Trikafta Side Effects Center

Last updated on RxList: 10/14/2021
Trikafta Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Trikafta?

Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) is a combination of ivacaftor, a CFTR potentiator, tezacaftor, and elexacaftor used to treat cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation.

What Are Side Effects of Trikafta?

Side effects of Trikafta include:

Dosage for Trikafta

The morning dose of Trikafta for adults and pediatric patients aged 12 years and older is two elexacaftor 100 mg, tezacaftor 50 mg and ivacaftor 75 mg tablets. The evening dose of Trikafta for adults and pediatric patients aged 12 years and older is one ivacaftor 150 mg tablet. The morning and evening doses of Trikafta should be taken approximately 12 hours apart with fat-containing food.

Trikafta In Children

The safety and effectiveness of Trikafta in patients with CF younger than 12 years of age has not been established.

What Drugs, Substances, or Supplements Interact with Trikafta?

Trikafta may interact with other medicines such as:

Tell your doctor all medications and supplements you use.

Trikafta During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Trikafta; it is unknown how it would affect a fetus. It is unknown if any of the drugs in Trikafta pass into breast milk or how they might affect a nursing infant. Consult your doctor before breastfeeding.

Additional Information

Our Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) Co-Packaged for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

COPD (chronic obstructive pulmonary disease) is the same as adult-onset asthma. See Answer
Trikafta Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • vision changes; or
  • liver problems--loss of appetite, stomach pain (upper right side), dark urine, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • headache;
  • diarrhea, stomach pain;
  • rash;
  • abnormal lab tests;
  • flu symptoms such as fever, chills, body aches; or
  • cold symptoms such as stuffy nose, sinus pain, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Trikafta (Lexacaftor, Tezacaftor and Ivacaftor Tablets; Ivacaftor Tablets)

SLIDESHOW

COPD Foods to Boost Your Health - COPD Diet Tips See Slideshow
Trikafta Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

  • Elevated Transaminases and Hepatic Injury [see WARNINGS AND PRECAUTIONS]
  • Cataracts [see WARNINGS AND PRECAUTIONS]

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 aged 12 years and older 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 addition, the following clinical trials have also been conducted [see Use In Specific Populations and CLINICAL PHARMACOLOGY]:

  • a 24-week open-label trial in 66 patients with CF aged 6 to less than 12 years who were either homozygous for the F508del mutation or heterozygous for the F508del mutation and a mutation on the second allele that results in either no CFTR protein or a CFTR protein that is not responsive to ivacaftor and tezacaftor/ivacaftor (Trial 3)

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.

In Trial 1, 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, 2 and 3.

Table 4 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 4: Adverse Drug Reactions in ≥5% of TRIKAFTA-Treated Patients and Higher than Placebo by ≥1% in Trial 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)
aIncludes upper respiratory tract infection and viral upper respiratory tract infection
bIncludes abdominal pain, abdominal pain upper, abdominal pain lower
cIncludes: rash, rash generalized, rash erythematous, rash macular, rash pruritic

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.

The safety profile for the CF patients enrolled in Trial 2 and Trial 3 was similar to that observed in Trial 1.

Rash Events

In Trial 1, the overall incidence of rash events was 10% in TRIKAFTA-treated and 5% in placebo-treated patients (see Table 4). 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% in 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.

During Trial 3, in patients aged 6 to less than 12 years, the incidence of maximum transaminase (ALT or AST) >8, >5, and >3 x ULN were 0%, 1.5%, and 10.6%, respectively. No TRIKAFTA-treated patients had transaminase elevation >3 x ULN associated with elevated total bilirubin >2 x ULN or discontinued treatment due to transaminase elevations.

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.

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of TRIKAFTA. Because these 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.

Liver failure leading to transplantation in a patient with pre-existing cirrhosis and portal hypertension. Liver injury characterized by concomitant transaminase (ALT and AST) and total bilirubin elevations [see WARNINGS AND PRECAUTIONS].

