Motrin^® (Tablets) Instructions for Use

ATC Code

M01AE02 (Naproxen)

Active Substance

Naproxen (Rec.INN registered by WHO)

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

Nonsteroidal anti-inflammatory drug (NSAID)

Pharmacological Action

NSAID. It has anti-inflammatory, analgesic, and antipyretic effects associated with non-selective inhibition of the activity of COX-1 and COX-2, which regulate the synthesis of prostaglandins.

Pharmacokinetics

Absorption and Distribution

Absorption from the gastrointestinal tract is rapid and complete, bioavailability is 95% (food intake has practically no effect on either the completeness or the rate of absorption). Time to reach C_max is 2 hours.

Plasma protein binding is 99%. C_ss of the drug in blood plasma is reached after 2-3 days.

Metabolism and Excretion

It is metabolized in the liver to dimethylnaproxen with the participation of the CYP2C9 enzyme system. Clearance is 0.13 ml/min/kg.

T_1/2 is 12-15 hours. 98% is excreted by the kidneys, 10% of which is unchanged; 0.5-2.5% is excreted in the bile.

Pharmacokinetics in Special Clinical Cases

Accumulation of metabolites is possible in chronic renal failure.

Indications

Musculoskeletal system diseases

• Rheumatic soft tissue lesions;
• Osteoarthritis of peripheral joints and spine, including with radicular syndrome;
• Tenosynovitis;
• Bursitis.

Mild to moderate pain syndrome

• Neuralgia;
• Bone pain;
• Myalgia;
• Lumbosciatica;
• Post-traumatic pain syndrome (sprains and contusions) accompanied by inflammation;
• Postoperative pain (in traumatology, orthopedics, gynecology, maxillofacial surgery);
• Headache;
• Migraine;
• Dysmenorrhea;
• Adnexitis;
• Toothache.

As part of complex therapy of infectious and inflammatory diseases of the ear, throat, and nose with severe pain syndrome, including:

• Pharyngitis;
• Tonsillitis;
• Otitis.

Febrile conditions in influenza and colds.

The drug is used for symptomatic therapy (to reduce pain, inflammation, and lower elevated body temperature) and does not affect the progression of the underlying disease.

ICD codes

Dosage Regimen

Tablets

Orally, for adults and children over 15 years of age.

Tablets should be swallowed whole with a sufficient amount of liquid; they can be taken with food.

For pain relief, the initial dose is 2 tablets (500 mg), then, if necessary, 1 tablet (250 mg) every 8 hours.

Usually, the daily dose used for pain relief is 2-3 tablets (500-750 mg).

To relieve pain in migraine, a dose of 2 tablets (500 mg) is recommended, then, if necessary, 1 tablet (250 mg) every 8-12 hours. However, treatment should be discontinued if the frequency, intensity, and duration of migraine attacks do not decrease within 4-6 weeks.

To relieve menstrual pain, pain after insertion of an intrauterine device, and other gynecological pains (adnexitis), the initial dose is 2 tablets (500 mg), then, if necessary, 1 tablet (250 mg) every 8 hours for 3-4 days.

For symptomatic therapy of pain syndrome in musculoskeletal diseases (rheumatic soft tissue lesions, osteoarthritis of peripheral joints and spine, including with radicular syndrome, tenosynovitis, bursitis), the usual daily dose of the drug is 2-3 tablets (500-750 mg), initial dose – 2 tablets (500 mg), then 1 tablet (250 mg) every 8 hours.

When using the drug as an antipyretic, the initial dose is 2 tablets (500 mg), then, if necessary, 1 tablet (250 mg) every 8 hours.

For elderly patients over 65 years of age, the drug should be taken as needed every 12 hours.

The drug is not recommended for use as an analgesic for more than 5 days without consulting a doctor. If symptoms persist, the patient should consult a doctor.

Adverse Reactions

Definition of adverse reaction (AR) frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from available data).

Most commonly, ARs from the gastrointestinal tract were observed. Development of peptic ulcer, gastric perforation, or gastrointestinal bleeding, sometimes fatal, especially in elderly patients, is possible (see section “Special Precautions”).

Within each group, ARs are listed in descending order of severity.

From the blood and lymphatic system uncommon – eosinophilia, granulocytopenia, leukopenia, thrombocytopenia.

