Imcitin

Imcitin

imipenem + cilastatin

Manufacturer:

M & H Manufacturing

Distributor:

B L H Trading

Marketer:

M & H Manufacturing
Full Prescribing Info
Contents
Imipenem, cilastatin Na.
Description
Each vial contains sterile mixture of Imipenem and Cilastatin Sodium with sodium bicarbonate equivalent to Imipenem 500 mg and Cilastatin 500 mg.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: IMCITIN (imipenem and cilastatin sodium) is a broad spectrum beta­-lactam antibiotic. IMCITIN consists of two components: Imipenem, beta-lactam antibiotic, is a potent inhibitor of bacterial cell wall synthesis by binding to one or more of the penicillin binding protein (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Cilastatin is a specific enzyme inhibitor of dehydropeptidase (DHPI) that blocks the metabolism of imipenem in the kidney, and substantially increases the concentration of intact imipenem in the urinary tract. The antibacterial spectrum of Imipenem is broad including a number of significant pathogens in vitro. Organisms against which lmipenem is usually active include: Aerobic Gram-positive Microorganisms: Staphylococcus aureus (including penicillinase-and nonpenicillinase-producing strains); Staphylococcus epidermidis; Staphylococcus saprophyticus; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Viridans group streptococci; Streptococcus Group C; Streptococcus Group G; Streptococcus Group H; Enterococcus faecalis; Listeria monocytogenes; Bacillus spp.; Nocardia asteroids; Erysipelothrix rhusiopathiae.
But Enterococcus faecium and methicillin-resistant staphylococci are not susceptible to imipenem.
Aerobic Gram-negative Microorganisms: Neisseria gonorrhoeae (including penicillinase-and nonpenicillinase-producing strains); Neisseria meningitides; Haemophilus ducreyi; Haemophilus influenzae (including beta-lactamase and non-beta-lactamase producing strains); Haemophilus parainfluenzae; Enterobacter spp.; Enterobacter agglomerans; Enterobacter cloacae; Enterobacter aerogenes; Escherichia coli; Hafnia alvei; Klebsiella spp.; Klebsiella oxytoca; Klebsiella pneumoniae; Morganella morganii (formerly Proteus morganii); Proteus spp.; Proteus mirabilis; Proteus vulgaris; Providencia spp.; Providencia rettgeri (formerly Proteus rettgetrit); Providencia stuartii; Serratia spp.; Serratia proteamaculans (formerly Serratia liquefaciens); Serratia marcescens; Salmonella spp.; Salmonella typhi; Shigella spp.; Yersinia spp. (formerly Pasteurella); Yersinia enterocolitica; Yersinia pseudotuberculosis; Pseudomonas spp.**; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pseudomonas putida; Acinetobacter spp.; Moraxella catarrhallis (formerly Branhamella catarrhalis); Bordetella bronchiseptica; Eikenella corrodens; Pasteurella multocida; Brucella melitensis; Alcaligenes denitrificans; Alcaligenes xylosoxidans; Aeromonas hydrophila; Plesiomonas shigelloides; Brevundimonas diminuta (formerly Ps. diminuta); Capnocytophaga spp.; Campylobacter spp.; Helicobacter pylori (C.pylori); Legionella pneumophila; Gardnerella vaginalis (formerly Haemophilus vaginalis).
** Stenotrophomonas mallophilia (formerly Pseudomonas meltophilia) and some strains of Burkholderia cepacia (formerly Pseudomonas cepacia) are generally not susceptible to imipenem.
Anaerobic Microorganisms: Actinomyces spp.; Bifidobacterium spp.; Clostridium spp.; Clostridium perfringens; Eubacterium spp.; Lactobacillus spp.; Peptococcus spp.; Peptostreptococcus spp.; Propionbacterium spp.; Bacteroides spp.; Bacteroides fragilis; Bacteroides distasonis; Bacteroides ovatus; Bacteroides thetaiotaomicron; Bacteroides vulgatus; Fusobacterium spp.; Prevotella spp.; Prevotella bivia; Prevotella disiens; Prevotella melaninogenica; Prevotella oralis; Veillonella spp.
Other organism: Mycobacterium fortuitum; Mycobacterium fallax.
Pharmacokinetics: Distribution: Rapidly and widely to most tissues and fluids including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, reproductive organs and bone; highest concentrations in pleural fluid, interstitial fluid, peritoneal fluid and reproductive organ; low concentration in CSF; crosses placenta; enters breast milk.
