INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KETONAL® DUO (KETONAL® DUO)

Composition:

active substance: ketoprofen;

1 capsule contains 150 mg of ketoprofen;

excipients:

contents of the capsule: microcrystalline cellulose, lactose monohydrate, povidone, sodium croscarmellose, polysorbate 80, methacrylic acid copolymer (type B), methacrylic acid copolymer (type A), triethyl citrate, talc, yellow iron oxide (E 172), colloidal anhydrous silicon dioxide;

capsule shell: gelatin, titanium dioxide (E 171), indigo carmine (E 132).

Pharmaceutical form. Modified release hard capsules.

Main physicochemical properties: capsules with a transparent body and blue cap containing white and yellow pellets.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Ketoprofen. ATC code M01A E03.

Pharmacological Properties

Pharmacodynamics

Ketoprofen is a non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic effects.

In inflammation, ketoprofen inhibits the synthesis of prostaglandins and leukotrienes by suppressing cyclooxygenase activity and, to a lesser extent, lipoxygenase activity. It also inhibits bradykinin synthesis and stabilizes lysosomal membranes.

It exerts central and peripheral analgesic effects and alleviates symptoms of inflammatory-degenerative disorders of the musculoskeletal system.

In women, ketoprofen reduces symptoms of primary dysmenorrhea due to inhibition of prostaglandin synthesis.

Pharmacokinetics

Absorption. Ketalong® Duo capsules represent a new dosage form differing from conventional capsules in the method of active substance release. The capsules contain two types of pellets: standard (white) and coated (yellow). Ketoprofen is rapidly released from the white pellets (60% of the total amount) and slowly from the yellow pellets (40% of the total amount), providing both immediate and prolonged action of the drug.

After oral administration of Ketalong® Duo capsules, ketoprofen is rapidly absorbed in the gastrointestinal tract. The bioavailability of ketoprofen is 90%.

Food intake does not affect the overall bioavailability of ketoprofen but reduces the rate of absorption. Fatty food increases the time to reach maximum concentration but does not reduce the bioavailability or maximum plasma concentration of ketoprofen. Concomitant administration of agents that reduce gastric acidity does not affect the rate or extent of ketoprofen absorption. Maximum plasma concentration—9036.64 ng/mL—is achieved within 1.76 hours.

Distribution. Plasma protein binding is 99%. Volume of distribution is 0.1 L/kg. Ketoprofen penetrates into synovial fluid and reaches concentrations there equivalent to 30% of plasma levels. Although ketoprofen concentration in synovial fluid is somewhat lower than in plasma, it is more stable (maintained up to 30 hours), resulting in prolonged reduction of pain and joint stiffness.

Metabolism and Elimination. Ketoprofen is extensively metabolized in the liver via microsomal enzymes. It is excreted from the body as a glucuronic acid conjugate. Approximately 80% of the administered dose of ketoprofen is excreted in urine, predominantly (over 90%) as glucuronide, and about 10% in feces. Ketoprofen has no active metabolites. Plasma clearance of ketoprofen is approximately 0.08 L/kg/h.

In patients with renal insufficiency, elimination of ketoprofen is delayed and elimination half-life is prolonged by 1 hour. In patients with hepatic insufficiency, ketoprofen may accumulate in tissues. In elderly patients, metabolism and elimination of ketoprofen are slowed, although this is clinically significant only when renal function is impaired.

Clinical characteristics.

Indications.

Joint diseases: rheumatoid arthritis; seronegative spondyloarthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis); gout, pseudogout; osteoarthritis; periarticular rheumatism (tendinitis, bursitis, shoulder capsulitis).

Pain syndromes: lumbar pain (lumbago), post-traumatic pain, postoperative pain, bone metastasis pain, algodysmenorrhea.

Contraindications.

Hypersensitivity to ketoprofen or to any excipients of the medicinal product. Ketalog® Duo is contraindicated in patients in whom administration of ketoprofen, acetylsalicylic acid, or other nonsteroidal anti-inflammatory drugs (NSAIDs) induces bronchospasm, asthmatic attacks, urticaria, angioneurotic edema, acute rhinitis, or other allergic reactions.

Severe heart failure.

Should not be used for the treatment of perioperative pain associated with coronary artery bypass graft (CABG) surgery.

