Dialrapid^® (Powder) Instructions for Use

Marketing Authorization Holder

MRA, CJS (Lithuania)

Manufactured By

Mipharm S.p.A. (Italy)

ATC Code

M01AB05 (Diclofenac)

Active Substance

Diclofenac (Rec.INN registered by WHO)

Dosage Form

Dialrapid®

Powder for preparation of oral solution 50 mg: sachet 900 mg 3, 6, 9, 12, 21, 24 or 30 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of oral solution from white to light yellow, homogeneous, with a specific odor; the reconstituted solution is clear, slightly opalescent, with a specific odor.

Excipients: glyceryl dibehenate – 2 mg, sodium saccharin – 5 mg, anise flavor – 15 mg, potassium bicarbonate – 22 mg, mint flavor – 35 mg, aspartame – 50 mg, mannitol – 721 mg.

900 mg – sachets^× (3) – cardboard packs.
900 mg – sachets^× (6) – cardboard packs.
900 mg – sachets^× (9) – cardboard packs.
900 mg – sachets^× (12) – cardboard packs.
900 mg – sachets^× (21) – cardboard packs.
900 mg – sachets^× (24) – cardboard packs.
900 mg – sachets^× (30) – cardboard packs.

^× hermetically sealed sachets made of paper/aluminum/polyethylene or paper/polyethylene terephthalate/aluminum/low-density polyethylene with child-resistant opening protection.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID, a derivative of phenylacetic acid. It has a pronounced anti-inflammatory, analgesic, and moderate antipyretic effect.

The mechanism of action is associated with the inhibition of COX activity, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins that play an important role in the pathogenesis of inflammation, pain, and fever.

The analgesic effect is due to two mechanisms: peripheral (indirectly, through suppression of prostaglandin synthesis) and central (due to inhibition of prostaglandin synthesis in the central and peripheral nervous system).

In vitro, at concentrations equivalent to those achieved in the treatment of patients, it does not inhibit the biosynthesis of proteoglycans in cartilage tissue.

In rheumatic diseases, it reduces joint pain at rest and during movement, as well as morning stiffness and joint swelling, and helps to increase the range of motion.

It reduces post-traumatic and postoperative pain, as well as inflammatory edema.

In post-traumatic and postoperative inflammatory conditions, it quickly relieves pain (occurring both at rest and during movement), reduces inflammatory edema and postoperative wound edema.

It inhibits platelet aggregation. With long-term use, it has a desensitizing effect.

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract. Food intake slows down the rate of absorption, but the extent of absorption does not change. About 50% of the active substance is metabolized during the “first pass” through the liver.

The time to reach C_max in plasma after oral administration is 2-4 hours, depending on the dosage form used. The concentration of the active substance in plasma is linearly dependent on the applied dose.

It does not accumulate. Plasma protein binding is 99.7% (primarily with albumin). It penetrates into the synovial fluid; C_max is reached 2-4 hours later than in plasma.

It is extensively metabolized to form several metabolites, two of which are pharmacologically active, but to a lesser extent than Diclofenac.

The systemic clearance of the active substance is approximately 263 ml/min. T_1/2 from plasma is 1-2 hours, from synovial fluid – 3-6 hours. Approximately 60% of the dose is excreted by the kidneys as metabolites, less than 1% is excreted unchanged in the urine, the remainder is excreted as metabolites with bile.

Indications

Inflammatory and degenerative diseases of the musculoskeletal system, including rheumatoid, juvenile, chronic arthritis; ankylosing spondylitis and other spondyloarthropathies; osteoarthritis; gouty arthritis; bursitis, tenosynovitis; pain syndrome from the spine (lumbago, sciatica, ossalgia, neuralgia, myalgia, arthralgia, radiculitis); post-traumatic postoperative pain syndrome accompanied by inflammation (for example, in dentistry and orthopedics); algodysmenorrhea; inflammatory processes in the pelvis (including adnexitis); infectious and inflammatory diseases of the ENT organs with severe pain syndrome (as part of complex therapy): pharyngitis, tonsillitis, otitis.

Isolated fever is not an indication for the use of the drug.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

ICD codes

Dosage Regimen

Select the minimum effective dose for the shortest possible duration.

For adults, the typical dose is 100-150 mg/day, administered in 2 or 3 divided doses.

