Ketonal

Package leaflet: Information for the patient

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Ketonal, 50 mg/ml, solution for injection
Ketoprofen
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Ketonal is and what it is used for
2. Important information before using Ketonal
3. How to use Ketonal
4. Possible side effects
5. How to store Ketonal
6. Contents of the pack and other information

1. What Ketonal is and what it is used for

Ketonal contains the active substance ketoprofen – a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic, and analgesic properties.
Ketonal is used for symptomatic treatment of inflammatory and degenerative rheumatic disorders of the musculoskeletal system and for relief of certain painful conditions.

Intramuscular administration indications:

• Rheumatoid arthritis
• Osteoarthritis
• Moderate pain

Intravenous administration indications:

• Postoperative pain

2. Important information before using Ketonal

When not to use Ketonal

• If the patient is allergic to ketoprofen or to any of the other ingredients of this medicine (listed in section 6).
• In patients who have previously experienced hypersensitivity reactions such as bronchospasm, asthma attack, rhinitis, urticaria, or other types of allergic reactions following administration of ketoprofen, acetylsalicylic acid, or other non-steroidal anti-inflammatory drugs (NSAIDs). Severe, rarely fatal, anaphylactic reactions have been reported in such patients.
• In women during the third trimester of pregnancy.
• In the following patients:
  • with severe heart failure
  • with active or recurrent gastric or duodenal ulcer and (or) gastrointestinal bleeding
  • with a history of gastrointestinal bleeding or perforation
  • with a history of gastrointestinal bleeding or perforation related to previous use of non-steroidal anti-inflammatory drugs
  • with a tendency to bleeding
  • with severe liver failure
  • with severe renal failure.

The use of Ketonal is contraindicated in cases of cerebral haemorrhage or any active bleeding.
Intramuscular administration of Ketonal is contraindicated in patients with blood coagulation disorders or those receiving anticoagulant therapy.
This medicine must not be used in children under 15 years of age.

Warnings and precautions
Before using Ketonal, discuss with your doctor if any of the following warnings currently apply to you or have applied in the past.

• It is very important to use the medicine at the lowest effective dose for the shortest duration necessary to relieve symptoms.
• Use of medicines such as Ketonal may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. This risk is increased with long-term use of high doses. Do not use higher doses or longer treatment duration than recommended.
• If the patient has heart function disorders, including heart failure, angina pectoris (chest pain), or has previously had a myocardial infarction, coronary artery bypass grafting, peripheral vascular disease (circulatory disorders in legs or feet due to arterial narrowing or blockage), or any type of stroke (including transient ischaemic attack), the treatment approach should be discussed with a doctor or pharmacist.
• The use of Ketonal should also be discussed with a doctor if the patient smokes, has high blood pressure, high cholesterol levels, diabetes, or a family history of heart disease or stroke.
• Non-steroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, may cause gastrointestinal bleeding, ulceration, or perforation (very rarely fatal). Particular caution is required in patients receiving high doses of Ketonal, in patients with a history of peptic ulcer disease (especially if complicated by bleeding or perforation), ulcerative colitis, Crohn’s disease, and in elderly patients. All patients, especially elderly ones, who experience unusual gastrointestinal symptoms (particularly bleeding) while taking Ketonal must inform their doctor immediately.
• The risk of allergic reactions is increased in patients with asthma, chronic rhinitis, chronic sinusitis, and (or) nasal polyps. Administration of Ketonal may trigger an asthma attack or bronchospasm, especially in patients allergic to acetylsalicylic acid and (or) NSAIDs.
• In patients after coronary artery bypass surgery, some non-steroidal anti-inflammatory drugs have increased the risk of arterial thrombotic events.
• Inform your doctor if the patient has diabetes or is taking potassium-sparing medicines. Monitoring of blood potassium levels may be indicated.
• In patients with coagulation disorders, haemophilia, von Willebrand disease, severe thrombocytopenia, renal or liver failure, and in patients taking anticoagulants (such as coumarins and heparin), the risk of bleeding is increased.
• Very rarely, NSAIDs may cause serious skin reactions (some life-threatening), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The risk of such reactions is likely highest at the beginning of treatment (especially during the first month of use).

At the first signs of rash, mucosal lesions, or other allergic symptoms, Ketonal should be discontinued and medical advice should be sought immediately.

