Imipenem and Cilastatin Jodas, 500 mg+500 mg powder 10 ml

Beta-lactam antibiotic of wide spectrum of action. Inhibits bacterial cell wall synthesis and has bactericidal effect against a wide range of Gram-positive and Gram-negative microorganisms, aerobic and anaerobic.

Indications

Infectious and inflammatory diseases caused by susceptible microorganisms (polymicrobial or mixed aerobic-anaerobic infections):

– lower respiratory tract infections;

– urinary tract infections;

– intra-abdominal infections;

– skin and soft tissue infections;

– bone and joint infections;

– peritonitis;

– sepsis;

– endocarditis;

– inflammatory diseases of the pelvic organs.

Prevention of postoperative complications.

How to take, the dosage

Intravenous (IV) drip.

The doses given below are for a body weight of 70 kg or more and a CK of 70 ml/min/1.73 sq.m or more. For patients with a CKR less than 70 ml/min/1.73 sq.m. and/or lower body weight, the dose should be reduced proportionately.

The average therapeutic dose for adults (imipenem calculation) when administered by IV is 1-2 g/day divided into 3-4 injections; the maximum daily dose is 4 g or 50 mg/kg, whichever is lower.

Patients with mild infection – 250 mg 4 times a day, moderate – 500 mg 3 times a day or 1 g 2 times a day, severe – 500 mg 4 times a day, with life-threatening infection – 1 g 3-4 times a day.

The dose of imipenem less than or equal to 500 mg should be administered by IV for 20-30 minutes. Doses over 500 mg should be administered by IV for 40-60 minutes. Patients who experience nausea during the infusion should slow the rate of administration.

For prevention of postoperative infections, 1 g during introductory anesthesia and 1 g after 3 h. In case of high risk surgical interventions (colorectal surgery) 500 mg is administered additionally 8 and 16 hours after general anesthesia.

The maximum daily doses for intravenous administration in patients with renal failure depending on the severity of infection and CK values (ml/min/1.73 sq.m) and body weight > 70 kg:

– for mild infection and CK values of 41-70 mL/min, 250 mg every 8 hours, CK 21-40 mL/min, 250 mg every 12 hours, and CK 6-20 mL/min, 250 mg every 12 hours;

– for moderate infection and a BK of 41-70 mL/min – 250 mg after 6 h, BK 21-40 mL/min – 250 mg after 8 h, BK 6-20 mL/min – 250 mg after 12 h;

– in severe course (highly sensitive strains) and BK 41-70 ml/min – 500 mg after 8 hours, BK 21-40 ml/min – 250 mg after 6 hours, BK 6-20 ml/min – 250 mg after 12 hours;

– in severe course (moderately sensitive strains, incl.ч. Pseudomonas aeruginosa) and CK 41-70 ml/min – 500 mg after 6 h, CK 21-40 ml/min – 500 mg after 8 h, CK 6-20 ml/min – 500 mg after 12 h;

– In a severe course of life-threatening infection and a BK of 41-70 mL/min, 750 mg every 8 hours, BK 21-40 mL/min, 500 mg every 6 hours, BK 6-20 mL/min, 500 mg every 12 hours.

Patients with a CKR of less than 5 mL/min are administered only if hemodialysis is performed no later than 48 h after the infusion of the drug, with subsequent administration 12 h later (from the end of the procedure).

There are currently insufficient data on the dosing regimen for preoperative prophylaxis in patients with CK less than 70 ml/min/1.73 sq.m.

In children with a body weight of 40 kg or more, the same doses as in adults are prescribed. Children over 3 months of age and with body weight less than 40 kg – 15 mg/kg 4 times/day; maximum daily dose is 2 g.

Preparation of solution for intravenous infusion

Imipenem+cilastatin for intravenous infusion must not be mixed or added to other antibiotics.

The following solvents are used for preparation of the infusion solution: 0.9% sodium chloride solution, 5% aqueous dextrose solution, 10% aqueous dextrose solution, 5% dextrose solution and 0.9% sodium chloride solution. In the ratio of 100 ml of solvent and 500 mg of imipenem. The concentration of imipenem in the resulting solution is 5 mg/ml.

