Medicines that may promote hyperkalemia, such as potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim.
Tenofovir (a medicine used to treat certain viral infections): may increase the risk of renal failure.
Medicines used to treat high blood pressure, such as beta-blockers, diuretics, ACE inhibitors, and angiotensin II antagonists. You should be adequately hydrated before starting concomitant therapy, and renal function should be monitored after starting concomitant therapy (see subsection “Warnings and Precautions”). NSAIDs may reduce the effect of diuretics.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see subsection “Warnings and precautions”).
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and some cancers) at low doses, less than 15 mg/week. During the first weeks of combination therapy, weekly complete blood count monitoring should be performed. If you are elderly or have impaired renal function, monitoring should be more frequent.
Pentoxifylline (a medicine used to improve blood circulation in the limbs): may increase the risk of bleeding. More frequent clinical checks of bleeding time may be necessary.
Zidovudine (a medicine used to treat HIV infection): risk of increased blood toxicity with possible severe anemia. Blood tests should be performed after starting treatment with the NSAID.
Sulfonylureas (diabetes medicines such as gliclazide): NSAIDs may enhance the hypoglycemic effect of sulfonylureas.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase cardiac glycoside levels; however, a pharmacokinetic interaction between ketoprofen and cardiac glycosides has not been demonstrated.

Combinations with other medicines to consider:

Antihypertensive medicines (beta-blockers, ACE inhibitors, diuretics): NSAIDs may reduce the effect of antihypertensive medicines.
Mifepristone (a medicine used for medical termination of pregnancy): the effectiveness of the contraceptive method may theoretically decrease due to the properties of NSAIDs.
Intrauterine contraceptive devices: the effectiveness of the device may be reduced, leading to pregnancy.
Cyclosporine and tacrolimus (medicines used after transplantation or for treating immune system disorders): renal function should be monitored during combination therapy.
Probenecid (a medicine also used for gout): co-administration of probenecid may increase ketoprofen blood concentrations.
Thrombolytic medicines (medicines that facilitate clot dissolution): increased risk of bleeding. Several substances are involved in interactions due to their antiplatelet effect: tirofiban, eptifibatide, abciximab, and iloprost. Using multiple antiplatelet agents increases the risk of bleeding.
Antiplatelet agents (ticlopidine and clopidogrel) and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see subsection “Warnings and precautions”).
Quinolone antibiotics: possible increased risk of seizures.
Diphenylhydantoin and sulfamides: dosage reduction may be necessary.
Gemeprost (a medicine used in gynecological procedures): reduced effectiveness.
Avoid alcohol consumption.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Use of ketoprofen during the first and second trimesters of pregnancy should be avoided.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.
Epidemiological studies suggest an increased risk of spontaneous abortion, cardiac malformations, and gastroschisis (fetal abdominal wall defect) following use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with dose and duration of treatment.
During the first and second trimesters of pregnancy, take this medicine only if strictly necessary and under medical advice.
If ketoprofen is used by a woman trying to conceive, or during the first and second trimesters of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:

cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension, i.e., increased pressure in the pulmonary circulation);
renal dysfunction, which may progress to renal failure with oligo-hydramnios (reduced amniotic fluid volume);

and the mother and newborn at the end of pregnancy to:

possible prolongation of bleeding time and antiplatelet effect, which may occur even at very low doses;
inhibition of uterine contractions, resulting in delayed or prolonged labor.

Use of the drug near delivery may cause alterations in the hemodynamics of the newborn’s small circulation, with serious consequences for respiration.
Therefore, DO NOT use OKi during the third trimester of pregnancy (see subsection “Do not take OKi”).
Breastfeeding
There is no available information on the excretion of ketoprofen in breast milk. Ketoprofen is not recommended during breastfeeding.
Fertility
Use of NSAIDs, including OKi, may reduce female fertility and is not recommended in women attempting to conceive. Administration of OKi should be discontinued in women with fertility problems or undergoing fertility investigations.
Driving and use of machinery
If visual disturbances, drowsiness, dizziness, vertigo, or convulsions occur after administration of ketoprofen, avoid driving, operating machinery, or performing activities requiring special alertness.
OKi 160 mg/2 ml injectable solution for intramuscular use contains benzyl alcohol.
This medicine contains 80 mg of benzyl alcohol per dose (one vial), equivalent to 80 mg/2 ml.
Benzyl alcohol may cause allergic reactions.
Consult your doctor or pharmacist if you are pregnant or breastfeeding, or if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause undesirable effects (such as metabolic acidosis).
OKi 160 mg/2 ml injectable solution for intramuscular use contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per dose (one vial), i.e., essentially “sodium-free.”

