Dexil

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXIL (DEXIL)

Composition:

Active substance: dexketoprofen;

1 ml of injection solution contains 36.909 mg of dexketoprofen trometamol, equivalent to 25 mg of dexketoprofen;

Excipients: sodium chloride, 96% ethanol, 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 M01A E17.

Pharmacological properties.

Pharmacodynamics.

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

Mechanism of action

The mechanism of action of NSAIDs is based on reducing prostaglandin synthesis by inhibiting 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.

Pharmacodynamic effects

In experiments on animals and in humans, inhibitory effects of dexketoprofen on the activity of cyclooxygenase-1 and cyclooxygenase-2 have been demonstrated.

Clinical efficacy and safety

Clinical studies using various pain models have demonstrated the analgesic efficacy of dexketoprofen.

The analgesic effect of dexketoprofen after intramuscular and intravenous administration in moderate and severe pain has been studied in various surgical pain models (orthopedic and gynecological/abdominal surgical procedures), as well as in musculoskeletal pain (acute low back pain model) and renal colic.

Studies have shown that the analgesic effect was rapid and reached its peak within the first 45 minutes. 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 opioid dosage when used concomitantly to manage postoperative pain in clinical studies. In patients receiving morphine via a patient-controlled analgesia device and dexketoprofen for postoperative pain management, significantly less morphine (30–45% less) was required compared to patients receiving placebo.

Pharmacokinetics.

Absorption

After intramuscular administration of dexketoprofen trometamol in humans, maximum concentration is reached approximately within 20 minutes (10–45 minutes). It has been demonstrated that after single intramuscular or intravenous administration of 25–50 mg of the drug, the area under the AUC (concentration-time) curve is proportional to the dose.

Distribution

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 half-life is approximately 0.35 hours, and the elimination half-life is 1–2.7 hours. Pharmacokinetic studies of repeated drug administration have demonstrated that AUC and Cmax (mean maximum value) after the last intramuscular or intravenous administration do not differ from those after single administration, indicating absence of drug accumulation.

Metabolism and elimination

After administration of dexketoprofen trometamol, only the S-(+) optical isomer is detected in urine, indicating absence of transformation of the drug into the R-(–) optical isomer in humans. Metabolism of dexketoprofen occurs mainly via conjugation with glucuronic acid followed by renal excretion.

Elderly patients

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 volunteers; however, no statistically significant differences in maximum concentration and time to reach it were observed. The mean elimination half-life increased after single and repeated doses (by up to 48%), and apparent total clearance decreased.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the medicinal product.
• Contraindicated in patients in whom agents of similar action, such as acetylsalicylic acid or other NSAIDs, provoke attacks of bronchial asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria, or angioedema.
• Photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates.
• Active phase of peptic ulcer, gastrointestinal bleeding, or history of peptic ulcer, bleeding, or perforation.
• Chronic dyspepsia.
• Other active bleeding or increased bleeding tendency.
• History of gastrointestinal bleeding or perforation associated with NSAID therapy.
• Crohn’s disease or ulcerative colitis.
• Severe heart failure.
• Moderate to severe renal impairment (creatinine clearance < 59 mL/min).
• Severe hepatic impairment (Child–Pugh score 10–15 points).
• Hemorrhagic diathesis and other coagulation disorders.
• Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).
• Third trimester of pregnancy and breastfeeding period.
• Neuroaxial (intrathecal or epidural) administration is contraindicated due to ethanol content.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of the following agents with NSAIDs is not recommended:

• Other NSAIDs, including selective cyclooxygenase-2 inhibitors and high-dose salicylates (≥ 3 g/day). Concomitant use of multiple NSAIDs increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to mutual enhancement of effects.
• Anticoagulants: NSAIDs enhance the effects of anticoagulants, such as warfarin, due to the high degree of plasma protein binding of dexketoprofen, as well as inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under strict medical supervision and with appropriate laboratory monitoring.
• Heparins: increased risk of bleeding (due to inhibition of platelet function and damage to the gastric and duodenal mucosa). If concomitant use is necessary, it should be performed under strict medical supervision and with appropriate laboratory monitoring.
• Corticosteroids: increased risk of gastrointestinal ulceration and gastrointestinal bleeding.
• Lithium (reports with several NSAIDs): NSAIDs increase lithium blood levels, potentially leading to toxicity (reduced renal lithium excretion). Therefore, lithium blood levels should be monitored at the start of dexketoprofen therapy, during dose adjustments, or upon discontinuation of the drug.
• High-dose methotrexate (≥ 15 mg per week): NSAIDs in general reduce renal methotrexate clearance, thereby enhancing its adverse effects on the blood system.
• Hydantoin derivatives and sulfonamides: possible increase in toxicity of these agents.

