Voltaren solution for injection 75 mg/3 ml in 3 ml ampoules 5 pcs.

Pharmacodynamics. Voltaren is a nonsteroidal drug with pronounced analgesic / anti-inflammatory properties. It is an inhibitor of prostaglandin synthetase (COX). Diclofenac sodium in vitro at concentrations equivalent to those achieved in humans does not inhibit the biosynthesis of proteoglycans in cartilage tissue. If the drug is used simultaneously with drops to eliminate postoperative pain, Voltaren significantly reduces the need for opioids.

Pharmacokinetics. Absorption. After administration of 75 mg of diclofenac by intramuscular injection, absorption begins immediately, and the average C _max in blood plasma is about 2.558 ± 0.968 μg/ml (2.5 μg/ml = 8 μmol/l) and is reached after about 20 minutes. The extent of absorption is linearly proportional to the dose.

When 75 mg of diclofenac is administered by intravenous infusion over 2 hours, the mean Cmax _in plasma is about 1.875 ± 0.436 μg/ml (1.9 μg/ml = 5.9 μmol/l). Shorter infusion times lead to higher Cmax _in plasma, while longer infusions lead to a plateau concentration proportional to the infusion rate after 3-4 hours. In contrast to the corresponding results after oral administration, when the drug is administered in the form of suppositories or intramuscularly, the plasma concentration decreases rapidly immediately after reaching maximum levels.

Bioavailability. AUC after IM or IV administration is approximately twice that after oral or rectal administration, as this route avoids 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 Cmax _is achieved 2-4 hours after peak plasma levels. The expected T½ _from synovial fluid is 3-6 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. The 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 effect is much less pronounced than for diclofenac.

Elimination. The total systemic clearance of diclofenac in plasma is 263 ± 56 ml/min (mean ± SD). The terminal T½ _from plasma is 1-2 h. Four metabolites, including 2 active ones, also have a short T½ _of 1-3 h. About 60% of the administered dose is excreted in the urine as a 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 age-related differences in absorption, metabolism, or excretion of the drug were observed, except that in 5 elderly patients, a 15-minute infusion resulted in plasma concentrations that were 50% higher than those observed in young healthy volunteers.

Patients with renal impairment. In patients with renal impairment, 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. At a creatinine clearance of 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 of the liver, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.

The drug for intramuscular administration 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.

The drug should be used in the minimum effective doses for the minimum period of time, taking into account the treatment objectives of each individual patient.

Adults. Voltaren solution for injection should not be used for more than 2 days. If necessary, treatment can be continued with Voltaren 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 dose is usually 1 ampoule of 75 mg/day 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 2 injections of 75 mg, with an interval of several hours between them (1 injection into each buttock). Alternatively, the 75 mg solution for injection can be combined with other dosage forms of Voltaren (e.g. tablets, suppositories) up to a total maximum daily dose of 150 mg diclofenac sodium.

In the setting of a migraine attack, clinical experience is limited to cases with the initial use of 1 ampoule of 75 mg, the dose being 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 1st day. There are no data available on the use of Voltaren for the treatment of migraine attacks for more than one day.

In / in infusion. Immediately before the start of the / in infusion, Voltaren should be diluted in 100-500 ml of 0.9% sodium chloride solution or 5% glucose solution. Both solutions must 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.

Voltaren, solution for injection, should not be administered as an intravenous bolus injection.

Two alternative dosing regimens for Voltaren, solution for injection, are recommended:

For the treatment of moderate to severe postoperative pain, 75 mg of the drug should be administered continuously for 30 minutes to 2 hours; if necessary, the treatment can be repeated after a few hours, but the dose should not exceed 150 mg/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 about 5 mg/h up to a maximum daily dose of 150 mg.

Elderly patients. Although the pharmacokinetics of Voltaren are not altered to any clinically significant extent in elderly patients, NSAIDs should be used with caution in these patients, who are generally more susceptible to adverse reactions. In particular, the lowest effective dose is recommended for debilitated elderly patients or patients with low body weight (see Precautions); patients should also be monitored for gastrointestinal bleeding during treatment with NSAIDs.