Interaction

Pharmaceutically incompatible with lactic acid salt, solutions of other antibiotics.

In concomitant use with penicillins and cephalosporins cross-allergy is possible; shows antagonism to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

Concomitant use with ganciclovir increases the risk of generalized seizures. These drugs should not be used concomitantly unless the potential benefits exceed the possible risks.

Drugs that block tubular secretion slightly increase plasma concentrations and T1/2 of imipenem (if high concentrations of imipenem are required, concomitant use of these drugs is not recommended).

When using the drug the serum concentration of valproic acid decreases, which reduces the effectiveness of anticonvulsant therapy, therefore it is recommended to monitor serum valproic acid concentration during treatment.

Special Instructions

It is not recommended for the treatment of meningitis.

Strict adherence to the recommended dosage and route of administration is strongly required, especially in patients predisposed to seizure activity. Therapy with anticonvulsants in patients with a history of epilepsy should be continued for the duration of treatment with the drug. If local tremor, myoclonia or seizures are observed, patients should undergo neurological examination with the prescription of anticonvulsant therapy. The dosage of the drug in this case should be reviewed to determine if it should be reduced or if the drug should be discontinued.

The drug formulation contains 37.56 mg (1.63 mEq) of sodium.

A thorough history of previous allergic reactions to beta-lactam antibiotics should be taken before starting therapy. If an allergic reaction develops, the drug should be discontinued immediately.

People with a history of gastrointestinal disease (especially colitis) have an increased risk of pseudomembranous colitis.

When using the drug both against the background of administration and 2-3 weeks after discontinuation of treatment, development of diarrhea caused by Clostridium difficile (pseudomembranous colitis) is possible. In mild cases, treatment withdrawal and use of ion exchange resins (colestiramine, colestipol) is sufficient, in severe cases compensation of fluid, electrolyte and protein loss, prescription of vancomycin and metronidazole is indicated. Do not use drugs that inhibit intestinal peristalsis.

As with other beta-lactam antibiotics, Pseudomonas aeruginosa can develop resistance to the drug fairly quickly during treatment. Therefore, periodic antibiotic sensitivity tests are recommended during the treatment of infections caused by Pseudomonas aeruginosa as appropriate to the clinical situation.

In elderly patients there may be age-related renal dysfunction, which may require dose reduction.

It stains the urine a reddish color.

Influence on driving and operating machinery

Caution should be exercised when driving and engaging in other potentially hazardous activities that require increased attention and rapid psychomotor reactions.

Contraindications

– hypersensitivity to one of the components of the drug, as well as to other carbapenems, beta-lactam antibiotics, penicillins and cephalosporins;

– chronic renal failure with CK less than 5 ml/min/1.73 m2 without hemodialysis;

– early childhood (under 3 months);

– in children – severe renal failure (serum creatinine concentration greater than 2 mg/dL).

With caution

Central nervous system (CNS) disease, pseudomembranous colitis, patients with a history of GI disease, with a CKR less than 70 ml/min/173 m2, patients on hemodialysis, anticonvulsant therapy with valproic acid (decreased effectiveness of therapy), elderly age.

Side effects

Nervous system disorders: myoclonia, psychiatric disorders, hallucinations, confusion, epileptic seizures, paresthesias.

Urinary system disorders: oliguria, anuria, polyuria, acute renal failure (rare).

In the digestive system: nausea, vomiting, diarrhea, pseudomembranous enterocolitis, hepatitis (rare).

Hematopoietic and hemostatic system disorders: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, Hb decrease, prothrombin time prolongation, positive Coombs reaction.

Laborary parameters: increased activity of “hepatic” transaminases and alkaline phases, hyperbilirubinemia, hypercreatininemia, increased concentration of urea nitrogen; direct positive Coombs test.

Allergic reactions: skin rash, pruritus, urticaria, erythema multiforme (including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis (rare), exfoliative dermatitis (rare), fever, anaphylactic reactions.

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

Others: candidiasis, taste disorders.

Overdose

Symptoms:possible increased side effects.

Treatment is symptomatic. Imipenem and cilastatin are subjected to hemodialysis. However, the effectiveness of this procedure in case of drug overdose is unknown.