Analgodex

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANALGODEX

Composition:

Active substance: dexketoprofen;

1 ml of solution contains 25 mg of dexketoprofen (in the form of dexketoprofen trometamol);

Excipients: sodium chloride, ethanol 96%, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Dexketoprofen. ATC code M01AE17.

Pharmacological properties.

Pharmacodynamics.

Dexketoprofen trometamol is the tromethamine salt of (S)-(+)-2-(3-benzoylphenyl) propionic acid, exerting analgesic, anti-inflammatory, and antipyretic effects and belonging to the class of nonsteroidal anti-inflammatory drugs (NSAIDs).

The mechanism of action is based on reducing the synthesis of prostaglandins by inhibiting the activity of cyclooxygenase. Specifically, the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2 is inhibited, from which prostaglandins PGE1, PGE2, PGF2α, PGD2, as well as prostacyclin PGI2 and thromboxanes TxА2 and TxВ2 are formed. In addition, inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of the drug. Dexketoprofen has been shown to inhibit the activity of both cyclooxygenase-1 and cyclooxygenase-2. It has been established that dexketoprofen has a pronounced analgesic effect with rapid onset and reaching maximum effect within the first 45 minutes in various types of pain, including pain associated with surgical procedures (orthopedic and gynecological surgeries, abdominal surgeries), musculoskeletal pain (acute back pain), and renal colic. The duration of analgesic effect after administration of 50 mg of dexketoprofen is generally 8 hours. It is known that the use of dexketoprofen allows a significant reduction in the dose of opioids when used concomitantly to manage postoperative pain. When patients receiving morphine via a patient-controlled analgesia device for postoperative pain relief were also administered dexketoprofen, they required significantly less morphine (by 30–45%) compared to patients who received placebo along with morphine.

Pharmacokinetics.

After intramuscular administration of dexketoprofen, maximum concentration is reached on average within 20 minutes (10–45 minutes). It has been demonstrated that after single intramuscular or intravenous administration of 25–50 mg of dexketoprofen, the area under the concentration-time curve (AUC) is dose-proportional. Multiple-dose pharmacokinetic studies have shown that AUC and Cmax after the last intramuscular or intravenous dose do not differ from those after single administration, indicating absence of accumulation. Similar to other drugs with a high degree of plasma protein binding (99%), the volume of distribution of dexketoprofen averages 0.25 L/kg. The distribution half-life is approximately 0.35 hours, and the elimination half-life is 1–2.7 hours. Metabolism of dexketoprofen occurs mainly via conjugation with glucuronic acid, followed by renal excretion. After administration of dexketoprofen, only the S-(+) optical isomer is detected in urine, indicating absence of transformation of the drug into the R-(–) optical isomer. After administration of single and multiple doses, the exposure to the drug in elderly healthy volunteers (aged 65 years and older) was significantly higher (up to 55%) compared to younger individuals, although no statistically significant differences were observed in maximum concentration or time to reach it. The mean elimination half-life increased (by up to 48%), and the total clearance decreased.

Preclinical safety data.

Standard preclinical studies — including studies on pharmacological safety, genotoxicity, and immunopharmacology — revealed no particular hazard to humans. Chronic toxicity studies in animals identified the no-observed-adverse-effect level (NOAEL), which was 2 times higher than the recommended human dose. When higher doses were administered to monkeys, the main adverse reactions were fecal blood, reduced body weight gain, and, at the highest dose, gastrointestinal tract pathologies such as erosions. These reactions occurred at doses where drug exposure was 14–18 times higher than at the maximum recommended human dose. Carcinogenicity studies in animals have not been conducted.

Like all NSAIDs, dexketoprofen may lead to embryonic or fetal death in animals, either directly by affecting embryonic/fetal development or indirectly via harmful effects on the gastrointestinal tract of the mother.

Clinical characteristics.

Indications.

Symptomatic treatment of moderate to severe acute pain when oral administration of the drug is inappropriate, for example in postoperative pain, renal colic, and back pain.

Contraindications.

• Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the medicinal product;
• if substances with similar action, such as acetylsalicylic acid or other NSAIDs, provoke in the patient the development of asthma attacks, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria, or angioedema;
• if during treatment with ketoprofen or fibrates the patient experienced photoallergic or phototoxic reactions;
• active phase of peptic ulcer disease or gastrointestinal bleeding, suspicion thereof, or recurrent peptic ulcer disease, or gastrointestinal bleeding in history (two or more confirmed episodes of ulcer or bleeding), or chronic dyspepsia;
• gastrointestinal bleeding, other bleeding in active phase, or increased bleeding tendency;
• gastrointestinal bleeding or perforation in history associated with previous NSAID therapy;
• Crohn’s disease or ulcerative colitis;
• history of bronchial asthma;
• severe heart failure;
• moderate to severe renal impairment (creatinine clearance < 50 ml/min);
• severe hepatic impairment (10–15 points on the Child–Pugh scale);
• hemorrhagic diathesis and other coagulation disorders;
• third trimester of pregnancy and breastfeeding period.

Due to ethanol content, ANALEDODEX is not intended for neuroaxial (intrathecal or epidural) administration.

Interaction with other medicinal products and other types of interactions.

The following combinations with dexketoprofen are not recommended:

Other NSAIDs. Concomitant use of multiple NSAIDs increases the risk of gastrointestinal ulcers and gastrointestinal bleeding due to mutual potentiation of their effects. It is not recommended to use other NSAIDs, including salicylates in high doses (≥ 3 g/day), simultaneously with dexketoprofen.

Anticoagulants. NSAIDs enhance the effect of anticoagulants, such as warfarin, due to the high degree of binding of dexketoprofen to plasma proteins, as well as inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be carried out under strict medical supervision and with appropriate laboratory monitoring.

Heparin. The risk of bleeding increases (due to inhibition of platelet function and damage to the gastric and duodenal mucosa) when NSAIDs are used concomitantly with heparin. If concomitant use is necessary, it should be carried out under strict medical supervision and with appropriate laboratory monitoring.

Corticosteroids. Concomitant use of NSAIDs with corticosteroids increases the risk of gastrointestinal ulcers and gastrointestinal bleeding.

Lithium. Some NSAIDs increase lithium levels in blood, which may lead to intoxication (due to reduced renal excretion of lithium). Therefore, lithium blood levels should be monitored at the start of dexketoprofen treatment, during dose adjustment, or upon discontinuation of the drug.

High-dose methotrexate (more than 15 mg per week). Due to reduced renal clearance of methotrexate under the influence of NSAIDs, its negative effect on the blood system is generally enhanced.

Hydantoin derivatives and sulfonamides. The toxicity of these substances may be increased when used concomitantly with NSAIDs.

NSAIDs should be used with caution when combined with:

• diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycosides, and angiotensin II receptor antagonists. Dexketoprofen reduces the effectiveness of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., in dehydrated patients or elderly individuals), concomitant use of cyclooxygenase inhibitors with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycosides may worsen renal function, which is usually reversible. When using dexketoprofen with any diuretic, ensure the patient is not dehydrated, and monitor renal function at the beginning of treatment;
• low-dose methotrexate (less than 15 mg per week): due to reduced renal clearance of methotrexate under the influence of NSAIDs, its negative effect on the blood system is enhanced. During the first weeks of concomitant use, weekly blood tests should be performed. Treatment should be conducted under strict medical supervision, even in patients with mild renal impairment or in elderly patients;
• pentoxifylline: there is a risk of bleeding. Monitoring should be intensified, and bleeding time should be checked more frequently;
• zidovudine: there is a risk of increased toxic effect on erythrocytes due to effects on reticulocytes, which after 1 week of NSAID use may lead to severe anemia. Blood tests and reticulocyte count should be performed within 1–2 weeks after starting NSAID treatment;
• sulfonylurea agents: NSAIDs may enhance the hypoglycemic effect of these agents by displacing sulfonylureas from plasma protein binding sites.

