Gofen 200

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT HOFEN 200

Composition:

Active ingredient: ibuprofen;

1 soft capsule contains 200 mg of ibuprofen;

Excipients: polyethylene glycol 600, potassium hydroxide, purified water;

gelatin capsule shell: gelatin, sorbitol solution, non-crystallizing (E 420), purified water.

Pharmaceutical form. Soft capsules.

Main physico-chemical properties: elongated soft capsules with transparent, naturally colored shell; capsule contents – clear, colorless oily liquid.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives.

ATC code M01A E01.

Pharmacological properties.

Pharmacodynamics.

Exerts analgesic, antipyretic, and anti-inflammatory effects. The mechanism of action involves inhibition of prostaglandin synthesis—mediators of pain, inflammation, and temperature response.

Experimental data indicate that ibuprofen may competitively attenuate the effect of low-dose acetylsalicylic acid on platelet aggregation when these drugs are used concomitantly. Some pharmacodynamic studies have shown that administration of single 400 mg doses of ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) was associated with reduced effect of aspirin (acetylsalicylic acid) on thromboxane formation or platelet aggregation. Although uncertainty exists regarding extrapolation of these findings to clinical settings, it cannot be excluded that regular long-term use of ibuprofen may diminish the cardioprotective effect of low-dose acetylsalicylic acid. With occasional, non-systematic use of ibuprofen, such a clinically significant interaction is considered unlikely.

Pharmacokinetics.

After oral administration, ibuprofen is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentration of the active substance is reached within 1–2 hours after intake. Ibuprofen is metabolized in the liver and excreted by the kidneys (90%) unchanged and as metabolites, as well as in bile. Elimination half-life in healthy individuals is approximately 1.8 hours; in patients with hepatic or renal impairment, it ranges from 1.8 to 3.5 hours. Ibuprofen is highly bound (99%) to plasma proteins and slowly penetrates into synovial spaces, where its concentration may remain high even as plasma concentration decreases.

Clinical Characteristics.

Indications.

Symptomatic treatment of headache, dental pain, and menstrual pain.

Fever and muscle pain associated with colds.

Contraindications.

• Hypersensitivity to ibuprofen or to any of the components of the drug.
• Patients with a history of bronchospasm, asthma, rhinitis, angioedema, or skin rashes associated with the use of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Concomitant use with other NSAIDs should be avoided, including selective cyclooxygenase-2 (COX-2) inhibitors.
• Patients with a history of gastrointestinal bleeding or perforation following the use of NSAIDs.
• Active peptic ulcer/gastrointestinal bleeding or a history of such (two or more distinct episodes of peptic ulceration or bleeding).
• Patients with severe renal, hepatic, or cardiac (NYHA class IV) insufficiency.
• Third trimester of pregnancy.
• Children with body weight less than 20 kg.
• Patients with cerebrovascular or other active forms of bleeding.
• Patients with unexplained etiology of blood disorders.
• Patients with dehydration caused by vomiting, diarrhea, or insufficient fluid intake.

Interaction with other medicinal products and other forms of interaction.

Ibuprofen (like other NSAIDs) should be used with caution when administered concomitantly with the following drugs:

• Other NSAIDs, including salicylates: increased risk of gastrointestinal ulcers and bleeding;

• Digoxin: increased plasma levels of both drugs;

• Corticosteroids: increased risk of gastrointestinal bleeding or ulceration;

• Antithrombotic agents: increased risk of gastrointestinal bleeding;

• Anticoagulants: NSAIDs may enhance the effect of anticoagulants, such as warfarin;

• Antiplatelet agents and selective serotonin reuptake inhibitors: may increase the risk of gastrointestinal bleeding;

• Acetylsalicylic acid or other NSAIDs and glucocorticosteroids: may increase the risk of adverse effects of these drugs on the gastrointestinal tract. Experimental data indicate that concomitant use of ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation. However, limitations in extrapolating these data to clinical settings do not allow definitive conclusions about whether regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional use of ibuprofen, such clinically significant effects are considered unlikely;