3. How to use OKi

Recommended doses:
Adults: The recommended daily dose is 160–320 mg of ketoprofen lysine salt (1–2 vials per day).
The maximum daily dose is 320 mg of ketoprofen lysine salt. Higher doses are not recommended (see also subsection “Warnings and precautions”).

Special populations
Elderly: Dosage must be carefully determined by the doctor, who should consider a possible reduction of the above-mentioned doses.

Patients with mild or moderate hepatic (liver) dysfunction: It is recommended to initiate therapy at the lowest daily dosage.

Patients with mild or moderate renal impairment: It is recommended to monitor urine output and renal function, and to maintain therapy using the lowest effective dose. Individual dose adjustments may be considered only after good drug tolerability has been established.

OKi 160 mg/2 ml injectable solution for intramuscular use must not be used in patients with severe hepatic or renal dysfunction.

Paediatric population
The safety and efficacy of intramuscular ketoprofen have not been studied in children. Paediatric dosing has not been established.
OKi 160 mg/2 ml injectable solution for intramuscular use must not be used in children under 15 years of age.

Method of administration
Administer as a deep intramuscular injection into the upper outer quadrant of the buttock.
Do not use injectable therapy for longer than three days. After three days, oral or rectal therapy should be initiated.

If you use more OKi than you should
In case of accidental ingestion/overdose of OKi, contact your doctor immediately or go to the nearest hospital.
In adults, the main signs of overdose are headache, dizziness, drowsiness, nausea, vomiting, diarrhoea, and abdominal pain. In cases of severe poisoning, hypotension, respiratory depression, and gastrointestinal bleeding have been observed.
The patient must be immediately transferred to a specialist centre to begin symptomatic treatment.
There are no specific antidotes in case of ketoprofen overdose.
In case of renal failure, haemodialysis may be useful to remove the drug from the body.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The most commonly observed adverse events are gastrointestinal in nature.
The following adverse reactions have been observed with the use of ketoprofen in adults:

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

dyspepsia (indigestion), nausea, abdominal pain, vomiting.

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

headache, dizziness, vertigo, somnolence (drowsiness)
constipation, diarrhoea, flatulence (gas in the intestine), gastritis, abdominal discomfort
rash, pruritus (itching)
oedema (fluid retention causing swelling), fatigue, peripheral oedema (swelling in extremities), chills
pain and burning sensation at injection site, including medicamentosa cutis embolia (Nicolau syndrome).

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

haemorrhagic anaemia (anaemia due to blood loss)
paraesthesia (abnormal skin sensation, tingling)
blurred vision (see section “Warnings and precautions”)
tinnitus (ringing in the ears)
asthma
stomatitis (mouth ulcer), peptic ulcer (gastric or duodenal ulcer), colitis
hepatitis, increased transaminases (liver enzymes), increased blood bilirubin (elevated serum bilirubin levels due to liver disorders), jaundice
weight increased.

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

dyskinesia (movement disorder), syncope (fainting)
hypotension (low blood pressure)
oedema (swelling) of the larynx
haematuria (blood in urine)
asthenia (physical weakness), facial oedema (facial swelling).