Metabolism/Excretion: Imipenem is metabolized in the kidney by dehydropeptidase 1; activity is blocked by cilastatin; cilastatin is partially metabolized renally. Half-life elimination is 60 minutes; prolonged with renal impairment. Both drugs are excreted in urine (-70% as unchanged drug).
Indications/Uses
IMCITIN against an unusually broad spectrum of pathogens makes it particularly useful in the treatment of polymicrobial, serious infection and mixed aerobic/anaerobic infections. IMCITIN is indicated for the treatment of the following infections due to susceptible organisms: Respiratory tract infections, intra-abdominal infections, gynecological infections, bone and joint infections, skin and skin structure infections, septicemia, genitourinary tract infections, infective endocarditis.
However, many strain of methicillin-resistant staphylococci are resistant to imipenem.
IMCITIN is not indicated for the treatment of meningitis.
Dosage/Direction for Use
IMCITIN is available in intravenous infusion.
The dosage recommendations for IMCITIN represent the quantity of imipenem to be administered. An equivalent amount of cilastatin is also present.
The total daily dosage and route of administration of IMCITIN should be based on the type or severity of infection and given in equally divided doses based on consideration of degree of susceptibility of the pathogen(s), renal function and body weight. (See Tables 1, 2 and 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Patients with creatinine clearance of ≤5 mL/min/1.73 m2 should not receive IMCITIN unless hemodialysis is instituted within 48 hours.
Patients weighing <30 kg with impaired renal function should not receive IMCITIN.
Hemodialysis: Use the dosing recommendation for patients with a ClCr 6-20 mL/min/1.73 m2.
Peritoenal dialysis: Dose as for ClCr <10 mL/min/1.73 m2.
Administration: Not for direct infusion; vial contents must be transferred to 100 ml of infusion solution; final concentration should not exceed 5 mg/ml; Each dose of 250-500 mg of IMCITIN should be given by intravenous infusion over 20 to 30 minutes. Each dose 1 g of IMCITIN should be infused over 40 to 60 minutes; watch for convulsion. In patients who develop nausea during the infusion, the rate of infusion may be slowed.
Overdosage
Symptoms include neuromuscular hypersensitivity and seizures. Hemodialysis may be helpful to aid in removal of the drug from the blood, otherwise most treatment is supportive or symptom­ directed.
Contraindications
Hypersensitivity to imipenem or any component of this product.
Special Precautions
GENERAL: There is clinical and laboratory evidence of partial cross-allergenicity between imipenem/cilastatin sodium and the other beta-lactam antibiotics, penicillins and cephalosporins. Severe hypersensitivity reactions have been reported with most beta-lactam antibiotics. Before therapy with imipenem/cilastatin sodium, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics. If an allergic reaction to imipenem/cilastatin sodium occurs, the drug should be discontinued and appropriate measures undertaken.
Case reports in the literature have shown that co-administration of carbapenems, including imipenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing tile risk of breakthrough seizures. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction. The concomitant use of imipenem and valproic acid/divalproex sodium is generally not recommended. Anti-bacterials other than carbapenems should be considered to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of IMCITIN is necessary, supplemental anti-convulsant therapy should be considered (see Interactions).
Because Clostridium difficile-associated colitis has been reported with imipenem/cilastatin sodium, therefore, it should be considered and prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
Central Nervous System: As with other beta-lactam antibiotics, CNS side effects such as myoclonic activity, confusional states, or seizures have been reported, especially when recommended dosages based on renal function and body weight were exceeded. These experiences have been reported most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) and/or compromised renal function in whom accumulation of the administered entities could occur. Hence, close adherence to recommended dosage schedules is urged, especially in these patients (see Dosage & Administration).
