Diphenadrim^® Kombi (Capsules) Instructions for Use

Marketing Authorization Holder

Kronopharm, LLC (Russia)

Manufactured By

Canonpharma Production, CJS (Russia)

ATC Code

M01AE51 (Ibuprofen in combination with other drugs)

Active Substances

Ibuprofen (Rec.INN registered WHO)

Diphenhydramine (Rec.INN registered WHO)

Dosage Form

Diphenadrim® Kombi

Capsules 25 mg+200 mg

Dosage Form, Packaging, and Composition

Capsules

10 pcs. – blister packs contour – carton packs (10 pcs.) – Over-the-counter
10 pcs. – blister packs contour (2 pcs.) – carton packs (20 pcs.) – Over-the-counter
10 pcs. – blister packs contour (3 pcs.) – carton packs (30 pcs.) – Over-the-counter
30 pcs. – jars – carton packs (30 pcs.) – Over-the-counter

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs; non-steroidal anti-inflammatory and antirheumatic drugs; propionic acid derivatives

Indications

• Symptomatic relief of mild to moderate pain of various origins, including headache, dental pain, muscle pain (myalgia), back pain, and pain associated with menstruation (primary dysmenorrhea).
• Reduction of fever (antipyretic) in adults and adolescents over 12 years of age when associated with colds and other infectious and inflammatory diseases.
• Short-term symptomatic treatment of exacerbations of osteoarthritis and rheumatoid arthritis.
• The combination with diphenhydramine is particularly aimed at conditions where pain is accompanied by difficulty falling asleep, as the sedative effect of diphenhydramine can facilitate sleep.

The use of the drug should be limited to the minimum effective dose and the shortest duration necessary to control symptoms.

Contraindications

• Hypersensitivity to ibuprofen, diphenhydramine, other NSAIDs, or any of the excipients of the drug. A history of asthma attacks, bronchospasm, rhinitis, urticaria, or other allergic-type reactions after taking acetylsalicylic acid or other NSAIDs.
• History of gastrointestinal bleeding or perforation in connection with previous NSAID therapy.
• Active peptic ulcer or a history of recurrent ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding).
• Severe hepatic impairment or active liver disease.
• Severe renal impairment (creatinine clearance less than 30 ml/min).
• Confirmed hyperkalemia.
• Third trimester of pregnancy and breastfeeding.
• Children under 12 years of age.
• Concomitant use with other NSAIDs, including selective COX-2 inhibitors.
• Conditions associated with an increased risk of bleeding.
• Severe heart failure.
• Angle-closure glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction.
• Prostatic hyperplasia with urinary retention.

Dosage Regimen

For oral administration. The capsules should be swallowed whole with a sufficient amount of water. It is recommended to take the drug during or after a meal to reduce the potential for gastrointestinal discomfort.

Adults and adolescents over 12 years of age: The usual dose is one capsule every 6-8 hours as needed for pain or fever. The maximum single dose is one capsule. Do not exceed three capsules (600 mg ibuprofen / 75 mg diphenhydramine) in 24 hours.

The duration of self-medication without consulting a doctor should not exceed 3 days for fever and 5 days for pain. If symptoms persist or worsen, the patient should discontinue the drug and consult a physician. For the treatment of chronic conditions (e.g., arthritis), the dosage regimen should be determined by a doctor.

Special Populations: The drug is contraindicated in patients with severe hepatic or renal impairment. Use with caution in elderly patients; it is recommended to start with the lowest effective dose due to an increased frequency of adverse reactions. Not recommended for use in children under 12 years of age.

Adverse Reactions

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Blood and lymphatic system disorders: Uncommon: anemia, leukopenia, thrombocytopenia; Rare: agranulocytosis, aplastic anemia, hemolytic anemia.

Immune system disorders: Uncommon: hypersensitivity reactions (e.g., skin rash, urticaria, pruritus); Rare: anaphylactic/anaphylactoid reactions, including shock, angioedema, bronchospasm, severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis).

Nervous system disorders: Very common: drowsiness, sedation; Common: dizziness, headache; Uncommon: paresthesia; Rare: aseptic meningitis, optic neuritis.

Eye disorders: Uncommon: visual disturbance (blurred vision, diplopia); Rare: toxic amblyopia.

Cardiac disorders: Uncommon: palpitations, tachycardia; Rare: heart failure, increased blood pressure.

Vascular disorders: Rare: vasculitis.

Respiratory, thoracic and mediastinal disorders: Uncommon: asthma exacerbation, dyspnea; Rare: bronchospasm.