The recommended maximum daily dose of Voltaren is 150 mg.

Only for IV use

• Concomitant use of NSAIDs or anticoagulants (including low-dose heparin).
• History of hemorrhagic diathesis, confirmed or suspected history of cerebrovascular bleeding.
• Surgeries associated with a high risk of bleeding.
• History of asthma.
• Moderate or severe renal impairment (plasma creatinine 160 μmol/l).
• Hypovolemia or dehydration from any cause.

Adverse drug reactions are described by frequency: very common (≥1/10); common (≥1/100, 1/10); uncommon (≥1/1000, 1/100); rare (≥1/10,000, 1/1000); very rare (1/10,000); frequency unknown (cannot be estimated from the available data).

The following side effects include those associated with the administration of Voltaren in both short-term and long-term use.

From the blood and lymphatic system: very rarely – thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), agranulocytosis.

Immune system disorders: Rare: hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock); very rare: angioedema (including facial swelling).

Mental disorders: very rarely – disorientation, depression, insomnia, nightmares, irritability and other mental disorders.

From the nervous system: often – headache, dizziness; rarely – drowsiness, fatigue; very rarely – paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disturbance, stroke; frequency unknown – confusion, hallucinations, sensory disturbances, general malaise.

On the part of the organ of vision: very rarely – visual impairment, blurred vision, diplopia; frequency unknown – optic neuritis.

From the side of the organs of hearing and labyrinth: often – vertigo; very rarely – tinnitus, hearing impairment.

On the part of the heart: very rarely – palpitations, chest pain, heart failure, myocardial infarction.

From the vascular system: very rarely – arterial hypertension, arterial hypotension, vasculitis.

Respiratory, thoracic and mediastinal disorders: rarely – asthma (including dyspnoea); very rarely – pneumonitis.

On the part of the digestive system: often – nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia; rarely – gastritis, gastrointestinal bleeding, vomiting with blood, hemorrhagic diarrhea, melena, gastric or intestinal ulcer with or without bleeding or perforation (sometimes fatal, especially in elderly patients); very rarely – colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis (including ulcerative), glossitis, esophageal disorders, membranous intestinal strictures, pancreatitis.

Hepatobiliary disorders: often – increased transaminase levels; rarely – hepatitis, jaundice, impaired liver function; very rarely – transient hepatitis, hepatonecrosis, hepatic failure.

Skin and subcutaneous tissue disorders: common: rash; rare: urticaria; very rare: bullous rash, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exfoliative dermatitis, hair loss, photosensitivity reaction, purpura, allergic purpura, pruritus.

From the kidneys and urinary tract: very rarely – acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.

General disorders and administration site conditions: common: injection site reaction, pain, induration; rare: injection site edema, injection site necrosis; very rare: injection site abscess.

From the reproductive system and mammary glands: very rarely – impotence.

Clinical trial data and epidemiological data suggest an increased risk of thrombotic complications (e.g. myocardial infarction or stroke) associated with the use of diclofenac, particularly at high therapeutic doses (150 mg/day) and with long-term use.

General: Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

The use of Voltaren with systemic NSAIDs, including selective COX-2 inhibitors, should be avoided due to the lack of any synergistic benefit and the possibility of additional side effects.

Caution should be exercised when prescribing the drug to elderly patients. In particular, for elderly patients with frail health and for patients with low body mass index, it is recommended to use the lowest effective dose.

As with other non-steroidal anti-inflammatory drugs, allergic reactions, including anaphylactic/anaphylactoid reactions, may also occur without prior exposure to diclofenac.

Like other nonsteroidal anti-inflammatory drugs, Voltaren, due to its pharmacodynamic properties, may mask the signs and symptoms of infection.

Sodium metabisulfite in solution for injection may cause isolated severe hypersensitivity reactions and bronchospasm.

Effects on the digestive system. With the use of all NSAIDs, including diclofenac, cases of gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and occur at any time during treatment, with or without warning symptoms, as well as in the presence of a history of serious gastrointestinal events. These events usually have a more serious consequence in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.