• Antihypertensive and diuretic agents: NSAIDs may reduce the therapeutic effect of these drugs; in patients with impaired renal function, concomitant use of ACE inhibitors, beta-blockers, angiotensin II receptor antagonists, and cyclooxygenase inhibitors may lead to further deterioration of renal function. Therefore, such drug combinations should be used with caution, especially in elderly patients;

• Lithium and methotrexate: evidence suggests a potential increase in plasma levels of lithium and methotrexate;

• Probenecid and sulfinpyrazone: may delay the elimination of ibuprofen;

• Potassium-sparing diuretics: may lead to hyperkalemia (plasma potassium levels should be monitored);

• Cyclosporine and tacrolimus: increased risk of nephrotoxicity;

• Zidovudine: evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients receiving concomitant treatment with zidovudine and ibuprofen;

• Sulfonylureas: blood glucose levels should be monitored;

• Quinolone antibiotics: risk of seizures may occur.

• Cytochrome CYP2C9 inhibitors: may increase the effect of ibuprofen, such as voriconazole or fluconazole.

Special precautions for use.

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

The drug should be used with caution in patients with:

• systemic lupus erythematosus and systemic connective tissue diseases;
• inherited disorders of porphyrin metabolism (e.g., acute intermittent porphyria);
• history of arterial hypertension and/or heart failure associated with fluid retention and edema during NSAID therapy;
• impaired renal and/or hepatic function;
• immediately following surgery.

This medicinal product contains sorbitol solution. It is not recommended for use in patients with hereditary fructose intolerance.

Elderly patients have an increased risk of adverse reactions when using NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

Gastrointestinal bleeding, ulceration, or perforation, which may be fatal, have been reported with the use of all NSAIDs, both with and without serious gastrointestinal complications in medical history, and independently of treatment duration.

Increased NSAID dosage, advanced age, and history of peptic ulcer disease are risk factors for gastrointestinal adverse reactions. During treatment in such cases, the lowest effective doses are recommended.

Concomitant use of protective agents (e.g., misoprostol or proton pump inhibitors) should be considered, especially in patients requiring long-term low-dose acetylsalicylic acid or other medications that may increase the risk of gastrointestinal side effects.

Clinical trial data indicate that the use of ibuprofen, particularly at high doses (2400 mg per day), may be associated with an increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g., ≤1200 mg per day) is associated with an increased risk of arterial thrombotic complications.

Patients with uncontrolled arterial hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful clinical assessment. High doses (2400 mg per day) should be avoided.

Careful clinical evaluation should also be performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen (2400 mg per day) are required.

Cases of Kounis syndrome have been reported in patients receiving treatment with GOHFEN 200. 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.

Patients who experience gastrointestinal disturbances, particularly elderly individuals, should discontinue treatment and consult a physician if any adverse symptoms occur (especially gastrointestinal bleeding).

The drug should be used with caution in patients receiving concomitant therapy with medications that may increase the risk of peptic ulceration or bleeding, including oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid.

NSAIDs should be used with caution in patients with a history of ulcerative colitis or Crohn’s disease, as their condition may worsen.

Severe skin reactions.

Rare but serious skin reactions, which may be fatal, have been reported with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), including exfoliative dermatitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis (see section "Adverse reactions").

The risk of these reactions is highest at the beginning of therapy. Onset usually occurs within the first month of treatment. Cases of acute generalized exanthematous pustulosis have also been reported following administration of drugs containing ibuprofen.

Ibuprofen should be discontinued at the first signs or symptoms of skin involvement, such as skin rash, mucosal lesions, or any other signs of hypersensitivity.

Masking symptoms of underlying infections.

GOHFEN 200 may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby complicating the course of illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When GOHFEN 200 is used for fever or to relieve pain associated with infection, monitoring for infection is recommended. In outpatient settings, patients should seek medical advice if symptoms persist or worsen.

Bronchospasm may occur in patients who have or have had bronchial asthma or allergic diseases.

