Faspik

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FASPIK

Composition:

Active substance: 1 sachet of granules with mint flavour contains ibuprofen (as L-arginine salt) 200 mg;

Excipients: L-arginine, sodium bicarbonate, sodium saccharin, aspartame (E 951), mint flavouring, sucrose.

Pharmaceutical form. Granules for oral solution with mint flavour.

Main physicochemical properties: white granules with characteristic mint odour.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and anti-rheumatic drugs. Propionic acid derivatives. ATC code M01AE01.

Pharmacological properties.

Pharmacodynamics.

Ibuprofen is a derivative of phenylpropionic acid that exerts anti-inflammatory, analgesic, and moderate antipyretic effects. The anti-inflammatory effect is due to inhibition of prostaglandin synthesis; the antipyretic effect results from action on the hypothalamus. Ibuprofen reduces or eliminates pain syndrome, including joint pain at rest and during movement, helps reduce morning stiffness and joint swelling, and increases range of motion. It inhibits platelet aggregation.

Pharmacokinetics.

After oral administration, ibuprofen is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentrations of ibuprofen – 26 μg/mL and 56 μg/mL – are reached within 15–30 minutes after administration of a 200 mg and 400 mg dose, respectively, taken on an empty stomach.

Ibuprofen is metabolized in the liver and excreted by the kidneys as inactive metabolites. The plasma half-life ranges from 1 to 2 hours.

Clinical characteristics.

Indications.

Symptomatic treatment of headache, migraine, toothache, menstrual pain, rheumatic pain, and muscle and back pain.

Symptomatic treatment of symptoms of cold, influenza, and fever.

Contraindications.

• Hypersensitivity to ibuprofen or to any component of the medicinal product.
• Hypersensitivity reactions (e.g., bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after taking ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
• Active peptic ulcer/gastrointestinal bleeding or history of recurrent episodes (two or more distinct episodes of peptic ulcer disease or bleeding).
• Duodenal ulcer.
• History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• Severe impairment of liver function, renal dysfunction, or severe heart failure.
• Third trimester of pregnancy.
• Cerebrovascular or other bleeding disorders.
• Disorders of blood coagulation or hemostasis.
• Severe dehydration.
• Phenylketonuria, as the medicinal product contains aspartame.

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 when aspirin (at a dose not exceeding 75 mg per day) has been prescribed by a physician;
• other NSAIDs, including selective cyclooxygenase-2 inhibitors, as this may increase the risk of adverse reactions.

Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose acetylsalicylic acid (aspirin). However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical situations preclude definitive conclusions about regular ibuprofen use; clinically significant effects with occasional ibuprofen use are considered unlikely.

Ibuprofen should be used with caution in combination with the following medicinal products:

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

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may attenuate the effects of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant use of ACE inhibitors or angiotensin II antagonists with cyclooxygenase-inhibiting drugs may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, particularly in elderly patients. In cases of long-term treatment, adequate hydration should be ensured, and monitoring of renal function should be considered at the start of combination therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulcers and bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): may increase the risk of gastrointestinal bleeding.

Cardiac glycosides: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides.

Lithium: evidence suggests a potential increase in plasma lithium levels.

Metotrexate: evidence suggests a potential increase in plasma methotrexate levels.

Cyclosporine: increased risk of nephrotoxicity.

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

Tacrolimus: possible increased risk of nephrotoxicity when used concomitantly with NSAIDs.

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

Quinolone antibiotics: concomitant use with ibuprofen may increase the risk of seizures.

Probenecid and sulfinpyrazone: may cause delayed elimination of ibuprofen from the body.

Baclofen: baclofen toxicity may develop after initiation of ibuprofen therapy.

Ritonavir: may increase plasma concentrations of NSAIDs.

Aminoglycosides: NSAIDs may reduce the elimination of aminoglycosides.

Captopril: experimental studies have shown that ibuprofen inhibits the sodium-excreting effect of captopril.

Voriconazole and fluconazole (CYP2C9 inhibitors): the need to reduce the dose of ibuprofen should be considered when used concomitantly with strong CYP2C9 inhibitors, especially at high ibuprofen doses.

Cholestyramine: ibuprofen and cholestyramine should be taken several hours apart due to delayed and reduced (by 25%) absorption of ibuprofen when administered simultaneously.

Sulfonylurea derivatives and phenytoin: possible potentiation of effect. Interactions between NSAIDs and hypoglycemic agents (sulfonylurea derivatives) have been observed. Blood glucose levels should be monitored when sulfonylurea derivatives are used concomitantly with ibuprofen.

Special precautions for use.

Adverse effects associated with the use of ibuprofen and NSAIDs in general can be minimized by using the lowest effective dose required to treat symptoms for the shortest possible duration.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which can be fatal.

Respiratory system effects

Bronchospasm may occur in patients suffering from bronchial asthma or allergic diseases, or with a history of these conditions.

Other NSAIDs

Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions and should therefore be avoided.