As with all NSAIDs, including diclofenac, close medical supervision is necessary; special care should be taken when prescribing diclofenac to patients with symptoms suggestive of gastrointestinal disorders, or with a history of gastric or intestinal ulcer, bleeding or perforation. The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs, including diclofenac, and in patients with a history of ulcer, especially if complicated by bleeding or perforation.

Elderly patients have an increased incidence of adverse reactions to 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 the elderly, 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 or other drugs 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. acetylsalicylic acid), or selective serotonin reuptake inhibitors.

Effects on the liver: Careful medical supervision is necessary if Voltaren is prescribed to patients with impaired liver function, as their condition may be aggravated.

As with other nonsteroidal anti-inflammatory drugs, including diclofenac, the level of one or more liver enzymes may increase. With long-term treatment with Voltaren, regular monitoring of liver function is 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), Voltaren should be discontinued.

The course of diseases such as hepatitis can occur without prodromal symptoms.

Caution is necessary if Voltaren is used in patients with hepatic porphyria, due to the possibility of provoking an attack.

Renal effects: 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 a significant decrease in extracellular fluid volume for any reason, for example, before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually leads to a return to pre-treatment status.

Skin effects. Serious skin reactions (some of which were fatal) have been reported very rarely in association with the use of NSAIDs, including Voltaren, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk of these reactions appears to be greatest at the beginning of therapy, in most cases within the first month of treatment. Voltaren should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

Systemic lupus erythematosus and mixed connective tissue diseases: Patients with systemic lupus erythematosus and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects. 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.

For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and advice should be provided, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.

Clinical trial data and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) for long periods, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Diclofenac is not recommended for use in patients with uncontrolled hypertension, congestive heart failure, stable coronary artery disease, peripheral arterial disease and/or cerebrovascular disease, and should only be used after careful risk-benefit assessment at doses not exceeding 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 informed of the possibility of serious thrombotic events (chest pain, shortness of breath, weakness, speech disorders), which may occur at any time. In this case, a doctor should be consulted immediately.

Effect on hematological parameters. With prolonged use of the drug, as with other NSAIDs, monitoring of blood tests is recommended.

Like other nonsteroidal anti-inflammatory drugs, Voltaren may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis or hematological disorders should be carefully monitored.

History of asthma. Patients with bronchial asthma, seasonal allergic rhinitis, patients with swelling of the nasal mucosa (nasal polyps), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially associated with allergic rhinitis-like symptoms) are more likely than others to experience reactions to NSAIDs that resemble exacerbations of asthma (so-called analgesic intolerance/analgesic asthma), angioedema, and urticaria. Therefore, special measures are recommended for such patients (emergency preparedness). This also applies to patients with allergies to other substances, manifested by skin reactions, itching, or urticaria.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other nonsteroidal anti-inflammatory drugs can provoke the development of bronchospasm in patients with bronchial asthma or in patients with a history of bronchial asthma.

Female fertility. The use of Voltaren may impair female fertility and is not recommended when attempting to conceive. In women who may have difficulty conceiving or are undergoing investigation for infertility, discontinuation of Voltaren should be considered.

Use during pregnancy and breastfeeding

Pregnancy. In the I and II trimesters of pregnancy, Voltaren can be prescribed only if the expected benefit to the mother outweighs the potential risk to the fetus, only in the minimum effective dose, the duration of treatment should be as short as possible. Like other nonsteroidal anti-inflammatory drugs, the drug is contraindicated in the last trimester of pregnancy (possible inhibition of uterine contractility and premature closure of the ductus arteriosus in the fetus).

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological studies have shown 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 has increased from less than 1% to approximately 1.5%.

It is possible that the risk increases with increasing dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation losses and embryo/fetal lethality.

In addition, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various malformations, including those of the cardiovascular system, has been reported. If Voltaren is used in women attempting to conceive or in the first trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible.

In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can affect the fetus in the following ways:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• renal impairment, which may progress to renal failure with oligohydramnios.

