Instructions Naklofen solution for injection 75 mg ampoule 3 ml No. 5
Composition
active ingredient: diclofenac;
3 ml of solution (1 ampoule) contains diclofenac sodium – 75 mg;
Excipients: benzyl alcohol, propylene glycol, sodium metabisulfite (E 223), sodium hydroxide, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent solution from colorless to slightly yellow, practically free of mechanical impurities.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Diclofenac. ATC code M01A B05.
Pharmacological properties
Pharmacodynamics
Naklofen is a nonsteroidal drug with pronounced analgesic/anti-inflammatory properties. It is an inhibitor of prostaglandin synthetase (cyclooxygenase). Diclofenac sodium in vitro at concentrations equivalent to those achieved in humans does not inhibit the biosynthesis of proteoglycans in cartilage tissue. When used concomitantly with opioids for the relief of postoperative pain, Naklofen significantly reduces the need for opioids.
In rheumatic diseases, the anti-inflammatory and analgesic properties of the drug cause a clinical response characterized by a marked reduction in signs and symptoms: pain at rest and during movement, morning stiffness and swelling of the joints, and improvement in their function. In post-traumatic and postoperative conditions with the presence of inflammation, Naklofen also relieves pain and swelling.
Pharmacokinetics
Absorption
After administration of 75 mg diclofenac by intramuscular injection, absorption begins immediately and the mean maximum plasma concentration of approximately 2.558 ± 0.968 μg/ml (2.5 μg/ml ≡ 8 μmol/l) is reached after approximately 20 minutes. The extent of absorption is linearly proportional to the dose.
When 75 mg diclofenac is administered by intravenous infusion over 2 hours, the mean maximum plasma concentration is approximately 1.875 ± 0.436 μg/ml (1.9 μg/ml ≡ 5.9 μmol/l). Shorter infusion times lead to higher maximum plasma concentrations, while longer infusions lead to a plateau concentration proportional to the infusion rate after 3–4 hours. In contrast to the corresponding results for oral administration, when the drug is administered as a suppository or intramuscular injection, the plasma concentration decreases rapidly after reaching maximum levels.
Bioavailability
The area under the concentration curve (AUC) after intramuscular or intravenous administration is approximately twice as large as after oral or rectal administration, because this route allows for the avoidance of first-pass metabolism through the liver.
Distribution
99.7% of diclofenac is bound to proteins, mainly to albumin (99.4%).
Diclofenac enters the synovial fluid, where maximum concentrations are reached 2–4 hours after peak plasma levels. The expected elimination half-life from synovial fluid is 3 to 6 hours. 2 hours after peak plasma levels, the concentration of diclofenac in the synovial fluid exceeds that in plasma and remains higher for up to 12 hours.
Diclofenac was detected in low concentrations (100 ng/ml) in breast milk from one breastfeeding woman. The estimated amount of drug reaching the infant in breast milk is equivalent to 0.03 mg/kg/day.
Metabolism
Biotransformation of diclofenac occurs partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and methoxylation, leading to the formation of several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, but their activity is much less pronounced than for diclofenac.
Breeding
The total systemic clearance of diclofenac in plasma is 263 ± 56 ml/min (mean ± SD). The terminal half-life in plasma is 1–2 hours. Four metabolites, including two active ones, also have short half-lives in plasma – 1–3 hours. Approximately 60% of the administered dose is excreted in the urine as the glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% is excreted as unchanged substance. The remainder of the dose is eliminated as metabolites via the bile and feces.
Special patient groups
Elderly patients
No difference in drug absorption, metabolism, or excretion was observed based on patient age, except that in five elderly patients, a 15-minute intravenous infusion resulted in plasma concentrations that were 50% higher than those observed in young healthy volunteers.
In patients with impaired renal function, no accumulation of unchanged active substance is expected based on the kinetics of the drug after a single dose when the usual dosage regimen is followed. In patients with creatinine clearance less than 10 ml/min, the plasma levels of hydroxymetabolites are approximately 4 times higher than in healthy volunteers. However, the metabolites are ultimately excreted in the bile.
Patients with liver disease
In patients with chronic hepatitis or compensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.
Indication
The drug, when administered intramuscularly, is intended for the treatment of:
- inflammatory and degenerative forms of rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, vertebral pain syndrome, non-articular rheumatism;
- acute attacks of gout;
- renal and biliary colic;
- pain and swelling after injuries and surgeries;
- severe migraine attacks.
The drug, when administered as an intravenous infusion, is intended for the treatment or prevention of postoperative pain.
