Nurofen® for children

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NUROFEN® FOR CHILDREN (NUROFEN® FOR CHILDREN)

Composition:

Active ingredient: ibuprofen;

1 suppository contains 60 mg of ibuprofen;

Excipient: hard fat.

Pharmaceutical form. Suppositories.

Main physicochemical properties: torpedo-shaped, smooth suppositories, white or almost white in color.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. ATC code M01AE01

Pharmacological properties.

Pharmacodynamics. The mechanism of action involves inhibition of the synthesis of prostaglandins—mediators of pain, inflammation, and temperature response. The drug exerts analgesic, anti-inflammatory, and antipyretic effects. In addition, ibuprofen inhibits platelet aggregation.

The clinical efficacy of ibuprofen has been demonstrated in the treatment of mild to moderate pain, such as pain associated with teething and dental pain, headache, earache, sore throat, postoperative pain, soft tissue injuries, and fever, including fever following vaccination, as well as pain and fever associated with colds and influenza.

Pharmacokinetics. After rectal administration, ibuprofen is rapidly and almost completely absorbed, reaching maximum plasma concentration within 45 minutes. Ibuprofen binds to plasma proteins and penetrates into synovial fluid. It is metabolized in the liver to two inactive metabolites, which are rapidly and almost completely excreted by the kidneys. A certain amount is excreted unchanged. The elimination half-life is 2 hours.

Clinical characteristics

Indications. For symptomatic treatment of mild to moderate pain. For symptomatic treatment of fever. Nurofen® for children, suppositories, is recommended for use when oral administration is not possible, for example, in case of vomiting.

Contraindications.

• Hypersensitivity to ibuprofen or other NSAIDs or to any excipient.
• History of hypersensitivity reactions (e.g. bronchospasm, angioneurotic edema, bronchial asthma, rhinitis or urticaria) following administration of acetylsalicylic acid (aspirin), ibuprofen or other NSAIDs.
• Active peptic ulcer/gastrointestinal bleeding or history of recurrence (two or more episodes of confirmed peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• Severe hepatic insufficiency, severe renal insufficiency or severe heart failure.
• Severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake).
• Third trimester of pregnancy.
• Active cerebrovascular or other bleeding.
• Blood dyscrasias of unknown etiology.
• Contraindicated in children with body weight less than 6 kg or age under 3 months.

Interaction with other medicinal products and other forms of interaction.

Ibuprofen, like other NSAIDs, should not be used in combination with:

• acetylsalicylic acid (aspirin), as this may increase the risk of adverse reactions, except in cases where low-dose acetylsalicylic acid is prescribed by a physician according to clinical guidelines.

Experimental data indicate that ibuprofen may inhibit the antiplatelet effect of low-dose aspirin when administered concomitantly. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical outcomes preclude definitive conclusions about the systemic use of ibuprofen. Therefore, clinically significant effects are considered unlikely with occasional (non-systemic) use of ibuprofen.

• other NSAIDs, including selective cyclooxygenase-2 inhibitors. Concomitant use of two or more NSAIDs should be avoided, as this may increase the risk of adverse effects.

Ibuprofen (like other NSAIDs) should be used with caution in combination with the following drugs:

Glucocorticoids: increased risk of gastrointestinal ulceration and bleeding;

Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin;

Phenytoin: concomitant use of ibuprofen with phenytoin may increase serum levels of these drugs. With proper use (maximum for 3 days), monitoring of phenytoin serum levels is usually not required;

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding;

Antihypertensive agents (ACE inhibitors, beta-blockers, angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of these drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), concomitant use of ACE inhibitors, beta-blockers or angiotensin II antagonists and cyclooxygenase inhibitors may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should maintain adequate fluid intake, and renal function should be monitored after initiation of concomitant therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Lithium: evidence suggests a potential increase in plasma lithium levels. With proper use (maximum for 3 days), monitoring of serum lithium levels is usually not required;

Probenecid and sulfinpyrazone: medications containing probenecid or sulfinpyrazone may delay elimination of ibuprofen;

Potassium-sparing diuretics: concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (monitoring of serum potassium levels is recommended);

Cardiac glycosides, e.g. digoxin: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma glycoside levels. Concomitant use of ibuprofen with digoxin may increase serum levels of these drugs. With proper use (maximum for 3 days), monitoring of serum digoxin levels is usually not required;

Methotrexate: there is a potential for increased methotrexate plasma levels. Administration of ibuprofen within 24 hours before or after methotrexate may increase methotrexate concentration and enhance its toxic effects;

Tacrolimus: possible increased risk of nephrotoxicity when used concomitantly with tacrolimus;

Cyclosporine: limited data suggest a possible interaction leading to increased risk of nephrotoxicity;

Zidovudine: increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. Evidence indicates increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen;

