Altinam-AG (Powder) Instructions for Use

Marketing Authorization Holder

Altegra, JSC (Russia)

ATC Code

J01DH51 (Imipenem and Cilastatin)

Active Substances

Imipenem (Rec.INN registered by WHO)

Cilastatin (Rec.INN registered by WHO)

Dosage Forms

	Altinam-AG	Powder for concentrate for solution for infusion 250 mg+250 mg
		Powder for concentrate for solution for infusion 500 mg+500 mg

Dosage Form, Packaging, and Composition

Powder for concentrate for solution for infusion

500 mg – vials – carton packs – By prescription

Powder for concentrate for solution for infusion

1000 mg – vials – carton packs – By prescription

Pharmacotherapeutic Group

Systemic antibacterial agents; other beta-lactam antibacterial agents; carbapenems

Pharmacological Action

Broad-spectrum beta-lactam antibiotic. It suppresses the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic.

Imipenem is a thienamycin derivative belonging to the carbapenem group.

Cilastatin sodium inhibits dehydropeptidase, an enzyme that metabolizes Imipenem in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cilastatin has no intrinsic antibacterial activity and does not inhibit bacterial beta-lactamase.

It is active against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis and Bacteroides fragilis.

It is resistant to destruction by bacterial beta-lactamase, which makes it effective against many microorganisms such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp., which are resistant to most beta-lactam antibiotics.

The antibacterial spectrum includes almost all clinically significant pathogenic microorganisms.

It is active against gram-negative aerobic bacteria: Achromobacter spp., Acinetobacter spp. (formerly Mima – Herellea), Aeromonas hydrophila, Alcaligenes spp., Bordetella bronchicanis, Bordetella bronchiseptica, Bordetella pertussis, Brucella melitensis, Campylobacter spp., Capnocytophaga spp., Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii), Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including beta-lactamase producing strains), Haemophilus parainfluenzae, Hafnia alvei, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella ozaenae, Klebsiella pneumoniae), Moraxella spp., Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Yersinia spp. (formerly Pasteurella), including Yersinia multocida, Yersinia enterocolitica, Yersinia pseudotuberculosis; Plesiomonas shigelloides, Proteus spp. (including Proteus mirabilis, Proteus vulgaris), Providencia spp. (including Providencia alcalifaciens, Providencia rettgeri (formerly Proteus rettgeri), Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudomallei, Pseudomonas putida, Pseudomonas stutzeri), Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marcescens, Serratia proteamaculans), Shigella spp.; gram-positive aerobic bacteria: Bacillus spp., Enterococcus faecalis, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Nocardia spp., Pediococcus spp., Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis (including penicillinase-producing strains), Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus group C, Streptococcus group G, viridans streptococci including alpha- and gamma-hemolytic strains); gram-negative anaerobic bacteria: Bacteroides spp. (including Bacteroides distasonis, Bacteroides fragilis, Prevotella melaninogenica (formerly Bacteroides melaninogenicus), Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus), Bilophila wadsworthia, Fusobacterium spp., including (Fusobacterium necrophorum, Fusobacterium nucleatum), Porphyromonas asaccharolytica (formerly Bacteroides asaccharolyticus), Prevotella bivia (formerly Bacteroides bivius), Prevotella disiens (formerly Bacteroides disiens), Prevotella intermedia (formerly Bacteroides intermedius), Veillonella spp.; gram-positive anaerobic bacteria: Actinomyces spp., Bifidobacterium spp., Clostridium spp. (including Clostridium perfringens), Eubacterium spp., Lactobacillus spp., Microaerophilic streptococcus, Mobiluncus spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp. (including Propionibacterium acne); other microorganisms: Mycobacterium fortuitum, Mycobacterium smegmatis. Some Staphylococcus spp. (methicillin-resistant), Streptococcus spp. (group D), Stenotrophomonas maltophilia, Enterococcus faecium and some strains of Pseudomonas cepacia are not susceptible to imipenem.

