Zinforo® Summary of 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 (≥18 years of age) patients with Community-acquired pneumonia and Complicated skin and soft tissue infections  (cSSTI). Dosage and Administration: For cSSTI and CAP, Standard dose - 600 mg administered every 12 hours by  intravenous infusion over 5-60 minutes in patients ≥18 years of age and with creatinine clearance (CrCL) >50 mL/min.  cSSTI High dose - cSSTI confirmed or suspected to be caused by S. aureus with an MIC = 2 mg/L or 4 mg/L to  ceftaroline, 600mg administered over 120 mins every 8 hourly. The recommended durations of treatment are 5-14 days  for cSSTI 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 ≤50 mL/min. Standard dose (CAP & cSSTI) – CrCl >30 to ≤50 mL/min – 400 mg every  12 hours with infusion time of 5-60 mins ; CrCl ≥15 to ≤30 mL/min- 300 mg every 12 hours with infusion time of 5-60  mins; ESRD, including haemodialysis- 200mg every 12 hours with infusion time of 5-60 mins. cSSTI confirmed or  suspected to be caused by S. aureus with an MIC = 2 mg/L or 4 mg/L to Ceftaroline-CrCl >30 to ≤50 mL/min 400 mg  every 8 hours with infusion time of 120 mins; CrCl ≥15 to ≤30 mL/min- 300 mg every 8 hours with infusion time of 120  mins; CrCl ESRD, including haemodialysis- 200mg 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 ≤1 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 cSSTI  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 betalactam 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 cSSTI 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 cSSTI 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 (OCT2,  OAT1, and OAT3) 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 ≥3% 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 cSSTI conducted with ceftaroline fosamil  600 mg administered over 120 minutes every 8 hours. Very common reactions ( frequency ≥ 1/10) were Coombs Direct  Test Positive; common reactions (frequency ≥ 1/100 to < 1/10) were rash, pruritus, headache, dizziness, phlebitis,  diarrhea, nausea, vomiting, abdominal pain, increased transaminases, pyrexia, infusion site reactions (erythema,  phlebitis, pain). Pharmaceutical precautions- Shelf-life: 36 months. Storage: Store below 30°C. 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 2-8°C. 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 full prescribing information for complete information.
Adapted from approved Local Product Document of Ceftaroline; LPDZIN072021 effective 31-8-2021. Date of the  document- 03-09-2021.

®Trademark Proprietor ― Forest Laboratories, LLC  
Licensed User ― Pfizer Limited, India.

Reference:
1. Zinforo® (ceftaroline fosamil). Local Product Document of Ceftaroline. LPDZIN072021.

 

PP-ZFO-IND-0352 22 February 2022
Please click on Prescribing Information link to view safety and adverse events information of Zinforo.
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