Chronic dyspepsia in medical history; active phase or recurrence of gastric or duodenal ulcer or ulceration/perforation (two or more separate episodes) in medical history; gastrointestinal bleeding/perforation/ulcers in medical history associated with previous NSAID therapy; cerebrovascular or other hemorrhages; tendency to hemorrhage; hemorrhagic diatheses; severe impairment of liver or kidney function; severe renal insufficiency; bronchial asthma and rhinitis in medical history. Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Concomitant use with ketoprofen is not recommended

Concomitant use of ketoprofen with other NSAIDs and salicylates, including selective cyclooxygenase-2 inhibitors, should be avoided. The risk of gastrointestinal bleeding/ulceration is increased.

Anticoagulants (heparin, warfarin) and medicinal products that inhibit platelet aggregation (ticlopidine, clopidogrel), when used concomitantly with ketoprofen, increase the risk of gastrointestinal bleeding.

When used concomitantly with lithium preparations, excretion of lithium is reduced and plasma concentration increases to toxic levels.

Severe, sometimes fatal, toxicity occurred after administration of ketoprofen together with methotrexate (doses above 15 mg/week). This toxicity is due to increased and prolonged methotrexate plasma concentration.

Concomitant use with ketoprofen requires safety measures

Diuretics may increase the risk of nephrotoxicity of NSAIDs. Patients receiving diuretics should be adequately rehydrated before initiating ketoprofen therapy, and renal function should be closely monitored during treatment.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists, when used concomitantly with ketoprofen in patients with impaired renal function (e.g., dehydrated patients, elderly patients), increase the risk of nephrotoxicity, potentially leading to acute renal failure.

Concomitant use with corticosteroids increases the risk of gastrointestinal ulceration or bleeding.

When ketoprofen is used concomitantly with methotrexate (doses below 15 mg/week), weekly monitoring of blood cell counts is recommended. In patients with impaired renal function and elderly patients, monitoring should be performed more frequently.

Concomitant use of ketoprofen with pentoxifylline increases the risk of bleeding. Monitoring of blood coagulation status is required.

Concomitant use with ketoprofen requires caution

Ketoprofen may reduce the efficacy of antihypertensive agents (beta-blockers, ACE inhibitors) and diuretics due to inhibition of prostaglandin synthesis; diuretics increase the risk of NSAID-induced nephrotoxicity.

Use of ketoprofen together with thrombolytics and selective serotonin reuptake inhibitors increases the risk of gastrointestinal bleeding.

Concomitant administration of probenecid may lead to a significant reduction in plasma clearance of ketoprofen.

Ketoprofen is protein-bound; when used concomitantly with other drugs that are also protein-bound (e.g., anticoagulants, sulfonamides, hydantoins), dose adjustments may be required to prevent increased plasma levels of these drugs due to competition for plasma protein binding sites.

Potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II antagonists, nonsteroidal anti-inflammatory drugs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim may cause hyperkalemia.

Ketoprofen enhances the effects of oral antidiabetic and antiepileptic agents (phenytoin).

Concomitant use of NSAIDs and cardiac glycosides may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of glycosides.

Concomitant use with cyclosporine or tacrolimus increases the risk of nephrotoxicity, especially in elderly patients.

When used concomitantly with NSAIDs, the effect of mifepristone may be reduced. Nonsteroidal antirheumatic drugs should be administered 8–12 days after mifepristone use.

It should be noted that reduced efficacy of intrauterine contraceptives may occur with concomitant use of ketoprofen. Also, potentiation of the hypoglycemic effect of oral hypoglycemic agents is possible.

Ketoprofen may reduce glomerular filtration rate and increase serum concentration of cardiac glycosides.

Aluminum-containing compounds with neutralizing action do not reduce ketoprofen absorption.

In patients with impaired renal function who concomitantly used tenofovir disoproxil and high doses or multiple types of NSAIDs, cases of acute hepatic failure have been observed. Appropriate monitoring of renal function is required when NSAIDs and tenofovir disoproxil are used concomitantly.

Special precautions for use.

Special warnings.

Adverse effects (particularly those affecting the gastrointestinal tract and cardiovascular system) can be avoided by using the lowest effective dose for the shortest duration necessary to relieve symptoms.

The medicinal product should be used with caution in patients taking concomitant medications that may increase the risk of bleeding or ulceration, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, and antiplatelet agents (acetylsalicylic acid).

Concomitant use of ketoprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Ketoprofen should be prescribed with caution in patients with a history of gastrointestinal disorders. Gastrointestinal bleeding and perforation may occur suddenly without preceding symptoms.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, particularly with complications such as hemorrhage or perforation, in elderly patients, in patients with low body weight, in individuals with impaired platelet function, and in those taking anticoagulants or antiplatelet agents. Such patients should start treatment with the lowest dose. These patients should be considered for concomitant therapy with gastroprotective agents (e.g., misoprostol or proton pump inhibitors).

