Primaxin I.m.

Treatment: The activity of Primaxin I.m. against an unusually broad spectrum of pathogens makes it particularly useful in the treatment of polymicrobic and mixed aerobic/anaerobic infections, as well as initial therapy prior to the identification of the causative organisms. Primaxin I.m. is indicated for the treatment of the following infections due to susceptible organisms: Intra-abdominal infections; lower respiratory tract and gynecological infections; septicemia; genitourinary tract, bone and joint, and skin and soft tissue infections; infective endocarditis.

Primaxin I.m. is indicated for the treatment of mixed infections caused by susceptible strains of aerobic and anaerobic bacteria. The majority of these mixed infections are associated with contamination by fecal flora or flora originating from the vagina, skin and mouth. In these mixed infections, Bacteroides fragilis is the most commonly encountered anaerobic pathogen and is usually resistant to aminoglycosides, cephalosporins and penicillins. However, Bacteroides fragilis is usually susceptible to Primaxin I.m..

Primaxin I.m. has demonstrated efficacy against many infections caused by aerobic and anaerobic gram-positive and gram-negative bacteria resistant to the cephalosporins, including cefazolin, cefoperazone, cephalothin, cefoxitin, cefotaxime, moxalactam, cefamandole, ceftazidime and ceftriaxone. Similarly, many infections caused by organisms resistant to aminoglycosides (gentamicin, amikacin, tobramycin) and/or penicillins (ampicillin, carbenicillin, penicillin-G, ticarcillin, piperacillin, azlocillin, mezlocillin) responded to treatment with Primaxin I.m.. However, many strains of methicillin-resistant Staphylococci are resistant to Imipenem (Primaxin I.m.).

Primaxin I.m. is not indicated for the treatment of meningitis.

Prophylaxis: Primaxin I.m. is also indicated for the prevention of certain post-operative infections in patients undergoing contaminated or potentially contaminated surgical procedures or where the occurrence of postoperative infection could be especially serious.

Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) combination is used in the treatment of infections caused by bacteria. It works by killing bacteria or preventing their growth. Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) will not work for colds, flu, or other virus infections.

Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) combination is used to treat infections in many different parts of the body. It is sometimes given with other antibiotics.

Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) combination is used in certain patients with the following medical conditions:

• Febrile neutropenia (treatment)
• Melioidosis (treatment)

Primaxin I.m. is available as IV infusion.

The dosage recommendations for Primaxin I.m. represent the quantity of Imipenem (Primaxin I.m.) to be administered. An equivalent amount of Cilastatin (Primaxin I.m.) is also present.

The total daily dosage and route of administration of Primaxin I.m. 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.

IV Infusion: Treatment: Adults with Normal Renal Function: Doses cited in Table 1 are based on a patient with normal renal function (CrCl >70 mL/min/1.73 m²) and a body weight of ≥70 kg.

A reduction in dose must be made for a patient with a CrCl ≤70 mL/min/1.73 m² and/or a body weight <70 kg. The reduction for body weight is especially important for patients with much lower body weights and/or moderate/severe renal insufficiency.

When the 500-mg dose is used in patients with CrCl 6-20 mL/min/1.73 m², there may be an increased risk of seizures.

Patients with CrCl ≤5 mL/min/1.73 m² should not receive Primaxin I.m. IV unless hemodialysis is instituted within 48 hrs.

Hemodialysis: When treating patients with CrCl ≤5 mL/min/1.73 m² who are undergoing hemodialysis, use the dosage recommendations for patients with CrCl 6-20 mL/min/1.73 m².

Both Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) are cleared from the circulation during hemodialysis. The patient should receive Primaxin I.m. IV after hemodialysis and at 12-hr intervals timed from the end of that hemodialysis session. Dialysis patients, especially those with background CNS disease, should be carefully monitored; for patients on hemodialysis, Primaxin I.m. IV is recommended only when the benefit outweighs the potential risk of seizures.

Currently, there are inadequate data to recommend use of Primaxin I.m. IV for patients on peritoneal dialysis.

Renal status of elderly patients may not be accurately portrayed by measurement of BUN or creatinine alone. Determination of CrCl is suggested to provide guidance for dosing in such patients.

Prophylaxis: Adults: For prophylaxis against post-surgical infections in adults, 1000 mg Primaxin I.m. IV should be given IV on induction of anesthesia and 1000 mg 3 hrs later. For high-risk (eg, colorectal) surgery, 2 additional 500-mg doses can be given at 8 and 16 hrs after induction.

There are insufficient data on which to base a dosage recommendation for prophylaxis in patients with a CrCl ≤70 mL/min/1.73 m².

Treatment: Children ≥3 months: For children and infants, the following dosage schedule is recommended: Children ≥40 kg body weight should receive adult doses. Children and infants <40 kg body weight should receive 15 mg/kg at 6-hr intervals. The total daily dose should not exceed 2 g.

Clinical data are insufficient to recommend dosing for children <3 months or pediatric patients with impaired renal function (serum creatinine >2 mg/dL).