Concomitant use of the following agents with NSAIDs requires caution:

• Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists. Dexketoprofen reduces the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., due to dehydration or in elderly patients), concomitant use of agents that inhibit cyclooxygenase with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics 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 (< 15 mg per week): reduced renal clearance of methotrexate due to NSAID use generally enhances its adverse effects on the blood system. Weekly blood tests are required during the first weeks of concomitant use. Treatment should be closely supervised by a physician, especially in patients with even mild renal impairment or in elderly patients.
• Pentoxifylline: risk of bleeding. Monitoring should be intensified, and bleeding time should be checked more frequently.
• Zidovudine: risk of increased hematotoxicity due to effects on reticulocytes, leading to severe anemia after one week of NSAID use. Blood tests and reticulocyte counts should be performed within 1–2 weeks after initiating NSAID therapy.
• Sulfonylurea agents: NSAIDs may enhance the hypoglycemic effect of these agents by displacing them from plasma protein binding sites.
• 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 (SSRIs): increased risk of gastrointestinal bleeding.
• Probenecid: possible increase in plasma concentration of dexketoprofen, 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: there is a theoretical possibility that prostaglandin synthetase inhibitors may reduce the efficacy of mifepristone. However, according to some data, concomitant use of NSAIDs on the day of prostaglandin administration does not reduce the efficacy of mifepristone and prostaglandins regarding cervical ripening or uterine contractions, nor does it reduce the clinical efficacy of medical abortion.
• Quinolone antibiotics: animal studies have shown that high-dose quinolones in combination with NSAIDs increase the risk of seizures.
• Tenofovir: concomitant use with NSAIDs may increase plasma urea nitrogen and creatinine levels; renal function should be monitored to detect potential synergistic effects on kidney function.
• Deferasirox: concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity. Careful clinical monitoring is required when using this combination.
• Pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, particular caution is required when using high-dose NSAIDs. Concomitant use of pemetrexed with NSAIDs should be avoided in patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min) for 2 days before and 2 days after pemetrexed administration.

Special precautions for use.

Use with caution in patients with a history of allergic conditions. Avoid using the medicinal product Dexil in combination with other NSAIDs, including selective cyclooxygenase-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, in some cases fatal, have been reported during treatment with all NSAIDs at any stage of therapy, regardless of the presence of preceding symptoms or a history of serious gastrointestinal disorders. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, particularly complicated by bleeding or perforation, and in elderly patients. Elderly patients have a higher frequency of adverse NSAID reactions, especially gastrointestinal bleeding and perforation, sometimes fatal. Treatment of such patients should be initiated with the lowest possible dose. NSAIDs should be prescribed with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as there is a risk of exacerbation.

For such patients and those taking low-dose acetylsalicylic acid or other agents increasing the risk of gastrointestinal adverse reactions, combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) may be required.

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

Exercise caution when prescribing the medicinal product to patients concurrently using agents that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents like aspirin.

Renal effects

Use with caution in patients with impaired renal function. In such patients, NSAID use may lead to worsening renal function, fluid retention, and edema. Caution is also required in patients receiving diuretic therapy or those at risk of hypovolemia, as there is an increased risk of nephrotoxicity.

During treatment, adequate fluid intake should be ensured to prevent dehydration and potential associated increases in renal toxicity.

Like all NSAIDs, the drug may increase blood urea nitrogen 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 impairment occurs more frequently in elderly patients.

Hepatic effects

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

Hepatic function impairment occurs more frequently in elderly patients.

Cardiovascular and cerebrovascular effects

Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure should be closely monitored due to possible fluid retention and peripheral edema reported during NSAID therapy.

Particular caution is required in treating patients with a history of heart disease, especially previous episodes of heart failure, as the risk of developing heart failure increases during treatment.

Clinical trials and epidemiological data suggest that the use of certain NSAIDs, particularly at high doses and over prolonged periods, may slightly increase the risk of arterial thrombotic events such as myocardial infarction or stroke. Data to exclude such a risk with dexketoprofen are insufficient.

