TEFLARO SIDE EFFECTS
- Generic Name: ceftaroline fosamil injection for intravenous (iv) use
- Brand Name: Teflaro
- Drug Class: Cephalosporins, Other
SIDE EFFECTS
The following serious adverse reactions are described in greater detail in the Warnings and Precautions section
- Hypersensitivity Reactions
- Clostridioides difficile-Associated diarrhea
- Neurological Adverse Reactions
- Direct Coombs’ Test Seroconversion
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared directly to rates from clinical trials of another drug and may not reflect rates observed in practice.
Adult Patients
Teflaro was evaluated in four controlled comparative Phase 3 clinical trials (two in ABSSSI and two in CABP) which included 1300 adult patients treated with Teflaro (600 mg administered by IV over 1 hour every 12h) and 1297 patients treated with comparator (vancomycin plus aztreonam or ceftriaxone) for a treatment period up to 21 days. The median age of patients treated with Teflaro was 54 years, ranging between 18 and 99 years old. Patients treated with Teflaro were predominantly male (63%) and Caucasian (82%).
Serious Adverse Reactions And Adverse Reactions Leading To Discontinuation
In the four pooled adult Phase 3 clinical trials, serious adverse reactions (SARs) occurred in 98/1300 (7.5%) of patients receiving Teflaro and 100/1297 (7.7%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 35/1300 (2.7%) of patients receiving Teflaro and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse reactions leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the Teflaro group and 0.5% in comparator group.
Most Common Adverse Reactions
No adverse reactions occurred in greater than 5% of adult patients receiving Teflaro. The most common adverse reactions occurring in > 2% of patients receiving Teflaro in the pooled adult phase 3 clinical trials were diarrhea, nausea, and rash.
Table 1 lists adverse reactions occurring in ≥ 2% of patients receiving Teflaro in the pooled adult Phase 3 clinical trials.
Table 1: Adverse Reactions Occurring in ≥ 2% of Patients Receiving Teflaro in the Pooled Adult Phase 3 Clinical Trials
| Adverse Reactions | Pooled Phase 3 Clinical Trials (four trials, two in ABSSSIand two in CABP) | |
| Teflaro (N=1300) |
Pooled Comparatorsa (N=1297) |
|
| Gastrointestinal Disorders | ||
| Diarrhea | 5 % | 3 % |
| Nausea | 4 % | 4 % |
| Constipation | 2 % | 2 % |
| Vomiting | 2 % | 2 % |
| Laboratory Investigations | ||
| Increased transaminases | 2% | 3 % |
| Metabolism and Nutrition disorders | ||
| Hypokalemia | 2 % | 3 % |
| Skin and Subcutaneous Tissue Disorders | ||
| Rash | 3% | 2% |
| Vascular Disorders | ||
| Phlebitis | 2% | 1% |
| a Comparators included vancomycin 1gram IV every 12h plus aztreonam 1 gram IV every 12 hin the Phase 3 ABSSSI trials, and ceftriaxone 1 gram IV every 24 hin the Phase 3 CABP trials. | ||
Other Adverse Reactions Observed During Clinical Trials Of Teflaro
Following is a list of additional adverse reactions reported by the 1740 adult patients who received Teflaro in any clinical trial with incidences less than 2%.
Blood and lymphatic system disorders –Anemia, Eosinophilia, Neutropenia, Thrombocytopenia
Cardiac disorders –Bradycardia, Palpitations
Gastrointestinal disorders –Abdominal pain
General disorders and administration site conditions –Pyrexia
Hepatobiliary disorders –Hepatitis
Immune system disorders –Hypersensitivity, Anaphylaxis
Infections and infestations –Clostridioides difficile colitis
Metabolism and nutrition disorders –Hyperglycemia, Hyperkalemia
Nervous system disorders –Dizziness, Convulsion
Renal and urinary disorders –Renal failure
Skin and subcutaneous tissue disorders –Urticaria
Pediatric Patients
Teflaro was evaluated in three clinical trials (one in ABSSSI and two in CABP) which included 257 pediatric patients 2 months to < 18 years of age treated with Teflaro, and 102 patients treated with comparator agents for a treatment period up to 21 days. In two trials, one in ABSSSI and one in CABP, the dose was selected to result in exposures comparable to adult exposure with 600 mg administered by IV infusion every 12h. In an additional pediatric trial in complicated CABP the dose was higher. The median age of pediatric patients treated with Teflaro was 5 years, ranging from 2 months to < 18 years of age. Patients treated with Teflaro were predominantly male (55%) and Caucasian (92%).
A single study enrolled 11 pediatric patients with a gestational age of ≥34 weeks and a postnatal age of 12 days to less than 2 months of age. The safety findings were similar to those observed in adult and pediatric patients 2 months of age and older.
Serious Adverse Reactions And Adverse Reactions Leading To Discontinuation
In the three pooled pediatric clinical trials, SARs occurred in 10/257 (4%) of patients receiving Teflaro and 3/102 (3%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 10/257 (3.9%) of patients receiving Teflaro and 2/102 (2%) of patients receiving comparator drugs with the most common adverse reaction leading to discontinuation being rash in 2/257 (0.8%) of patients treated with Teflaro.
Most Common Adverse Reactions
No adverse reactions occurred in greater than 8% of pediatric patients receiving Teflaro. The most common adverse reactions occurring in ≥ 3% of patients receiving Teflaro in the pooled pediatric clinical trials were diarrhea, nausea, vomiting, pyrexia and rash.
Table 2 lists adverse reactions occurring in ≥ 3% of patients receiving Teflaro in the pooled pediatric clinical trials.
Table 2: Adverse Reactions Occurring in ≥ 3% of Patients Receiving Teflaroin the Pooled Pediatric Clinical Trials
| Adverse Reactions | Pooled Pediatric Clinical Trials (three trials, one in AB SSSI and two in CABP) | |
| Teflaro (N=257) |
Pooled Comparatorsa (N=l 02) |
|
| Gastrointestinal Disorders | ||
| Diarrhea | 8 % | 10 % |
| Nausea | 3 % | 1 % |
| Vomiting | 5 % | 12 % |
| General and Administrative Site disorders | ||
| Pyrexia | 3% | 2 % |
| Skin and Subcutaneous Tissue Disorders | ||
| Rash | 7% | 4% |
| a Comparators included vancomycin or cefazolin with or without aztreonam in the ABSSSI trial and ceftriaxone alone or ceftriaxone plus vancomycin in the CABP trials | ||
Following is a list of additional adverse reactions reported by the 257 patients who received Teflaro in the pediatric clinical trials with incidences less than 3%.
Investigations – Alanine aminotransferase increased, Aspartate aminotransferase increased
Nervous system disorders – Headache
Skin and subcutaneous tissue disorders-Pruritus
Postmarketing Experience
The following adverse reactions have been identified during post approval use of Teflaro in adult patients. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: Agranulocytosis, leukopenia, eosinophilic pneumonia.
Nervous system disorders: Encephalopathy, seizures.
SRC: NLM .