Tvaxipim

Each combipack contains:

One Vial of Cefepime Hydrochloride USP eq. to Cefepime 1 gm.

(Sterile Mixture of Cefepime Hydrochloride USP and L-Arginine USP)

One 10 ml Ampoule of Sterile water for Injection USP.

Tvaxipim should be used with the following indications:

Adults

Tvaxipim is indicated in the treatment of the infections listed below when caused by susceptible bacteria. Culture and susceptibility studies should be performed to determine susceptibility of the causative organism(s) to cefepime:

• Lower respiratory tract infections: Nosocomial and Community-Acquired Pneumonia caused by Staphylococcus aureus (methicillin-susceptible strains), Pseudomonas aeruginosa, Klebsiella species (including Klebsiella pneumoniae), Enterobacter species, Escherichia coli, Proteus mirabilis, Streptococcus pneumoniae (including intermediate penicillin resistant strains), Haemophilus influenzae (including beta-lactamase producing strains), Haemophilus parainfluenzae and Moraxella (Branhamella) catarrhalis (including beta-lactamase producing strains), including cases associated with Bacteremia. When P. aeruginosa is isolated or suspected, combination therapy with an aminoglycoside should be used.
  Acute Bacterial Exacerbation of Chronic Bronchitis and Acute Bronchitis due to Streptococcus pneumoniae (including intermediate penicillin resistant strains), Haemophilus influenzae (including beta-lactamase producing strains), Moraxella (Branhamella) catarrhalis (including beta-lactamase producing strains).
• Urinary tract infections: Complicated Urinary Tract Infections caused by Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis and Enterobacter species, including cases associated with Bacteremia. When P. aeruginosa is isolated or suspected, combination therapy with an aminoglycoside should be used. Uncomplicated Urinary Tract Infections due to Escherichia coli, Proteus mirabilis, Klebsiella species and Enterobacter species.
• Skin and skin structure infections: caused by Staphylococcus aureus (methicillin-susceptible strains), Streptococcus pyogenes (Group A streptococci), Streptococcus agalactiae (Group B streptococci), other betahaemolytic Streptococcus species, Enterobacter species, Klebsiella species, Proteus mirabilis, Morganella morganii, Escherichia coli, Serratia marcescens and Acinetobacter calcoaceticus.
• Intra-abdominal infections: Complicated Intra-abdominal Infections Including Peritonitis and Biliary Tract Infections caused by Escherichia coli, sensitive Pseudomonas aeruginosa. Peritonitis is often polymicrobial and may include anaerobic microorganisms such as Bacteroides species which are resistant to cefepime. When resistant anaerobes are suspected, cefepime should be combined with an antibiotic effective against these microorganisms, including cases associated with Bacteremia. In patients who are at risk of mixed aerobic-anaerobic infection, including infections in which Bacteroides fragilis may be present, concurrent therapy with an anti-anaerobic agent is recommended.
• Empiric treatment in febrile neutropenia: Combination of cefepime with other appropriate antimicrobial agents should be considered in patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, hypotension at presentation, an underlying haematologic malignancy, or severe or prolonged neutropenia) or when called for by host or local epidemiological factors.

Paediatrics:

Indicated in paediatric patients (2 months and older) for the treatment of the infections listed below when caused by susceptible bacteria, (when P. aeruginosa is isolated or suspected, combination therapy with an aminoglycoside should be used):

• Lower respiratory tract infection: Pneumonia caused by S. aureus, S. pneumoniae, H. influenzae.
• Urinary tract infections: caused by E. coli.
• Skin and skin structure: Infections caused by Staphylococcus epidermidis, streptococcus, S. aureus, S. pyogenes.
• Empiric treatment in febrile neutropenia: Combination of cefepime with other appropriate antimicrobial agents should be considered in patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, hypotension at presentation, an underlying haematologic malignancy, or severe or prolonged neutropenia) or when called for by host or local epidemiological factors.

Tvaxipim can be administered either intravenously or intramuscularly.

The dosage and route vary according to the susceptibility of the causative organisms, the severity of the infection, and the overall condition and renal function of the patient.

Recommended dosage for Adults with Normal Renal Function aged 12 years and older:

Mild to moderate urinary tract infections (uncomplicated and complicated) – 500 mg – 1g, IV or IM, q12h.

Mild to moderate infections including bronchitis, skin and skin-structure infections – 1g, IV or IM, q12h.

Severe infections including pneumonia, urinary tract infections, complicated intra-abdominal infections, including cases with an associated bacteremia – 2g, IV, q12h.

Empiric treatment of fever in neutropenic patients – 2g, IV, q 8h.

Usual duration of therapy is 7-10 days; more severe infections may require longer treatment. In the treatment of betahaemolytic streptococcal infections, a therapeutic dose must be administered for at least 10 days. For empirical treatment of Febrile neutropenia, usual duration of therapy is 7 days or until resolution of neutropenia.

Paediatrics (aged 1 month up to 12 years with normal renal function):
Usual Recommended dosages:

Pneumonia, urinary tract infections, and skin structure infections: Patients 2 months of age with body weight <40 kg: 50 mg/kg q 12 h for 10 days. For more severe infections, a dosage schedule of q 8 h can be used.
Empiric treatment of febrile neutropenia: Patients >2 months of age with body weight <40 kg: 50 mg/kg q8h for 7-10 days.

Experience with the use of Tvaxipim in paediatric patients <2 months of age is limited. While this experience has been attained using the 50 mg/kg dose, modelling of pharmacokinetic data obtained in patients >2 months of age suggests that a dosage of 30 mg/kg q12h or q8h may be considered for patients aged 1 month up to 2 months.

Administration of Tvaxipim in these patients should be carefully monitored.

For paediatric patients with body weights > 40 kg, adult dosing recommendations apply. For patients older than 12 years who are <40 kg, the dosage recommendations for younger patients <40 kg should be used. Dosage in paediatric patients should not exceed the maximum recommended dosage in adults (2g q 8 h). Experience with intramuscular administration in paediatric patients is limited.
Elderly: Dose adjustment is not required, unless there is concurrent renal impairment.
Impaired hepatic function: No adjustment is necessary for patients with impaired hepatic function.

Impaired renal function:

The recommended maintenance doses of cefepime in patients with renal insufficiency:
Creatinine clearance (mL/min) Recommended Maintenance Dosage > 50 Usual doses, no adjustment necessary 2g q 8h, 2g q12h, 1g q 12h, 500 mg q 12h. 30 – 50 1g q 8h, 2g q 24h, 1g q 24h, 500 mg q 24h. 11 – 29 1g q 12h, 1g q 24h, 500 mg q 24h,500 mg q 24h. <10 1g q 24h, 500 mg q 24h, 250 mg q 24h, 250 mg q 24h.

Dialysis Patients:

In patients undergoing haemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period. A repeat dose, equivalent to the initial dose, should be given at the completion of each dialysis session. In patients undergoing continuous ambulatory peritoneal dialysis, cefepime may be administered at the same doses recommended for patients with normal renal function, i.e., 500 mg, 1g or 2g depending on infection severity, but at a dosage interval of every 48 hours.