Treatment Eligibility
ARE YOUR PATIENTS ELIGIBLE FOR
SYMDEKO® (tezacaftor/ivacaftor and ivacaftor)?
Enter your patient’s mutations below to see if they are eligible for SYMDEKO.
You may determine eligibility for up to 5 patients at once.
Enter your patient’s mutations below to see if they are eligible for SYMDEKO.
SYMDEKO is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.
SYMDEKO is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.
Most patients have 1 CFTR mutation on each allele. However, in rare instances, a single allele can have more than 1 mutation. This is called a compound, or complex, mutation.
To enter 2 or more mutations into 1 entry field, separate them with a semicolon, space, comma, or forward slash. For example, if your patient's genotype is R74WN201M/D1270N and W1282R, use the Mutation 1 field to enter: R74WN201M/D1270N and the Mutation 2 field to enter: W1282R.
Alternatively, please see the responsive mutations below:
Bold=Mutations approved in December 2020
CFTR Mutations That Produce CFTR Protein and Are Responsive to SYMDEKO 1-3†
546insCTA
F575Y
L346P
R553Q
711+3A→G*
F1016S
L967S
R668C
2789+5G→A*
F1052V
L997F
R751L
3272-26A→G*
F1074L
L1324P
R792G
3849+10kbC→T*
F1099L
L1335P
R933G
A120T
G126D
L1480P
R1066H
A234D
G178E
M152V
R1070Q
A349V
G178R
M265R
R1070W*
A455E*
G194R
M952I
R1162L
A554E
G194V
M952T
R1283M
A1006E
G314E
P5L
R1283S
A1067T
G551D
P67L*
S549N
D110E
G551S
P205S
S549R
D110H*
G576A
Q98R
S589N
D192G
G576A;
R668C‡
Q237E
S737F
D443Y
G622D
Q237H
S912L
D443Y;G576A;R668C‡
G970D
Q359R
S945L*
D579G*
G1069R
Q1291R
S977F*
D614G
G1244E
R31L
S1159F
D836Y
G1249R
R74Q
S1159P
D924N
G1349D
R74W
S1251N
D979V
H939R
R74W;
D1270N‡
S1255P
D1152H*
H1054D
R74W;V201M‡
T338I
D1270N
H1375P
R74W;V201M;D1270N‡
T1036N
E56K
I148T
R75Q
T1053I
E60K
I175V
R117C*
V201M
E92K
I336K
R117G
V232D
E116K
I601F
R117H
V562I
E193K
I618T
R117L
V754M
E403D
I807M
R117P
V1153E
E588V
I980K
R170H
V1240G
E822K
I1027T
R258G
V1293G
E831X
I1139V
R334L
W1282R
F191V
I1269N
R334Q
Y109N
F311del
I1366N
R347H*
Y161S
F311L
K1060T
R347L
Y1014C
F508C
L15P
R347P
Y1032C
F508C;
S1251N‡
L206W*
R352Q*
F508del†
L320V
R352W
*Clinical data for these mutations appears in Clinical Studies can be found here and here or within section 14.1 and 14.2 of the Prescribing Information.
†A patient must have 2 copies of the F508del mutation or at least 1 copy of a responsive mutation listed above in this table to be indicated for SYMDEKO.
‡Complex/compound mutations in which a single allele of the CFTR gene has multiple mutations; these exist independent of the presence of mutations on the other allele.
Indications and Usage
SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.
If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.
Indications and Usage
SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.
If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.
Important Safety Information
Transaminase (ALT or AST) Elevations
- Elevated transaminases have been observed in patients with CF treated with SYMDEKO, as well as with ivacaftor monotherapy. Assessments of transaminases (ALT and AST) are recommended prior to initiating SYMDEKO, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of transaminase elevations, more frequent monitoring should be considered
- Dosing should be interrupted in patients with significant elevations of transaminases (e.g., ALT or AST >5x upper limit of normal [ULN], or ALT or AST >3x ULN with bilirubin >2x ULN) and laboratory tests should be closely followed until abnormalities resolve. Following resolution of transaminase elevations, consider the benefits and risks of resuming treatment
Concomitant Use With CYP3A Inducers
- Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by concomitant use of CYP3A inducers, which may reduce the therapeutic effectiveness of SYMDEKO. Co-administration of SYMDEKO with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John’s wort, is not recommended
Cataracts
- Cases of non-congenital lens opacities have been reported in pediatric patients treated with SYMDEKO, as well as with ivacaftor monotherapy. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with SYMDEKO
Pediatric Use
- The safety and effectiveness of SYMDEKO in patients with CF younger than 6 years of age have not been studied
Serious Adverse Reactions
- Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with SYMDEKO compared to placebo included distal intestinal obstruction syndrome, 3 (0.6%) patients treated with SYMDEKO vs. 0 placebo patients
Most Common Adverse Reactions
- The most common adverse reactions in Trials 1 and 3 occurring in ≥3% of patients treated with SYMDEKO (N=334) and at a higher rate than for placebo (N=343) were headache, nausea, sinus congestion, and dizziness
- The safety profile in patients age 6 to less than 12 years from an open-label Phase 3 trial (N=70) was similar to that observed in Trials 1 and 3
Click here to access full Prescribing Information.