Potential interactions should be considered when using with:

• beta-blockers: NSAIDs may reduce their antihypertensive effect by inhibiting prostaglandin synthesis;
• cyclosporine and tacrolimus: possible increase in nephrotoxicity due to the effect of NSAIDs on renal prostaglandins. Renal function should be monitored during combination therapy;
• thrombolytic agents: increased risk of bleeding;
• antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding;
• probenecid: possible increase in dexketoprofen plasma concentration, likely due to inhibition of renal tubular secretion and glucuronide conjugation of the drug, requiring dose adjustment of dexketoprofen;
• cardiac glycosides: NSAIDs may increase glycoside plasma concentrations;
• mifepristone: due to the theoretical possibility of reduced mifepristone efficacy under the influence of NSAID prostaglandin synthetase inhibitors, NSAIDs should be administered only 8–12 days after mifepristone therapy;
• quinolones: animal studies have shown that high-dose quinolone derivatives used in combination with NSAIDs increase the risk of seizures;
• tenofovir: concomitant use with NSAIDs may increase plasma concentrations of blood urea nitrogen and creatinine; therefore, renal function should be monitored to assess possible synergistic effects of these medicinal products;
• deferasirox: concomitant use with NSAIDs increases the risk of gastrointestinal toxicity. Careful patient monitoring is required when using the drug concomitantly with deferasirox;
• pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, particular caution is required when using NSAIDs at high doses. Patients with mild to moderate renal impairment (creatinine clearance 45–79 ml/min) should avoid using NSAIDs for two days before and two days after pemetrexed administration.

Special precautions for use.

Use with caution in patients with a history of allergic conditions. Avoid combining ANAlGODEX with other NSAIDs, including selective COX-2 inhibitors. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Gastrointestinal effects

Gastrointestinal bleeding, ulceration, or perforation, sometimes fatal, have been reported at various stages of NSAID therapy, regardless of the presence of initial symptoms or a history of serious gastrointestinal disorders. If gastrointestinal bleeding occurs, the drug should be discontinued. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, particularly in patients with a history of peptic ulcer, especially complicated by bleeding or perforation, and in elderly patients.

The incidence of adverse reactions associated with NSAID use, particularly gastrointestinal bleeding and perforation (sometimes fatal), is higher in elderly patients. Treatment in such patients should begin with the lowest effective dose. NSAIDs should be used cautiously in patients with a history of gastrointestinal disorders due to the risk of exacerbation.

Before initiating dexketoprofen trometamol, ensure that patients with a history of esophagitis, gastritis, and/or peptic ulcer disease are in remission. Patients with gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored during treatment for possible complications, particularly gastrointestinal bleeding. NSAIDs should be used cautiously in patients with inflammatory bowel diseases (e.g., ulcerative colitis, Crohn’s disease) due to the risk of disease flare-up.

For such patients and those taking low-dose acetylsalicylic acid or other agents increasing gastrointestinal risk, consider concomitant use of gastroprotective agents such as misoprostol or proton pump inhibitors.

Patients, especially elderly individuals, with a history of gastrointestinal adverse reactions should be advised to inform their physician of any unusual gastrointestinal symptoms, particularly gastrointestinal bleeding, especially during the initial stages of treatment.

Renal effects

Use with caution in patients with impaired renal function, as NSAIDs may cause deterioration of kidney function, fluid retention, and peripheral edema. Due to the increased risk of nephrotoxicity, ANAlGODEX should be used cautiously in patients receiving diuretics or those at risk of hypovolemia. Adequate fluid intake should be maintained during treatment to prevent dehydration and associated increased toxicity.

Like all NSAIDs, dexketoprofen may increase plasma urea and creatinine levels. Similar to other prostaglandin synthesis inhibitors, its use may be associated with renal adverse reactions, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure.

Renal function disturbances occur most frequently in elderly patients.

Hepatic effects

Use with caution in patients with impaired liver function. Like other NSAIDs, dexketoprofen may cause transient, mild increases in certain liver function tests, as well as significant elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). If such increases occur, ANAlGODEX should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular effects

Patients with hypertension and/or mild to moderate congestive heart failure should be closely monitored due to the potential for fluid retention and peripheral edema.

Particular caution is required in patients with a history of heart disease, especially previous episodes of heart failure, as dexketoprofen use may increase the risk of heart failure (fluid retention and edema have been reported with NSAID use).