Patients who have previously experienced adverse gastrointestinal reactions, especially elderly patients, should report any unusual abdominal symptoms (including gastrointestinal bleeding), particularly at the beginning of treatment.

Gastrointestinal bleeding, ulceration, or perforation, in some cases fatal, have been observed during treatment with all NSAIDs at various stages of therapy, regardless of the presence of warning symptoms or a history of serious gastrointestinal pathology. If bleeding or ulceration occurs in patients being treated with ketoprofen, therapy should be discontinued.

Epidemiological data suggest that ketoprofen may be associated with a high risk of severe gastrointestinal toxicity, typical of some other NSAIDs, especially when used at high doses. Clinical studies and epidemiological data also suggest that the use of some NSAIDs (particularly at high doses and during prolonged treatment) may be associated with an increased risk of arterial thrombosis (e.g., myocardial infarction or stroke). There is insufficient data to exclude such a risk with ketoprofen use.

In rare cases, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been observed during NSAID use. The highest risk of such reactions occurs at the beginning of therapy (most reactions occur within the first months of treatment). Ketoprofen should be discontinued at the first signs of skin rash, mucosal lesions, or other signs of hypersensitivity.

Clinical studies and epidemiological data indicate that the use of some NSAIDs (particularly at high doses and during prolonged treatment) may be associated with an increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). There is insufficient data to exclude such a risk for ketoprofen.

Precautionary measures.

NSAIDs should be used with caution in patients with gastrointestinal disorders such as gastritis, duodenitis, a history of ulcerative colitis, or Crohn’s disease, as these conditions may be exacerbated.

The medicinal product should be used with caution in patients with renal or hepatic impairment, as well as in individuals taking anticoagulants (coumarin derivatives and heparins, particularly low-molecular-weight heparins).

Careful monitoring of diuresis and renal function is required in patients with hepatic disorders, in patients receiving diuretics, in patients with hypovolemia following major surgery, especially in elderly patients.

At the beginning of treatment, renal function should be monitored in patients with heart failure, chronic renal insufficiency, nephrotic syndrome, hepatic dysfunction, cirrhosis, or fluid imbalances (e.g., dehydration due to diuretic use, hypovolemia after surgery), particularly in elderly patients. In such patients, ketoprofen may cause a reduction in renal blood flow due to inhibition of prostaglandin synthesis. During the initial treatment period, diuresis and other renal function parameters should be closely monitored. Impaired renal function may lead to edema and increased serum non-protein nitrogen concentration.

In patients with heart failure, especially elderly patients, fluid and sodium retention may lead to an increased incidence of adverse reactions. In such patients, cardiac and renal function should be monitored.

Careful monitoring is necessary for patients with arterial hypertension and/or a history of mild to moderate chronic heart failure, as fluid retention and edema have been reported during NSAID therapy.

Masking symptoms of underlying infections: Ketalong® Duo, like other NSAIDs with analgesic, anti-inflammatory, and antipyretic properties, may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby complicating the disease course. Such cases have been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When Ketalong® Duo is used to relieve pain associated with infection, monitoring for infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

In patients with abnormal liver function tests or a history of liver disease, transaminase levels should be periodically monitored, and the dosage of the medicinal product should be individually adjusted, especially during long-term therapy.

Ketoprofen should be prescribed with particular caution in elderly patients, especially those with impaired liver or kidney function; such patients may require a reduced dose. During prolonged treatment with ketoprofen, blood morphology, liver, and renal function should be monitored.

Cases of jaundice and hepatitis associated with ketoprofen treatment have been reported.

During prolonged treatment with ketoprofen, especially in elderly patients, blood counts, as well as liver and kidney function, should be monitored. Dose adjustment of ketoprofen is required when creatinine clearance is below 0.33 mL/sec (20 mL/min).

Ketoprofen may adversely affect female fertility; therefore, it should not be used in women planning pregnancy. Women who are infertile or undergoing fertility investigations should discontinue ketoprofen use.

Patients with chronic bronchial asthma, rhinitis, sinusitis, and/or nasal polyps have an increased risk of hypersensitivity to acetylsalicylic acid and other NSAIDs. Ketoprofen may trigger asthma attacks or bronchospasm in these individuals, especially in those with hypersensitivity to acetylsalicylic acid or other NSAIDs.

Patients with uncontrolled arterial hypertension, chronic heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease may take ketoprofen only after careful monitoring. Before initiating long-term treatment, patients with risk factors such as hypertension, hyperlipidemia, diabetes, or smoking should undergo thorough evaluation.