From the nervous system common – headache, vertigo, dizziness, drowsiness; uncommon – depression, sleep disorder, impaired concentration, insomnia, malaise.

From the organ of vision common – visual impairment.

From the organ of hearing and labyrinthine disorders common – tinnitus, hearing impairment; uncommon – hearing loss.

From the heart common – edema, palpitations; uncommon – congestive heart failure.

From the respiratory system common – dyspnea; uncommon – eosinophilic pneumonia.

From the gastrointestinal tract common – constipation, abdominal pain, dyspepsia, nausea, diarrhea, stomatitis, flatulence; uncommon – gastrointestinal bleeding and/or gastric perforation, hematemesis, melena, vomiting; very rare – relapse or exacerbation of ulcerative colitis or Crohn’s disease; frequency unknown – gastritis.

From the liver and biliary tract uncommon – increased activity of liver enzymes, jaundice.

From the skin and subcutaneous tissues common – skin itching, skin rash, ecchymosis, purpura, increased sweating; uncommon – alopecia, photodermatoses; very rare – bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

From the musculoskeletal system uncommon – myalgia and muscle weakness.

From the kidneys and urinary tract uncommon – glomerulonephritis, hematuria, interstitial nephritis, nephrotic syndrome, renal failure, renal papillary necrosis.

General disorders thirst; uncommon – hypersensitivity reactions, menstrual cycle disorders, hyperthermia (chills and fever).

During NSAID therapy, reports of edema and symptoms of heart failure, increased blood pressure have been received.

Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially in high doses during long-term therapy) may be associated with a slight increase in the risk of arterial thrombosis (e.g., myocardial infarction or stroke).

Adverse effects for which a causal relationship with the use of naproxen has not been established

From the blood and lymphatic system: aplastic anemia, hemolytic anemia.

From the nervous system: aseptic meningitis, cognitive dysfunction.

From the skin and subcutaneous tissues: erythema multiforme; photosensitivity reactions similar to porphyria cutanea tarda and epidermolysis bullosa; urticaria.

From the vessels: vasculitis.

General disorders: angioedema, hyperglycemia, hypoglycemia.

If the patient notices such ARs, they should stop taking the drug and, if possible, consult a doctor.

Contraindications

• Hypersensitivity to naproxen or naproxen sodium;
• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history);
• Period of coronary artery bypass grafting;
• Erosive and ulcerative lesions of the stomach and duodenum in the acute phase; active gastrointestinal bleeding;
• Inflammatory bowel diseases in the acute phase (nonspecific ulcerative colitis, Crohn’s disease);
• Lactose intolerance;
• Cerebrovascular bleeding or other bleeding;
• Severe hepatic failure or active liver disease;
• Severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney disease, confirmed hyperkalemia;
• Decompensated heart failure;
• Hemophilia and other bleeding disorders and hemostasis disorders;
• Pregnancy;
• Breastfeeding period;
• Children under 15 years of age.

With caution

Coronary artery disease, cerebrovascular diseases, congestive heart failure, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery diseases, impaired renal function (creatinine clearance 30-60 ml/min), history of gastrointestinal ulcerative lesions, presence of Helicobacter pylori infection, systemic lupus erythematosus or mixed connective tissue diseases (Sharp’s syndrome), long-term use of NSAIDs, severe somatic diseases, use in elderly patients, smoking, frequent alcohol consumption, concomitant therapy with the following drugs: anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), oral corticosteroids (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline).

Use in Pregnancy and Lactation

The use of the drug Motrin^® is contraindicated during pregnancy and breastfeeding.

The use of naproxen, like other drugs that block prostaglandin synthesis, may affect fertility, so it is not recommended for women planning pregnancy.

Use in Hepatic Impairment

Contraindication: severe hepatic failure or active liver disease.

The drug should be prescribed with caution to patients with liver diseases.

Use in Renal Impairment

Contraindication: severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney disease, confirmed hyperkalemia.

The drug should be prescribed with caution in creatinine clearance of 30-60 ml/min.

Pediatric Use

The use of the drug is contraindicated in children under 15 years of age.

Geriatric Use

The drug should be prescribed with caution to elderly patients.

Special Precautions

Do not exceed the doses indicated in the instructions.