DRUG INTERACTIONS

Potential for other drugs to affect elexacaftor/tezacaftor/ivacaftor

Inducers Of CYP3A

Elexacaftor, tezacaftor and ivacaftor are substrates of CYP3A (ivacaftor is a sensitive substrate of CYP3A). Concomitant use of CYP3A inducers may result in reduced exposures and thus reduced TRIKAFTA efficacy. Co-administration of ivacaftor with rifampin, a strong CYP3A inducer, significantly decreased ivacaftor area under the curve (AUC) by 89%. Elexacaftor and tezacaftor exposures are expected to decrease during co-administration with strong CYP3A inducers. Therefore, co-administration of TRIKAFTA with strong CYP3A inducers is not recommended [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Examples of strong CYP3A inducers include:

  • rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin and St. John’s wort (Hypericum perforatum)

Inhibitors Of CYP3A

Co-administration with itraconazole, a strong CYP3A inhibitor, increased elexacaftor AUC by 2.8-fold and tezacaftor AUC by 4.0 to 4.5-fold. When co-administered with itraconazole and ketoconazole, ivacaftor AUC increased by 15.6-fold and 8.5-fold, respectively. The dosage of TRIKAFTA should be reduced when co-administered with strong CYP3A inhibitors [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Examples of strong CYP3A inhibitors include:

  • ketoconazole, itraconazole, posaconazole and voriconazole
  • telithromycin and clarithromycin

Simulations indicated that co-administration with moderate CYP3A inhibitors may increase elexacaftor and tezacaftor AUC by approximately 1.9 to 2.3-fold and 2.1-fold, respectively. Co-administration of fluconazole increased ivacaftor AUC by 2.9-fold. The dosage of TRIKAFTA should be reduced when co administered with moderate CYP3A inhibitors [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Examples of moderate CYP3A inhibitors include:

  • fluconazole
  • erythromycin

Co-administration of TRIKAFTA with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure of elexacaftor, tezacaftor and ivacaftor; therefore, food or drink containing grapefruit should be avoided during treatment with TRIKAFTA [see DOSAGE AND ADMINISTRATION].

Ciprofloxacin

Ciprofloxacin had no clinically relevant effect on the exposure of tezacaftor or ivacaftor and is not expected to affect the exposure of elexacaftor. Therefore, no dose adjustment is necessary during concomitant administration of TRIKAFTA with ciprofloxacin [see CLINICAL PHARMACOLOGY].

Potential for elexacaftor/tezacaftor/ivacaftor to affect other drugs

CYP2C9 Substrates

Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) during co administration of TRIKAFTA with warfarin is recommended. Other medicinal products for which exposure may be increased by TRIKAFTA include glimepiride and glipizide; these medicinal products should be used with caution [see CLINICAL PHARMACOLOGY].

Transporters

Co-administration of ivacaftor or tezacaftor/ivacaftor with digoxin, a sensitive P-gp substrate, increased digoxin AUC by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor. Administration of TRIKAFTA may increase systemic exposure of medicinal products that are sensitive substrates of P-gp, which may increase TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor; ivacaftor) Tablets or prolong their therapeutic effect and adverse reactions. When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as cyclosporine, everolimus, sirolimus and tacrolimus, caution and appropriate monitoring should be used [see CLINICAL PHARMACOLOGY].

Elexacaftor and M23-ELX inhibit uptake by OATP1B1 and OATP1B3 in vitro. Co-administration of TRIKAFTA may increase exposures of medicinal products that are substrates of these transporters, such as statins, glyburide, nateglinide and repaglinide. When used concomitantly with substrates of OATP1B1 or OATP1B3, caution and appropriate monitoring should be used [see CLINICAL PHARMACOLOGY]. Bilirubin is an OATP1B1 and OATP1B3 substrate.

Hormonal Contraceptives

TRIKAFTA has been studied with ethinyl estradiol/levonorgestrel and was found to have no clinically relevant effect on the exposures of the oral contraceptive.

TRIKAFTA is not expected to have an impact on the efficacy of oral contraceptives.

Read the entire FDA prescribing information for Trikafta (Lexacaftor, Tezacaftor and Ivacaftor Tablets; Ivacaftor Tablets)

© Trikafta Patient Information is supplied by Cerner Multum, Inc. and Trikafta Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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