• Ketoprofen may impair kidney function in patients with:
  • heart failure;
  • cirrhosis;
  • nephrotic syndrome;
  • chronic renal failure;
  • liver function disorders;
  • chronic kidney function disorders;
  • fluid and electrolyte imbalances (e.g., in dehydrated patients);
  • elderly patients.
• In patients with liver impairment, the doctor may recommend dose adjustment.

Inform your doctor if:

• the patient has previously experienced photosensitivity or phototoxicity,
• the patient has a history of gastrointestinal diseases (peptic ulcer of the stomach and (or) duodenum, ulcerative colitis, Crohn’s disease, hiatal hernia), blood disorders and (or) coagulation disorders,
• the patient consumes large amounts of alcohol and (or) smokes,
• the patient has hypertension, heart failure, or oedema,
• the patient has an infection – see section below titled “Infections”
• the patient has liver and (or) renal impairment or is taking diuretics,
• the patient is scheduled for surgery.

Infections
Ketonal may mask symptoms of infection such as fever and pain. Therefore, Ketonal may delay the initiation of appropriate treatment of infection and consequently increase the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If the patient is taking this medicine during an infection and symptoms persist or worsen, immediate medical advice should be sought.

Use of Ketonal in elderly patients
In elderly patients, the risk of adverse effects associated with the use of non-steroidal anti-inflammatory drugs is increased. This particularly includes gastrointestinal bleeding and perforation, which may be potentially life-threatening.

Ketonal with other medicines
Tell your doctor about all medicines currently or recently taken, as well as any medicines the patient plans to use.
Ketonal must not be used concomitantly with other non-steroidal anti-inflammatory drugs (including selective COX-2 inhibitors) and salicylates (e.g., acetylsalicylic acid).
Ketonal and other medicines may affect each other’s actions and the occurrence of adverse effects.
This particularly applies to the following medicines:

• other NSAIDs and salicylates (including acetylsalicylic acid) in high doses,
• corticosteroids (anti-inflammatory medicines),
• anticoagulants such as heparin and warfarin, dabigatran, apixaban, rivaroxaban, edoxaban,
• antiplatelet agents such as acetylsalicylic acid, ticlopidine, clopidogrel, tirofiban,
• nicorandil (a medicine used in the treatment of ischaemic heart disease),
• lithium (a medicine used in the treatment of certain psychiatric disorders),
• methotrexate (a medicine used, among others, in cancer and rheumatoid diseases),
• diuretics,
• antihypertensive medicines,
• selective serotonin reuptake inhibitors (medicines used in the treatment of depression),
• potassium salts,
• tacrolimus (an immunosuppressive medicine),
• cyclosporine (an immunosuppressive medicine used to prevent rejection of transplanted organs or bone marrow),
• trimethoprim (an antibiotic),
• oral antidiabetic medicines,
• antiepileptic medicines (e.g., phenytoin),
• cardiac glycosides (medicines used in heart diseases),
• mifepristone (a medicine used, among others, in the treatment of uterine fibroids),
• quinolone antibiotics,
• beta-adrenolytics (medicines used in heart diseases),
• tenofovir (an antiretroviral medicine used in the treatment of HIV infection and chronic viral hepatitis B).

The use of ketoprofen may reduce the effectiveness of oral contraceptives.
If in doubt about the identity of any of the listed medicines, consult your doctor or pharmacist.

Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Do not take Ketonal if the patient is in the last 3 months of pregnancy, as it may harm the unborn child or cause complications during delivery. Ketonal may cause kidney and heart dysfunction in the unborn child. It may increase the risk of bleeding in both the mother and the child and may delay or prolong labour.
During the first 6 months of pregnancy, Ketonal should not be used unless the doctor considers it absolutely necessary. If treatment is required during this period or when trying to conceive, the lowest possible dose should be used for the shortest possible duration.
From the 20th week of pregnancy, Ketonal may cause kidney dysfunction in the unborn child if used for longer than a few days. This may lead to low levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is required for longer than a few days, the doctor may recommend additional monitoring.

Breastfeeding
It is not known whether ketoprofen passes into breast milk. Ketonal should not be given to breastfeeding women.

