Azeonam powder for injection 1g No. 1

Instructions for Azeonam powder for injection 1g No. 1

Composition

active ingredient: aztreonam;

1 vial contains aztreonam 1 g;

excipient: L-arginine.

Dosage form

Powder for solution for injection or infusion.

Main physicochemical properties: white, odorless crystalline powder.

Pharmacotherapeutic group

Antimicrobial agents for systemic use.

ATX code J01D F01.

Pharmacological properties

Pharmacodynamics.

Aztreonam is a monocyclic beta-lactam antibiotic with potent bactericidal activity against a broad spectrum of Gram-negative aerobic pathogens. Unlike most beta-lactam antibiotics, it is not an inducer of beta-lactamase activity in vitro. Aztreonam is generally active in vitro against those resistant aerobic microorganisms whose beta-lactamases hydrolyze other antibiotics.

Pharmacokinetics.

Single 30-minute intravenous infusions of 0.5 g, 1.0 g, and 2.0 g in healthy volunteers produced peak serum levels of 54, 90, and 204 mg/L, respectively, and single 3-minute intravenous injections of the same doses produced peak levels of 58, 125, and 242 mg/L. Peak aztreonam concentrations are achieved approximately one hour after intramuscular administration. After identical single intramuscular and intravenous doses, serum concentrations at 1 hour (1.5 hours after the start of the intravenous infusions) were comparable.

The serum elimination half-life of aztreonam averaged 1.7 hours in patients with normal renal function, regardless of dose or route of administration. In healthy volunteers, 60–70% of a single intramuscular or intravenous dose was excreted in the urine within 8 hours, and excretion was essentially complete by 12 hours.

Indication

Azeonam is indicated for the treatment of the following infections caused by susceptible aerobic Gram-negative microorganisms:

Urinary tract infections, including pyelonephritis and cystitis (initial and recurrent), asymptomatic bacteriuria, caused, in particular, by pathogens resistant to aminoglycosides, cephalosporins or penicillins.

Gonorrhea: An acute uncomplicated urogenital or anorectal infection caused by beta-lactamase-producing or non-beta-lactamase-producing strains of N. gonorrhoeae.

Lower respiratory tract infections, including pneumonia, bronchitis, and lung infections in patients with cystic fibrosis.

Bacteremia/septicemia.

Meningitis caused by Haemophilus influenzae or Neisseria meningitidis. Because aztreonam is active only against gram-negative organisms, it should not be used as initial blind therapy alone, but may be used in conjunction with an antibiotic active against gram-positive organisms until susceptibility testing is available.

Bone and joint infections.

Skin and soft tissue infections, including infections associated with postoperative wounds, ulcers and burns.

Intra-abdominal infections: peritonitis.

Gynecological infections: pelvic inflammatory disease, endometritis, and parametritis.

Azeonam is indicated for supportive therapy in surgical interventions in the treatment of infections caused by susceptible organisms, including abscesses, infections complicating perforations of hollow organs, skin infections, and infections of serous surfaces.

Bacteriological studies should be performed to identify the causative organism and its susceptibility to aztreonam. Therapy may be initiated pending susceptibility results.

In patients at risk of infection with non-susceptible pathogens, additional antibiotic therapy should be administered concurrently with Azeonam to ensure broad-spectrum coverage before identifying and determining susceptibility of the pathogens. Based on these results, appropriate antibacterial therapy should be continued.

Patients with serious Pseudomonas infections may be treated concurrently with Azeonam and an aminoglycoside because of their synergistic effects. If such concomitant therapy is indicated in these patients, in vitro susceptibility testing should be performed to determine activity in combination therapy. Routine monitoring of serum levels and renal function is recommended during aminoglycoside therapy.

Contraindication

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Aztreonam is contraindicated during pregnancy. Aztreonam crosses the placenta and enters the fetal circulation.

Interaction with other medicinal products and other types of interactions

Concomitant use of probenecid or furosemide and aztreonam causes clinically insignificant increases in serum aztreonam levels.

