TRIKAFTA SIDE EFFECTS
- Generic Name: lexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets
- Brand Name: Trikafta
- Drug Class: How Do CFTR Correctors Work?, CFTR Potentiators
SIDE EFFECTS
The following adverse reaction is discussed in greater detail in other sections of the label:
- Liver Function Test Elevations
- Cataracts
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety profile of TRIKAFTA is based on data from 510 CF patients in two double-blind, controlled trials of 24 weeks and 4 weeks treatment duration (Trials 1 and 2). Eligible patients were also able to participate in an open-label extension safety study (up to 96 weeks of TRIKAFTA). In the two controlled trials, a total of 257 patients aged 12 years and older received at least one dose of TRIKAFTA.
In Trial 1, the proportion of patients who discontinued study drug prematurely due to adverse events was 1% for TRIKAFTA-treated patients and 0% for placebo-treated patients.
Serious adverse reactions that occurred more frequently in TRIKAFTA-treated patients compared to placebo were rash (1% vs <1%) and influenza (1% vs 0). There were no deaths in Trials 1 and 2.
Table 1 shows adverse reactions occurring in ≥5% of TRIKAFTA-treated patients and higher than placebo by ≥1% in the 24-week placebo-controlled, parallel-group trial (Trial 1).
Table 1: Incidence of Adverse Drug Reactions in ≥5% of TRIKAFTA-Treated Patients and Higher than Placebo by ≥1%
| Adverse Drug Reactions (Preferred Term) | TRIKAFTA N=202 n (%) |
Placebo N=201 n (%) |
| Headache | 35 (17) | 30 (15) |
| Upper respiratory tract infectiona | 32 (16) | 25 (12) |
| Abdominal painb | 29 (14) | 18 (9) |
| Diarrhea | 26 (13) | 14 (7) |
| Rashc | 21 (10) | 10 (5) |
| Alanine aminotransferase increased | 20 (10) | 7 (3) |
| Nasal congestion | 19 (9) | 15 (7) |
| Blood creatine phosphokinase increased | 19 (9) | 9 (4) |
| Aspartate aminotransferase increased | 19 (9) | 4 (2) |
| Rhinorrhea | 17 (8) | 6 (3) |
| Rhinitis | 15 (7) | 11 (5) |
| Influenza | 14 (7) | 3 (1) |
| Sinusitis | 11 (5) | 8 (4) |
| Blood bilirubin increased | 10 (5) | 2 (1) |
| a Includes upper respiratory tract infection and viral upper respiratory tract infection b Includes abdominal pain, abdominal pain upper, abdominal pain lower c Includes: rash, rash generalized, rash erythematous, rash macular, rash pruritic |
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Additional adverse reactions that occurred in TRIKAFTA-treated patients at a frequency of 2 to <5% and higher than placebo by ≥1% include the following: Flatulence, abdominal distension, conjunctivitis, pharyngitis, respiratory tract infection, tonsillitis, urinary tract infection, c-reactive protein increased, hypoglycemia, dizziness, dysmenorrhea, acne, eczema, and pruritus.
Rash Events
In Trial 1, the overall incidence of rash events was 10% in TRIKAFTA-treated and 5% in placebo-treated patients (see Table 3). The incidence of rash events was higher in female TRIKAFTA-treated patients (16%) than in male TRIKAFTA-treated patients (5%).
Hormonal contraceptives may play a role in the occurrence of rash. For patients taking hormonal contraceptives who develop rash, consider interrupting TRIKAFTA and hormonal contraceptives. Following the resolution of rash, consider resuming TRIKAFTA without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.
Laboratory And Vital Sign Abnormalities
Liver Function Test Elevations
In Trial 1, the incidence of maximum transaminase (ALT or AST) >8, >5, or >3 x ULN was 1%, 2%, and 8% in TRIKAFTA-treated patients and 1%, 1%, and 5% in placebo-treated patients. The incidence of adverse reactions of transaminase elevations (AST and/or ALT) was 11% in TRIKAFTA-treated patients and 4% placebo-treated patients.
In Trial 1, the incidence of maximum total bilirubin elevation >2 x ULN was 4% in TRIKAFTA-treated patients and <1% in placebo-treated patients. Maximum indirect and direct bilirubin elevations >1.5 x ULN occurred in 11% and 3% of TRIKAFTA-treated patients, respectively. No TRIKAFTA-treated patients developed maximum direct bilirubin elevation >2 x ULN.
Increased Creatine Phosphokinase
In Trial 1, the incidence of maximum creatine phosphokinase elevation >5 x ULN was 10% in TRIKAFTA-treated and 5% in placebo-treated patients. Among the TRIKAFTA-treated patients with creatine phosphokinase elevation >5 x ULN, 14% (3/21) required treatment interruption and none discontinued treatment.
Increased Blood Pressure
In Trial 1, the maximum increase from baseline in mean systolic and diastolic blood pressure was 3.5 mmHg and 1.9 mmHg, respectively for TRIKAFTA-treated patients (baseline: 113 mmHg systolic and 69 mmHg diastolic) and 0.9 mmHg and 0.5 mmHg, respectively for placebo-treated patients (baseline: 114 mmHg systolic and 70 mmHg diastolic).
The proportion of patients who had systolic blood pressure >140 mmHg and 10 mmHg increase from baseline on at least two occasions was 4% in TRIKAFTA-treated patients and 1% in placebo-treated patients. The proportion of patients who had diastolic blood pressure >90 mmHg and 5 mmHg increase from baseline on at least two occasions was 1% in TRIKAFTA-treated patients and 2% in placebo-treated patients.
With the exception of sex differences in rash, the safety profile of TRIKAFTA was generally similar across all subgroups of patients, including analysis by age, sex, baseline percent predicted FEV1 (ppFEV1), and geographic regions.
The safety profile for the CF patients enrolled in Trial 2 was similar to that observed in Trial 1.
SRC: NLM .