Anticonvulsant therapy should be continued in patients with a known seizure disorder.
If focal tremors, myoclonus or seizures occur, patients should be evaluated neurologically and placed on anticonvulsant therapy if not already instituted. If CNS symptoms continue, the dosage of imipenem/cilastatin sodium should be decreased or discontinued.
Patients with creatinine clearances of ≤5 mL/min/1.73 m2 should not receive imipenem/cilastatin sodium unless hemodialysis is instituted within 48 hours. For patients on hemodialysis, imipenem/cilastatin sodium is recommend only when the benefit outweighs the potential risk of seizures.
Use in Children: Clinical data are insufficient to recommend the use of imipenem/cilastatin sodium for children under 3 months of age, or pediatric patients with impaired renal function. (See also Dosage & Administration.)
Use In Pregnancy & Lactation
Use in Pregnancy: (Pregnancy Risk Factor: C).
There are no well-controlled or adequate studies in pregnant women. IMCITIN should be used during pregnancy only if the potential benefit justifies the potential risk to mother and fetus.
Use in Lactation: Imipenem has been detected in human milk. If the use of IMCITIN is deemed essential, the patient should stop nursing.
Adverse Reactions
Gastrointestinal Reactions: Nausea, diarrhea, vomiting, staining of teeth and/or tongue. In common with virtually all other broad spectrum antibiotics, pseudomembranous colitis has been reported.
Hematological Effects: Eosinophilia, leukopenia, neutropenia, including agranulocytosis, thrombocytopenia, thrombocytosis, and decreased hemoglobin, pancytopenia and prolonged prothrombin time have been reported. A positive direct Coomb's test may develop in some individuals.
Nervous System/Psychiatric: As with other beta-lactam antibiotics, CNS side effects such as myoclonic activity, psychic disturbances, including hallucination, confusional states, or seizures have been reported, paresthesia, encephalopathy.
Allergic Reactions/Skin: Rash, pruritus, urticaria, erythema multiforme, Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis (rarely), exfoliative dermatitis (rarely), candidiasis, fever including drug fever, anaphylactic reactions.
Renal Function: Oliguria/anuria, polyuria, acute renal failure (rarely). The role of imipenem/cilastatin sodium in changes in renal function is difficult to assess, since factors predisposing to pre-renal azotemia or to impaired renal function usually have been present. Elevations in serum creatinine and blood urea nitrogen have been observed. Urine discoloration. This is harmless and should not be confused with hematuria.
Local Reaction: Erythema, local pain and induration, phlebitis and/or thrombophlebitis.
Liver Function: Increases in serum transaminases, bilirubin and/or serum alkaline phosphatase; hepatic failure (rarely), hepatitis (rarely) and fulminant hepatitis (very rarely).
Other: Hypotension.
Drug Interactions
Generalized seizures have been reported in patients who received ganciclovir and imipenem/cilastatin. These drugs should not be used concomitantly unless the potential benefits outweigh the risks. (See Storage.)
Case reports in the literature have shown that co-administration of carbapenems, including imipenem, to patients receiving valproic acid or divaproex sodium results in a reduction of valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid. (See Precautions.)
Storage
For sterile powder: Store below 30°C.
For reconstituted solution: Table 4 shows the stability period for IMCITIN when reconstituted with selected infusion solutions, and stored at temperature 25°C or under refrigeration (4°C).
Caution: IMCITIN is chemically incompatible with lactate and should not be reconstituted in diluents containing lactate. IMCITIN can be administered, however, into an I.V. system through which a lactate solution is being infused. IMCITIN should not be mixed with or physically added to other antibiotics. (See Table 4.)

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MIMS Class
ATC Classification
J01DH51 - imipenem and cilastatin ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
Presentation/Packing
Powd for inj (vial) (white to light yellow sterile powder) 1's.
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