Systemic lupus erythematosus and mixed connective tissue diseases

Ibuprofen should be used with caution in patients with manifestations of systemic lupus erythematosus or mixed connective tissue diseases due to an increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects

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 therapy with ibuprofen and other NSAIDs.

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

Renal effects

Ibuprofen should be used with caution in patients with impaired renal function, as kidney function may deteriorate.

Hepatic effects

Impaired liver function may occur.

Effects on female fertility

Limited data suggest that medicinal products which inhibit cyclooxygenase/prostaglandin synthesis, when used long-term (referring to a dose of 2400 mg per day and treatment duration exceeding 10 days), may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Gastrointestinal effects

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated. Cases of gastrointestinal bleeding, perforation, and ulcers, possibly fatal, have been reported during NSAID therapy at any stage, regardless of the presence of prior warning symptoms or a history of severe gastrointestinal disorders.

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

Patients with a history of gastrointestinal disorders, particularly elderly patients, should be informed about any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.

Caution is advised when treating patients receiving concomitant 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., aspirin).

If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued immediately.

Severe skin reactions

Very rarely, severe skin reactions, which may be fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur during NSAID therapy. The highest risk of such reactions occurs early in treatment; in most cases, onset occurs within the first month of therapy. Acute generalized exanthematous pustulosis (AGEP) has been reported in association with ibuprofen-containing products. Ibuprofen should be discontinued at the first signs of skin rash, mucosal lesions, or any other signs of hypersensitivity.

Masking symptoms of underlying infections

Faspic may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby complicating the course of the illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When Faspic is used for fever or to relieve pain associated with infection, monitoring for infection is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

This medicinal product contains sucrose. If intolerance to certain sugars has been diagnosed, consult a physician before taking this product. It may be harmful to teeth.

This medicinal product contains aspartame (E951), a phenylalanine derivative, which may be hazardous for patients with phenylketonuria.

Use during pregnancy or breastfeeding

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 the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy.

NSAIDs should not be used during the first two trimesters of pregnancy unless, in the physician’s opinion, the potential benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by women attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible duration.

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

• For the fetus: cardiopulmonary toxicity (characterized by premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure accompanied by oligohydramnios;

• For the mother and newborn, at the end of pregnancy: prolonged bleeding time, antiplatelet effects (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.

In limited studies, ibuprofen has been detected in breast milk at very low concentrations; therefore, it is unlikely to adversely affect a breastfed infant.

Ability to affect reaction speed when driving or operating machinery

The product may affect the ability to drive or operate machinery due to the possible occurrence of somnolence, dizziness, and depression.

Patients should refrain from driving and other activities requiring heightened attention and rapid mental and motor responses if they experience somnolence, dizziness, or depression during ibuprofen therapy.

Method of Administration and Dosage.

Dissolve the contents of the sachet in 100 ml of water and take orally immediately after preparing the solution, preferably during or after a meal.

To be used in children aged 6 years and older with body weight of at least 20 kg. The maximum daily dose of ibuprofen is 20–30 mg per kilogram of body weight, divided into 3–4 doses administered at intervals of 6–8 hours. Do not exceed the maximum recommended daily dose.

Children aged 6–9 years with body weight 20–29 kg: the recommended initial dose is 1 sachet (equivalent to 200 mg of ibuprofen). The maximum daily dose is 3 sachets (equivalent to 600 mg of ibuprofen).

Children aged 9–12 years with body weight 30–39 kg: the recommended initial dose is 1 sachet (equivalent to 200 mg of ibuprofen). The maximum daily dose is 4 sachets (equivalent to 800 mg of ibuprofen).

Adults: the single dose for adults is 2 sachets (400 mg of ibuprofen). If necessary, 2 sachets may be taken every 6 hours. The maximum daily dose is 1200 mg (3 sachets per day).

For short-term use only.

Use the lowest effective dose required to relieve symptoms for the shortest possible duration (see section "Special Instructions").

Elderly patients do not require special dose adjustment, except in cases of severe renal or hepatic impairment.

If symptoms worsen or persist for more than 3 days, consult a physician for diagnosis clarification and treatment adjustment. The duration of treatment is determined individually by a physician, depending on the course of the disease and the patient's condition.

Children.

The use of the drug is possible in children aged 6 years and older with body weight of at least 20 kg.

Overdose.

Administration of the drug to children at doses exceeding 400 mg/kg may cause symptoms of intoxication. In adults, the effect of overdose is less pronounced. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients who have taken clinically significant amounts of NSAIDs, only nausea, vomiting, epigastric pain, or very rarely diarrhea developed. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may occur, manifesting as vertigo, drowsiness, occasionally agitation, disorientation, or coma. Seizures may sometimes be observed in patients. In severe poisoning, hyperkalemia and metabolic acidosis may develop; prolongation of prothrombin time/increased prothrombin index may be observed, possibly due to effects on circulating blood coagulation factors. Acute renal failure, liver damage, arterial hypotension, respiratory failure, and cyanosis may also occur. In patients with bronchial asthma, exacerbation of the disease may occur.

