MIG^® 400 (Tablets) Instructions for Use

Marketing Authorization Holder

Berlin-Chemie/Menarini Pharma, GmbH (Germany)

Manufactured By

Berlin-Chemie, AG (Germany)

ATC Code

M01AE01 (Ibuprofen)

Active Substance

Ibuprofen (Rec.INN registered by WHO)

Dosage Form

MIG® 400

Film-coated tablets 400 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, oval, with a double-sided score for dividing and an embossing “E” and “E” on both sides of the score on one side.

Excipients: corn starch – 215 mg, sodium carboxymethyl starch (type A) – 26 mg, colloidal silicon dioxide – 13 mg, magnesium stearate – 5.6 mg.

Shell composition hypromellose (viscosity 6 mPa×s) – 2.946 mg, titanium dioxide (E171) – 1.918 mg, povidone K30 – 0.518 mg, macrogol 4000 – 0.56 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID. Ibuprofen is a propionic acid derivative and has analgesic, antipyretic, and anti-inflammatory effects due to non-selective blockade of COX-1 and COX-2, as well as an inhibitory effect on prostaglandin synthesis.

The analgesic effect is most pronounced in inflammatory pain. The analgesic activity of the drug is not of the narcotic type.

Like other NSAIDs, Ibuprofen has antiplatelet activity.

Pharmacokinetics

After oral administration, the drug is well absorbed from the gastrointestinal tract. C_max of ibuprofen in plasma is approximately 30 µg/ml and is reached approximately 2 hours after taking the drug at a dose of 400 mg.

Plasma protein binding is about 99%. Ibuprofen is slowly distributed into the synovial fluid and is eliminated from it more slowly than from plasma.

It is metabolized in the liver mainly by hydroxylation and carboxylation of the isobutyl group. The metabolites are pharmacologically inactive.

It is characterized by biphasic elimination kinetics. T_1/2 from plasma is 2-3 hours. Up to 90% of the dose can be found in the urine as metabolites and their conjugates. Less than 1% is excreted unchanged in the urine and, to a lesser extent, in bile.

Indications

• Headache;
• Migraine;
• Toothache;
• Neuralgia;
• Muscle and joint pain;
• Menstrual pain, febrile conditions in colds and flu.

ICD codes

Dosage Regimen

Take orally. The dosage regimen is set individually depending on the indications.

Adults and children over 12 years are usually prescribed an initial dose of 200 mg 3-4 times/day. To achieve a rapid therapeutic effect, the dose can be increased to 400 mg 3 times/day. After achieving the therapeutic effect, the daily dose is reduced to 600-800 mg.

The drug should not be taken for more than 7 days or in higher doses. If it is necessary to use it for a longer period or in higher doses, a doctor’s consultation is required.

In patients with impaired renal, hepatic, or cardiac function, the dose of the drug should be reduced.

Adverse Reactions

From the digestive system NSAID-gastropathy – abdominal pain, nausea, vomiting, heartburn, loss of appetite, diarrhea, flatulence, constipation; rarely – ulceration of the gastrointestinal mucosa, which in some cases is complicated by perforation and bleeding; irritation or dryness of the oral mucosa, mouth pain, ulceration of the gum mucosa, aphthous stomatitis, pancreatitis, hepatitis are possible.

From the respiratory system: shortness of breath, bronchospasm.

From the sensory organs: hearing loss, ringing or noise in the ears, toxic damage to the optic nerve, blurred vision or double vision, scotoma, dryness and irritation of the eyes, swelling of the conjunctiva and eyelids (of allergic origin).

From the nervous system: headache, dizziness, insomnia, anxiety, nervousness and irritability, psychomotor agitation, drowsiness, depression, confusion, hallucinations, rarely – aseptic meningitis (more often in patients with autoimmune diseases).

From the cardiovascular system: heart failure, tachycardia, increased blood pressure.

From the urinary system: acute renal failure, allergic nephritis, nephrotic syndrome (edema), polyuria, cystitis.

Allergic reactions: skin rash (usually erythematous or urticarial), skin itching, angioedema, anaphylactoid reactions, anaphylactic shock, bronchospasm or dyspnea, fever, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), eosinophilia, allergic rhinitis.

From the hematopoietic system: anemia (including hemolytic, aplastic), thrombocytopenia and thrombocytopenic purpura, agranulocytosis, leukopenia.