Not known (frequency cannot be estimated from the available data):

thrombocytopenia (reduced number of platelets in the blood), agranulocytosis (severe reduction in white blood cells), bone marrow failure (reduced production of blood cells), haemolytic anaemia (anaemia due to abnormal destruction of red blood cells), neutropenia (decrease in neutrophil white blood cells), aplastic anaemia (anaemia due to insufficient production of blood cells in the bone marrow), leucocytosis (increased number of white blood cells), thrombocytopenic purpura, leucopenia (reduced number of white blood cells)
anaphylactic reactions (including shock), hypersensitivity
depression, hallucinations, confusion, mood alterations, excitability, insomnia
convulsions
dysgeusia (altered taste)
tremor, hyperkinesia
burning sensation (local reaction at infusion site)
cardiac failure (weak heart), atrial fibrillation (irregular heart rhythm), palpitations, hypertension (increased blood pressure), vasodilation (dilation of blood vessels), vasculitis (inflammation of blood or lymphatic vessels) (including leukocytoclastic vasculitis), tachycardia (increased heart rate)
bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea (difficulty breathing), laryngospasm, acute respiratory failure (one fatal case has been reported in an asthmatic patient sensitive to aspirin)
gastralgia (stomach pain), exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage, gastrointestinal perforation (sometimes fatal, particularly in the elderly), pyrosis (heartburn), gastric ulcer, duodenal ulcer, oedema (swelling) of the mouth, pancreatitis, erosive gastritis, haematemesis (vomiting blood) or melena (passing digested blood in stools), hyperchlorhydria (excess hydrochloric acid in gastric juice), gastric pain (stomach pain), oedema of the tongue
photosensitisation (reaction upon exposure to sunlight or UV lamps), alopecia (hair loss), urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome, Lyell's syndrome and toxic epidermal necrolysis (severe skin reactions), erythema (redness of the skin), exanthema (skin rash), maculopapular exanthema, purpura, acute generalised exanthematous pustulosis (skin eruption with pustule formation), dermatitis
acute renal failure, tubulointerstitial nephritis, nephritis or nephritic syndrome, nephrotic syndrome, glomerular nephritis, fluid/sodium retention with possible oedema, acute tubular necrosis (damage to kidney tubular cells), renal papillary necrosis (damage to renal papillae), oliguria (reduced urine output), abnormal renal function tests
periorbital oedema (swelling around the eyes)
aseptic meningitis (inflammation of the membranes covering the brain not caused by bacteria)
lymphangitis (inflammation of lymphatic vessels)
hyperkalaemia (increased potassium levels in blood), hyponatraemia (decreased sodium levels in blood).

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

5. How to store OKi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
The shelf life applies to the product in its original, undamaged packaging, correctly stored.
Protect from heat. Store in the original container to protect it from light.
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 OKi contains

The active substance is ketoprofen lysine salt. Each 2 ml vial contains 160 mg of ketoprofen lysine salt (equivalent to 100 mg of ketoprofen).
The other components are benzyl alcohol, sodium hydrogen carbonate, sodium hydroxide, water for injection.

Description of the appearance of OKi and package contents
Injectable solution for intramuscular use.
Box containing 6 vials of 2 ml
Marketing Authorization Holder
Dompé farmaceutici S.p.A. - Via San Martino, 12 – 20122 Milan
Manufacturer
Alfasigma S.p.A – Via Enrico Fermi, 1 - Alanno (PE)
or
Abiogen Pharma S.p.A. – Via Meucci 36 – 56014 Ospedaletto (PI)
Package leaflet: information for the user

OKi 160 mg suppositories

ketoprofen lysine salt
Please read this leaflet carefully before using this medicine as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
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:

What OKi is and what it is used for
What you need to know before using OKi
How to use OKi
Possible side effects
How to store OKi
Contents of the pack and other information

1. What OKi is and what it is used for

OKi 160 mg suppositories contain the active substance ketoprofen lysine salt, which belongs to a group of medicines used against pain and inflammation called "Non-Steroidal Anti-Inflammatory Drugs" (NSAIDs).
OKi 160 mg suppositories are used for the symptomatic treatment of inflammatory conditions associated with pain, such as: rheumatoid arthritis (an autoimmune disease causing joint pain and stiffness), ankylosing spondylitis (a chronic inflammatory disease affecting the spine and joints), painful osteoarthritis (a disease affecting the joints), extra-articular rheumatism (rheumatic diseases affecting structures outside the joints), and post-traumatic inflammation (inflammatory condition following trauma).