Careful observation is also required during ketoprofen use in patients with known photosensitivity or a history of phototoxic reactions.

Ketoprofen treatment should be discontinued if visual disturbances, such as blurred vision, occur.

The product contains lactose and therefore should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

The use of the medicinal product should be discontinued prior to major surgical procedures.

Ketoprofen should be used with caution in individuals who abuse alcohol.

Elderly patients: Absorption of ketoprofen is not altered, but elimination half-life is prolonged (by 3 hours), and renal and plasma clearance are reduced. Elderly patients have an increased incidence of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, sometimes fatal. Monitoring for gastrointestinal bleeding should be performed after 4 weeks of treatment initiation.

Patients with renal impairment: Renal and plasma clearance are reduced, and elimination half-life is prolonged proportionally to the severity of renal impairment.

Patients with hepatic impairment: Plasma clearance and elimination half-life are unchanged; however, the amount of unbound (free) drug increases almost twofold.

Use during pregnancy or breastfeeding.

Pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis with the use of prostaglandin synthesis inhibitors during early pregnancy. The absolute risk of cardiovascular malformations increases from 1% to approximately 1.5%. It is believed that the risk of such events increases with higher drug doses and longer duration of treatment. In animal studies, administration of prostaglandin synthesis inhibitors increased pre- and post-implantation fetal loss and embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of various developmental abnormalities, including cardiovascular malformations, was observed. Use of Ketalong® Duo from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation of the drug. Moreover, cases of fetal ductus arteriosus constriction after second-trimester treatment have been reported, most of which resolved after discontinuation of the drug. Therefore, ketoprofen should not be used during the first and second trimesters of pregnancy unless clearly indicated. If ketoprofen is used in women planning pregnancy or during the first and second trimesters, the dose should be as low as possible and the duration of treatment as short as possible.

Fetal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to Ketalong® Duo for several days starting from the 20th gestational week. Use of Ketalong® Duo should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose risks:

for the fetus:

cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction (see above);

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

possible prolongation of bleeding time, anti-aggregatory effect, which may occur even at very low doses;
inhibition of uterine contractions, leading to delayed or prolonged labor.

Breastfeeding. Data on the excretion of ketoprofen into breast milk are lacking. Ketoprofen is contraindicated during breastfeeding, as the safety of ketoprofen during lactation has not been established.

Ability to influence reaction speed when driving or operating machinery.

Until individual response to the medicinal product is known (dizziness, drowsiness, or convulsions may occur), it is recommended to refrain from driving or operating machinery.

Method of Administration and Dosage

Dosage should be individually adjusted depending on the patient's condition and response to treatment.

The recommended dose is 150 mg (1 capsule) per day.

The duration of treatment depends on the severity and course of the disease. However, adverse effects may be minimized by using the lowest effective dose for the shortest possible duration. The lowest effective dose should be used for the minimum duration necessary to relieve symptoms (see section "Special Instructions").

When combining different dosage forms of the drug (capsules, tablets, suppositories, injectable solution), the maximum daily dose of ketoprofen must not exceed 200 mg.

Take capsules during meals with water or milk (at least 100 ml).

To prevent the negative effects of ketoprofen on gastrointestinal mucosa, antacids or proton pump inhibitors may be taken concomitantly after consultation with a physician.

Elderly patients. In elderly patients, the risk of adverse reactions is increased. If NSAID therapy is required, it is recommended to use the lowest effective dose of ketoprofen. After 4 weeks of treatment initiation, mandatory monitoring for signs of gastrointestinal bleeding should be performed.

Children.

The drug is contraindicated in children.

Overdose.

Symptoms: tinnitus, disorientation, excitement, dyspnea, headache, dizziness, drowsiness, arterial hypotension or arterial hypertension, nausea, vomiting, diarrhea, abdominal pain, hematemesis, respiratory depression, convulsions, epigastric pain, black-colored stools, impaired consciousness. In severe intoxication, gastrointestinal bleeding (melena, hematemesis), impaired renal function, and renal failure may occur; coma is rare.

Treatment: gastric lavage and administration of activated charcoal. Symptomatic and supportive therapy to correct dehydration, monitor diuresis, and correct acidosis if present. In case of renal failure, hemodialysis should be performed. H2-receptor antagonists, proton pump inhibitors, and prostaglandins may alleviate the harmful effects of ketoprofen on the gastrointestinal tract. There is no specific antidote.

Side effects

The frequency of adverse reactions is classified as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency not known (cannot be estimated from the available data).