Contraindication
- Known hypersensitivity to the active substance, sodium metabisulfite or to any of the other ingredients of the drug.
- History of gastrointestinal bleeding or perforation associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
- Active ulcer/bleeding or history of recurrent ulcer/bleeding (two or more separate episodes of established ulceration or bleeding).
- Liver failure.
- Renal failure (glomerular filtration rate (GFR) < 15 ml/min/1.73 m2).
- Congestive heart failure (NYHA II-IV).
- III trimester of pregnancy.
- Like other NSAIDs, diclofenac is contraindicated in patients in whom the use of ibuprofen, acetylsalicylic acid or other NSAIDs provokes attacks of bronchial asthma, angioedema, urticaria or acute rhinitis/nasal polyps, or allergy-like symptoms.
- Inflammatory bowel diseases (e.g. Crohn's disease or ulcerative colitis).
- Acute stomach or intestinal ulcer; gastrointestinal bleeding or perforation.
- High risk of developing postoperative bleeding, blood clotting disorders, hemostasis disorders, hematopoietic disorders or cerebrovascular bleeding.
- Treatment of perioperative pain during coronary artery bypass grafting (or the use of a cardiopulmonary bypass machine).
- Ischemic heart disease in patients with angina pectoris or previous myocardial infarction.
- Cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks.
- Peripheral artery disease.
In this dosage form, the drug is contraindicated in children.
For intravenous use only.
- Concomitant use of NSAIDs or anticoagulants (including low-dose heparin).
- History of hemorrhagic diathesis, confirmed or suspected cerebrovascular bleeding in history.
- Surgeries associated with a high risk of bleeding.
- History of bronchial asthma.
- Moderate or severe renal impairment (serum creatinine > 160 μmol/l).
- Hypovolemia or dehydration from any cause.
Interaction with other medicinal products and other types of interactions
The following are interactions observed with the use of Naklofen, solution for injection, and/or other dosage forms of diclofenac.
Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.
Digoxin: Diclofenac may increase plasma concentrations of digoxin when used concomitantly. Monitoring of serum digoxin levels is recommended.
Diuretics and antihypertensives: As with other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensives (e.g. beta-blockers, angiotensin-converting enzyme (ACE) inhibitors) may lead to a reduction in their antihypertensive effect due to inhibition of the synthesis of vasodilator prostaglandins. Therefore, such a combination should be used with caution and patients, especially the elderly, should be closely monitored for blood pressure. Patients should be adequately hydrated and monitoring of renal function is recommended at the beginning of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors due to the increased risk of nephrotoxicity (see section 4.4).
Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increases in serum potassium, and patients should be monitored more frequently.
Anticoagulants and antithrombotic agents: Caution is advised as concomitant administration may increase the risk of bleeding. Although clinical studies have not shown an effect of diclofenac on the activity of anticoagulants, there is some evidence of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly.
Therefore, careful monitoring of patients receiving diclofenac and anticoagulants is recommended and, if necessary, adjustment of the anticoagulant dosage. Like other NSAIDs, diclofenac in high doses may temporarily inhibit platelet aggregation.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Antidiabetic agents. Clinical studies have shown that diclofenac can be used concomitantly with oral antidiabetic agents without affecting their clinical effect. However, isolated cases of both hypoglycemic and hyperglycemic effects have been reported, requiring a change in the dosage of antidiabetic agents during treatment with diclofenac. Such conditions require monitoring of blood glucose levels, which is a precautionary measure during concomitant therapy.
There have also been isolated reports of metabolic acidosis with concomitant use with diclofenac, especially in patients with pre-existing renal impairment.
Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended that diclofenac be administered at least 1 hour before or 4–6 hours after colestipol/cholestyramine.
Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. Caution should be exercised when NSAIDs, including diclofenac, are administered less than 24 hours before methotrexate, as this may increase the blood concentration of methotrexate and increase its toxicity. Serious toxicity has been reported when methotrexate and NSAIDs, including diclofenac, were administered within 24 hours of each other. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
Cyclosporine: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine through its effects on renal prostaglandins. Therefore, diclofenac should be used at lower doses than in patients not taking cyclosporine.
Tacrolimus: When NSAIDs are used with tacrolimus, there is a possible increased risk of nephrotoxicity, which may be mediated through the renal antiprostaglandin effects of NSAIDs and calcineurin inhibitors, therefore diclofenac should be used at lower doses than in patients not taking tacrolimus.