2. What you need to know before using OKi

Do not use OKi

if you are allergic to ketoprofen or to any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”);
if you have a history of hypersensitivity reactions (allergy) such as bronchospasm, asthma attacks, rhinitis, urticaria, nasal polyps, angioedema (swelling of deep dermal and subcutaneous tissues, which may also affect mucous membranes), or other allergic reactions to ketoprofen, acetylsalicylic acid (ASA), or other NSAIDs. Severe anaphylactic reactions, rarely fatal, have been observed in these patients (see section 4 “Possible side effects”);
if you suffer from pre-existing bronchial asthma;
if you have severe heart failure (inability of the heart to pump sufficient blood to meet the body’s needs);
if you currently have a peptic ulcer (in the stomach) or gastrointestinal bleeding, or if you have previously suffered from recurrent peptic ulcer or bleeding (two or more distinct, documented episodes of bleeding or ulceration);
if you have previously experienced gastrointestinal bleeding, ulceration, or perforation, or chronic dyspepsia;
if you have previously experienced gastrointestinal perforation or bleeding due to prior treatment with other NSAIDs;
if you have leukopenia (reduced number of white blood cells) or thrombocytopenia (reduced number of platelets in the blood);
if you suffer from Crohn’s disease or ulcerative colitis;
if you suffer from gastritis;
if you currently have bleeding or suffer from hemorrhagic diathesis (predisposition to develop bleeding);
if you have coagulation disorders;
if you suffer from severe hepatic (liver cirrhosis, severe hepatitis, reduced liver function) or renal (reduced kidney function) insufficiency;
if you have severe blood clotting disorders;
if you are in the last three months of pregnancy (see subsection “Pregnancy, breastfeeding and fertility”);
if you are of pediatric age;
if you are undergoing intensive diuretic therapy;
if you currently suffer from proctitis (inflammation of the rectal mucosa), have previously suffered from proctorrhagia (rectal bleeding), or suffer from hemorrhoidal disorders or have other local lesions currently present or recently in your medical history.

Warnings and precautions
Warnings
Side effects can be minimized by using the shortest possible duration of treatment necessary to control symptoms (see subsection “How to take OKi” and the sections below on gastrointestinal and cardiovascular risks).
Concomitant use of OKi with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
During treatment with all NSAIDs, including OKi, cases of gastrointestinal ulceration, perforation, or bleeding have been reported at any time, with or without warning symptoms or previous history of serious gastrointestinal events. These events may be fatal.
Your doctor may recommend concomitant use of gastroprotective agents (e.g., misoprostol or proton pump inhibitors), especially if you are elderly, have a history of ulcers, or are taking low-dose acetylsalicylic acid or other medicines that may increase the risk of gastrointestinal events (see subsection “Other medicines and OKi”).
Report any unusual abdominal signs or symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.
Exercise caution if you are taking medications that could increase the risk of ulceration or bleeding, such as oral corticosteroids (medicines used to treat inflammatory conditions), selective serotonin reuptake inhibitors (e.g., medicines used to treat depression), anticoagulants (medicines that thin the blood, such as warfarin), or antiplatelet agents such as acetylsalicylic acid (see subsection “Other medicines and OKi”).
The risk of gastrointestinal bleeding is increased in patients with low body weight.
Immediately discontinue treatment with OKi at the first sign of gastrointestinal bleeding or ulceration.
Due to the severity of gastrointestinal side effects, gastric symptoms must be carefully monitored.
Patients with active or previous peptic ulcer:
Exercise caution if you have a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease), as these conditions may recur with NSAID use (see section 4 “Possible side effects”).
Ketoprofen, especially at high doses, may be associated with a higher risk of severe gastrointestinal toxicity compared to other NSAIDs.
Elderly patients are at greater risk of developing adverse reactions to NSAIDs, particularly gastrointestinal bleeding or perforation, which may be fatal (see section 3 “How to use OKi”). Elderly patients are more prone to reduced kidney, heart, and liver function.
Skin reactions:
Severe skin reactions (of the skin), some of which are fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely reported with NSAID use (see section 4 “Possible side effects”). The risk is higher in the early stages of therapy, and the reaction typically occurs within the first month of treatment.
Discontinue use of OKi at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Talk to your doctor or pharmacist before using OKi:

If you have impaired kidney function, OKi should be administered with caution.
If you suffer from heart failure (a condition in which the heart is weakened), liver dysfunction such as cirrhosis (severe liver impairment), kidney dysfunction such as nephrosis (degenerative kidney disease), or chronic renal insufficiency (impaired kidney function), if you are taking diuretics (medicines used to increase urine production), or if you may have low blood volume (hypovolemia), especially if you are elderly at the start of treatment, as kidney function must be closely monitored.
As with all NSAIDs, the medicine may increase certain laboratory test values, such as blood urea nitrogen and creatinine.
If you have liver disease or abnormal liver function tests, as liver transaminase levels (liver enzymes) should be periodically evaluated, especially during long-term therapy.
As with other NSAIDs, the medicine may cause small, transient increases in some liver parameters and even significant increases in GPT/ALT and GOT/AST transaminases (liver enzymes) (see section 4 “Possible side effects”). If substantial increases in these parameters occur, treatment must be discontinued. Rare cases of jaundice (yellowing of the skin and eyes) and hepatitis (liver disease) have been reported with ketoprofen use. Liver and kidney function tests and blood counts should be performed during long-term therapy.
If you suffer from uncontrolled hypertension (high blood pressure), congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate heart pumping function), established ischemic heart disease (heart disease due to reduced blood flow caused by narrowing of the coronary arteries), peripheral arterial disease, and/or cerebrovascular disease (disease of blood vessels in the brain), as treatment with ketoprofen lysine salt, as with all NSAIDs, should only be initiated after careful evaluation.
If you have heart problems, history of stroke (cerebrovascular accident), or believe you may be at risk for these conditions (e.g., if you have high blood pressure, diabetes, high cholesterol, or smoke).
If you have a history (even familial) of mild to moderate hypertension (high blood pressure) and/or congestive heart failure (fluid accumulation in the lungs, abdominal organs, and peripheral tissues due to inadequate heart pumping function), as adequate monitoring and appropriate instructions are required. Fluid retention and edema (swelling) have been observed during NSAID treatment.
Medicines such as OKi may be associated with a modest increase in the risk of heart attack (myocardial infarction) or stroke (cerebrovascular accident). Any risk is more likely with high doses and prolonged treatment.
An increased risk of atrial fibrillation (heart rhythm disorder) has been reported with NSAID use.
Hyperkalemia may occur, especially if you have diabetes, renal insufficiency, and/or are taking agents that promote hyperkalemia (see subsection “Other medicines and OKi”). In these circumstances, potassium levels should be monitored.
If you have an infection – see section «Infections» below.
If you have allergic manifestations or have previously suffered from allergies, as the medicine should be administered with caution.
As with all non-steroidal drugs, the use of ketoprofen in patients with bronchial asthma or allergic diathesis (predisposition to develop allergies) may trigger an asthma attack. If you have asthma associated with chronic rhinitis, chronic sinusitis, and/or nasal polyposis, you are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to the general population. Administration of this medicine may cause asthma attacks or bronchospasm, shock, and other allergic phenomena, especially in individuals allergic to acetylsalicylic acid or NSAIDs (see subsection “Do not use OKi”). Consult your doctor if you experience visual disturbances, such as blurred vision, as treatment must be discontinued.
If you suffer from hematopoietic disorders (affecting the formation and maturation of blood cells), systemic lupus erythematosus (an immune system disease), or mixed connective tissue disorders, as OKi should be administered with caution.

Infections
OKi 160 mg suppositories may mask symptoms of infections such as fever and pain. Therefore, OKi 160 mg suppositories may delay appropriate treatment of the infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to varicella. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.

Other medicines and OKi
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.