For the mother and newborn, as well as at the end of pregnancy:

• possible prolongation of bleeding time, antiplatelet effect, which is possible even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, Voltaren is contraindicated in the third trimester of pregnancy.

Breastfeeding. Like other non-steroidal anti-inflammatory drugs, diclofenac passes into breast milk in small amounts. Therefore, to avoid undesirable effects on the infant, Voltaren should not be used during breastfeeding.

Fertility. Like other nonsteroidal anti-inflammatory drugs, Voltaren may affect female fertility. The drug is not recommended for women planning to become pregnant. Women who have difficulty conceiving or have undergone investigation for infertility should discontinue use of Voltaren.

Children. Voltaren in the dosage form of solution for injection is contraindicated for use in children.

Ability to influence the reaction rate when driving vehicles or working with other mechanisms. Patients who experience visual disturbances, dizziness, drowsiness or other central nervous system disorders during treatment with Voltaren should refrain from driving vehicles and working with other mechanisms.

Below are the interactions that have been identified with the use of Voltaren, solution for injection, and/or other dosage forms of diclofenac.

Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of plasma lithium levels is recommended.

Digoxin: Diclofenac may increase plasma concentrations of digoxin when used concomitantly. Monitoring of digoxin plasma levels is recommended.

Diuretics and antihypertensives. As with other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensives (e.g. β-blockers, 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 after initiation of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors, given the increased risk of nephrotoxicity.

Drugs known to cause hyperkalemia. Concomitant treatment with potassium-sparing diuretics, ciclosporin, tacrolimus or trimethoprim may be associated with increases in plasma potassium levels, therefore 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 do not indicate an effect of diclofenac on the activity of anticoagulants, there is some evidence of an increased risk of bleeding in patients receiving diclofenac and these drugs concomitantly. Therefore, close monitoring of these patients is recommended to ensure that no changes in the dosage of anticoagulants are necessary. As with other NSAIDs, diclofenac in high doses may transiently inhibit platelet aggregation.

Other NSAIDs, including selective COX-2 inhibitors and corticosteroids. Concomitant administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. The concomitant use of two or more NSAIDs should be avoided.

Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.

Antidiabetic drugs. Clinical studies have shown that diclofenac can be used together with oral antidiabetic drugs 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 drugs during treatment with diclofenac. Such conditions require monitoring of blood glucose levels, which is a precautionary measure during concomitant therapy.

Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. Caution is advised when nonsteroidal anti-inflammatory drugs, including diclofenac, are administered less than 24 hours before methotrexate treatment, as blood concentrations and toxicity of methotrexate may increase. 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, it should be used at lower doses than in patients not taking cyclosporine.

Tacrolimus: The use of NSAIDs with tacrolimus may increase the risk of nephrotoxicity, which may be mediated through the renal antiprostaglandin effects of the NSAID and the calcineurin inhibitor.

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.

Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4-6 hours after colestipol/cholestyramine.

Cardiac glycosides. Concomitant use of cardiac glycosides and nonsteroidal anti-inflammatory drugs may exacerbate heart failure, reduce glomerular filtration rate, 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 CYP 2C9 inhibitors: Caution is recommended when prescribing diclofenac with potent CYP 2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in plasma Cmax and exposure to diclofenac due to inhibition of its metabolism _.

Incompatibility. As a rule, Voltaren solution for injection should not be mixed with other solutions for injection.

Symptoms. There is no typical clinical picture of the consequences of diclofenac overdose. Overdose can cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, agitation, coma, drowsiness, tinnitus, loss of consciousness or convulsions. In case of severe poisoning, acute respiratory distress syndrome and liver damage are possible.

Treatment. Activated charcoal should be considered within 1 hour of oral administration of a potentially toxic amount of the drug. In addition, gastric lavage should be considered in adults within 1 hour of oral administration of a potentially toxic amount of the drug. Diazepam should be administered intravenously if seizures are frequent or prolonged. Other measures may be indicated depending on the clinical condition of the patient. Treatment is symptomatic.

In the original packaging at a temperature not exceeding 30 °C.