For mild to moderate pain, initiate with a 50 mg dose up to three times daily.

For primary dysmenorrhea, the recommended daily dosage is 50-150 mg in divided doses.

For children 6 years and older and adolescents, the daily dose is 1-2 mg/kg body weight.

Administer the pediatric daily dose in 2 or 3 divided doses.

Do not exceed the maximum daily dose of 150 mg for any patient.

For geriatric patients and those with renal or hepatic impairment, use the lowest effective dose with increased monitoring.

Prepare the oral solution immediately before use by emptying the sachet contents into a glass of water.

Stir well until the powder is completely dissolved.

Administer the solution preferably before meals.

Adverse Reactions

From the digestive system: frequently – abdominal pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, decreased appetite, anorexia, increased activity of serum aminotransferases; rarely – gastritis, gastrointestinal bleeding, hematemesis, melena, diarrhea with blood, gastric and intestinal ulcers (with or without bleeding or perforation), hepatitis, jaundice, impaired liver function; very rarely – stomatitis, glossitis, esophageal lesions, formation of diaphragm-like strictures in the intestine, colitis (non-specific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease), constipation, pancreatitis, fulminant hepatitis, liver necrosis, hepatic failure.

From the nervous system: frequently – headache, dizziness; rarely – drowsiness; very rarely – sensory disturbances, including paresthesia, memory disorders, tremor, convulsions, anxiety, acute cerebrovascular accidents, aseptic meningitis; very rarely – disorientation, depression, insomnia, nightmares, irritability, mental disorders.

From the sensory organs: frequently – vertigo; very rarely – visual disturbances (blurred vision), diplopia, hearing impairment, tinnitus, dysgeusia.

From the skin and subcutaneous tissues: frequently – skin rash; rarely – urticaria; very rarely – bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, pruritus, hair loss, photosensitivity reactions; purpura, Henoch-Schönlein purpura.

From the urinary system: very rarely – acute renal failure, hematuria, proteinuria, tubulointerstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoietic system: very rarely – thrombocytopenia, leukopenia, hemolytic anemia, aplastic anemia, agranulocytosis.

Allergic reactions: rarely – hypersensitivity, anaphylactic/anaphylactoid reactions, including decreased blood pressure and shock; very rarely – angioedema (including facial edema).

From the cardiovascular system: very rarely – palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction. There is evidence of a slight increase in the risk of cardiovascular thrombotic complications (e.g., myocardial infarction), especially with long-term use of diclofenac in high doses (daily dose more than 150 mg).

From the respiratory system: rarely – asthma (including shortness of breath); very rarely – pneumonitis.

General reactions: rarely – edema.

Contraindications

Hypersensitivity to diclofenac and excipients of the drug used; “aspirin triad” (attacks of bronchial asthma, urticaria and acute rhinitis when taking acetylsalicylic acid or other NSAIDs); erosive and ulcerative lesions of the gastrointestinal tract in the acute phase; severe renal failure (creatinine clearance <30 ml/min), progressive kidney disease; severe hepatic failure, active liver disease; clinically confirmed coronary artery disease, diseases of peripheral arteries and cerebral vessels, uncontrolled arterial hypertension, decompensated heart failure; cerebrovascular bleeding; hemostasis disorders; early postoperative period after coronary artery bypass surgery; confirmed hyperkalemia; third trimester of pregnancy; breastfeeding; children under 6 years of age; children and adolescents under 18 years of age (for prolonged-release dosage forms).

With caution

Suspected gastrointestinal disease; history of gastrointestinal bleeding and ulcer perforation (especially in elderly patients), Helicobacter pylori infection, ulcerative colitis, Crohn’s disease; mild and moderate hepatic impairment, hepatic porphyria (Diclofenac may provoke porphyria attacks); in patients with gastrointestinal anastomosis (risk of anastomosis integrity impairment), after gastrointestinal surgery (patient condition should be monitored); in patients with bronchial asthma, seasonal allergic rhinitis, edema of the nasal mucosa (including with nasal polyps), COPD, chronic infectious diseases of the respiratory tract (especially associated with allergic rhinitis-like symptoms); cardiovascular diseases (including coronary artery disease, cerebrovascular diseases, compensated heart failure, peripheral vascular diseases); renal impairment, including chronic renal failure (creatinine clearance 30-60 ml/min); dyslipidemia/hyperlipidemia; diabetes mellitus; arterial hypertension; significant decrease in circulating blood volume of any etiology (e.g., in the periods before and after major surgical interventions); risk of thrombosis (including myocardial infarction and stroke); systemic connective tissue diseases; elderly patients, especially debilitated or with low body weight (Diclofenac should be used in the minimum effective dose); simultaneous use with drugs that increase the risk of gastrointestinal bleeding, including systemic corticosteroids (e.g., prednisolone), anticoagulants (e.g., warfarin), antiplatelet agents (e.g., clopidogrel, acetylsalicylic acid), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline); simultaneous treatment with diuretics or other drugs that can impair renal function; when treating smoking patients or patients who abuse alcohol.