To reduce the risk of gastrointestinal adverse events, the minimum effective dose should be used for the shortest possible course. If pain and fever persist or become stronger, the patient should consult a doctor.

Before taking the drug Motrin^®, patients with bronchial asthma, bleeding disorders, as well as patients with hypersensitivity to other analgesics should consult a doctor.

The drug should be prescribed with caution to patients with liver diseases and renal failure. In patients with renal failure, creatinine clearance should be monitored. Use of Naproxen is not recommended if creatinine clearance is less than 30 ml/min. In chronic alcoholic cirrhosis and other forms of liver cirrhosis, the concentration of unbound naproxen increases, so lower doses are recommended for such patients.

After two weeks of using the drug, monitoring of liver function parameters is necessary.

The drug Motrin^® should not be taken together with other anti-inflammatory and analgesic drugs, except as prescribed by a doctor.

Lower doses of the drug are also recommended for elderly patients (≥ 65 years).

Avoid taking naproxen for 48 hours before surgery.

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study. Similarly, Naproxen may affect the determination of 5-hydroxyindoleacetic acid in urine.

The use of naproxen, like other drugs that block prostaglandin synthesis, may affect fertility, so it is not recommended for women planning pregnancy.

If the medicine is no longer usable or the expiration date has passed, do not dispose of it in wastewater. It is necessary to place the medicine in a bag and put it in a trash container. These measures will help protect the environment.

Effect on the ability to drive vehicles and mechanisms

Naproxen slows down the reaction speed in patients. This should be taken into account when driving vehicles and performing tasks requiring increased attention.

Overdose

Symptoms significant overdose of the drug may be characterized by drowsiness, headache, dizziness, impaired consciousness, dyspeptic disorders (heartburn, nausea and vomiting, abdominal pain), weakness, tinnitus, irritability, in severe cases – hematemesis, melena, impaired consciousness, convulsions, hallucinations, gastrointestinal bleeding, ulcerative lesions of the gastrointestinal tract, metabolic acidosis, renal failure.

Arterial hypotension, respiratory depression, and cyanosis may also be observed.

Treatment: gastric lavage, intake of activated charcoal, and symptomatic therapy: antacids, histamine H₂-receptor blockers, proton pump inhibitors. Hemodialysis is not effective.

In case of drug overdose, it is necessary to seek medical help immediately.

Drug Interactions

When treating with anticoagulants, it should be taken into account that Naproxen may increase bleeding time.

The drug should not be used simultaneously with other NSAIDs (increased risk of side effects).

According to clinical pharmacodynamics, the simultaneous use of naproxen and acetylsalicylic acid for more than one day may inhibit the effect of low-dose acetylsalicylic acid on platelet activity; the inhibition may persist for several days after discontinuation of naproxen therapy. The clinical significance of this interaction is unknown.

With simultaneous use of hydantoin derivatives, anticoagulants, or other drugs that bind significantly to plasma proteins, the effect of these drugs may be potentiated.

Naproxen may reduce the antihypertensive effect of propranolol and other beta-blockers and may also increase the risk of renal failure associated with the use of ACE inhibitors.

Under the influence of naproxen, the natriuretic effect of furosemide is inhibited.

Inhibition of renal lithium clearance leads to increased plasma lithium concentrations.

Taking probenecid increases the plasma level of naproxen.

Cyclosporine increases the risk of renal failure.

Naproxen slows the excretion of methotrexate, phenytoin, and sulfonamides, increasing the risk of their toxic effects.

Antacid preparations containing magnesium and aluminum reduce the absorption of naproxen.

Simultaneous use of naproxen and antiplatelet drugs, selective serotonin reuptake inhibitors, or alcohol increases the risk of gastrointestinal bleeding.

Myelotoxic drugs enhance the manifestations of the drug’s hematotoxicity.

According to in vitro studies, simultaneous use of naproxen and zidovudine increases the plasma concentration of zidovudine.

Simultaneous use of corticosteroids may increase the risk of ulcer formation or gastrointestinal bleeding.

Concomitant use of NSAIDs is not recommended for 8-12 days after mifepristone use.

Simultaneous use of NSAIDs and tacrolimus increases the risk of nephrotoxicity.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life is 3 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is available without a prescription.

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.