Reference:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. The Clinical and Functional Translation of CFTR (CFTR2); Available at http://cftr2.org. List of CFTR2 mutations. https://www.cftr2.org/mutations_history/CFTR2_11March2019.xlsx. Accessed September 1, 2022. 3. National Center for Biotechnology Information. ClinVar. Available at https://www.ncbi.nlm.nih.gov/clinvar/. Accessed September 1, 2022.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for phe508del. N Engl J Med. 2017;377(21):2013-2023. 3. Cystic Fibrosis Foundation. Patient Registry Annual Data Report 2015. Bethesda, MD. Cystic Fibrosis Foundation; 2016. 4. Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for phe508del. NEngl J Med. 2017;377(21)(suppl1-29):2013-2023. 5. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-0258 (v2.0); 2019. 6. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-0551 (v2.0); 2019. 7. Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest. 2009;135(6):1610-1618.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med. 2017;377(21):2024-2035. 3. Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med. 2017;377(21)(suppl1-25):2024-2035. 4. CFQ-R Cystic Fibrosis Questionnaire-REVISED. Cystic Fibrosis Foundation. Quittner, Modi, Watrous and Messer, 2000. Revised 2002. CFQ-R—Parent, English Version 2.0. 5. Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest. 2009;135(6):1610-1618.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. Walker S, Flume P, McNamara J, et al. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 to 11 years with cystic fibrosis. J Cyst Fibros. 2019:1-6. doi: 10.1016/j.jcf.2019.06.009. 3. Walker S, Flume P, McNamara J, et al. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 to 11 years with cystic fibrosis. J Cyst Fibros. 2019:(suppl1-10). doi: 10.1016/j.jcf.2019.06.009. 4. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-2254; 2019. 5. CFQ-R Cystic Fibrosis Questionnaire- REVISED. Cystic Fibrosis Foundation. Quittner, Modi, Watrous and Messer, 2000. Revised 2002. CFQ-R—Parent, English Version 2.0.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-0004 (v2.0); 2019.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison’s Manual of Medicine. 17th ed. New York, NY: McGraw-Hill Medical; 2009.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-10745 (v2.0); 2021. 3. FDA U.S. Food & Drug Administration. Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed September 1, 2022.
Indications and Usage
SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.
If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.
Important Safety Information
Transaminase (ALT or AST) Elevations
- Elevated transaminases have been observed in patients with CF treated with SYMDEKO, as well as with ivacaftor monotherapy. Assessments of transaminases (ALT and AST) are recommended prior to initiating SYMDEKO, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of transaminase elevations, more frequent monitoring should be considered
- Dosing should be interrupted in patients with significant elevations of transaminases (e.g., ALT or AST >5x upper limit of normal [ULN], or ALT or AST >3x ULN with bilirubin >2x ULN) and laboratory tests should be closely followed until abnormalities resolve. Following resolution of transaminase elevations, consider the benefits and risks of resuming treatment
Concomitant Use With CYP3A Inducers
- Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by concomitant use of CYP3A inducers, which may reduce the therapeutic effectiveness of SYMDEKO. Co-administration of SYMDEKO with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John’s wort, is not recommended
Cataracts
- Cases of non-congenital lens opacities have been reported in pediatric patients treated with SYMDEKO, as well as with ivacaftor monotherapy. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with SYMDEKO
Pediatric Use
- The safety and effectiveness of SYMDEKO in patients with CF younger than 6 years of age have not been studied
Serious Adverse Reactions
- Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with SYMDEKO compared to placebo included distal intestinal obstruction syndrome, 3 (0.6%) patients treated with SYMDEKO vs. 0 placebo patients
Most Common Adverse Reactions
- The most common adverse reactions in Trials 1 and 3 occurring in ≥3% of patients treated with SYMDEKO (N=334) and at a higher rate than for placebo (N=343) were headache, nausea, sinus congestion, and dizziness
- The safety profile in patients age 6 to less than 12 years from an open-label Phase 3 trial (N=70) was similar to that observed in Trials 1 and 3
Click here to access full Prescribing Information.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2022. 2. The Clinical and Functional Translation of CFTR (CFTR2); Available at http://cftr2.org. List of CFTR2 mutations. https://www.cftr2.org/mutations_history/CFTR2_11March2019.xlsx. Accessed September 1, 2022. 3. National Center for Biotechnology Information. ClinVar. Available at https://www.ncbi.nlm.nih.gov/clinvar/. Accessed September 1, 2022.