Clinical and epidemiological data suggest that the use of certain NSAIDs, particularly at high doses and for prolonged periods, may slightly increase the risk of arterial thrombotic events such as myocardial infarction or stroke. Data are insufficient to exclude this risk with dexketoprofen. Therefore, dexketoprofen should be prescribed only after careful assessment in patients with uncontrolled hypertension, congestive heart failure, confirmed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Careful evaluation is also recommended before initiating long-term treatment in patients with cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes, or smoking.

Non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. It is known that concomitant use of dexketoprofen trometamol and prophylactic doses of low-molecular-weight heparin in the postoperative period does not affect coagulation parameters. However, patients receiving dexketoprofen trometamol together with anticoagulants (e.g., warfarin, other coumarins, or heparins) should be closely monitored.

Cardiovascular adverse events occur most frequently in elderly patients.

Skin reactions

Very rare cases of serious skin reactions (some fatal) have been reported with NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The highest risk occurs early in treatment, particularly during the first month. If skin rashes, mucosal lesions, or other signs of hypersensitivity occur, ANAlGODEX should be discontinued.

Other information

Special caution is required when prescribing the drug to patients:

• with inherited porphyrin metabolism disorders (e.g., acute intermittent porphyria);
• with dehydration;
• immediately after major surgical procedures.

If long-term dexketoprofen use is deemed necessary by the physician, regular monitoring of liver and kidney function is recommended.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If signs of severe hypersensitivity occur after drug administration, treatment should be discontinued immediately. Depending on symptoms, appropriate management should be initiated under medical supervision.

Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyps have a higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to other individuals. This medication may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

Severe infectious complications involving skin and soft tissues may occur during varicella infection. The role of NSAIDs in exacerbating this infection cannot currently be excluded. Therefore, dexketoprofen is not recommended during varicella.

The drug should be administered cautiously in patients with coagulation disorders, systemic lupus erythematosus, or mixed connective tissue diseases.

Like other NSAIDs, dexketoprofen may mask symptoms of infectious diseases during treatment. In isolated cases, NSAID use has been associated with the worsening of soft tissue infections. Therefore, if signs or symptoms of bacterial infection appear or worsen during ANAlGODEX use, patients should seek immediate medical attention.

Each ANAlGODEX ampoule contains 200 mg of ethanol (per dose), equivalent to 5 mL of beer or 2.08 mL of wine. The product may adversely affect individuals suffering from alcoholism. The ethanol content should be considered when using the drug during the first and second trimesters of pregnancy, in high-risk patients (e.g., those with liver disease), and in patients with epilepsy. ANAlGODEX contains less than 1 mmol of sodium (23 mg) per dose and is practically sodium-free.

Use during pregnancy or breastfeeding.

ANAlGODEX is contraindicated during the third trimester of pregnancy and during breastfeeding.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. It is known that using prostaglandin synthesis inhibitors early in pregnancy increases the risk of miscarriage and congenital malformations such as cardiac defects and gastroschisis. The absolute risk of cardiovascular abnormalities increases from <1% to approximately 1.5%. This risk is considered to increase with higher drug doses and longer treatment duration.

In animal studies, prostaglandin synthesis inhibitors have caused increased pre- and post-implantation loss and higher embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, a higher incidence of fetal developmental abnormalities, including cardiovascular malformations, was observed. However, animal studies with dexketoprofen trometamol did not reveal reproductive organ toxicity.

Starting from week 20 of pregnancy, dexketoprofen use may cause oligohydramnios due to fetal renal dysfunction. This effect may occur soon after starting treatment and is usually reversible upon discontinuation. Dexketoprofen should not be prescribed during the first and second trimesters of pregnancy except in cases of extreme necessity. If used in women attempting to conceive or during the first and second trimesters, the dose should be as low as possible and the duration as short as possible. Prenatal monitoring for oligohydramnios may be advisable after exposure to dexketoprofen for several days starting from week 20 of pregnancy. Treatment should be discontinued if oligohydramnios is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may cause:

Risks to the fetus:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• impaired renal function (see above);

Risks near term for mother and child:

• prolonged bleeding time and anti-aggregatory effects, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed labor and prolonged delivery.

Dexketoprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding

There are no data on the passage of dexketoprofen into breast milk.