Quinolone antibacterials. There are isolated reports of seizures that may result from the concomitant use of quinolones and NSAIDs. This may occur in patients with or without a history of epilepsy or seizures. Therefore, caution should be exercised when considering the use of quinolones in patients already receiving NSAIDs.
Phenytoin: When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to the expected increase in phenytoin exposure.
Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce GFR, and increase plasma glycoside levels.
Mifepristone: NSAIDs should not be used for 8–12 days after mifepristone administration, as NSAIDs may reduce its effect.
Potent CYP2C9 inhibitors: Caution is advised when co-administering diclofenac with potent CYP2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in maximum plasma concentrations and exposure to diclofenac due to inhibition of its metabolism.
Probenecid: Medicines containing probenecid may delay the elimination of diclofenac.
CYP2C9 inducers: Caution is advised when co-administering diclofenac with CYP2C9 inducers (e.g. rifampicin). This may lead to a significant increase in plasma concentrations and exposure to diclofenac.
Application features
General
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control (relieve) symptoms (see section “Method of administration and dosage” and gastrointestinal and cardiovascular risks below).
The use of Naklofen with systemic NSAIDs, including selective COX-2 inhibitors, should be avoided due to the lack of any synergistic benefit and the possibility of developing additional side effects (see section "Interaction with other medicinal products and other types of interactions").
The use of NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic bleeding. Close medical supervision and caution are recommended when prescribing diclofenac after gastrointestinal surgery.
The renal effects of NSAIDs include fluid retention with oedema and/or hypertension. Therefore, diclofenac should be used with caution in patients with impaired cardiac function and other conditions predisposing to fluid retention. Caution should also be exercised in patients taking concomitant diuretics or ACE inhibitors or who are at increased risk of hypovolaemia.
In rare cases, as with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac. Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that may cause myocardial infarction. Symptoms of such reactions may include chest pain associated with an allergic reaction to diclofenac.
Due to its pharmacodynamic properties, diclofenac, like other NSAIDs, may mask the signs and symptoms of infection.
Injection site reactions
Instructions for intramuscular injection must be strictly followed to avoid adverse reactions at the injection site, which may lead to muscle weakness, muscle paralysis, hypoesthesia, skin embolism (Nicolaou syndrome) and necrosis at the injection site.
Injection site reactions have been reported following intramuscular administration of diclofenac, including injection site necrosis and drug embolism of the skin, also known as Nicolau's syndrome (especially after inadvertent subcutaneous injection). Appropriate needle and injection technique should be used for intramuscular administration of diclofenac.
Effects on the digestive system
Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and can occur at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal events, have been reported with NSAIDs, including diclofenac. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients taking diclofenac, the drug should be discontinued.
As with all NSAIDs, including diclofenac, close medical supervision is necessary; particular caution should be exercised when prescribing diclofenac to patients with symptoms suggestive of gastrointestinal disorders, or with a history of gastric or intestinal ulcer, bleeding or perforation (see section "Adverse reactions"). The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing doses of NSAIDs, including diclofenac, and in patients with a history of ulcer, particularly complicated by bleeding or perforation.
Elderly patients have an increased frequency of adverse reactions when using NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
To reduce the risk of gastrointestinal toxicity in patients with a history of ulcer, especially those complicated by bleeding or perforation, and in elderly patients, treatment should be initiated and maintained at the lowest effective dose.
For such patients, as well as patients who require concomitant use of medicinal products containing low doses of acetylsalicylic acid (ASA) or other medicinal products that are likely to increase the risk of adverse effects on the digestive system, combination therapy with protective medicinal products (e.g. proton pump inhibitors or misoprostol) should be considered.
Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding).
Caution is also required in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agents (e.g. ASA) or SSRIs (see section “Interaction with other medicinal products and other forms of interaction”).
Close medical supervision and special caution should be exercised when prescribing diclofenac to patients with ulcerative colitis or Crohn's disease, as their condition may worsen.
Cardiovascular and cerebrovascular effects
Clinical trial and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and for long periods, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). The patient's need for diclofenac to relieve symptoms and the response to therapy should be reassessed periodically, especially if the duration of therapy exceeds 4 weeks.
Diclofenac should only be prescribed to patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) after careful clinical evaluation. Since the cardiovascular risks of diclofenac may increase with increasing dose and duration of treatment, it should be used for the shortest possible period and at the lowest effective dose. The patient's need for diclofenac should be periodically reviewed for symptom relief and response to therapy. Use with caution in patients over 65 years of age.