Prolonged use of analgesics in high doses may lead to medication-overuse headache, which cannot be treated by increasing the dose of the drug.

Long-term and uncontrolled use of analgesics, particularly combinations of different analgesic active substances, may lead to chronic kidney damage with risk of renal failure (analgesic nephropathy).

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

Ibuprofen may temporarily impair blood/coagulation function (platelet aggregation). Therefore, special monitoring is recommended in patients with coagulation disorders.

With prolonged use of the drug, regular monitoring of liver function tests, renal function, and blood cell counts is necessary.

The use of the drug should be avoided in cases of varicella.

Concomitant alcohol consumption may enhance adverse effects, particularly those affecting the gastrointestinal tract or central nervous system, after NSAID administration.

There is a risk of renal failure in dehydrated children and adolescents.

Use during pregnancy or breastfeeding.

Pregnancy.

Prostaglandin synthesis inhibitors may adversely affect pregnant women and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and congenital heart defects following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increases from 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy.

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. Additionally, there have been reports of arterial duct constriction following treatment in the second trimester, most of which resolved after stopping treatment. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by women attempting to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of ibuprofen exposure starting from the 20th gestational week. The drug should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

Risks to the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the arterial duct 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, GOHFEN 200 is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding period.

Ibuprofen and its metabolites may pass into breast milk in low concentrations. To date, no harmful effects on infants have been reported; therefore, in general, breastfeeding need not be discontinued during short-term treatment of pain and fever at recommended doses.

Ability to affect reaction speed when driving or operating machinery.

When used short-term, the drug does not affect or has a negligible effect on the ability to drive vehicles or operate machinery. However, during long-term use, central nervous system side effects such as increased fatigue and dizziness may occur.

Dosage and Administration.

Adults and children with body weight ≥ 40 kg.

The recommended initial dose is 1–2 capsules, followed, if necessary, by 1–2 capsules (200–400 mg of ibuprofen) every 4–6 hours. Do not exceed 6 capsules (1200 mg) within 24 hours.

Children with body weight ≤ 39 kg.

The use of the drug is possible in children 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 allowable daily dose.

Children with body weight 20–29 kg: the recommended initial dose is 1 capsule (equivalent to 200 mg of ibuprofen). The maximum daily dose is 3 capsules (equivalent to 600 mg of ibuprofen).

Children with body weight from 30 to 39 kg: the recommended initial dose is 1 capsule (equivalent to 200 mg of ibuprofen). The maximum daily dose is 4 capsules (equivalent to 800 mg of ibuprofen).

Capsules should generally be taken during meals, without chewing, with water.

Elderly patients do not require special dose adjustment.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Instructions"). If symptoms persist for more than 3 days, or more than 4 days when used for pain relief, consult a physician for diagnosis clarification and treatment regimen adjustment.

Children.

The use of the drug is contraindicated in children with body weight less than 20 kg.

Overdose.

In case of acute overdose, symptoms depend on the amount of drug ingested and the time elapsed since ingestion. The first symptoms usually observed are: nausea, vomiting, headache and dizziness, epigastric pain or, less commonly, diarrhea, drowsiness, nystagmus, blurred vision, tinnitus, gastrointestinal bleeding. In case of overdose, coma, arterial hypotension, hyperkalemia with cardiac rhythm disturbances, metabolic acidosis, elevated body temperature, respiratory disturbances and cyanosis, renal function impairment, and liver damage may occur. Occasionally, excitement, disorientation, and seizures may occur. After prolonged use, hemolytic anemia, granulocytopenia, and thrombocytopenia may rarely be observed.

If less than 1 hour has passed after acute overdose, induce vomiting, perform gastric lavage, or administer activated charcoal.

In cases of ibuprofen overdose, there is no specific antidote or specific treatment. Symptomatic treatment is based on monitoring vital functions, measuring arterial blood pressure, performing ECG, and interpreting symptoms indicating possible gastrointestinal bleeding, metabolic acidosis, or central nervous system disturbances.