Sulfonylurea agents: clinical studies have demonstrated interactions between NSAIDs and antidiabetic agents (sulfonylureas). Although interactions between ibuprofen and sulfonylureas have not been specifically reported, monitoring of blood glucose levels is recommended as a precaution when these drugs are used concomitantly;

Quinolone antibiotics: animal studies indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones may have an increased risk of developing seizures;

CYP2C9 inhibitors: concomitant use of ibuprofen with CYP2C9 inhibitors may increase exposure to ibuprofen (a CYP2C9 substrate). A study using voriconazole and fluconazole (CYP2C9 inhibitors) demonstrated an approximately 80–100% increase in exposure to S(+)-ibuprofen. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, a reduction in ibuprofen dose is recommended, especially when high doses of ibuprofen are used with voriconazole or fluconazole;

Mifepristone: NSAIDs should not be used earlier than 8–12 days after administration of mifepristone, as they may reduce its efficacy.

Special precautions for use.

Adverse effects associated with ibuprofen can be minimized by using the lowest effective dose required to treat symptoms for the shortest possible duration.

Elderly individuals have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal. Patients of advanced age are at increased risk of complications from adverse reactions.

Caution should be exercised in patients with the following conditions:

• systemic lupus erythematosus and mixed connective tissue disease – due to an increased risk of aseptic meningitis;
• inherited disorders of porphyrin metabolism, such as acute intermittent porphyria;
• gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease);
• history of hypertension and/or heart failure, as there have been reports of fluid retention and edema associated with NSAID therapy;
• renal impairment – due to the potential for worsening kidney function;
• hepatic dysfunction;
• immediately following major surgical procedures;
• hay fever, nasal polyps, or chronic obstructive respiratory diseases – due to an increased risk of allergic reactions such as asthma attacks (so-called analgesic-induced asthma), Quincke's edema, or urticaria;
• history of allergic reactions to other substances – due to an increased risk of hypersensitivity reactions to ibuprofen.

Other NSAIDs.

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

Effects on the cardiovascular and cerebrovascular systems.

Patients with a history of hypertension and/or heart failure should begin treatment with caution (medical consultation is required), as fluid retention, hypertension, and edema have been reported during ibuprofen therapy, as with other NSAIDs.

Clinical trial data and epidemiological evidence suggest that ibuprofen use, particularly at high doses (2400 mg daily) and during long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not indicate that low-dose ibuprofen (e.g., ≤1200 mg daily) is associated with an increased risk of myocardial infarction.

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with coronary artery spasm, which may potentially lead to myocardial infarction.

Effects on the gastrointestinal tract.

There have been reports of gastrointestinal bleeding, perforation, and ulcers, which may be fatal, occurring at any stage of NSAID therapy, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders, rectal disorders, or anorectal conditions.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, a history of peptic ulcer disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment at the lowest dose.

Such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other medications that may increase gastrointestinal risk, should be considered for combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors).

Patients with a history of gastrointestinal toxicity, particularly elderly individuals, should be advised to report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.

Caution is advised when treating patients who are concurrently using medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., acetylsalicylic acid).

If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued. NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as their condition may worsen.

Effects on the respiratory system. Bronchospasm may occur in patients with bronchial asthma, chronic rhinitis, sinusitis, nasal polyps, or a history of such conditions.

Other. Severe acute hypersensitivity reactions (e.g., anaphylactic shock) are very rare. If early signs of hypersensitivity occur after ibuprofen administration, treatment should be discontinued immediately and medical attention sought for appropriate symptomatic therapy.

Ibuprofen may temporarily inhibit platelet aggregation. Therefore, careful monitoring is recommended in patients with coagulation disorders.

With prolonged use of ibuprofen, liver function, kidney function, and hematological parameters should be monitored regularly.

Long-term use of any analgesic for headache treatment may worsen the condition. In such cases, patients should consult a physician and discontinue treatment. Medication-overuse headache should be considered in patients suffering from frequent or daily headaches despite (or because of) regular use of headache medications. Headache may develop with long-term, off-label use of high-dose analgesics and should not be treated with higher doses of the same medication.

Concomitant use of alcohol and NSAIDs may intensify adverse reactions related to the active substance, particularly those affecting the gastrointestinal tract or central nervous system.

NSAIDs may mask symptoms of infection and fever.

Careful monitoring of diuresis and renal function is required when treating patients with heart failure, renal or hepatic impairment receiving diuretics, or patients after major surgery with fluid deficiency.

Effects on the kidneys. Regular use of analgesics, especially combinations of different analgesics, may generally lead to chronic kidney damage with a risk of renal failure (analgesic nephropathy).

Children. There is a risk of renal failure in dehydrated children.

