Prescribing Information

ZINFORO^® Summary of Product Information
 

Generic Name: Ceftaroline fosamil powder for concentrate for solution for infusion.

Presentation: Each vial contains ceftaroline fosamil acetic acid solvate monohydrate equivalent to ceftaroline fosamil 600 mg. Dosage Form: Sterile powder for concentrate for solution for infusion. Strength: 600 mg/vial. Pack Size: The medicinal product is supplied in packs of 10 vials. Active ingredient: Ceftaroline Fosamil. 

Indications: Treatment of adult (218 years of age) patients with Community-acquired pneumonia and Complicated skin and soft tissue infections (cSSTl).

Dosage and Administration: For cSSTl and CAP, Standard dose - 600 mg administered every 12 hours by intravenous infusion over 5-60 minutes in patients 218 years of age and with creatinine clearance (CrCL) > 50 mL/min. cSSTl High dose - cSSTl confirmed or suspected to be caused by S. aureus with an MIC = 2 mg/L or 4 mg/L to ceftaroline, 600 mg administered over 120 mins every 8 hourly. The recommended durations of treatment are 5-14 days for cSSTl and 5-7 days for CAP. For patients with supranormal renal clearance receiving the standard dose, an infusion time of 60 minutes may be preferable. Infusion times of less than 60 minutes and high dose recommendations are based on pharmacokinetic and pharmacodynamic analyses only. For treatment of S. aureus for which the ceftaroline MIC is 1 mg/L, the standard dose is recommended. For patients with Renal impairment- The dose should be adjusted when creatinine clearance (CrCL) is mL/min. Standard dose (CAP & cSSTl) — CrCl >30 to ml/ min — 400 mg every 12 hours with infusion time of 5-60 mins ; CrCl 215 to GO mL/min- 300 mg every 12 hours with infusion time of 5-60 mins; ESRD, including haemodialysis- 200 mg every 12 hours with infusion time of 5- 60 mins. cSSTl confirmed or suspected to be caused by S. aureus with an MIC = 2 mg/L or 4 mg/L to Ceftaroline- CrCl >30 to mL/min 400 mg every 8 hours with infusion time of 120 mins; CrCl 215 to GO mL/min- 300 mg every 8 hours with infusion time of 120 mins; CrCl ESRD, including haemodialysis- 200 mg every 8 hours with infusion time of 120 mins. CrCL should be closely monitored and the dose adjusted according to changing renal function. Ceftaroline is haemodialyzable; thus ceftaroline fosamil should be administered after haemodialysis on haemodialysis days. For treatment of S. aureus for which the ceftaroline MIC is Sl mg/L, the standard dose is recommended. Hepatic impairment- No dosage adjustment is considered necessary in patients with hepatic impairment and for the elderly with creatinine clearance (CrCL) values >50 ml/min. Pregnancy - As a precautionary measure, it is preferable to avoid the use of ceftaroline fosamil during pregnancy unless the clinical condition of the woman requires treatment with an antibiotic with ceftaroline fosamil's antibacterial profile. Breast feeding- It is unknown whether ceftaroline fosamil or ceftaroline is excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ceftaroline fosamil therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Method of administration- intravenous use. Ceftaroline fosamil is administered by intravenous infusion over 5 to 60 minutes for standard dose or 120 minutes for high dose (for cSSTl caused by S. aureus with MIC of 2 or 4 mg/L to ceftaroline) in infusion volumes of 50 ml, 100 ml or 250 ml. Infusion related reactions (such as phlebitis) can be managed by prolonging the infusion duration.

Contraindication: Hypersensitivity to the active substance or to any of its excipients. Hypersensitivity to the cephalosporin class of antibacterials. Immediate and severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins or carbapenems).