From laboratory parameters an increase in bleeding time, a decrease in serum glucose concentration, a decrease in creatinine clearance, a decrease in hematocrit or hemoglobin, an increase in serum creatinine concentration, an increase in the activity of liver transaminases are possible.

With long-term use of the drug in high doses the risk of developing ulceration of the gastrointestinal mucosa, bleeding (gastrointestinal, gingival, uterine, hemorrhoidal), visual impairment (impaired color vision, scotomas, damage to the optic nerve) increases.

Contraindications

• Erosive and ulcerative diseases of the gastrointestinal tract organs (including peptic ulcer of the stomach and duodenum in the acute phase, Crohn’s disease, ulcerative colitis);
• “aspirin triad”;
• Hemophilia and other blood clotting disorders (including hypocoagulation), hemorrhagic diatheses;
• Bleeding of various etiologies;
• Glucose-6-phosphate dehydrogenase deficiency;
• Diseases of the optic nerve;
• Pregnancy;
• Lactation period;
• Children under 12 years of age;
• Hypersensitivity to the components of the drug;
• History of hypersensitivity to acetylsalicylic acid or other NSAIDs.

With caution the drug should be used in the following cases: elderly age; heart failure; arterial hypertension; liver cirrhosis with portal hypertension; hepatic and/or renal failure, nephrotic syndrome, hyperbilirubinemia; history of peptic ulcer of the stomach and duodenum, gastritis, enteritis, colitis; blood diseases of unclear etiology (leukopenia and anemia).

Use in Pregnancy and Lactation

There are no adequate and strictly controlled studies on the safety of ibuprofen use during pregnancy. The drug is contraindicated for use during pregnancy and during lactation (breastfeeding).

The use of ibuprofen may adversely affect female fertility and is not recommended for women planning pregnancy.

Use in Hepatic Impairment

The drug should be used with caution in hepatic insufficiency.

Use in Renal Impairment

The drug should be used with caution in renal insufficiency.

Pediatric Use

Contraindicated for use in children under 12 years of age.

Geriatric Use

Should be used with caution in the elderly.

Special Precautions

If signs of gastrointestinal bleeding occur, Ibuprofen should be discontinued.

Ibuprofen may mask objective and subjective symptoms, so the drug should be prescribed with caution to patients with infectious diseases.

The occurrence of bronchospasm is possible in patients suffering from bronchial asthma or with a history or presence of allergic reactions.

Side effects can be reduced by using the drug at the minimum effective dose. With long-term use of analgesics, there is a risk of developing analgesic nephropathy.

Patients who note visual impairment during ibuprofen therapy should stop treatment and undergo an ophthalmological examination.

Ibuprofen may increase the activity of liver enzymes.

During treatment, monitoring of the peripheral blood picture and the functional state of the liver and kidneys is necessary.

If symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, blood test with determination of hemoglobin, hematocrit, stool test for occult blood.

To prevent the development of NSAID-gastropathy, Ibuprofen is recommended to be combined with prostaglandin E drugs (misoprostol).

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

During treatment, ethanol intake is not recommended.

Effect on the ability to drive vehicles and mechanisms

Patients should refrain from all activities requiring increased attention and speed of psychomotor reactions.

Drug Interactions

A decrease in the effectiveness of furosemide and thiazide diuretics is possible due to sodium retention associated with inhibition of prostaglandin synthesis in the kidneys.

Ibuprofen may enhance the effect of oral anticoagulants (concomitant use is not recommended).

When co-administered with acetylsalicylic acid, Ibuprofen reduces its antiplatelet effect (an increase in the frequency of acute coronary insufficiency is possible in patients receiving small doses of acetylsalicylic acid as an antiplatelet agent).

Ibuprofen may reduce the effectiveness of antihypertensive agents.

Single cases of increased plasma concentrations of digoxin, phenytoin and lithium with simultaneous administration of ibuprofen have been described in the literature.

Ibuprofen, like other NSAIDs, should be used with caution in combination with acetylsalicylic acid or other NSAIDs and corticosteroids, as this increases the risk of adverse effects of the drug on the gastrointestinal tract.

Ibuprofen may increase the plasma concentration of methotrexate.

With combination therapy with zidovudine and ibuprofen, an increased risk of hemarthrosis and hematoma is possible in HIV-infected patients with hemophilia.

Combined use of ibuprofen and tacrolimus may increase the risk of nephrotoxic effects due to impaired prostaglandin synthesis in the kidneys.

Ibuprofen enhances the hypoglycemic effect of oral hypoglycemic agents and insulin; dose adjustment may be necessary.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.