It is effective against many infections caused by bacteria resistant to cephalosporins, aminoglycosides, penicillins. In vitro, it acts synergistically with aminoglycosides against some strains of Pseudomonas aeruginosa.

Pharmacokinetics

With intramuscular administration, the bioavailability of imipenem is 95%, cilastatin is 75%.

Plasma protein binding of imipenem is 20%, cilastatin is 40%. C_max of imipenem with intravenous administration of 250, 500 or 1000 mg over 20 min is 14-24, 21-58 and 41-83 µg/ml respectively; with intramuscular administration of 500 or 750 mg is 10 and 12 µg/ml respectively. C_max of cilastatin with intravenous administration of 250, 500 or 1000 mg over 20 min is 15-25, 31-49 and 56-80 µg/ml; with intramuscular administration of 500 or 750 mg is 24 and 33 µg/ml respectively.

It is rapidly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids and reproductive organs. It is found in low concentrations in the CSF. V_d in adults is 0.23-0.31 l/kg, in children 2-12 years old is 0.7 l/kg, in newborns is 0.4-0.5 l/kg.

Blocking of imipenem tubular secretion by cilastatin leads to inhibition of its renal metabolism and accumulation in urine unchanged. Cilastatin is metabolized to an N-acetyl compound.

With intramuscular administration, T_1/2 of imipenem is 2-3 hours. With intravenous administration, T_1/2 of imipenem and cilastatin in adults is 1 hour, in children 2-12 years old is 1-1.2 hours, in newborns T_1/2 of imipenem is 1.7-2.4 hours, cilastatin is 3.8-8.4 hours; in case of impaired renal function T_1/2 of imipenem is 2.9-4 hours, cilastatin is 13.3-17.1 hours.

It is excreted mainly by the kidneys (70-76% within 10 hours) by glomerular filtration (2/3) and active tubular secretion (1/3); 1-2% is excreted through bile with feces and 20-25% by non-renal route (mechanism unknown).

It is rapidly and effectively (73-90%) removed by hemodialysis (75% of the administered dose is removed as a result of a 3-hour session of intermittent hemofiltration).

Indications

Intra-abdominal infections; lower respiratory tract infections; genitourinary system infections; bone and joint infections; skin and soft tissue infections; pelvic infections; sepsis; bacterial endocarditis; prevention of postoperative infections; mixed infections; nosocomial infections.

ICD codes

Dosage Regimen

Determine the dosage regimen individually based on the indication, severity of infection, patient’s age, renal function, and body weight.

Administer via intravenous infusion over 20 to 60 minutes or via intramuscular injection.

For intravenous infusion, reconstitute the powder with an appropriate diluent such as 0.9% Sodium Chloride solution or 5% Dextrose solution to a concentration not exceeding 5 mg/mL of imipenem.

For intramuscular injection, reconstitute the 500 mg vial with 2 mL of 1% Lidocaine Hydrochloride solution without epinephrine; do not use this suspension for intravenous administration.

For adults with normal renal function, the total daily dose for mild infections is 1000-1500 mg, for moderate infections 1500-2000 mg, and for severe infections or those caused by less susceptible organisms 2000-3000 mg or 50 mg/kg/day, whichever is lower.

Divide the total daily dose into 3 or 4 equal administrations, typically every 6 to 8 hours; do not exceed a single dose of 1000 mg for intravenous infusion or 750 mg for intramuscular injection.

For pediatric patients (3 months and older), the recommended dosage is 15-25 mg/kg every 6 hours; do not exceed 2000 mg per day for children or 4000 mg per day for adolescents.

For prophylaxis of postoperative infections, administer a 1000 mg intravenous dose one hour before the procedure and a second 1000 mg dose three hours later.

Adjust the dosage in patients with renal impairment based on creatinine clearance (CrCl): for CrCl 31-70 mL/min, administer 500 mg every 8 hours; for CrCl 21-30 mL/min, administer 500 mg every 12 hours; for CrCl 6-20 mL/min, administer 250 mg every 12 hours.