Primaxin I.m. is not recommended for the therapy of meningitis. If meningitis is suspected, an appropriate antibiotic should be used.

Primaxin I.m. may be used in children with sepsis as long as they are not suspected of having meningitis.

Reconstitution: Primaxin I.m. for IV infusion is supplied as a sterile powder in vials containing 500 mg Imipenem (Primaxin I.m.) equivalent and 500 mg cilastin equivalent.

Primaxin I.m. IV is buffered with sodium bicarbonate to provide solutions in the pH range of 6.5-8.5. There is no significant change in pH when solutions are prepared and used as directed.

Sterile powder Primaxin I.m. should be reconstituted as shown in Table 3. It should be shaken until a clear solution is obtained. Variations of color, from colorless to yellow, do not affect the potency of the product.

Stability: Table 4 shows the stability period for Primaxin I.m. IV when reconstituted with selected infusion solutions and stored at room temperature or under refrigeration.

Caution: Primaxin I.m. IV is chemically incompatible with lactate and should not be reconstituted in diluents containing lactate. Primaxin I.m. IV can be administered, however, into an IV system through which a lactate solution is being infused.

Primaxin I.m. IV should not be mixed with or physically added to other antibiotics.

See also:
What is the most important information I should know about Primaxin I.m.?

Primaxin I.m. is contraindicated in patients with preexisting renal impairment. Primaxin I.m. should not be employed in myelosuppressed patients, or patients with hearing impairment.

Primaxin I.m. is contraindicated in patients with a history of allergic reactions to cisplatin or other platinum-containing compounds.

Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) is injected into a vein (IV) or into a muscle (IM).

Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) is usually given in a clinic or hospital setting. The IV medicine must be given as a slow infusion and can take up to an hour to complete. Tell your caregiver if you feel nauseated during the infusion. You may need to receive the medicine at a slower rate.

The IM form of Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) is given as a rapid injection into a muscle. You may be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

Primaxin IM (for the muscle) and Primaxin I.m. (for the vein) are different forms of this medicine and should be used only for their specific type of injection. Do not inject Primaxin IM into a vein and do not inject Primaxin I.m. into a muscle.

Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) is usually given as long as needed until your infection has cleared or you have been symptom-free for at least 48 hours.

Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) will not treat a viral infection such as the common cold or flu.

Do not give this medication to another person, even if they have the same symptoms you do.

Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) is a powder that must be mixed with a liquid (diluent). Primaxin IM and Primaxin I.m. are each mixed with different types of diluent.

Prepare your dose in a syringe only when you are ready to give yourself an injection.

After mixing Primaxin I.m., you may keep it in a refrigerator and use it within 24 hours.

You may also store the mixed IV medicine at room temperature if you use it within 4 hours. Store unmixed Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) powder at room temperature away from moisture and heat.

Use: Labeled Indications

Bacterial septicemia: Treatment of septicemia caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing), Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Serratia species, Enterobacter species, Bacteroides species (including Bacteroides fragilis).

Bone and joint infections: Treatment of bone and joint infections caused by E. faecalis, S. aureus (penicillinase-producing), Staphylococcus epidermidis, Enterobacter species, P. aeruginosa.

Endocarditis: Treatment of endocarditis caused by S. aureus (penicillinase-producing).

Gynecologic infections: Treatment of gynecologic infections caused by E. faecalis; S. aureus (penicillinase-producing), S. epidermidis, Streptococcus agalactiae (group B streptococci), E. coli, Klebsiella species, Proteus species, Enterobacter species, Bifidobacterium species, Bacteroides species (including B. fragilis), Gardnerella vaginalis; Peptococcus species, Peptostreptococcus species, Cutibacterium species.

Intra-abdominal infections: Treatment of intra-abdominal infections caused by E. faecalis, S. aureus (penicillinase-producing), S. epidermidis, E. coli, Klebsiella species, Enterobacter species, Proteus species, Morganella morganii, P. aeruginosa, Citrobacter species, Clostridium species, Bacteroides species (including B. fragilis), Fusobacterium species, Peptococcus species, Peptostreptococcus species, Eubacterium species, Cutibacterium species, Bifidobacterium species.

Lower respiratory tract infections: Treatment of lower respiratory tract infections caused by S. aureus (penicillinase-producing), E. coli, Klebsiella species, Enterobacter species, Haemophilus influenzae, Haemophilus parainfluenzae, Acinetobacter species, Serratia marcescens.

Skin and skin structure infections: Treatment of skin and skin structure infections caused by E. faecalis, S. aureus (penicillinase-producing), S. epidermidis, E. coli, Klebsiella species, Enterobacter species, Proteus vulgaris, Providencia rettgeri, M. morganii, P. aeruginosa, Serratia species, Citrobacter species, Acinetobacter species, Bacteroides species (including B. fragilis), Fusobacterium species, Peptococcus species, Peptostreptococcus species.