Warnings & Precautions: Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity reactions are possible. Patients who have a history of hypersensitivity to cephalosporins, penicillins or other beta-lactam antibacterials may also be hypersensitive to ceftaroline fosamil. Ceftaroline should be used with caution in patients with a history of non- severe hypersensitivity reactions to any other beta-lactam antibiotics (e.g. penicillins or carbapenems). If a severe allergic reaction or SCAR occurs during treatment with ceftaroline fosamil, the medicinal product should be discontinued and appropriate measures taken. Clostridium difficile-associated diarrhoea- Antibacterial- associated colitis and pseudomembranous colitis have been reported with ceftaroline fosamil and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of ceftaroline fosamil. In such circumstance, the discontinuation of therapy with ceftaroline fosamil and the use of supportive measures together with the administration of specific treatment for Clostridium difficile should be considered. Non-susceptible organisms- Superinfections may occur during or following treatment with ceftaroline fosamil. Patients with pre-existing seizure disorder: Seizures have occurred in toxicology studies at 7-25 times human ceftaroline Cmax levels. Clinical study experience with ceftaroline fosamil in patients with preexisting seizure disorders is very limited. Therefore, ceftaroline fosamil should be used with caution in this patient population. Direct antiglobulin test (Coombs test) seroconversion and potential risk of haemolytic anaemia: The development of a positive direct antiglobulin test (DAGT) may occur during treatment with cephalosporins. In clinical studies there was no evidence of haemolysis in patients who developed a positive DAGT on treatment. However, the possibility that haemolytic anaemia may occur in association with cephalosporins including ceftaroline fosamil treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with ceftaroline fosamil should be investigated for this possibility. Limitations of the clinical data: There is no experience with ceftaroline in the treatment of CAP in the following patient groups: the immunocompromised, patients with severe sepsis/septic shock, severe underlying lung disease, those with PORT Risk Class V, and/or CAP requiring ventilation at presentation, CAP due to methicillin-resistant S. aureus or patients requiring intensive care. Caution is advised when treating such patients. There is no experience with ceftaroline in the treatment of cSSTl in the following patient groups: the immunocompromised, patients with severe sepsis/septic shock, necrotizing fasciitis, perirectal abscess and patients with third degree and extensive burns. There is limited experience in treating patients with diabetic foot infections. Caution is advised when treating such patients. Ceftaroline fosamil should not be used to treat cSSTl due to S. aureus for which the ceftaroline MIC is >4 mg/L.

Drug Interactions: No clinical drug-drug interaction studies have been conducted with ceftaroline fosamil. The interaction potential of ceftaroline or ceftaroline fosamil on medicinal products metabolised by CYP450 enzymes is expected to be low since they are not inhibitors nor inducers of CYP450 enzymes in vitro. Ceftaroline or ceftaroline fosamil are not metabolised by CYP450 enzymes in vitro, therefore co-administered CYP450 inducers or inhibitors are unlikely to influence the pharmacokinetics of ceftaroline. Ceftaroline is neither a substrate, nor an inhibitor of renal uptake transporters (OCT 2, OAT 1, and OAT 3) in vitro. Therefore, interactions of ceftaroline with medicinal products that are substrates or inhibitors (e.g. probenecid) of these transporters would not be expected.

Overdose: Limited data in patients receiving higher than recommended Zinforo dosages show similar adverse reactions as observed in the patients receiving recommended dosages. Relative overdosing could occur in patients with moderate renal impairment. Treatment of overdose should follow local standard medical practice. Ceftaroline can be removed by haemodialysis; over a 4-hour dialysis period, approximately 74% of a given dose was recovered in the dialysate.

Adverse reactions: The most common adverse reactions occurring in 23% of approximately 3242 patients treated with Ceftaroline in clinical studies were diarrhoea, headache, nausea, and pruritus, and were generally mild or moderate in severity. CDAD and severe hypersensitivity reactions may also occur. A greater incidence of rash in Asian patients and a greater incidence of DAGT seroconversion (see section were observed in a study of adult patients with cSSTl conducted with ceftaroline fosamil 600 mg administered over 120 minutes every 8 hours. Very common reactions (frequency 21/10) were Coombs Direct Test Positive; common reactions (frequency 21/100 to < 1/10) were rash, pruritus, headache, dizziness, phlebitis, diarrhoea, nausea, vomiting, abdominal pain, increased transaminases, pyrexia, infusion site reactions (erythema, phlebitis, pain). 

Pharmaceutical precautions- Shelf-life: 36 months. Storage: Store below 300C. Store in the original package in order to protect from light. The constituted vial should be used immediately. After dilution- Once the intravenous solution is prepared with diluents it should be administered within 6 hours of preparation. The chemical and physical in-use stability has been demonstrated for up to 24 hours at 2-80C. Once removed from refrigeration to room temperature, the diluted product must be used within 6 hours. 

Pharmacodynamics/pharmacokinetics- The mean plasma ceftaroline M-1 to ceftaroline AUC ratio following a single 600 mg intravenous infusion of ceftaroline fosamil in healthy subjects is approximately 20-30%. The mean terminal elimination half-life of ceftaroline in healthy adults is approximately 2.5 hours.

Refer to the full prescribing information for complete information.
Adapted from approved Local Product Document of Ceftaroline; LPDZlN072021 effective 31-8-2021.

Date of the document: 03-09-2021
Trademark Proprietor — Forest Laboratories, LLC
Licensed User — Pfizer Limited, India