Gastrointestinal disorders: Common: abdominal pain, nausea, dyspepsia, diarrhea, flatulence, constipation, vomiting; Uncommon: gastritis, gastrointestinal ulcer (with or without bleeding or perforation), melena, hematemesis; Rare: stomatitis, glossitis, pancreatitis, exacerbation of Crohn’s disease and ulcerative colitis.

Hepatobiliary disorders: Uncommon: increased liver enzymes; Rare: hepatitis, jaundice, liver failure.

Skin and subcutaneous tissue disorders: Common: skin rash; Uncommon: photosensitivity reactions, alopecia; Rare: bullous eruptions, erythema multiforme.

Renal and urinary disorders: Uncommon: impaired renal function (elevated serum creatinine and/or urea), acute renal failure; Rare: nephrotic syndrome, papillary necrosis, interstitial nephritis.

General disorders and administration site conditions: Uncommon: fatigue, edema; Rare: asthenia.

If any adverse reactions occur, the use of the drug should be discontinued and a doctor should be consulted.

Drug Interactions

Concomitant use of Diphenadrim^® Kombi with the following drugs is contraindicated: Other NSAIDs, including selective COX-2 inhibitors (increased risk of adverse effects, particularly gastrointestinal ulcers and bleeding).

Monoamine oxidase inhibitors (MAOIs): Concomitant use with diphenhydramine is contraindicated or should be avoided due to the risk of intensified and prolonged anticholinergic (drying) and sedative effects. A minimum 14-day washout period after discontinuing an MAOI is recommended before starting this drug.

Alcohol, sedatives, hypnotics, and other CNS depressants: Diphenhydramine may potentiate the sedative effects of alcohol, barbiturates, benzodiazepines, opioids, antipsychotics, and other drugs with CNS depressant activity. This combination can lead to dangerous impairment of mental and physical abilities required for performing potentially hazardous tasks such as driving or operating machinery. Concurrent use should be avoided.

Anticoagulants and Antiplatelet Agents: NSAIDs like ibuprofen may enhance the effects of anticoagulants (e.g., warfarin) and antiplatelet agents (e.g., clopidogrel, acetylsalicylic acid), increasing the risk of gastrointestinal bleeding. Close monitoring of coagulation parameters is essential if co-administration is unavoidable.

Antihypertensive Agents: NSAIDs may reduce the effect of diuretics, ACE inhibitors, angiotensin II receptor antagonists, and beta-blockers. The risk of acute renal impairment is increased, especially in dehydrated patients or the elderly. Blood pressure and renal function should be monitored regularly.

Corticosteroids: Concomitant use increases the risk of gastrointestinal ulceration or bleeding.

Methotrexate: NSAIDs may decrease the elimination of methotrexate, leading to increased plasma levels and toxicity, especially with high-dose methotrexate therapy. Caution is advised, and blood counts should be monitored.

Lithium: Ibuprofen may decrease the renal clearance of lithium, leading to increased plasma lithium levels and potential toxicity. Serum lithium levels should be monitored frequently if co-administration is necessary.

Selective Serotonin Reuptake Inhibitors (SSRIs): Concomitant use with NSAIDs increases the risk of gastrointestinal bleeding.

Anticholinergic Drugs: Concurrent use with other drugs possessing anticholinergic properties (e.g., tricyclic antidepressants, antiparkinsonian agents, atropine) may lead to an increase in anticholinergic side effects such as dry mouth, blurred vision, urinary retention, and constipation.

Overdose

Symptoms of overdose are primarily a consequence of the effects of the two components and may be additive or synergistic. Ibuprofen overdose may manifest as abdominal pain, nausea, vomiting, lethargy, drowsiness, headache, nystagmus, blurred vision. In severe cases, metabolic acidosis, gastrointestinal bleeding, hypotension, acute renal failure, respiratory depression, coma, and convulsions may occur. Diphenhydramine overdose symptoms can include marked sedation, drowsiness, dizziness, nervousness, dry mouth, fixed dilated pupils, flushing, gastrointestinal disturbances, urinary retention, tachycardia, and in severe cases, hallucinations, convulsions, CNS depression (especially in children), respiratory collapse, and death.

Treatment: There is no specific antidote. Management is supportive and symptomatic. Gastric lavage or administration of activated charcoal may be considered within one hour of ingestion of a potentially toxic amount. Forced diuresis is not recommended due to the potential for fluid overload. Hemodialysis is not effective for removing ibuprofen or diphenhydramine due to their high protein binding. Close monitoring of vital signs, electrolyte balance, and renal function is essential. In cases of severe CNS depression, physostigmine may be considered but should be used with extreme caution due to the risk of inducing seizures. Seek immediate medical attention in case of suspected overdose.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.