Due to the induction of beta-lactamases, certain antibiotics (e.g. cefoxitin, imipenem) have been shown to cause antagonistic effects with many beta-lactams, including aztreonam, against some Gram-negative aerobes, such as Enterobacter species and Pseudomonas species.

Single-dose pharmacokinetic studies have shown no significant interactions between aztreonam and gentamicin, cephradine, clindamycin, or metronidazole.

Unlike broad-spectrum antibiotics, aztreonam does not affect normal anaerobic intestinal flora. No disulfiram-like reactions with alcohol have been reported.

Application features

Allergic reactions

Caution should be exercised when prescribing both antibiotics and other medicinal products to patients with a history of allergic reactions to structurally related compounds. If an allergic reaction occurs, the drug should be discontinued and appropriate supportive therapy should be initiated. Severe hypersensitivity reactions may require the administration of adrenaline and other emergency measures. Appropriate studies have not shown significant cross-sensitivity between aztreonam and antibodies to penicillins or cephalosporins. The incidence of hypersensitivity to aztreonam in clinical trials was low, but until further data are available, caution should be exercised in patients with a history of hypersensitivity to beta-lactam antibiotics.

Renal/hepatic failure

Encephalopathy (e.g., confusion, impaired consciousness, epilepsy, movement disorders) has been observed with beta-lactams, particularly aztreonam, particularly in patients with renal impairment and in the setting of beta-lactam overdose.

Patients with impaired hepatic and renal function are recommended to undergo appropriate monitoring during therapy.

Serious blood/skin disorders

Serious blood disorders (including pancytopenia) and skin disorders (including toxic epidermal necrolysis) have been reported with aztreonam. Discontinuation of aztreonam is recommended in the event of serious skin and blood changes.

Convulsions

Convulsions have been reported rarely during treatment with beta-lactams, including aztreonam (see section 4.8).

Clostridium difficile-associated diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including aztreonam. It may range in severity from mild diarrhea to fatal colitis. The diagnosis of CDAD should be considered in all patients presenting with diarrhea following antibiotic therapy. A careful review of the medical history is necessary, as CDAD has been reported to occur up to 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, discontinuation of antibiotics not directed against C. difficile may be necessary. Drugs that inhibit intestinal motility should not be administered.

Concomitant therapy with other antimicrobials and aztreonam is recommended as initial therapy for patients at risk of infection with pathogens nonsusceptible to aztreonam.

As with other antibiotics, when treating pulmonary exacerbations in patients with cystic fibrosis, while clinical improvement is usually noted, sustained eradication of the bacteria is not achieved.

Overgrowth of non-susceptible microorganisms

Therapy with the drug may lead to overgrowth of non-susceptible microorganisms, including gram-positive microorganisms and fungi. In the event of superinfection during therapy, appropriate measures should be taken. In comparative studies, the number of patients treated for superinfection was the same as in the control group of drugs.

Prolongation of prothrombin time/increased activity of oral anticoagulants

Prolongation of prothrombin time has been observed rarely in patients receiving aztreonam. In addition, numerous cases of increased activity of oral anticoagulants have been reported in patients receiving antibiotics, including beta-lactams. Severe infections or inflammation, as well as advanced age and general condition of the patient, are risk factors. Appropriate monitoring should be performed when anticoagulants are used concomitantly. Adjustment of the oral anticoagulant dose may be necessary to maintain the desired level of anticoagulation (see sections “Interaction with other medicinal products and other forms of interaction” and “Adverse reactions”).

Concomitant use with aminoglycosides

If aminoglycosides are used concomitantly with aztreonam, especially at high initial doses or during prolonged therapy, renal function should be monitored due to the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics.

Children

Data on safety and efficacy in newborns under one week of age are limited, therefore the appropriateness of using Azeonam in such patients requires careful evaluation.

Arginine

Aztreonam for injection contains arginine. Studies in low birth weight neonates have shown that arginine administered with aztreonam may result in increases in serum arginine, insulin, and indirect bilirubin. The effects of exposure to this amino acid during treatment of neonates have not been fully established.