ANAlGODEX is contraindicated during breastfeeding.

Fertility

Like all other NSAIDs, dexketoprofen may impair female fertility and should not be used in women attempting to conceive. If a woman experiences difficulties conceiving or is undergoing infertility evaluation, discontinuation of ANAlGODEX should be considered. Dexketoprofen use during the first and second trimesters of pregnancy may be considered only in cases of extreme necessity.

Ability to influence reaction speed when driving or operating machinery.

Dizziness, drowsiness, and increased fatigue may occur during ANAlGODEX use. In such cases, the ability to react quickly, orient in traffic situations, and drive or operate machinery may be impaired.

Method of Administration and Dosage

Adults

The recommended dose is 50 mg administered at 8–12 hour intervals. If necessary, the next dose may be given after 6 hours. The maximum daily dose should not exceed 150 mg. ANALEDOL is intended for short-term treatment and should only be used during episodes of acute pain (no longer than 2 days). Patients should be switched to oral analgesics as soon as possible, if feasible. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. For moderate to severe postoperative pain, ANALEDOL may be used as indicated in the same recommended doses in combination with opioid analgesics.

Elderly Patients

Dose adjustment is generally not required. However, due to physiological decline in renal function, a lower maximum daily dose—50 mg—is recommended in patients with mild renal impairment.

Patients with Hepatic Impairment

For patients with mild to moderate liver disease (5–9 points on the Child–Pugh scale), the maximum daily dose should be reduced to 50 mg, and liver function should be closely monitored. ANALEDOL is contraindicated in patients with severe hepatic impairment (10–15 points on the Child–Pugh scale).

Patients with Renal Impairment

For patients with mild renal impairment (creatinine clearance 50–80 mL/min), the maximum daily dose should be reduced to 50 mg. ANALEDOL is contraindicated in patients with moderate to severe renal impairment (creatinine clearance < 50 mL/min).

Children and Adolescents

ANALEDOL should not be used in children and adolescents due to lack of data on efficacy and safety.

Intramuscular Injection

The injection solution should be administered slowly and deeply into the muscle.

Intravenous Infusion

For intravenous infusion, the contents of one ampoule (2 mL) should be diluted in 30–100 mL of 0.9% sodium chloride solution, glucose solution, or Ringer’s lactate solution. The infusion solution should be prepared under aseptic conditions, avoiding exposure to natural daylight. The prepared solution must be clear. The infusion should be administered over 10–30 minutes. The prepared solution must be protected from exposure to natural daylight.

Dexketoprofen diluted in 0.9% sodium chloride solution or glucose solution may be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine, and theophylline.

Dexketoprofen must not be mixed in the infusion solution with promethazine or pentazocine.

Intravenous Injection (Bolus Administration)

If necessary, the contents of one ampoule (2 mL of injection solution) may be administered intravenously over at least 15 seconds.

The medicinal product may be mixed in small volumes (e.g., in a syringe) with injection solutions of heparin, lidocaine, morphine, and theophylline.

Dexketoprofen must not be mixed in small volumes (e.g., in a syringe) with dopamine, promethazine, pentazocine, pethidine, or hydrocortisone solutions due to the formation of a white precipitate.

When administered intramuscularly or intravenously by injection, the medicinal product should be administered immediately after being drawn from the ampoule. The solution for intravenous infusion should be used immediately after preparation.

No changes in active substance content due to adsorption have been observed during storage of diluted solutions in polyethylene bags or in administration devices made of ethylene-vinyl acetate, cellulose propionate, low-density polyethylene, or polyvinyl chloride.

ANALEDOL is intended for single use only; any remaining solution should be discarded. Prior to administration, ensure that the solution is clear and colorless. Solutions containing visible foreign particles must not be used.

Children

ANALEDOL should not be used in children and adolescents due to lack of data on efficacy and safety.

Overdose

Symptoms of overdose are unknown. Similar medicinal products may cause gastrointestinal disturbances (vomiting, anorexia, abdominal pain) and nervous system effects (drowsiness, dizziness, disorientation, headache). In case of accidental overdose, symptomatic treatment appropriate to the patient's condition should be initiated immediately. Dexketoprofen trometamol is eliminated from the body by dialysis.

