Ambene^® (Solution) Instructions for Use

Marketing Authorization Holder

Ratiopharm, GmbH (Germany)

Manufactured By

Merckle, GmbH (Germany)

ATC Code

M01BA01 (Phenylbutazone and corticosteroids)

Dosage Forms

	Ambene®	Solution for intramuscular injection A and B 2 ml/1 ml: 2-chamber syringe 3 pcs. in a set with a disposable needle, wipe, and plaster
		Solution for intramuscular injection A and B in double ampoules 2 ml/1 ml: sets of 6 pcs.

Dosage Form, Packaging, and Composition

Solution for intramuscular injection set of injectable solutions A and B.

Solution for injection A is clear, from colorless to slightly yellowish in color.

Excipients: sodium hydroxide 49.08 mg, water for injection 1675.92 mg.

Solution for injection B is clear, red in color.

Excipients: water for injection 996.5 mg.

Double ampoules (6) of dark glass, containing solution A (2 ml) and solution B (1 ml) – plastic trays (1) – cardboard packs.
The ampoule of solution A has a white dot and 2 rings – light green and dark pink. The ampoule of solution B has a white dot.

Solution for intramuscular injection set of injectable solutions A and B.

Solution for injection A is clear, from colorless to slightly yellowish in color.

Excipients: sodium hydroxide 49.08 mg, water for injection 1675.92 mg.

Solution for injection B is clear, red in color.

Excipients: water for injection 996.5 mg.

Two-chamber glass syringes (3), having two separate chambers with solution A (2 ml) and solution B (1 ml) in a set with a disposable needle, wipe, and plaster – plastic cases (3) – cardboard packs.

Clinical-Pharmacological Group

Drug with anti-inflammatory and analgesic action

Pharmacotherapeutic Group

Anti-inflammatory agent

Pharmacological Action

A combined drug, the action of which is determined by the properties of its constituent components. It has anti-inflammatory, analgesic, and antipyretic effects, and causes a uricosuric effect.

Dexamethasone is a glucocorticoid that has a pronounced anti-inflammatory effect; its index of relative anti-inflammatory activity is 30 with an almost complete absence of mineralocorticoid activity.

Phenylbutazone is an NSAID, a pyrazolone derivative, that has anti-inflammatory, analgesic, and antipyretic effects, and causes a uricosuric effect.

Salicylamide-o-acetate sodium has an analgesic effect and also promotes better solubility of the drug.

Cyanocobalamin, which is involved in the synthesis of nucleic acids, activates lipid metabolism and, consequently, is important in cell regeneration and the formation of the myelin sheath of nerve fibers, is included in the drug in a sufficiently high dose to enhance the analgesic effect.

Due to the presence of lidocaine hydrochloride, injections of the drug are practically painless.

The active substances that make up Ambene^® potentiate each other’s action, which allows reducing the dose of dexamethasone.

The activity of the drug persists for a long time (36 months) due to the separation of solutions A and B from each other.

Pharmacokinetics

Absorption

After intramuscular injection, Dexamethasone is rapidly absorbed into the systemic circulation.

Distribution

Phenylbutazone has a high degree of binding to plasma proteins.

Dexamethasone and Phenylbutazone cross the placenta and are excreted in breast milk.

Metabolism

Due to high binding to plasma proteins, the metabolism of phenylbutazone occurs slowly, providing a long T_1/2.

Elimination

The T_1/2 of dexamethasone is about 3 hours.

Indications

Short-term treatment of acute conditions in

• Articular syndrome in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout;
• Neuritis, neuralgia, radiculitis (including in degenerative diseases of the spine).

ICD codes

Dosage Regimen

The drug is prescribed as 1 injection per day, daily or every other day. No more than 3 injections per week should be administered. If repeated courses of treatment are necessary, the interval between them should be at least several weeks. Injections of the drug are administered deep intramuscularly, slowly; the patient should be in a horizontal position.

Rules for preparing the injection solution

When using Ambene^® in the form of a set of 2 ampoules, first draw solution A into the syringe, then solution B.

When using the drug in the form of a ready-to-use syringe, remove the rubber cap from the conical part of the syringe; attach the supplied sterile needle, after removing the protective element, to the cone; slowly move the piston rod with the stopper forward until the first drop of solution appears. With the correct injection preparation technique, solution B enters the front chamber of the syringe through the connecting bridge and mixes with solution A. The drug is administered immediately after mixing the solutions. The temperature of the prepared solution should be close to the patient’s body temperature.

Adverse Reactions

From the digestive system ulcerogenic effect, anorexia, gastralgia, nausea, vomiting, diarrhea; rarely – impaired liver function; in some cases – gastrointestinal bleeding and perforations, hemorrhagic pancreatitis.

From the hematopoietic system leukopenia, agranulocytosis, thrombocytopenia, pancytopenia, aplastic anemia.

Allergic reactions exanthema, skin itching, fever; rarely – Stevens-Johnson syndrome, Lyell’s syndrome, lupus-like syndrome, bronchospasm.

From the central nervous system dizziness, headache, sleep disorders, agitation; rarely – visual and hearing disorders, mental disorders.

From the cardiovascular system rarely – arterial hypotension, orthostatic collapse.

Local reactions rarely – pain at the injection site; in some cases – development of abscesses and tissue necrosis.

Other rarely – Cushing’s syndrome, mycosis, impaired renal function, manifestation of immunosuppressive action (decreased resistance to infections, slow wound healing), lymphadenopathy, sialadenitis.