Dexketoprofen should be used only after careful patient assessment in cases of uncontrolled arterial hypertension, congestive heart failure, confirmed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. The same applies before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

All non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. Controlled clinical studies have shown that concomitant use of dexketoprofen and prophylactic doses of low-molecular-weight heparin in the postoperative period does not affect coagulation parameters. However, patients receiving dexketoprofen concurrently with agents affecting hemostasis (e.g., warfarin, other coumarins, or heparins) should be closely monitored by a physician.

Cardiovascular dysfunction occurs more frequently in elderly patients.

Skin effects

There have been reports of very rare cases of serious skin reactions (some fatal) during NSAID use, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The highest risk occurs early in treatment, with most cases appearing within the first month of therapy. If skin rashes, signs of mucosal involvement, or other hypersensitivity symptoms occur, the medicinal product Dexil should be discontinued.

Other warnings

Particular caution is required in patients:

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

If long-term therapy with dexketoprofen is deemed necessary by the physician, regular monitoring of liver and kidney function and complete blood count is recommended.

In very rare cases, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If early signs of severe hypersensitivity reactions occur after dexketoprofen administration, treatment should be discontinued. Depending on symptoms, medically necessary procedures should be prescribed and performed under physician supervision.

Patients with bronchial asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyps have a higher risk of developing allergy to acetylsalicylic acid and/or NSAIDs compared to other patients.

This medicinal product may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

In exceptional cases, chickenpox may lead to serious skin and soft tissue infections. At present, a role of NSAIDs in worsening the course of these infections cannot be excluded. Therefore, the use of dexketoprofen is not recommended in cases of chickenpox.

Dexketoprofen should be administered with caution in patients with coagulation disorders, systemic lupus erythematosus, and mixed connective tissue diseases.

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

Each ampoule of the medicinal product Dexil contains 200 mg of ethanol, equivalent to 5 ml of beer or 2.08 ml of wine per dose. The ethanol content should be considered when using the drug during pregnancy and breastfeeding, in high-risk patients (e.g., those with liver disease), and in patients with epilepsy. The medicinal product contains less than 1 mmol of sodium (23 mg) per dose and is therefore practically sodium-free.

Use during pregnancy or breastfeeding.

The use of the medicinal product Dexil is contraindicated during the third trimester of pregnancy and during breastfeeding.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. Epidemiological data suggest an increased risk of miscarriage, congenital heart defects, and gastroschisis in early pregnancy when using drugs that inhibit prostaglandin synthesis. For example, the absolute risk of cardiovascular malformations increases from <1% to approximately 1.5%. The risk of such events is considered to increase with higher drug doses and longer treatment duration. In animal studies, prostaglandin synthesis inhibitors have led to increased pre- and post-implantation losses and embryonic lethality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, the frequency of various developmental abnormalities, including cardiovascular malformations, increased. However, animal studies did not reveal reproductive toxicity of dexketoprofen. Starting from the 20th week of pregnancy, dexketoprofen use may cause oligohydramnios due to impaired fetal kidney function. This effect may occur soon after treatment initiation and is usually reversible upon discontinuation. Additionally, arterial duct constriction has been reported after second-trimester treatment, which in most cases was reversible after stopping therapy. The use of dexketoprofen trometamol during the first and second trimesters of pregnancy is possible only if absolutely necessary. When prescribing dexketoprofen trometamol to women planning pregnancy or during the first and second trimesters, the lowest effective dose for the shortest possible duration should be used. After several days of dexketoprofen use starting from the 20th week of pregnancy, antenatal monitoring for oligohydramnios and arterial duct constriction should be considered. If oligohydramnios or arterial duct constriction is detected, dexketoprofen should be discontinued.

During the third trimester, all prostaglandin synthesis inhibitors pose the following risks to the fetus:

• cardiopulmonary toxic syndrome (premature constriction/closure of the arterial duct and pulmonary hypertension);
• impaired renal function, potentially progressing to renal failure with oligohydramnios;

Risks at the end of pregnancy for mother and child:

• prolonged bleeding time (due to platelet aggregation inhibition), which may occur even with low-dose use;
• delayed uterine contractions, leading to prolonged labor.