Adverse Reactions

For classification of the frequency of adverse reactions, the following categories are used:

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), or not known (cannot be estimated from available data).

Below are listed adverse effects categorized by organ systems and frequency of occurrence, whose association with dexketoprofen trometamol, based on clinical trial data, is considered at least possible, as well as adverse reactions reported after marketing of dexketoprofen trometamol products.

Blood / Lymphatic system

Uncommon: Anaemia.
Very rare: Neutropenia, thrombocytopenia.

Immune system

Rare: Laryngeal edema.
Very rare: Anaphylactic reactions, including anaphylactic shock.

Nutritional and metabolic disorders

Rare: Hyperglycemia, hypoglycemia, hypertriglyceridemia, anorexia, loss of appetite.

Psychiatric disorders

Uncommon: Insomnia, restlessness.

Nervous system

Uncommon: Headache, dizziness, somnolence.
Rare: Paresthesia, syncope.

Eye disorders

Uncommon: Blurred vision.

Ear and labyrinth disorders

Uncommon: Vertigo.
Rare: Tinnitus.

Cardiac disorders

Uncommon: Palpitations.
Rare: Extrasystoles, tachycardia.

Vascular disorders

Uncommon: Arterial hypotension, flushing.
Rare: Arterial hypertension, superficial thrombophlebitis.

Respiratory, thoracic and mediastinal disorders

Rare: Bradypnea.
Very rare: Bronchospasm, dyspnea.

Gastrointestinal disorders

Common: Nausea, vomiting.
Uncommon: Abdominal pain, dyspepsia, diarrhea, constipation, vomiting with blood, dry mouth.
Rare: Peptic ulcer, gastrointestinal bleeding or perforation.
Very rare: Pancreatitis.

Hepatobiliary disorders

Rare: Hepatitis, jaundice.
Very rare: Hepatocellular pathology.

Skin and subcutaneous tissue disorders

Uncommon: Dermatitis, pruritus, rash, increased sweating.
Rare: Urticaria, acne.
Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), angioneurotic edema, facial edema, photosensitivity.

Musculoskeletal and connective tissue disorders

Rare: Muscle rigidity, joint stiffness, muscle cramps, back pain.

Renal and urinary disorders

Rare: Acute renal failure, polyuria, renal pain, ketonuria, proteinuria.
Very rare: Nephritis, nephrotic syndrome.

Reproductive system disorders

Rare: Menstrual disorders, prostatic gland function disorders.

General disorders and administration site conditions

Common: Injection site pain, injection site reactions including inflammation, hematoma, bleeding.
Uncommon: Hot flushes, fatigue, pain, chills, asthenia, malaise.
Rare: Tremor, peripheral edema.

Laboratory findings

Rare: Abnormal liver function tests.

The most frequently reported adverse reactions were gastrointestinal disorders.

Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, especially in elderly patients, may occur. Available data indicate that nausea, vomiting, diarrhea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melena, vomiting with blood, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may occur during treatment. Gastritis is observed less frequently. Edema, arterial hypertension, and heart failure, which may be induced by NSAID use, have also been reported. As with other NSAIDs, aseptic meningitis, generally occurring in patients with systemic lupus erythematosus or mixed connective tissue disorders, and blood disorders (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia) may occur. Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), are possible.

Clinical trial results and epidemiological data indicate that the use of certain NSAIDs, particularly at high doses and over prolonged periods, is associated with a slightly increased risk of thrombotic events such as myocardial infarction and stroke.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

After dilution, the solution should be stored for up to 24 hours at 2–8 °C.

Incompatibilities.

ANALGODEX must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, meperidine, or hydrocortisone, as a white precipitate forms.

Diluted infusion solutions, prepared as described in the section "Dosage and Administration. Intravenous infusion," must not be mixed with promethazine or pentazocine.

Packaging.

2 ml in a vial, 5 vials in a blister pack, 1 blister pack in a cardboard box.

Prescription category.

Prescription only.

Manufacturer.

Steril-Jen Life Sciences (P) Ltd.

Manufacturer's address and place of business.

No. 45, Mangalam Main Road, Villianur Commune, Puducherry, 605110, India.