Neodolpasse (Solution) Instructions for Use

Marketing Authorization Holder

Fresenius Kabi Deutschland, GmbH (Germany)

Manufactured By

Fresenius Kabi Austria, GmbH (Austria)

ATC Code

M01AB55 (Diclofenac in combination with other drugs)

Active Substances

Diclofenac (Rec.INN registered by WHO)

Orphenadrine (Prop.INN proposed by WHO)

Dosage Form

Neodolpasse

Infusion solution 75 mg+30 mg/250 ml: fl. 1, 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Infusion solution transparent, colorless.

Excipients: malic acid – 3185 mg, acetylcysteine – 250 mg, disodium edetate dihydrate – 25 mg, sodium hydroxide – 1900-1987.5 mg, water for injections – up to 250 ml.
Electrolytes: about 47.5 mmol Na⁺/250 ml.
Theoretical osmolarity: approximately 303 mOsmol/l.

250 ml – glass bottles (type II according to Eur.Pharm.) (1) with or without holders – cardboard boxes.
250 ml – glass bottles (type II according to Eur.Pharm.) (5) with or without holders – cardboard boxes.
250 ml – glass bottles (type II according to Eur.Pharm.) (10) with or without holders – cardboard boxes.

Clinical-Pharmacological Group

Nonsteroidal anti-inflammatory drug. Diclofenac in combination with other drugs

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs. Non-steroidal anti-inflammatory and antirheumatic drugs

Pharmacological Action

A combined medicinal product containing the NSAID diclofenac and the centrally acting muscle relaxant orphenadrine.

Diclofenac has analgesic, antipyretic, and anti-inflammatory effects. By non-selectively inhibiting COX-1 and COX-2, it disrupts the metabolism of arachidonic acid and the synthesis of prostaglandins, which are the main link in the development of inflammation.

Orphenadrine is a centrally acting muscle relaxant that reduces pathologically increased muscle tone, and has parasympatholytic, local anesthetic, and moderate antihistamine effects.

Pharmacokinetics

Diclofenac

The highest plasma concentrations are reached immediately after infusion, leading to a rapid onset of effect. After IV administration of 75 mg of diclofenac, its C_max in plasma is 1.9 µg/ml for more than 2 hours and is linearly dependent on the administered dose. Binding to plasma proteins is 99.7%, mainly to albumin (99.4%). The apparent V_d is 0.12-0.17 l/kg. Diclofenac penetrates into the synovial fluid, where its C_max is reached 2-4 hours later than in plasma. The total systemic plasma clearance of diclofenac is 263±56 ml/min. The terminal T_1/2 is 1-2 hours. About 60% of the dose is excreted in the urine as glucuronic conjugates of the unchanged active substance, as well as metabolites, most of which are also glucuronic conjugates. Less than 1% of diclofenac is excreted unchanged. The remaining part of the dose is excreted as metabolites with bile.

Orphenadrine

C_max in plasma is reached as early as 2 minutes after IV administration. During infusion, it is rapidly distributed to all organs and tissues of the body. Binding to plasma proteins is about 90%. Most of the orphenadrine is metabolized and predominantly excreted by the kidneys. T_1/2 is 14 hours.

Indications

Short-term treatment of pain syndrome in the following diseases: acute vertebrogenic pain syndrome, radicular and vertebrogenic pain; postoperative pain syndrome.

ICD codes

Dosage Regimen

Administer intravenously as an infusion. The standard adult dose is one 250 ml bottle once daily. Infuse the solution over a period of 30 to 60 minutes.

Use the shortest duration necessary for pain control. Limit treatment to a maximum of 2-3 days for postoperative pain. For acute vertebrogenic pain, limit treatment to the acute phase only.

Do not administer intramuscularly or intra-arterially. Ensure adequate hydration of the patient before and during treatment to mitigate renal risks.

For elderly patients or those with low body weight, use the lowest effective dose. Monitor renal function in patients with mild to moderate renal impairment (CrCl 30-60 ml/min).

Do not use in patients with severe renal impairment (CrCl <30 ml/min). Do not use in patients with severe hepatic impairment or active liver disease.

Inspect the solution visually for particulate matter and discoloration prior to administration. Do not mix with other drugs in the same infusion set. Use the solution immediately after opening the bottle.

Discontinue treatment immediately if signs of gastrointestinal bleeding, hepatotoxicity, or severe skin reactions occur.

Adverse Reactions

From the cardiovascular system tachycardia, development of edema, arterial hypertension, heart failure, palpitations, chest pain, myocardial infarction.

From the blood and lymphatic system inhibition of platelet aggregation, risk of bleeding, thrombocytopenia, purpura, leukopenia, pancytopenia, agranulocytosis, anemia (including hemolytic and aplastic anemia), pannyelopathy, eosinophilia.