Effect on fertility
Ketonal may make it more difficult to become pregnant. If the patient is planning a pregnancy, has difficulty becoming pregnant, or is undergoing fertility investigations, she should inform her doctor. The doctor may consider discontinuing Ketonal.

Driving and operating machinery
Ketonal may cause dizziness, drowsiness, convulsions, and visual disturbances in some patients. If these symptoms occur, do not drive or operate machinery.

Ketonal contains ethanol, benzyl alcohol, propylene glycol, and sodium
The Ketonal injection solution contains 200 mg of ethanol (alcohol) per dose (2 ml), equivalent to less than 5 ml of beer or 2 ml of wine per dose. Harmful for individuals with alcohol-related disorders. This should be taken into account when administering to pregnant or breastfeeding women, children, and individuals in high-risk groups, such as patients with liver disease or epilepsy.
The medicine contains 40 mg of benzyl alcohol in each 2 ml ampoule.
Benzyl alcohol may cause allergic reactions.
Pregnant or breastfeeding women, as well as patients with liver or kidney disease, should consult their doctor before using this medicine, as high amounts of benzyl alcohol may accumulate in their bodies and cause adverse effects (so-called metabolic acidosis).
The medicine contains 800 mg of propylene glycol in each 2 ml ampoule.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".

3. How to use Ketonal

This medicine should always be used exactly as directed by the physician. In case of doubt, consult
your doctor, nurse or pharmacist.
Adults and children over 15 years of age
Intramuscular administration
1 ampoule (100 mg ketoprofen) once or twice daily.
If necessary, treatment with the solution can be supplemented with oral or transdermal therapy.
Intravenous administration
Ketoprofen in intravenous infusion may be administered only in hospital settings. The infusion should
be given over ½ to 1 hour, for a maximum of 48 hours.
The maximum dose is 200 mg per day.
Short-term infusion
Contents of 1 to 2 ampoules (100 mg to 200 mg ketoprofen) should be diluted to 100 ml with 0.9%
sodium chloride solution and administered over ½ to 1 hour. The infusion may be repeated after 8
hours. The maximum dose is 200 mg per day.
Continuous infusion
Contents of 1 to 2 ampoules (100 mg to 200 mg ketoprofen) should be diluted to 500 ml with infusion
fluid (0.9% sodium chloride solution, Ringer's lactate solution, 5% glucose solution) and
administered over 8 hours. The infusion may be repeated after 8 hours.
The maximum dose is 200 mg per day.
Ketoprofen may be administered concomitantly with centrally-acting analgesics.
The solution may be mixed in the same bottle with morphine: 10 mg to 20 mg morphine and 100 mg to 200 mg
ketoprofen diluted in 500 ml of 0.9% sodium chloride solution or Ringer's lactate solution.
The infusion may be repeated after 8 hours.
The lowest effective dose for the shortest duration necessary to relieve symptoms should be used. If
symptoms of infection (such as fever and pain) persist or worsen during treatment, consult a doctor
immediately (see section 2).
The maximum daily dose is 200 mg. Before initiating treatment with a daily dose of 200 mg, the
physician should carefully evaluate the benefit-risk ratio. Higher doses are not recommended.
Elderly patients
In elderly patients, treatment with ketoprofen should be initiated at the lowest available dose and
continued at the lowest effective dose.
In elderly patients, the risk of severe adverse effects is higher.
Warning

• Tramadol and ketoprofen solutions must not be mixed in the same bottle due to the risk of precipitation.
• Infusion bottles should be wrapped in black paper or aluminum foil, as ketoprofen is light-sensitive.