Use in Pregnancy and Lactation

Use in the first and second trimesters of pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. Diclofenac (like other prostaglandin synthesis inhibitors) is contraindicated in the third trimester of pregnancy (possible suppression of uterine contractility and premature closure of the arterial duct in the fetus).

Although Diclofenac is excreted in breast milk in small amounts, use during lactation (breastfeeding) is not recommended. If use during lactation is necessary, breastfeeding should be discontinued.

Since Diclofenac (like other NSAIDs) may have a negative effect on fertility, it is not recommended for use in women planning pregnancy.

Diclofenac should be discontinued in patients undergoing examination and treatment for infertility.

Use in Hepatic Impairment

Contraindications: severe hepatic failure, active liver disease.

Use in Renal Impairment

Contraindications: severe renal failure (creatinine clearance <30 ml/min), progressive kidney disease.

Pediatric Use

Contraindicated in children under 6 years of age.

Contraindicated in children and adolescents under 18 years of age for prolonged-release dosage forms.

Geriatric Use

Use with particular caution in elderly patients.

Special Precautions

During treatment, systematic monitoring of liver and kidney function, peripheral blood picture is necessary.

The anti-inflammatory effect of diclofenac may complicate the diagnosis of infectious processes.

Alcohol consumption is not recommended during treatment.

Effect on ability to drive vehicles and machinery

During treatment, a decrease in the speed of psychomotor reactions is possible. If visual clarity deteriorates after using eye drops, you should not drive a car or engage in other potentially hazardous activities.

Drug Interactions

Potent CYP2C9 inhibitors – when co-administering diclofenac and potent CYP2C9 inhibitors (such as voriconazole), an increase in diclofenac serum concentration and enhanced systemic effects may occur due to inhibition of diclofenac metabolism.

Lithium, digoxin – an increase in the concentration of lithium and digoxin in plasma may occur. Monitoring of serum lithium and digoxin concentrations is recommended.

Diuretic and antihypertensive agents – when used concomitantly with diuretics and antihypertensive drugs (for example, beta-blockers, ACE inhibitors), Diclofenac may reduce their antihypertensive effect.

Cyclosporine – the effect of diclofenac on prostaglandin activity in the kidneys may enhance the nephrotoxicity of cyclosporine.

Drugs that can cause hyperkalemia – concomitant use of diclofenac with potassium-sparing diuretics, cyclosporine, tacrolimus and trimethoprim may lead to an increase in plasma potassium levels (in case of such a combination, this indicator should be monitored frequently).

Quinolone antibacterial agents – there are isolated reports of seizures in patients receiving quinolone derivatives and Diclofenac simultaneously.

NSAIDs and corticosteroids – with simultaneous systemic use of diclofenac and other systemic NSAIDs or corticosteroids, the frequency of adverse events (in particular, from the gastrointestinal tract) may increase.

Anticoagulants and antiplatelet agents – an increased risk of bleeding cannot be excluded when diclofenac is used concomitantly with drugs of these groups.

Selective serotonin reuptake inhibitors – an increased risk of gastrointestinal bleeding may occur.

Hypoglycemic drugs – cases of both hypoglycemia and hyperglycemia cannot be excluded, which necessitated a change in the dose of hypoglycemic drugs during the use of diclofenac.

Methotrexate – when diclofenac is used within 24 hours before or within 24 hours after methotrexate administration, an increase in methotrexate blood concentration and an enhancement of its toxic effects may occur.

Phenytoin – potentiation of phenytoin’s effect is possible.

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.