Impact on serological test results

A positive direct or indirect Coombs test may occur during treatment with aztreonam.

Use during pregnancy or breastfeeding

Pregnancy. Aztreonam is contraindicated during pregnancy. Aztreonam crosses the placenta and enters the fetal circulation.

There are no adequate and well-controlled studies in pregnant women. Studies in pregnant rats and rabbits given up to 15 daily doses, 5 times the maximum recommended human dose, have revealed no evidence of embryo- or fetotoxicity or teratogenicity. Since the results of animal studies are not always applicable to humans, aztreonam should be used during pregnancy only if clearly needed.

Breastfeeding: Aztreonam is excreted in breast milk at concentrations less than 1% of the maternal blood concentration. Women should refrain from breastfeeding during a course of aztreonam therapy.

Ability to influence reaction speed when driving vehicles or other mechanisms

This medicinal product may have a significant influence on the ability to drive and use machines in the event of encephalopathy (see sections “Special warnings and precautions for use” and “Overdose”).

Method of administration and doses

The drug should be administered by intramuscular or intravenous injection or intravenous infusion. Intramuscularly, by deep injection into a large muscle mass, such as the upper quadrant of the gluteus maximus or the lateral aspect of the thigh.

Adults

The dosage range for aztreonam is 1 to 8 g/day in equally divided doses. The usual dose is 3 to 4 g/day. The maximum recommended dose is 8 g/day. The dosage and route of administration should be guided by the susceptibility of the pathogen, the severity of the infection, and the condition of the patient.

Recommended doses for adults

The intravenous route of administration is recommended for patients requiring single doses greater than 1 g, as well as for patients with bacterial septicemia, localized parenchymal abscess (e.g., intra-abdominal abscess), peritonitis, meningitis, other severe systemic infections, or life-threatening infections.

Elderly patients

Renal status is the primary factor in determining dosage in the elderly; these patients may have decreased renal function. Serum creatinine may not be an accurate indicator of renal status. Therefore, as with all other antibiotics excreted by the kidney, creatinine clearance should be determined and the dosage adjusted if necessary.

Elderly patients usually have a creatinine clearance above 30 ml/min and should receive the normal recommended dose. If the creatinine clearance is below 30 ml/min, the dosage regimen should be adjusted (see section "Renal impairment").

Kidney dysfunction

Aztreonam serum clearance may be prolonged in patients with transient or persistent renal impairment; therefore, after the usual initial dose, the aztreonam dosage should be halved for patients with creatinine clearance between 10 and 30 mL/min/1.73 m2.

Patients with severe renal insufficiency (creatinine clearance less than 10 ml/min/1.73 m2) on haemodialysis should initially be given the usual dose. The maintenance dose should be one-fourth of the usual initial dose, administered at the usual fixed interval of 6, 8 or 12 hours. For serious or life-threatening infections, in addition to the maintenance doses, one-eighth of the initial dose should be given after each haemodialysis session.

Liver dysfunction

For long-term treatment of patients with chronic liver dysfunction with cirrhosis, it is recommended to reduce the dose by 20–25%, especially in cases of alcoholic cirrhosis and when renal function is also impaired.

Children

The usual dose for children over 1 week of age is 30 mg/kg every 6 to 8 hours. In severe infections, 50 mg/kg every 6 to 8 hours is recommended for patients over 2 years of age. The recommended dose for all patients for the treatment of infections caused by P. aeruginosa is 50 mg/kg every 6 to 8 hours.

The maximum daily dose for children should not exceed the maximum recommended dose for adults.

There is no dosage information for neonates less than 1 week of age.

Restoration

Aztreonam 1 g powder for solution for injection or infusion is available in 20 ml vials.

Reconstituted vials are for single use only; any remaining solution after administration of a single dose should be discarded.