For patients on hemodialysis, administer a supplemental dose after each dialysis session, as the drug is significantly removed; no supplemental dose is required for peritoneal dialysis.

For geriatric patients, adjust the dose based on renal function, not age alone.

Complete the full course of therapy, even if symptoms improve; duration of treatment depends on the site and severity of infection and the patient’s clinical response.

Adverse Reactions

From the central and peripheral nervous system myoclonus, mental disorders, hallucinations, confusion, epileptic seizures, paresthesia.

From the urinary system oliguria, anuria, polyuria, acute renal failure (rarely).

From the digestive system nausea, vomiting, diarrhea, pseudomembranous enterocolitis, hepatitis (rarely).

From the hematopoietic organs and hemostasis system eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, decreased hemoglobin, prolongation of prothrombin time, positive Coombs test.

From laboratory parameters increased activity of hepatic transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, increased blood urea nitrogen concentration; direct positive Coombs test.

Allergic reactions skin rash, itching, urticaria, multiform exudative erythema (including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis (rarely), exfoliative dermatitis (rarely), fever, anaphylactic reactions.

Local reactions skin hyperemia, painful infiltrate at the injection site, thrombophlebitis.

Other candidiasis, taste disturbance.

Contraindications

Hypersensitivity (including to carbapenems and other beta-lactam antibiotics); pregnancy (only for "vital" indications); early childhood (up to 3 months); in children – severe renal failure (serum creatinine concentration more than 2 mg/dl).

For suspension for intramuscular injection prepared using lidocaine hydrochloride as a solvent: hypersensitivity to local anesthetics of amide structure (shock, impaired intracardiac conduction).

With caution

CNS diseases, history of seizures, high seizure activity, anticonvulsant therapy with valproic acid (reduced therapy effectiveness), chronic renal failure (creatinine clearance less than 70 ml/min), patients on hemodialysis, elderly age, patients with a history of gastrointestinal diseases (including pseudomembranous colitis).

Use in Pregnancy and Lactation

Used during pregnancy only if the intended benefit to the mother outweighs the potential risk to the fetus.

The drug penetrates in small amounts into breast milk, so the issue of discontinuing breastfeeding during treatment should be considered.

Use in Renal Impairment

With caution: chronic renal failure (creatinine clearance less than 70 ml/min), patients on hemodialysis.

Pediatric Use

Contraindication — early childhood (up to 3 months). Contraindication: severe renal failure in children (serum creatinine concentration more than 2 mg/dl).

Geriatric Use

It should be borne in mind that elderly patients are likely to have age-related renal function impairments, which may require a dose reduction.

Special Precautions

Not recommended for the treatment of meningitis.

Stains urine reddish.

The dosage form for intramuscular administration should not be used for intravenous administration and vice versa.

Before starting therapy, a thorough history should be taken regarding previous allergic reactions to beta-lactam antibiotics.

In persons with a history of gastrointestinal diseases (especially colitis), there is an increased risk of developing pseudomembranous enterocolitis.

Antiepileptic therapy in patients with head injuries or a history of seizures should continue throughout the treatment period (to avoid side effects from the central nervous system).

It should be borne in mind that elderly patients are likely to have age-related renal function impairments, which may require a dose reduction.

Effect on ability to drive vehicles and mechanisms

Given the likelihood of developing side effects from the central nervous system, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Pharmaceutically incompatible with lactic acid salt, other antibacterial drugs.

When used simultaneously with penicillins and cephalosporins, cross-allergy is possible; exhibits antagonism towards other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

Ganciclovir increases the risk of developing generalized seizures.

Drugs that block tubular secretion slightly increase the plasma concentration and T_1/2 of imipenem (if high concentrations of imipenem are required, it is not recommended to use these drugs simultaneously).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.