Impairment of fertility in women. Some data suggest that inhibitors of cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of therapy.

Serious skin adverse reactions.

Serious skin adverse reactions (SSARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

If signs or symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

In rare cases, varicella may lead to severe skin and soft tissue infections. At present, the potential influence of NSAIDs in worsening such infections cannot be excluded; therefore, the use of ibuprofen is not recommended in cases of varicella.

Masking symptoms of underlying infections.

Nurofen® for children may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby complicating the course of illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When Nurofen® for children is used for fever or pain relief during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should seek medical advice if symptoms persist or worsen.

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 following use of prostaglandin synthesis inhibitors in early pregnancy.

The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy. In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation loss and embryonic/fetal mortality. Additionally, increased incidence of various developmental abnormalities, including cardiovascular malformations, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation. There have also been reports of ductus arteriosus constriction following second-trimester treatment, most of which resolved after stopping therapy. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by a woman attempting to conceive or during the first or second trimester of pregnancy, 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 several days of ibuprofen exposure starting from the 20th gestational week. Ibuprofen use should be discontinued if oligohydramnio or ductus arteriosus constriction is detected.

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

Risks to the fetus:

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

Risks to the mother at the end of pregnancy and to 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.

Therefore, ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding. Ibuprofen and its metabolites are excreted into breast milk in low concentrations. Currently, there are no data indicating adverse effects on the infant; therefore, interruption of breastfeeding is generally not required during short-term treatment of pain and fever at recommended doses.

Fertility.

There is some evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Ability to affect reaction speed when driving or operating machinery. When used according to recommended doses and treatment duration, the drug is not expected to affect reaction speed when driving or operating machinery.

Method of Administration and Dosage

The product is intended for rectal use only.

For short-term use only. The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use").

This medicinal product is intended for use only in children aged 3 months and older with body weight of at least 6 kg. The maximum single dose should not exceed 10 mg/kg body weight. The dosing interval should not be less than 6 hours. The maximum daily dose of ibuprofen is 20–30 mg/kg body weight, divided into 3–4 doses.

Children with body weight 6–8 kg (3–9 months of age): At the beginning of treatment – 1 suppository. If necessary, another suppository may be administered, but not earlier than 6–8 hours after the previous dose. Do not use more than 3 suppositories within 24 hours.

Children with body weight 8–12 kg (9 months–2 years of age): At the beginning of treatment – 1 suppository. If necessary, another suppository may be administered, but not earlier than 6 hours after the previous dose. Do not use more than 4 suppositories within 24 hours.

This medicinal product is contraindicated in children with body weight less than 6 kg and in infants under 3 months of age.

Patients with renal or hepatic impairment should consult a physician before using this medicinal product.

If symptoms worsen or persist in children aged 3–5 months after 24 hours from the start of treatment, immediate medical advice should be sought.

If symptoms persist for more than 3 days or worsen in children aged 6 months and older from the start of treatment, medical advice should be sought.

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Children. The product should be administered to children with body weight of at least 6 kg, aged from 3 months to 2 years.

Overdose.

Administration of doses exceeding 200 mg/kg body weight in children may result in intoxication.

Symptoms. Symptoms of overdose may include nausea, vomiting, epigastric pain, or less frequently, diarrhea. Other symptoms may include nystagmus, visual disturbances, tinnitus, headache, and gastrointestinal bleeding. More severe poisoning may lead to toxic central nervous system effects such as vertigo, dizziness, drowsiness, and occasionally, agitation, disorientation, or coma. Seizures may occasionally occur. Prolonged use at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia. In severe poisoning, prolonged prothrombin time/INR may occur (likely due to interaction with circulating blood coagulation factors). Acute renal failure, hepatic injury, hypotension, respiratory depression, and cyanosis may also occur. In patients with bronchial asthma, an exacerbation of asthma may be triggered.

Treatment. There is no specific antidote. Treatment should be symptomatic and supportive, including maintenance of airway patency and monitoring of cardiac function and vital signs until the patient's condition normalizes. In cases of frequent or prolonged seizures, intravenous administration of diazepam or lorazepam should be administered. In case of bronchial asthma exacerbation, bronchodilators should be administered.

Side effects.

The list of side effects presented below includes all adverse reactions reported during treatment with ibuprofen, including those observed during high-dose, long-term therapy in patients with rheumatic diseases. The frequency stated beyond very rare reports refers to short-term use of doses (maximum 1200 mg ibuprofen per day) for oral dosage forms and up to 1800 mg per day for suppositories.

It should be noted that the listed side effects are predominantly dose-dependent and may vary individually for each patient.