If the patient feels that the effect of Ketonal is too strong or too weak, they should consult
their doctor or pharmacist.
Overdose of Ketonal
In adults, the main symptoms of overdose are headache, dizziness, drowsiness,
nausea, vomiting, diarrhoea and abdominal pain. In case of severe poisoning, the patient should
be immediately transferred to a specialized hospital unit for symptomatic treatment.
There is no specific antidote.
Missed dose of Ketonal
Do not use a double dose to make up for a missed dose.
If you have any further doubts concerning the use of this medicine, consult your
doctor, nurse or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Adverse reactions may occur with the following frequency:
Very common (may occur in more than 1 in 10 people): increased results of liver function tests to borderline values.
Common (may occur in less than 1 in 10 people): depression, nervousness, nightmares, drowsiness,
general weakness, malaise, tingling sensation, oedema, nausea, loss of appetite, vomiting.
Uncommon (may occur in less than 1 in 100 people): anaemia, haemolysis (breakdown of red blood cells),
purpura and skin allergic reactions, headache, dizziness, somnolence, haemoptysis, dyspnoea,
pharyngitis, laryngeal oedema, constipation, diarrhoea, gastritis, rash, alopecia, pruritus, exanthema,
purpuric rash, excessive sweating, exfoliative dermatitis, menorrhagia or heavy irregular menstruation,
marked increase in aminotransferase activity (AspAT and AlAT), oedema, feeling of fatigue.
Rare (may occur in less than 1 in 1,000 people): haemorrhagic anaemia, delirium with visual and
auditory hallucinations, disorientation and speech disorders, visual disturbances, tinnitus, bronchial
asthma attack, stomatitis, gastric and (or) duodenal ulcer, hepatitis, increased aminotransferase
activity, increased serum bilirubin concentration due to hepatitis, colitis.
Very rare (may occur in less than 1 in 10,000 people): recurrence of ulcerative colitis or Crohn's disease,
enteropathy with perforation, ulceration or strictures (also with minor bleeding or protein loss), acute
tubulointerstitial nephritis.
One case of colonic perforation has been reported in an elderly woman.
Frequency not known (frequency cannot be estimated from the available data): complete or almost
complete absence of granulocytes (agranulocytosis), reduced platelet count (thrombocytopenia),
haemolytic anaemia (anaemia due to destruction of red blood cells), reduced white blood cell count
(leukopenia), anaphylactic reactions (including anaphylactic shock), mood changes, seizures, heart
failure, hypertension, bronchospasm (especially in patients with hypersensitivity to acetylsalicylic acid
and other NSAIDs), rhinitis, gastrointestinal bleeding and perforation (sometimes fatal), photosensitivity,
alopecia, urticaria, exacerbation of chronic urticaria, bullous reactions including Stevens-Johnson syndrome
and toxic epidermal necrolysis, acute generalised exanthematous pustulosis, acute renal failure,
tubulointerstitial nephritis, nephrotic syndrome, decreased sodium concentration in blood (hyponatraemia),
increased potassium concentration in blood (hyperkalaemia), confusion, aseptic meningitis, vasculitis (including
leukocytoclastic vasculitis), pancreatitis, angioedema, burning sensation, pain at the site of administration,
cutis marmorata.
Ketoprofen in high doses may inhibit platelet aggregation, thereby prolonging bleeding time and causing
epistaxis and tendency to bruising.
One case of pseudotumour cerebri and one case of conjunctivitis have been reported. Cases of gastrointestinal
discomfort and stomach pain have also been reported, as well as fluid/sodium retention (with possible oedema),
organic kidney damage which could lead to acute renal failure, single cases of acute tubular necrosis and renal
papillary necrosis.
The use of some NSAIDs (particularly long-term and at high doses) may increase the risk of arterial thrombotic
events (e.g. myocardial infarction or stroke). This may also apply to ketoprofen.
Reporting of adverse reactions
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor,
pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse
Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Ketonal

• 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 the stated month.
• Store below 25°C. Keep in the original packaging to protect from light.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Ketonal contains
The active substance is ketoprofen. Each 2 ml of injection solution (1 ampoule) contains
100 mg of ketoprofen.
The other ingredients are: propylene glycol, ethanol, benzyl alcohol, sodium hydroxide, water
for injections.

What Ketonal looks like and contents of the pack
Ketonal is a clear solution without visible particles.
It is available in 2 ml ampoules made of amber glass, packed in cardboard boxes.
Pack sizes: 5, 10, 50 ampoules.
For further information, please contact the Marketing Authorisation Holder or Parallel Importer.

Marketing Authorisation Holder in Latvia, country of export:
Sandoz d.d.
Verovškova 57
SI-1000 Ljubljana
Slovenia

Manufacturer:
Lek Pharmaceuticals d.d.
Verovškova 57
1526 Ljubljana
Slovenia

Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Poland

Repackaged by:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Poland

Marketing Authorisation Number in Latvia, country of export: 99-0070
Parallel Import Marketing Authorisation Number: 323/25