Urinary tract infections (complicated and uncomplicated): Treatment of uncomplicated and complicated urinary tract infections caused by E. faecalis, S. aureus (penicillinase-producing), E. coli, Klebsiella species, Enterobacter species, P. vulgaris, Providencia rettgeri, M. morganii, P. aeruginosa.

Limitations of use: Not indicated in patients with meningitis because safety and efficacy have not been established; not recommend in pediatric patients with CNS infections because of the risk of seizures.

Off Label Uses

Burkholderia pseudomallei (melioidosis)

Data from a randomized, comparative treatment study support the use of Imipenem (Primaxin I.m.)/Cilastatin (Primaxin I.m.) in the treatment of severe melioidosis ).

See also:
What other drugs will affect Primaxin I.m.?

Generalized seizures have been reported in patients who received ganciclovir and Primaxin I.m. IV. These drugs should not be used concomitantly unless the potential benefits outweigh the risks.

Also see Stability, Primaxin I.m. IV under Storage.

Case reports in the literature have shown that co-administration of carbapenems, including Imipenem (Primaxin I.m.), to patients receiving valproic acid or divalproex 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.

Incompatibilities: Caution: Primaxin I.m. IV is chemically incompatible with lactate and should not be reconstituted in diluents containing lactate. Primaxin I.m. IV can be administered, however, into an IV system through which a lactate solution is being infused.

Primaxin I.m. IV should not be mixed with or physically added to other antibiotics.

See also:
What are the possible side effects of Primaxin I.m.?

Imipenem (Primaxin I.m.)/Cilastatin (Primaxin I.m.) injection (Primaxin I.m.) is generally well tolerated. The most frequently reported systemic adverse clinical reactions that were reported as possibly, probably, or definitely, related to Imipenem (Primaxin I.m.)/Cilastatin (Primaxin I.m.) injection (Primaxin I.m.) were nausea (2%), diarrhea (1.8%), vomiting (1.5%), rash (0.9%), fever (0.5%), hypotension (0.4%), seizures (0.4%), dizziness (0.3%), pruritus (0.3%), urticaria (0.2%), somnolence (0.2%).

Additional adverse systemic clinical reactions reported as possibly, probably, or definitely drug related occurring in less than 0.2% of the patients or reported since the drug was marketed are listed within each body system in order of decreasing severity: Gastrointestinal: Pseudomembranous colitis (the onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment), hemorrhagic colitis, hepatitis, jaundice, gastroenteritis, abdominal pain, glossitis, tongue papillar hypertrophy, staining of the teeth and/or tongue, heartburn, pharyngeal pain, increased salivation.

Hematologic: Pancytopenia, bone marrow depression, thrombocytopenia, neutropenia, leukopenia, hemolytic anemia.

CNS: Encephalopathy, tremor, confusion, myoclonus, paresthesia, vertigo, headache, psychic disturbances including hallucinations.

Special Senses: Hearing loss, tinnitus, taste perversion.

Respiratory: Chest discomfort, dyspnea, hyperventilation, thoracic spine pain.

Cardiovascular: Palpitations, tachycardia.

Skin: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioneureticedema, flushing, cyanosis, hyperhidrosis, skin texture changes, candidiasis, pruritus vulvae.

Body as a Whole: Polyarthralgia, asthenia/weakness, drug fever.

Renal: Acute renal failure; oliguria/anuria, polyuria, urine discoloration. The role of Imipenem (Primaxin I.m.)/Cilastatin (Primaxin I.m.) injection (Primaxin I.m.) 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.

Each vial of powder for injection contains Imipenem (Primaxin I.m.) equivalent to anhydrous Imipenem (Primaxin I.m.) 500 mg and Cilastatin (Primaxin I.m.) sodium equivalent to anhydrous Cilastatin (Primaxin I.m.) 500 mg.

It also contains sodium bicarbonate as buffer.

Primaxin I.m. is a sterile formulation of Imipenem (Primaxin I.m.) (a thienamycin antibiotic) and Cilastatin (Primaxin I.m.) sodium (the inhibitor of the renal dipeptidase, dehydropeptidase l). Imipenem (Primaxin I.m.) and Cilastatin (Primaxin I.m.) combination is a potent broad spectrum antibacterial for intravenous administration.

Imipenem (Primaxin I.m.) (N-formimidoylthienamycin) is a derivative of thienamycin, which is produced by Streptomyces cattleya. Its chemical name is (5R,6S)-3-[[2-(formimidoylamino)ethyl]thio]-6-[(R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid. It has a molecular weight of 299.37 and an empirical formula of C₁₂H₁₇N₃O₄S.

Cilastatin (Primaxin I.m.) sodium is the sodium salt of a derivatized heptenoic acid. It is chemically designated as sodium (Z)-7[[(R)-2-amino-2-carboxyethyl]thio]-2-[(S)2,2-dimethylcyclopropanecarboxamido]-2-heptenoate. It has a molecular weight of 380.43 and an empirical formula of C₁₆H₂₅N₂O₅SNa.