Contraindications

• Acute gastritis;
• Gastric and duodenal ulcer (including history);
• Cardiovascular diseases (including acute myocardial infarction, chronic heart failure in the decompensation phase, myocardial diseases with conduction disorders, ventricular arrhythmias);
• Severe renal impairment;
• Severe hepatic impairment;
• Severe thyroid dysfunction;
• Viral infection (including herpes infection, chickenpox, mumps; poliomyelitis, except for the bulbar form of the disease);
• Systemic mycosis;
• Glaucoma;
• Myelosuppression;
• Severe myopathy, myasthenia;
• Sjögren’s syndrome;
• Systemic lupus erythematosus;
• Hemorrhagic diatheses;
• Giant cell (temporal) arteritis, polymyalgia rheumatica;
• Pancreatitis;
• Stomatitis;
• The period 8 weeks before and 2 weeks after planned vaccination;
• Lymphadenitis after BCG vaccination;
• Surgical operations;
• Pregnancy;
• Lactation (breastfeeding);
• Children under 14 years of age;
• Old age;
• History of urticaria, acute rhinitis, bronchospasm upon taking acetylsalicylic acid or other NSAIDs;
• Hypersensitivity to the components of the drug, pyrazolone derivatives, salicylates.

Use in Pregnancy and Lactation

Ambene^® is contraindicated for use during pregnancy.

If it is necessary to use Ambene^® during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment.

Use in Renal Impairment

Contraindicated in severe renal impairment.

Pediatric Use

The drug is contraindicated in children under 14 years of age.

Special Precautions

The drug should be prescribed with caution in cases of renal impairment, to patients with diabetes mellitus, tuberculosis, epilepsy, mental illness, bronchial asthma, hay fever, chronic nonspecific lung diseases, acute and chronic bacterial infections, amoebiasis, with arterial hypertension or hypotension, thromboembolism, severe osteoporosis. In the above cases, Ambene^® is used only with appropriate treatment of the underlying disease or syndrome.

Due to the long half-life of phenylbutazone, when using Ambene^® in high doses for a long time, the possibility of drug accumulation should be taken into account; this especially applies to patients with impaired liver function.

Before starting a course of treatment with Ambene^®, a thorough examination of the patient should be carried out, in particular to exclude gastric and duodenal ulcers.

To reduce the risk of developing side effects, the drug should be prescribed in the minimum possible dose; this especially applies to debilitated and elderly patients.

To prevent irritation at the site of intramuscular injection, which is possible when administering highly concentrated solutions of the drug, injections should be administered deeply, into different areas. The manipulation should be performed under absolutely sterile conditions.

During therapy with the drug, the patient’s food should contain a sufficient amount of potassium, protein, vitamins and little fat, carbohydrates and table salt.

If fever, headache, changes in the skin and mucous membranes occur, if leukopenia, agranulocytosis develop, or if the stool turns dark in color, the drug should be discontinued.

Phenylbutazone affects the results of thyroid function tests, so the corresponding tests should be performed no earlier than 2 weeks after discontinuation of Ambene^® treatment.

Medicines containing cyanocobalamin may distort clinical and laboratory parameters in patients with funicular myelosis and/or pernicious anemia.

Control of laboratory parameters

During long-term therapy with Ambene^®, systematic monitoring of the peripheral blood picture and renal and hepatic function is necessary.

In patients receiving diuretic drugs simultaneously with Ambene^®, regular monitoring of serum potassium levels is necessary.

In patients receiving anticoagulants simultaneously with Ambene^®, systematic analysis of blood coagulation system parameters (prothrombin time) should be performed.

Overdose

Symptoms nausea, vomiting, abdominal pain, gastrointestinal bleeding, dizziness, headache, metabolic alkalosis or acidosis, hyperventilation, respiratory depression, fever, arterial hypotension, hepatic and renal failure, bradycardia, cerebral and pulmonary edema, thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, increased transaminase activity, heart failure, anuria, convulsions, coma.

Treatment mechanical ventilation and other resuscitation measures; according to indications – anticonvulsants (for example, intravenous administration of diazepam), hemodialysis.

Drug Interactions

With simultaneous use of Ambene^® and other anti-inflammatory drugs and drugs containing ethanol, the risk of gastrointestinal bleeding increases.

With simultaneous use of Ambene^® with oral hypoglycemic agents (sulfonylurea derivatives) or insulin, hyper- or hypoglycemia is possible.

Simultaneous use of Ambene^® and indirect anticoagulants, heparin, dipyridamole or sulfinpyrazone may require adjustment of drug doses due to the risk of bleeding.

With simultaneous use with Ambene^®, an increase in plasma concentrations of sulfonamides and lithium preparations is possible.

With simultaneous use of Ambene^® and methotrexate, an increase in the toxicity of the latter is possible.

With simultaneous use of Ambene^® with phenytoin, symptoms of intoxication with the latter may develop.

With simultaneous use of Ambene^® with barbiturates, their hypnotic effect may be enhanced.

With simultaneous use of Ambene^® with cardiac glycosides, digitalization of patients may slow down or accelerate.

With simultaneous use of Ambene^® and antihypertensive drugs, the effect of the latter is reduced.

With simultaneous use of Ambene^® and diuretics, a decrease in diuresis and natriuresis, as well as the development of hypo- or hyperkalemia, is possible.

With simultaneous use of Ambene^® and hormonal contraceptives, the effectiveness of the latter may be reduced.

With simultaneous use of Ambene^® with sulfinpyrazone or probenecid, their uricosuric effect may be reduced.

Use of drugs – inducers of liver microsomal enzymes (for example, barbiturates, promethazine, rifampicin, hydantoin) before starting therapy with Ambene^® reduces the effect of Ambene^®.

With simultaneous use, anabolic steroids and methylphenidate enhance the effect of Ambene^®.

Storage Conditions

The drug should be stored in a light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.