Adverse reactions occurring during ibuprofen use are listed below by organ systems and frequency of occurrence: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and frequency not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Gastrointestinal side effects were the most commonly observed. These adverse reactions are mostly dose-dependent. In particular, the risk of gastrointestinal bleeding depends on both dose and duration of treatment. Gastrointestinal ulcers, perforation, or gastrointestinal hemorrhage, sometimes fatal, may occur, especially in elderly patients. Nausea, vomiting, diarrhea, bloating, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported after ibuprofen use. Gastritis was observed less frequently.

Edema, arterial hypertension, and heart failure have been reported in association with NSAID therapy.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses of 2400 mg per day and during prolonged treatment, may be associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

Cases of exacerbation of infection-related inflammation, such as development of necrotizing fasciitis, have been described temporally associated with NSAID use. This may be related to the mechanism of action of NSAIDs.

If signs of infection develop or worsen during ibuprofen use, patients are advised to seek immediate medical attention. It is necessary to determine whether antimicrobial/antibiotic therapy is indicated.

Regular blood tests are required during long-term therapy.

Patients should immediately consult a physician and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even after the first dose. Immediate medical assistance is required in such cases.

If severe epigastric pain, melena, or hematemesis occurs, the patient should discontinue the medication and seek immediate medical attention.

Infections and infestations.

Very rare: Exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis). In exceptional cases, varicella may lead to severe skin and soft tissue infections.

Blood and lymphatic system disorders.

Very rare: Blood disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms include malaise, sore throat, oral mucosal ulcers, influenza-like symptoms, severe fatigue, epistaxis, skin bleeding, and bruising. In such cases, patients should discontinue this medication, avoid self-medication with analgesics or antipyretics, and consult a physician.

Immune system disorders.

Hypersensitivity reactions¹

Uncommon: Urticaria and pruritus.

Very rare: Severe hypersensitivity reactions, symptoms of which may include facial, lingual, or laryngeal edema, dyspnea, tachycardia, hypotension (anaphylactic reaction, angioneurotic edema, or severe shock). Asthma exacerbation.

Psychiatric disorders.

Very rare: Psychotic reactions, depression.

Nervous system disorders.

Uncommon: Central nervous system disturbances such as headache, dizziness, insomnia, restlessness, irritability, or fatigue.

Very rare: Aseptic meningitis²

Eye disorders.

Uncommon: Visual disturbances.

Ear and labyrinth disorders.

Rare: Tinnitus.

Cardiac disorders.

Very rare: Heart failure, tachycardia, edema, myocardial infarction.

Frequency not known: Kounis syndrome.

Vascular disorders.

Very rare: Arterial hypertension, vasculitis.

Gastrointestinal disorders.

Common: Gastrointestinal complaints such as abdominal pain, nausea, dyspepsia, diarrhea, flatulence, constipation, heartburn, vomiting, and minor gastrointestinal blood loss, which in exceptional cases may lead to anemia.

Uncommon: Gastric and duodenal ulcers, perforation, or gastrointestinal hemorrhage, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease, gastritis, localized rectal irritation.

Very rare: Esophagitis, formation of diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders.

Very rare: Liver function abnormalities, hepatic injury, particularly during long-term therapy, liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders.

Uncommon: Various skin rashes.

Very rare: Severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis), alopecia.

Frequency not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); acute generalized exanthematous pustulosis; photosensitivity reactions.

Respiratory, thoracic and mediastinal disorders.

Frequency not known: Respiratory tract reactivity, including asthma, bronchospasm, or dyspnea.

Renal and urinary disorders.

Rare: Renal tissue injury (papillary necrosis) and increased blood urea concentration may occur.

Very rare: Edema formation, particularly in patients with arterial hypertension or renal impairment, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

Laboratory tests.

Rare: Decreased hemoglobin levels.

Description of selected adverse reactions

¹ Reports exist of hypersensitivity reactions following ibuprofen therapy. These include (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactions including bronchial asthma, asthma exacerbation, bronchospasm, or dyspnea, or (c) various skin disorders including rashes of different types, pruritus, urticaria, purpura, angioneurotic edema, and less frequently exfoliative and bullous dermatoses (including toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme).

² The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAID use suggest an immune-mediated reaction (based on temporal relationship to drug intake and resolution of symptoms after discontinuation). In particular, isolated cases of aseptic meningitis symptoms (such as nuchal rigidity, headache, nausea, vomiting, malaise, or disorientation) have been observed during ibuprofen treatment in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus or mixed connective tissue disease).

Shelf life. 2 years.

Storage conditions. Store in a place inaccessible to children at a temperature not exceeding 25 °C.

Packaging. 2 blisters of 5 suppositories each in a cardboard box.

Prescription status. Over-the-counter (without prescription).

Manufacturer. Famar A.V.E. Avlon Plant

Manufacturer's address and place of business.

49th km National Road Athens-Lamia Avlon Attiki, 19011, Greece.