Adverse Reactions

Below is a list of adverse reactions observed in individuals using ibuprofen for short-term treatment of mild to moderate pain and fever, as well as those observed during long-term, high-dose therapy in patients with rheumatic diseases.

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

The frequency of adverse effects is categorized as follows:

Very common: ≥1/10
Common: ≥1/100, <1/10
Uncommon: ≥1/1000, <1/100
Rare: ≥1/10,000, <1/1000
Very rare: <1/10,000, including isolated case reports

General disorders
Uncommon: hypersensitivity reactions such as urticaria and pruritus, increased sweating.
Very rare: severe hypersensitivity reactions including facial, tongue, and laryngeal swelling, dyspnea, tachycardia, hypotension, anaphylactoid reactions (anaphylaxis, Quincke's edema up to shock). Asthma exacerbation, bronchospasm or dyspnea, allergic rhinitis, eosinophilia.

Sensory organs
Rare: hearing disturbances (hearing loss, tinnitus).
Uncommon: visual disturbances (toxic optic neuropathy, blurred vision or diplopia, scotoma, dryness and irritation of eyes, allergic conjunctival and eyelid edema).

Gastrointestinal tract
Uncommon: abdominal pain, melena, hematemesis, dyspepsia, nausea.
Rare: diarrhea, flatulence, constipation, vomiting.
Very rare: heartburn, ulcerative stomatitis, gastritis, perforation or gastrointestinal hemorrhage (which may lead to anemia), potentially fatal especially in elderly patients. Exacerbation of ulcerative colitis and Crohn's disease, esophagitis, formation of intestinal diaphragm-like strictures. Irritation or dryness of the oral mucosa, oral mucosal ulcers of gums, aphthous stomatitis, pancreatitis.

Nervous system disorders
Uncommon: headache, dizziness, insomnia, anxiety, depression, nervousness and irritability or fatigue, psychomotor agitation, drowsiness, confusion, hallucinations.
Rare: aseptic meningitis (more frequently in patients with autoimmune disorders).

Cardiovascular system
Very rare: heart failure, tachycardia, increased blood pressure, vasculitis, myocardial infarction.
Kounis syndrome (frequency "unknown").

Urinary system
Very rare: decreased urea excretion and edema. Acute renal failure, allergic nephritis, glomerulonephritis, oliguria, polyuria, cystitis, hematuria. Papillary necrosis, particularly with prolonged use. Increased serum urea levels.

Hepatobiliary system
Very rare: liver function abnormalities, particularly with long-term use. Hepatitis, pancreatitis, duodenitis, esophagitis.

Blood and lymphatic system
Very rare: blood formation disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial signs include: high fever, sore throat, oral ulcers, flu-like symptoms, severe exhaustion, epistaxis, and bruising.

Skin and subcutaneous tissue
Very rare: severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Lyell's syndrome), alopecia.
Unknown: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); acute generalized exanthematous pustulosis; photosensitivity reactions.

Immune system
Uncommon: in patients with autoimmune disorders (systemic lupus erythematosus, connective tissue diseases), isolated cases of aseptic meningitis symptoms (neck stiffness, headache, nausea, vomiting, high fever, or disorientation), facial, tongue, and laryngeal swelling, dyspnea, tachycardia. Allergic reactions presenting as skin rash, pruritus, bronchial asthma attacks, hypotension.

Infections and parasitic diseases
Very rare: exacerbation of infection-related inflammation.

Laboratory investigations
Rare: decreased hemoglobin levels.

Shelf life

2 years.

Storage conditions

Store at temperatures not exceeding 25 °C in the original packaging.
Keep out of reach of children.

Packaging

10 capsules per blister, 1 blister per cardboard pouch. 5 or 6 cardboard pouches per cardboard box.

Prescription status

Over-the-counter (without prescription).

Manufacturer

Mega Lifesciences Public Company Limited.

Manufacturer's address and location of operations

Plant 2, 515/1 Moo 4, Soi 8, Bangpoo Industrial Estate, Pattana 3 Road, Phraeksa, Mueang, Samutprakarn 10280, Thailand.