It is not recommended that you take OKi in combination with:

Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates, as they may increase the risk of gastrointestinal bleeding and ulceration.
Medicines that thin the blood (anticoagulants such as heparin and warfarin, and antiplatelet agents such as ticlopidine and clopidogrel). NSAIDs can enhance the effects of these medicines, thereby increasing the risk of bleeding (see subsection “Warnings and Precautions”). If concomitant administration cannot be avoided, you must be closely monitored.
Lithium (a medicine used to treat manic-depressive psychosis). NSAIDs may increase plasma lithium levels to toxic levels.
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and some cancers) used at doses exceeding 15 mg/week: there may be an increased risk of methotrexate hematological toxicity. Allow at least 12 hours between discontinuation or initiation of ketoprofen treatment and methotrexate administration.
Hydantoins (such as phenytoin) and sulfonamides (such as certain antibiotics and other medicines): the toxic effects of these substances may be increased.

Caution is required if you take OKi in combination with:

Medicines that may promote hyperkalemia, such as potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim.
Tenofovir (a medicine used in the treatment of certain viral infections): may increase the risk of renal failure.
Medicines used to treat high blood pressure, such as beta-blockers, diuretics, ACE inhibitors, and angiotensin II antagonists. You should be adequately hydrated before starting concomitant therapy, and renal function monitoring should be considered after starting concomitant therapy (see subsection “Warnings and Precautions”). NSAIDs may reduce the effect of diuretics.
Methotrexate (a medicine indicated for the treatment of certain autoimmune diseases and some cancers) used at doses below 15 mg/week: during the first weeks of combination use, weekly monitoring of complete blood count is required. If you are elderly or have impaired renal function, monitoring should be more frequent.
Corticosteroids (medicines used to treat inflammatory conditions): there may be an increased risk of gastrointestinal ulceration or bleeding (see subsection “Warnings and Precautions”).
Pentoxifylline (a medicine used to improve blood circulation in the limbs): there may be an increased risk of bleeding. More frequent clinical checks and monitoring of bleeding time may be necessary.
Zidovudine (a medicine used to treat HIV): there may be an increased blood toxicity with possible severe anemia. Blood tests are necessary after starting treatment with NSAIDs.
Sulfonylureas (anti-diabetic medicines, such as glicazide): NSAIDs may enhance the hypoglycemic effect of sulfonylureas.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase cardiac glycoside levels; however, a pharmacokinetic interaction between ketoprofen and cardiac glycosides has not been demonstrated.

Combinations with other medicines to consider:

Antihypertensive medicines (beta-blockers, ACE inhibitors, diuretics): NSAIDs may reduce the effect of antihypertensive medicines. Mifepristone (a medicine used for voluntary termination of pregnancy): the effectiveness of the contraceptive method may theoretically be reduced due to the properties of NSAIDs.
Intrauterine contraceptive devices: the effectiveness of the device may be reduced, leading to pregnancy.
Thrombolytic medicines (medicines that facilitate the dissolution of blood clots): NSAIDs may increase the risk of bleeding.
Antiplatelet agents (ticlopidine and clopidogrel) and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see subsection “Warnings and Precautions”).
Phenytoin and sulfonamides: dosage reduction of phenytoin or sulfonamides may be necessary.
Cyclosporine, tacrolimus (medicines used after transplantation or for the treatment of immune system disorders): risk of additional toxic effects on the kidneys, especially in the elderly.
Probenecid (a medicine used to treat gout): co-administration of probenecid may increase ketoprofen blood concentrations.
Quinolone antibiotics: possible increased risk of seizures.
Gemeprost (a medicine used in gynecological procedures): reduced effectiveness.
Avoid alcohol consumption.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
The use of ketoprofen during the first and second trimesters of pregnancy should be avoided.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.
Epidemiological studies suggest an increased risk of miscarriage and cardiac malformations and gastroschisis (fetal abdominal wall defect) following the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of treatment.
During the first and second trimesters of pregnancy, take this medicine only if strictly necessary and under medical advice.
If ketoprofen is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:

cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension, i.e., increased pressure in the pulmonary circulation);
renal dysfunction, which may progress to renal failure with oligo-anhydramnios (reduced amniotic fluid volume);

and the mother and newborn at the end of pregnancy to:

possible prolongation of bleeding time, and antiplatelet effect, which may occur even at very low doses;
inhibition of uterine contractions, resulting in delayed or prolonged labor.