Depending on the type and amount of solvent, the pH ranges from 4.5 to 7.5, and the color can vary from colorless to slightly straw yellow, which may acquire a slight pink tint upon standing, but this does not affect its effectiveness.

For intramuscular injection: For each gram of aztreonam, add at least 3 mL of water for injection or 0.9% sodium chloride for injection and shake well.

For intravenous injection: add 6–10 ml of water for injection to the contents of the vial and shake well. Inject slowly directly into the vein over 3–5 minutes.

For intravenous infusion: For each gram of aztreonam, add at least 3 mL of water for injection and shake well. This stock solution should be diluted with an appropriate infusion solution to a final concentration of less than 2% w/v (at least 50 mL of solution per gram of aztreonam). The infusion should be administered over 20 to 60 minutes.

Suitable infusion solutions:

0.9% sodium chloride solution for injection;

5% glucose solution for intravenous infusion;

5% or 10% mannitol for intravenous infusion;

sodium lactate for intravenous infusion;

0.9%, 0.45% or 0.2% sodium chloride solution and 5% glucose solution for intravenous infusion;

Ringer's solution for injection;

Hartmann's solution for injection.

A volume adjustment set may be used to infuse aztreonam stock solution into a compatible infusion solution. When a Y-tube is used for administration, special care should be taken to calculate the volume of aztreonam solution required to administer the entire dose.

Intravenous infusion solutions of aztreonam for injection, prepared with 0.9% sodium chloride for injection or 5% glucose for intravenous administration, in PVC or glass containers, to which clindamycin phosphate, gentamicin sulfate, tobramycin sulfate, or cefazolin sodium have been added at concentrations commonly used clinically, are stable for 24 hours when refrigerated (2–8°C). The mixture of ampicillin sodium with aztreonam in 0.9% sodium chloride for injection is stable for 24 hours when refrigerated (2–8°C); 5% glucose for intravenous administration is stable for 8 hours when refrigerated.

If aztreonam and metronidazole are to be used together, they should be administered separately, as a cherry-red color develops after storage of solutions containing combinations of the two products.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Children

Data on the safety and efficacy of aztreonam in neonates under 1 week of age are limited, therefore the appropriateness of using Azeonam in such patients requires careful evaluation.

Overdose

Therapy with beta-lactams, including aztreonam, may cause encephalopathy (e.g., confusion, impaired consciousness, epilepsy, movement disorders), especially in patients with renal impairment and in the setting of beta-lactam overdose.

No cases of overdose have been reported. Aztreonam can be removed from the serum by hemodialysis and/or peritoneal dialysis if necessary. Aztreonam can also be removed from the serum by continuous arteriovenous hemofiltration.

Side effects

Adverse reactions are listed by system organ class according to MedDRA [Medical Dictionary for Regulatory Activities]. Frequencies are defined using the following categories: very common (≥1/10); common (≥1/100 <1/10); uncommon (≥1/1000 <1/100); rare (≥1/10000 <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).

* Usually reversible during therapy and without overt signs or symptoms of hepatobiliary dysfunction.

1 See section "Application features".

Reporting of adverse reactions

Reporting adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of a medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.

Expiration date

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Store the reconstituted solution at 2–8°C for 18 hours.

Incompatibility

Aztreonam should not be mixed with any other drug, antibiotic or diluent except those listed in the Dosage and Administration section.

In the case of intermittent infusion of aztreonam and another drug through a common line, the line should be flushed before and after administration of aztreonam with any infusion solution compatible with both drug solutions. The drugs should not be administered simultaneously.

Packaging

1 g of the drug in a glass vial closed with a rubber stopper and an aluminum cap with a flip-off component, one vial in a box.

Vacation category

According to the recipe.

Producer

"Venus Remedies Limited".

Location of the manufacturer and address of its place of business.

Hill Top Industrial Estate, Jarmajari, ERIR Phase-1 (Ext.), Batoli Kalan, Baddi, Dist. Solan, Himachal Pradesh, 173205, India.

Applicant

Ananta Medicare Ltd.

Location of the applicant.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.