From the nervous system fatigue, headache, vertigo, dizziness, drowsiness, restlessness, agitation, sensory disturbances (including paresthesia), memory disorders, disorientation, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, stroke.

From the organ of vision: visual disturbances (blurred vision or diplopia), pain, dry eyes, temporary accommodation disturbances, increased intraocular pressure.

From the organ of hearing and labyrinthine disorders: vertigo, temporary hearing impairment, tinnitus.

From the respiratory system : rhinitis, asthma (including dyspnea), pneumonitis.

From the digestive system dry mouth, epigastric pain, loss of appetite, nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, anorexia, flatulence, abdominal distension, gastritis, gastrointestinal bleeding (including occult), peptic ulcers, with and without bleeding and/or perforation, hematemesis, blood in stool, hemorrhagic diarrhea, complaints of symptoms in the lower abdomen (e.g., nonspecific hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal lesion, occurrence of diaphragm-like intestinal strictures, pancreatitis, ischemic colitis.

From the kidneys and urinary tract urinary retention, urinary incontinence, sodium and water retention, acute renal failure, hematuria, interstitial nephritis, nephrotic syndrome, proteinuria, papillary necrosis.

From the skin and subcutaneous tissue: reduced secretion of sweat glands (heat accumulation), skin redness, rash, exanthema, urticaria, reversible alopecia, bullous rash, eczema, erythroderma, purpura (including allergic purpura), Stevens-Johnson syndrome (multiform exudative erythema), Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, photosensitivity reactions, itching.

Infections and infestations: worsening of infectious inflammation (e.g., development of necrotizing fasciitis).

Vascular disorders: arterial hypertension, vasculitis.

Local reactions pain at the injection site, induration at the injection site, vein irritation, thrombophlebitis, edema, necrosis at the injection site, abscess at the injection site.

From the immune system: hypersensitivity, systemic anaphylactic and anaphylactoid reactions, including arterial, hypotension, shock and bronchospasm, angioedema (including facial edema), tongue edema, internal laryngeal edema including tracheal stenosis, dyspnea.

From the liver and biliary tract: temporary increase in transaminase activity, liver failure of varying severity, hepatitis with and without jaundice, fulminant hepatitis, liver necrosis, acute liver failure.

From the reproductive system and mammary glands impotence, burning in the genital area in women.

From the psyche euphoria, nervousness, sleep disorders, confusion, emotional lability, disorientation, depression, insomnia, anxiety, nightmares, irritability, psychotic disorders.

Contraindications

Hypersensitivity to diclofenac sodium, orphenadrine citrate; complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinusitis and intolerance to acetylsalicylic acid or other NSAIDs (including history); erosive and ulcerative changes in the gastric or duodenal mucosa in the acute stage, bleeding from the gastrointestinal tract, perforation of the gastrointestinal tract, recurrent peptic ulcer (history of two or more episodes of perforation or bleeding), gastrointestinal bleeding or perforation in history, associated with previous therapy or NSAID use, gastrointestinal stenosis, megacolon, paralytic ileus; hematological diseases (e.g., hematopoietic disorders, bone marrow damage, porphyria, hemorrhagic diathesis), cerebrovascular bleeding or other types of acute bleeding, chronic heart failure, functional class II-IV according to NYHA classification, coronary artery disease, peripheral arterial diseases, cerebrovascular diseases, tachyarrhythmia, patients with an increased risk of arterial thrombosis and thromboembolism; active liver disease, liver failure; progressive kidney diseases, severe renal failure (CrCl<30 ml/min); difficulty urinating (prostate adenoma, prostate hypertrophy, bladder obstruction); myasthenia gravis; cardiospasm; glaucoma; third trimester of pregnancy; children under 18 years of age; uncontrolled arterial hypertension; inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase; confirmed hyperkalemia; period after coronary artery bypass surgery; bulbar paralysis.

With caution

History of gastric and duodenal ulcer, ulcerative colitis and Crohn’s disease outside of exacerbation, presence of Helicobacter pylori infection, history of liver disease, hepatic porphyria, chronic renal failure (CrCl 30-60 ml/min), significant reduction in circulating blood volume (including after surgery), elderly patients (over 65 years) (including those receiving diuretics, debilitated patients and those with low body weight), bronchial asthma, seasonal allergic rhinitis, edema of the nasal mucosa (including with nasal polyps), chronic obstructive pulmonary disease, chronic infectious diseases of the respiratory tract (especially associated with allergic rhinitis-like symptoms), cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, smoking, long-term use of NSAIDs, alcoholism, severe somatic diseases, systemic connective tissue diseases (SLE and mixed connective tissue disease), conditions with systolic pressure below 100 mm Hg, mental illnesses, epilepsy, Parkinson’s disease, simultaneous use of glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

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. It is necessary to carefully monitor the condition of women who use diclofenac in the first or second trimester of pregnancy.