The use of the drug near delivery may cause hemodynamic alterations in the newborn’s pulmonary circulation with serious consequences for respiration.
Therefore, do not use OKi 160 mg suppositories during the third trimester of pregnancy (see “Do not take OKi”).

Breastfeeding
There is no available information on the excretion of ketoprofen in breast milk. Ketoprofen is not recommended during breastfeeding.

Fertility
The use of NSAIDs, including OKi, may reduce female fertility and is not recommended in women attempting to conceive. Administration of OKi should be discontinued in women experiencing fertility problems or undergoing fertility investigations.

Driving and use of machinery
If drowsiness, dizziness, or convulsions occur after taking ketoprofen, avoid driving, operating machinery, or performing activities requiring special alertness.

3. How to use OKi

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The lowest effective dose for the shortest duration necessary 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).
Recommended dose:
Adults: 1 suppository twice daily, or as prescribed by a physician.
The maximum daily dose is 320 mg of ketoprofen lysine salt; higher doses are not
recommended (see subsection “Warnings and precautions”).
Special populations
Patients with renal impairment and elderly patients
It is advisable to reduce the initial dose and maintain therapy with the lowest effective dose. Individual dose adjustments may be considered only after good tolerability of the drug has been established. Monitor urine output and kidney function (see subsection “Warnings and precautions”).
Patients with mild to moderate hepatic impairment: should be closely monitored and treated with the lowest effective daily dose (see subsection “Warnings and precautions”).
OKi 160 mg suppositories must not be used if you have severe hepatic or renal dysfunction (see subsection “Do not take OKi”).
Paediatric population
The safety and efficacy of OKi 160 mg suppositories have not been studied in children.
If you use more OKi than you should
In case of overdose or accidental ingestion, inform your doctor immediately or go to the nearest hospital.
Cases of overdose with doses exceeding 2.5 g of ketoprofen have been reported. In most
cases, the observed symptoms were mild and limited to lethargy, drowsiness, nausea, vomiting,
epigastric pain (in the upper part of the abdomen), abdominal pain, headache, dizziness and
diarrhoea.
In cases of severe overdose, hypotension, respiratory depression and gastrointestinal bleeding have been observed.
The patient should be immediately transferred to a specialist centre to start symptomatic treatment.
There are no specific antidotes for ketoprofen overdose. In case of suspected massive overdose, gastric lavage is recommended, and symptomatic and supportive treatment should be initiated.
In case of renal failure, haemodialysis may be useful to remove the drug from the body.

4. Possible adverse effects

dyspepsia (indigestion), nausea, abdominal pain, vomiting.

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

headache, dizziness, vertigo, somnolence
constipation, diarrhoea, flatulence (gas in the intestine), gastritis, abdominal discomfort
skin rash, pruritus (itching)
oedema (fluid retention causing swelling), fatigue, peripheral oedema (peripheral swelling), chills.

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

haemorrhagic anaemia (anaemia due to blood loss)
paraesthesia (abnormal skin sensation, tingling)
blurred vision (see subsection “Warnings and precautions”)
tinnitus (ringing in the ears)
asthma
stomatitis (mouth ulcer), peptic ulcer (gastric or duodenal ulcer), colitis
hepatitis, increased transaminases (liver enzymes), increased blood bilirubin (elevated serum bilirubin levels due to liver disorders), jaundice
weight increased.

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

dyskinesia (movement disorder), syncope
hypotension (low blood pressure)
oedema (swelling) of the larynx
haematuria (blood in the urine)
asthenia (physical weakness), facial oedema.