Treatment. Treatment should be symptomatic and supportive, including maintenance of airway patency and monitoring of cardiac and vital functions until condition stabilizes. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalizing agents may be administered to accelerate renal excretion of the acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. Bronchodilators should be used to treat bronchial asthma exacerbation.

Side effects.

The following adverse reactions are possible with short-term use of ibuprofen at doses not exceeding 1200 mg/day. Other adverse reactions may occur during treatment of chronic conditions or with prolonged use.

Adverse reactions associated with ibuprofen use are classified by organ systems and frequency. Frequency is defined as follows: very common: ≥1/10; common: ≥1/100 and <1/10; uncommon: ≥1/1000 and <1/100; rare: ≥1/10000 and <1/1000; very rare: <1/10000; frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders.

Very rare: blood dyscrasias¹.

Immune system disorders.

Uncommon: hypersensitivity reactions accompanied by urticaria and pruritus². Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal edema, dyspnea, tachycardia, hypotension (anaphylaxis, angioedema, or severe shock)².

Nervous system disorders.

Common: dizziness. Uncommon: headache, lethargy, somnolence. Very rare: aseptic meningitis³, confusion, meningeal signs. Frequency not known: depression, psychotic reactions.

Cardiac disorders.

Frequency not known: heart failure, edema⁴.

Vascular disorders.

Frequency not known: arterial hypertension⁴, arterial thrombosis.

Respiratory, thoracic and mediastinal disorders.

Frequency not known: bronchial reactivity, including asthma, bronchospasm, or dyspnea².

Gastrointestinal disorders.

Very common: epigastric discomfort. Common: heartburn. Uncommon: abdominal pain, nausea, dyspepsia⁵. Rare: diarrhea, flatulence, constipation, vomiting. Very rare: gastric and duodenal ulceration; gastrointestinal perforation or hemorrhage, melena, hematemesis (sometimes fatal); ulcerative stomatitis, gastritis. Frequency not known: exacerbation of colitis and Crohn’s disease⁶.

Hepatic disorders.

Very rare: hepatic dysfunction, jaundice.

Skin and subcutaneous tissue disorders.

Uncommon: various types of skin rashes². Very rare: bullous reactions, including Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis².

Frequency not known: acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (drug hypersensitivity syndrome/DRESS syndrome).

Renal and urinary disorders.

Very rare: acute renal impairment⁷.

Psychiatric disorders.

Frequency not known: only with prolonged use: depression, hallucinations, confusion.

Eye disorders.

Rare: amblyopia. Frequency not known: with prolonged treatment, visual disturbances and optic neuritis may occur.

Ear and labyrinth disorders.

Frequency not known: with prolonged treatment, tinnitus and vertigo may occur.

Musculoskeletal and connective tissue disorders.

Frequency not known: musculoskeletal stiffness.

Reproductive system and breast disorders.

Frequency not known: menstrual disorders.

Infections and infestations.

Frequency not known: exacerbation of skin reactions.

Metabolism and nutrition disorders.

Hyperuricemia, sodium and water retention, or edema.

Investigations.

Rare: increased transaminase levels, color vision disturbances. Very rare: decreased hemoglobin levels.

¹ Includes anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, granulocytopenia, and hemolytic anemia. Initial signs of these disorders include malaise, sore throat, oral mucosal ulcers, flu-like symptoms, severe fatigue, bleeding, and unexplained bruising or hematomas.

² Hypersensitivity reactions include: non-specific allergic reactions and anaphylaxis, bronchial reactivity including asthma, worsening of asthma, bronchospasm and dyspnea, or various forms of skin reactions including pruritus, urticaria, purpura, exanthema, skin eruptions, angioedema, and less frequently exfoliative and bullous dermatoses, including toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, and allergic vasculitis.

³ The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. Available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (based on temporal association with drug intake and resolution of symptoms after discontinuation). Isolated cases of aseptic meningitis symptoms (nuchal rigidity, headache, nausea, vomiting, malaise, or disorientation) have been observed in patients with autoimmune diseases (systemic lupus erythematosus and mixed connective tissue disease).

⁴ Clinical trial data and epidemiological evidence suggest that ibuprofen use (particularly at high doses ≥ 2400 mg/day and with long-term treatment) may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

⁵ Gastrointestinal adverse reactions are the most commonly observed.

⁶ See section "Special precautions".

⁷ Especially with long-term use of NSAIDs, associated with increased blood urea levels and development of edema. Also includes papillary necrosis, hematuria, dysuria, interstitial nephritis, renal insufficiency, acute renal failure.

Shelf life. 3 years.

Storage conditions.

No special storage conditions required.

Keep out of reach of children.

Packaging.

3 g of granules in a sachet. 12 paired sachets in a cardboard box.

Availability.

Over-the-counter (without prescription).

Manufacturer.

Zambon Switzerland Ltd.

Manufacturer's address.

Via Industria 13, 6814 Cadempino, Switzerland.

Marketing authorization holder.

Zambon S.P.A.

Address of the marketing authorization holder.

Via Lillo del Duca, 10 - 20091 Bresso, Milan, Italy.