Breastfeeding

There are no data on the passage of dexketoprofen into breast milk. Dexketoprofen is contraindicated in women during breastfeeding.

Fertility

Like other NSAIDs, dexketoprofen may negatively affect female fertility; therefore, its use is not recommended in women attempting to conceive. For women experiencing infertility or undergoing fertility investigations, discontinuation of dexketoprofen should be considered.

Ability to affect reaction speed when driving or operating machinery.

Dizziness, drowsiness, and visual disturbances may occur during treatment with the medicinal product Dexil. In such cases, the ability to react, participate in traffic, 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 repeat dose may be given after 6 hours. The maximum daily dose should not exceed 150 mg. The medicinal product is intended for short-term use; therefore, it should be administered only during the period 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, the drug 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 reduction in renal function, a lower dose is recommended — specifically, the maximum daily dose should be limited to 50 mg in patients with mild renal impairment.

Hepatic impairment. For patients with mild or moderate hepatic 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. The drug is contraindicated in patients with severe hepatic impairment (10–15 points on the Child–Pugh scale).

Renal impairment. For patients with mild renal impairment (creatinine clearance 60–89 mL/min), the maximum daily dose should be reduced to 50 mg. The drug is contraindicated in patients with moderate or severe renal impairment (creatinine clearance < 59 mL/min).

Children. The use of dexketoprofen in children has not been studied. The medicinal product should not be administered to children due to the lack of data on its efficacy and safety.

Method of Administration

The medicinal product Dexil can be administered by intramuscular or intravenous route:

• slow intramuscular injection;
• slow intravenous injection;
• intravenous infusion after dilution;
• intravenous bolus.

Intramuscular administration. The contents of the ampoule (2 mL) of Dexil solution for injection should be administered slowly and deeply into the muscle.

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

Intravenous injection (bolus administration). If necessary, the contents of one ampoule (2 mL of injection solution) should be administered intravenously over no less than 15 seconds.

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

Handling of the medicinal product. When administered by intramuscular or intravenous injection, the drug should be used immediately after being drawn from the ampoule made of colored glass. For intravenous infusion, the solution should be diluted under aseptic conditions and protected from exposure to natural daylight.

Dexil is intended for single use only; any unused portion of the prepared solution should be discarded. Before administration, ensure that the solution is clear and colorless. The solution containing particulate matter must not be used.

Any unused medicinal product or waste material should be disposed of in accordance with applicable regulations.

Children.

The medicinal product Dexil should not be administered to children due to the lack of data on its efficacy and safety.

Overdose.

The 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 or excessive administration, symptomatic treatment appropriate to the patient's condition should be initiated immediately. Dexketoprofen trometamol is eliminated from the body by dialysis.

Adverse reactions.

Adverse events reported as at least possibly related to the use of dexketoprofen trometamol in clinical trials, as well as adverse reactions reported during the post-marketing period of use of dexketoprofen, solution for injection/infusion, are listed below by organ systems and frequency of occurrence.

Gastrointestinal disorders were observed most frequently.

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

According to results of clinical trials and epidemiological data, the use of certain NSAIDs, particularly at high doses and for prolonged periods, has been associated with a small increased risk of arterial thrombotic events such as myocardial infarction and stroke.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicinal product registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging (to protect from light) at a temperature not exceeding 25 °C. After dilution, the solution should be stored for 24 hours at a temperature of 2 to 8 °C. Keep out of reach of children.

Incompatibility.

Dexketoprofen must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, meperidine, or hydrocortisone, as this may lead to precipitate formation.

Diluted infusion solutions prepared as described in the section "Method of administration and dosage. Intravenous infusion" must not be mixed with promethazine or pentazocine.

This medicinal product must not be mixed with other medicinal products except those specified in the section "Method of administration and dosage."

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-GENE LIFE SCIENCES (P) LTD / Steril-Gene Life Sciences (P) Ltd.

Manufacturer's address and location.

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

Marketing Authorization Holder.

JIVDHARA PHARMA PRIVATE LIMITED, India / JIVDHARA PHARMA PRIVATE LIMITED, India.

Address of the Marketing Authorization Holder.

504, Block-B, Shiv Angan Complex, Sallaiya, Bhopal, Bhopal, Madhya Pradesh, 462026, India / 504, Block-B, Shiv Angan Complex, Sallaiya, Bhopal, Bhopal, Madhya Pradesh, 462026, India.