Not known (frequency cannot be estimated from the available data):

thrombocytopenia (reduced number of platelets in the blood), agranulocytosis (severe reduction in white blood cells), bone marrow failure (reduced production of blood cells), haemolytic anaemia (anaemia due to abnormal destruction of red blood cells); neutropenia (decrease in number of neutrophil white blood cells); aplastic anaemia (anaemia due to insufficient production of blood cells in the bone marrow); leucocytosis (increase in the number of white blood cells in the blood), thrombocytopenic purpura; leucopenia (reduction in the number of white blood cells)
anaphylactic reactions (including shock); hypersensitivity
depression, hallucinations, confusion, mood alterations, excitability, insomnia
seizures
dysgeusia (altered taste)
tremor, hyperkinesia
heart failure (weak heart), atrial fibrillation (irregular heart rhythm), palpitations, tachycardia (increased heart rate)
hypertension (increased blood pressure), vasodilation (widening of blood vessels), vasculitis (inflammation of blood or lymphatic vessels) (including leukocytoclastic vasculitis)
bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea (difficulty breathing), laryngospasm, acute respiratory failure (a single fatal case has been reported in an asthmatic patient sensitive to aspirin)
gastralgia (stomach pain), exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage, gastrointestinal perforation (sometimes fatal, particularly in the elderly), gastric pyrosis (heartburn), gastric ulcer, duodenal ulcer, oedema (swelling) of the mouth, pancreatitis, erosive gastritis, haematemesis (vomiting blood) or melena (passing digested blood in stools), hyperchlorhydria (excess hydrochloric acid in gastric juice), gastric pain (stomach pain), oedema of the tongue
photosensitisation (reaction to sunlight or UV lamps), alopecia (hair loss), urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome, Lyell's syndrome and toxic epidermal necrolysis (serious skin reactions), erythema (skin redness), exanthema (skin rash), maculopapular exanthema, purpura, acute generalised exanthematous pustulosis (skin eruption with pustule formation), dermatitis
acute renal failure, tubulointerstitial nephritis, nephritis or nephritic syndrome, nephrotic syndrome, glomerular nephritis, fluid/sodium retention with possible oedema, acute tubular necrosis (damage to kidney tubular cells), renal papillary necrosis (damage to kidney papillae), oliguria (reduced urine output), abnormal kidney function tests
periorbital oedema (swelling around the eyes)
aseptic meningitis (inflammation of the membranes covering the brain not caused by bacteria)
lymphangitis (inflammation of lymphatic vessels)
hyperkalaemia (increased potassium levels in the blood), hyponatraemia (decreased sodium levels in the blood)
rectal tenesmus, soft stools.

Medicines such as OKi may be associated (particularly at high doses and with long-term treatment) with an increased risk of arterial thrombotic events (formation of blood clots in blood vessels), such as heart attack (myocardial infarction) or stroke (cerebrovascular accident) (see section 2 “What you need to know before taking OKi”).
Following the instructions provided in this leaflet reduces the risk of adverse effects.
Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report adverse effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store OKi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
The stated expiry date applies to the product if it has been stored unopened and correctly.
Do not store above 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What OKi contains

The active substance is ketoprofen lysine salt. Each suppository contains 160 mg of ketoprofen lysine salt.
The other components are semisynthetic glycerides.

Description of the appearance of OKi and contents of the pack
Pharmaceutical form: suppositories – Pack of 10 suppositories.
Marketing Authorization Holder
Dompé farmaceutici S.p.A.
Via San Martino, 12 – 20122 Milan, Italy
Manufacturer
Istituto De Angeli S.r.l. - Pharmaceutical Plant of Reggello (FI)

Oki

Package leaflet: Information for the user

OKi 80 mg granules for oral solution

1. What OKi is and what it is used for

2. What you need to know before taking OKi

3. How to take OKi

4. Possible adverse effects

5. How to store OKi

6. Package contents and other information

Package leaflet: information for the user

OKi 80 mg/ml oral drops, solution

1. What OKi is and what it is used for

2. What you need to know before taking OKi

3. How to take OKi

4. Possible side effects

5. How to store OKi

6. Package contents and other information

OKi 160 mg/2 ml intramuscular injection solution

1. What OKi is and what it is used for

2. What you should know before using OKi

3. How to use OKi

4. Possible side effects

5. How to store OKi

6. Package contents and other information

OKi 160 mg suppositories

1. What OKi is and what it is used for

2. What you need to know before using OKi

3. How to use OKi

4. Possible adverse effects

5. How to store OKi

6. Package contents and other information