Diclofenac is not recommended for use in patients with uncontrolled hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease, and should only be used if necessary after a careful risk/benefit assessment and only at doses up to 100 mg/day. A similar assessment should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus and smoking).
Patients should be advised to monitor for symptoms of serious arterial thromboembolic events (chest pain, shortness of breath, weakness, speech disorders), which may occur without warning. If such an event occurs, patients should seek medical attention immediately.
Effect on hematological parameters
With prolonged use of diclofenac, as with other NSAIDs, monitoring of complete blood counts is recommended.
Like other NSAIDs, Naklofen may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis or hematological disorders should be carefully monitored.
Effect on the liver
Close medical supervision is required if diclofenac must be prescribed to patients with impaired liver function, as their condition may worsen.
With the use of NSAIDs, including diclofenac, the level of one or more liver enzymes may increase. During long-term treatment, regular monitoring of liver function should be prescribed as a precautionary measure.
If liver function abnormalities persist or worsen, if clinical signs or symptoms suggestive of progressive liver disease or if other manifestations are observed (e.g. eosinophilia, rash), diclofenac should be discontinued.
In addition to elevated liver enzymes, there have been rare reports of severe hepatic reactions, including jaundice and fulminant hepatitis, hepatic necrosis and hepatic failure, which in some cases have resulted in fatal outcomes.
In patients treated with diclofenac, the course of diseases such as hepatitis may occur without prodromal symptoms.
Caution is necessary if diclofenac is to be used in patients with hepatic porphyria, due to the possibility of provoking an attack.
Effects on the kidneys
Due to the importance of prostaglandins in maintaining renal blood flow, long-term treatment with high doses of NSAIDs, including diclofenac, often leads to edema and hypertension.
Since fluid retention and oedema have been reported with NSAIDs, including diclofenac, special care should be taken in patients with impaired cardiac or renal function, a history of hypertension, the elderly, patients receiving concomitant therapy with diuretics or drugs that significantly affect renal function, and patients with significant depletion of extracellular fluid volume for any reason, e.g. before or after major surgery (see section 4.8). In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually results in a return to pre-treatment status.
Effects on the skin
Serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (see section 4.8), have been reported very rarely in association with the use of NSAIDs. The risk of these reactions appears to be highest at the beginning of therapy, in most cases within the first month of treatment.
The use of diclofenac should be discontinued at the first appearance of skin rashes, mucosal lesions, or any other signs of hypersensitivity.
Systemic lupus erythematosus (SLE) and mixed connective tissue diseases.
Patients with SLE and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.
Patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (nasal polyps), chronic obstructive pulmonary disease or chronic respiratory infections (especially those associated with allergic rhinitis-like symptoms) are more likely than others to experience reactions to NSAIDs that resemble asthma exacerbations (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Therefore, special precautions (emergency medical attention) are recommended for such patients. This also applies to patients with allergic reactions to other substances, manifested by skin reactions, itching or urticaria.
Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can provoke the development of bronchospasm in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.
Special precautions for inactive ingredients
Benzyl alcohol: Do not use in premature infants and newborns. May cause toxic and allergic reactions in infants and children under 3 years of age.
Metabisulfites may cause allergic-type reactions, including anaphylactic symptoms and bronchospasm in susceptible individuals, especially those with a history of asthma and allergies.
Sodium: contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially sodium-free.
Use during pregnancy or breastfeeding
Pregnancy
Unless absolutely necessary, diclofenac should not be used in women planning pregnancy or in the first and second trimesters of pregnancy. From the 20th week of pregnancy, the use of diclofenac may cause oligohydramnios due to fetal renal dysfunction. This pathology may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of narrowing of the ductus arteriosus after treatment in the second trimester, which in most cases disappeared after discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, diclofenac should be prescribed only if the expected benefit to the mother outweighs the potential risk to the fetus and only in the minimum effective dose, and the duration of treatment should be as short as possible.
It may be advisable to monitor the fetus for oligohydramnios and ductus arteriosus after diclofenac exposure for several days, starting from the 20th week of pregnancy. If oligohydramnios or ductus arteriosus is detected, diclofenac should be discontinued.
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryo/foetal development. Epidemiological data suggest an increased risk of miscarriage and/or cardiac malformations and gastroschisis following use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations was increased from less than 1% to approximately 1.5%.
It is possible that the risk increases with dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo/fetal lethality.