Adverse effects are usually transient. Gastrointestinal disorders are the most commonly observed.

Blood and lymphatic system disorders:
Rare – haemorrhagic anaemia; uncommon – haemolysis, purpura; frequency not known – thrombocytopenia, agranulocytosis, bone marrow suppression, leucopenia, haemolytic anaemia, neutropenia.

High doses of ketoprofen may inhibit platelet aggregation, thereby prolonging bleeding time, and may cause epistaxis and bruising.

Immune system disorders:
Hypersensitivity reactions of the respiratory system, including bronchial asthma and its exacerbation, bronchospasm or dyspnoea (especially in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs); rare – angioneurotic oedema and anaphylaxis, hypersensitivity, anaphylactic reactions, including shock.

Psychiatric disorders:
Common – nervousness, nightmares; rare – delirium with visual and auditory hallucinations, disorientation; rare – mood swings, speech disorders.

Nervous system disorders:
Common – headache, asthenia, dizziness, paraesthesia, somnolence, discomfort, weakness, increased fatigue, vertigo; uncommon – seizures; rare – speech disorders, dysgeusia; very rare – pseudotumour cerebri; frequency not known – depression, confusion, hallucinations, malaise; cases of aseptic meningitis (particularly in patients with autoimmune diseases such as systemic lupus erythematosus, mixed connective tissue disease) have been reported, with symptoms such as nuchal rigidity, nausea, vomiting, fever, and loss of orientation.

Eye disorders:
Common – visual disturbances; very rare – conjunctivitis; rare – blurred vision; frequency not known – optic neuritis, retinal haemorrhages, changes in retinal pigmentation.

Ear and labyrinth disorders:
Rare – tinnitus.

Cardiac and vascular disorders:
Common – oedema; uncommon – heart failure, hypertension, vasodilation; frequency not known – tachycardia, congestive heart failure, peripheral vascular disorders, vasodilation, arrhythmia, myocardial infarction, atrial fibrillation, vasculitis.

The use of some NSAIDs (particularly at high doses and for long duration) may be associated with an increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special precautions").

Respiratory system disorders:
Uncommon – haemoptysis, dyspnoea, pharyngitis, rhinitis; rare – bronchospasm (mainly in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs), asthma attacks, laryngeal oedema (signs of anaphylactic reaction); frequency not known – dyspnoea.

Gastrointestinal disorders:
Very common – dyspepsia; common – nausea, abdominal pain, diarrhoea, constipation, flatulence, anorexia, vomiting, stomatitis; rare – gastritis, peptic ulcer disease; very rare – colitis, intestinal perforation (as a complication of diverticulosis), exacerbation of ulcerative colitis or Crohn’s disease, enteropathy with perforation, stenosis; frequency not known – melena, haematemesis. Peptic ulcers, gastrointestinal perforation or gastrointestinal bleeding may occur. Cases of rectal perforation in elderly women have been reported. Enteropathy may be associated with occult bleeding and protein loss. Ulceration, haemorrhage or perforation may develop in 1% of patients within 3–6 months of treatment or in 2–4% of patients after 1 year of treatment with NSAIDs.

Hepatobiliary disorders:
Very rare – increased serum bilirubin and transaminases, severe liver dysfunction associated with jaundice and hepatitis; frequency not known – hepatitis, cholestatic hepatitis, jaundice.

Skin and subcutaneous tissue disorders:
Common – skin rashes; uncommon – alopecia, eczema, purpura-like rashes, pruritus, hyperhidrosis, urticaria, exfoliative dermatitis; rare – photosensitivity, photoallergic dermatitis; very rare – bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative and bullous dermatoses, erythema multiforme, angioneurotic oedema.

Renal and urinary disorders:
Very rare – abnormal renal function tests, acute renal failure, interstitial nephritis, nephrotic syndrome, acute pyelonephritis, abnormal kidney function tests.

Reproductive system disorders:
Uncommon – menometrorrhagia.

General disorders:
Rare – oedema; frequency not known – taste disturbances.

Laboratory findings:
Very common – abnormal liver function tests, increased serum transaminases and bilirubin levels due to diabetes-related disorders; uncommon – weight gain. During NSAID treatment, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may significantly increase. Ketoprofen reduces platelet aggregation, thereby prolonging bleeding time.

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 capsules per blister; 2 blisters (10 × 2) per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Lek Pharmaceuticals d.d., Slovenia (batch release).

Manufacturer's address and place of business.

Verovškova 57, 1526 Ljubljana, Slovenia
or
Trimojce 2d, 9220 Lendava, Slovenia.

Ketonal® duo