Use in the third trimester of pregnancy is contraindicated.

Breastfeeding should be discontinued during treatment.

Use in Hepatic Impairment

Use is contraindicated in active liver diseases, liver failure.

Use with caution in history of liver disease, hepatic porphyria.

Use in Renal Impairment

Use is contraindicated in progressive kidney diseases, severe renal failure (CrCl<30 ml/min).

Use with caution in chronic renal failure (CrCl 30-60 ml/min).

Pediatric Use

Use is contraindicated in children under 18 years of age.

Geriatric Use

Elderly patients receiving NSAIDs have an increased risk of side effects, especially gastrointestinal bleeding or perforation, which can be fatal. Special attention should be paid to elderly patients in connection with the general clinical condition. In particular, the lowest effective dose should be used in debilitated elderly patients and elderly patients with low body weight.

Special Precautions

Side effects can be minimized by using the lowest effective dose for the shortest period necessary to control symptoms.

Concomitant use of diclofenac and systemic NSAIDs, including selective COX-2 inhibitors, should be avoided.

Concomitant alcohol consumption may lead to an increased risk of gastrointestinal bleeding.

If a patient receiving diclofenac develops gastrointestinal bleeding or an ulcer, the use of diclofenac should be discontinued.

Caution is recommended in patients simultaneously receiving drugs that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants, e.g., warfarin, selective serotonin reuptake inhibitors or antiplatelet agents, e.g., acetylsalicylic acid.

Effect on ability to drive vehicles and operate machinery

Patients who experience visual disturbances, dizziness, drowsiness, vertigo or other CNS disorders while using this combination should refrain from driving vehicles, operating machinery, and engaging in activities requiring quick psychomotor reactions.

Drug Interactions

Combination with other NSAIDs – increased side effects (combination should be avoided), acetylsalicylic acid – reversible decrease in serum concentration, additional risk of gastrointestinal disorders (combination should be avoided); antiplatelet agents and anticoagulants – increased risk of bleeding (caution is recommended, careful monitoring of blood coagulation); cardiac glycosides (e.g., digoxin) – increased content of glycosides in the blood (recommended – constant monitoring of glycoside content in blood plasma and dose adjustment); ACE inhibitors, angiotensin II antagonists – decrease in hypotensive effect (recommended blood pressure monitoring, increased risk of nephrotoxicity, hyperkalemia (recommended monitoring of kidney function and potassium content, adequate hydration is necessary); antihypertensive drugs – decrease in hypotensive effect (recommended blood pressure monitoring); diuretics – decrease in hypotensive effect (recommended blood pressure monitoring), increased risk of nephrotoxicity (recommended monitoring of kidney function, adequate hydration is necessary); potassium-sparing diuretics – potentiation (control of serum potassium is necessary); corticosteroids – increased frequency of gastrointestinal ulceration or bleeding; selective serotonin reuptake inhibitors – increased risk of gastrointestinal bleeding; bisphosphonates – increased risk of gastrointestinal bleeding and development of renal failure (when using clodronate) (monitoring recommended); pentoxifylline, alcohol – increased risk of gastrointestinal bleeding (combination should be avoided); cyclosporines – increased risk of gastrointestinal disorders, nephro- and hepatotoxicity (combination should be avoided); triamterene – possible development of renal failure; tacrolimus – possible development of renal failure (combination should be avoided); potent cytochrome P450 2C9 inhibitors (e.g., sulfinpyrazone and voriconazole ) – significant increase in diclofenac plasma concentration (recommended reduction of diclofenac dose and monitoring); moclobemide – enhancement of diclofenac action; with cholestyramine, colestipol – delay or reduction of diclofenac absorption (diclofenac should be taken 1 hour before or 4-6 hours after taking these drugs); methotrexate – increased toxicity of methotrexate due to inhibition of clearance and increased methotrexate blood levels (caution is recommended when administering NSAIDs, including diclofenac, less than 24 hours before or after methotrexate administration); lithium, phenytoin – increased plasma concentrations (recommended constant monitoring of plasma levels and dose adjustment); oral antidiabetic drugs – possible fluctuations in blood glucose levels (recommended – enhanced monitoring of blood glucose levels); quinolones – possible convulsions (combination should be avoided); prostaglandin analogues – a single case of myocardial necrosis and anaphylactic shock has been described; zidovudine – increased risk of hematological toxicity; amantadine, monoamine oxidase inhibitors, quinidine, tricyclic antidepressants – enhancement of anticholinergic action; levodopa – enhancement of antiparkinsonian effect; tranquilizers – decrease in tranquilizer blood levels due to accelerated metabolism; dextropropoxyphene – tremor, disorientation, anxiety; thyroxine – effect on the results of thyroxine and other thyroid hormone determinations (increase in plasma levels of protein-bound thyroxine); chlorpromazine – increased risk of hypothermia.

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.