In addition, an increased incidence of various malformations, including those of the cardiovascular system, was recorded in animals treated with a prostaglandin synthesis inhibitor during organogenesis.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus in the following ways:
- cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
- impaired renal function, which may progress to renal failure with oligohydramnios (see above);
Effects at the end of pregnancy on the mother and newborn:
- possible prolongation of bleeding time, antiplatelet effect, which can be observed even at very low doses;
- suppression of uterine contractions, leading to delayed or prolonged labor.
Therefore, Naklofen is contraindicated in the third trimester of pregnancy.
Breastfeeding period
Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, diclofenac should not be used by women during breastfeeding to avoid undesirable effects on the infant.
Fertility
As with other NSAIDs, diclofenac may impair female fertility and is therefore not recommended for use in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of infertility, discontinuation of diclofenac should be considered.
Based on animal studies, impaired male reproductive function cannot be excluded. The relevance of these data to humans has not been established.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience visual disturbances, dizziness, vertigo, drowsiness, central nervous system disorders, lethargy or fatigue during therapy with Naklofen should not drive or operate machinery.
Method of administration and doses
The drug Naklofen, solution for injection, should not be used for more than 2 days; if necessary, treatment can be continued with the drug Naklofen in another dosage form (tablets or suppositories).
Intramuscular injection
To prevent damage to nerves or other tissues at the site of intramuscular injection, the following rules must be followed.
The usual dose is 75 mg (1 ampoule) per day, which should be administered by deep injection into the upper outer sector of the gluteus maximus muscle. In severe cases (e.g. colic), the daily dose can be increased to two injections of 75 mg, with an interval of several hours between them (1 injection in each buttock). Alternatively, 75 mg of the solution for injection can be combined with other dosage forms of Naklofen (e.g. tablets or suppositories) up to a maximum total daily dose of 150 mg of diclofenac.
In the setting of a migraine attack, clinical experience is limited to cases with an initial administration of 1 ampoule of 75 mg, the dose should be administered if possible immediately after the use of 100 mg suppositories on the same day (if necessary). The total daily dose should not exceed 175 mg on the first day.
There are no data available on the use of Naklofen for the treatment of migraine attacks lasting more than 1 day.
Intravenous infusions
Immediately before the start of intravenous infusion, Naklofen should be diluted in 100-500 ml of 0.9% sodium chloride solution or 5% glucose solution. Both solutions should be buffered with sodium bicarbonate solution (0.5 ml of 8.4% solution or 1 ml of 4.2%). Only clear solutions should be used.
Naklofen, solution for injection, should not be administered as an intravenous painful injection.
Two alternative dosing regimens for Naklofen, solution for injection, are recommended:
- for the treatment of moderate and severe postoperative pain, it is necessary to administer a solution of 75 mg continuously for 30 minutes to 2 hours; if necessary, the treatment can be repeated after 4–6 hours, but the dose should not exceed 150 mg per day;
- for the prevention of postoperative pain, a loading dose of 25–50 mg should be administered 15 minutes to 1 hour after surgery, followed by a continuous infusion of approximately 5 mg/hour up to a maximum daily dose of 150 mg.
Elderly patients
Although the pharmacokinetics of diclofenac are not altered to any clinically relevant extent in the elderly, NSAIDs should be used with caution in these patients, who are generally more susceptible to adverse reactions. In particular, it is recommended to use the lowest effective dose in debilitated elderly patients or in patients with low body mass and to monitor patients for gastrointestinal bleeding during treatment with NSAIDs (see section 4.4).
The recommended maximum daily dose of Naklofen is 150 mg.
Existing cardiovascular disease or significant risk factors
Diclofenac is contraindicated in patients with established congestive heart failure, ischemic heart disease, peripheral arterial disease and/or cerebrovascular accident (see section "Contraindications").
Patients with congestive heart failure or significant cardiovascular risk factors should only be prescribed diclofenac after careful clinical evaluation. Since the cardiovascular risks of diclofenac may increase with increasing dose and duration of treatment, it should be used for the shortest possible period and at the lowest effective dose (see section "Special instructions").
Kidney dysfunction
Diclofenac is contraindicated in patients with severe renal impairment (GFR <15 mL/min/1.73 m2) (see section "Contraindications").
No specific studies have been conducted in patients with hepatic impairment, therefore no dose adjustment recommendations can be made. Diclofenac should be used with caution in patients with mild to moderate renal impairment (see section 4.4).
Liver dysfunction
The use of diclofenac is contraindicated in patients with hepatic insufficiency (see section "Contraindications").
Special studies on
