Tezacaftor and ivacaftor

What is Tezacaftor and ivacaftor?

• Tezacaftor:

Tezacaftor

1. It is a white to off-white powder that is practically insoluble in water (<5 microgram/mL).
2. Chemical name: 1-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)-N-{1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1Hindol-5-yl}cyclopropane-1-carboxamide
3. Molecular formula: C26H27N2F3O6
4. Molecular weight: 520.50

• Ivacaftor:

Ivacaftor

1. It is a white to off-white powder that is practically insoluble in water (<0.05 microgram/mL).
2. Chemical name: N-(2,4-di-tert-butyl-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide
3. Molecular formula: C24H28N2O3
4. Molecular weight: 392.49

What are the uses of this medicine?

It 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.

How does this medicine work?

Tezacaftor facilitates the cellular processing and trafficking of select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface. For ivacaftor to function CFTR protein must be present at the cell surface. Ivacaftor can potentiate the CFTR protein delivered to the cell surface by tezacaftor, leading to a further enhancement of chloride transport than either agent alone. The combined effect of tezacaftor and ivacaftor is increased quantity and function of CFTR at the cell surface, resulting in increases in chloride transport.

Who Should Not Use this medicine?

None.

What are the brand names and dosage forms of this medicine?

• Brand name: Symdeko; NDC codes: 51167-113-01, 51167-661-01.
• Tablets: Tezacaftor 50 mg/ivacaftor 75 mg fixed-dose combination tablets co-packaged with ivacaftor 75 mg tablets

1. Tezacaftor 50 mg/ivacaftor 75 mg tablets are white, capsule-shaped, and debossed with "V50" on one side and plain on the other.
2. Ivacaftor 75 mg tablets are light blue, capsule-shaped, and printed with "V 75" in black ink on one side and plain on the other.

• Tablets: Tezacaftor 100 mg/ivacaftor 150 mg fixed-dose combination tablets co-packaged with ivacaftor 150 mg tablets

1. Tezacaftor 100 mg/ivacaftor 150 mg tablets are yellow, capsule-shaped, and debossed with "V100" on one side and plain on the other.
2. Ivacaftor 150 mg tablets are light blue, capsule-shaped, and printed with "V 150" in black ink on one side and plain on the other.

Is this medicine FDA approved?

It is approved by US FDA on February 12, 2018.

What are the active and inactive ingredients in Tezacaftor and ivacaftor?

• Active ingredients:

1. Tezacaftor
2. Ivacaftor

• Inactive ingredients:

1. Hypromellose Acetate Succinate
2. Sodium Lauryl Sulfate
3. Hypromellose, Unspecified
4. Microcrystalline Cellulose
5. Croscarmellose Sodium
6. Magnesium Stearate
7. Hydroxypropyl Cellulose, Unspecified
8. Titanium Dioxide
9. Talc
10. Ferric Oxide Yellow
11. Hypromellose 2910 (6 MPA.S)

How should this medicine be used?

• Take SYMDEKO exactly as your doctor tells you to take it.
• Take SYMDEKO by mouth only.
• SYMDEKO consists of 2 different tablets.
• SYMDEKO Tablets (age 6 to less than 12 years weighing less than 30 kg):

1. The white tablet is marked with 'V50' and contains the medicines tezacaftor and ivacaftor. Take 1 white tablet in the morning.
2. The light blue tablet is marked with 'V 75' and contains the medicine ivacaftor. Take 1 light blue tablet in the evening.

• SYMDEKO Tablets (age 6 to less than 12 years weighing 30 kg or more and age 12 years and older):

1. The yellow tablet is marked with 'V100' and contains the medicines tezacaftor and ivacaftor. Take 1 yellow tablet in the morning.
2. The light blue tablet is marked with 'V 150' and contains the medicine ivacaftor. Take 1 light blue tablet in the evening.

• Take the morning and the evening tablet about 12 hours apart.
• Always take SYMDEKO with food that contains fat. Examples of fat-containing foods include eggs, butter, peanut butter, cheese pizza, and whole-milk dairy products such as whole milk, cheese, and yogurt.
• If you miss a dose of SYMDEKO and:

1. it is 6 hours or less from the time you usually take the yellow tablet in the morning or the light blue tablet in the evening, take the missed dose with food that contains fat as soon as you can. Then take your next dose at your usual time.
2. it is more than 6 hours from the time you usually take the yellow tablet in the morning or the light blue tablet in the evening, do not take the missed dose. Take your next dose at the usual time with food that contains fat.

• Do not take more than your usual dose of SYMDEKO to make up for a missed dose.

What side effects can this medication cause?

• High liver enzymes in the blood
• Abnormality of the eye lens (cataract)
• Headache
• Nausea
• Sinus congestion
• Dizziness

What to do in case of emergency/overdose?

• No specific antidote is available for overdose with SYMDEKO. Treatment of overdosage consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

There are limited and incomplete human data from clinical trials and post-marketing reports on the use of SYMDEKO or its individual components, tezacaftor and ivacaftor, in pregnant women to inform a drug-associated risk.

Can this medicine be used in children?

The safety and effectiveness of SYMDEKO for the treatment of CF have been established in pediatric patients age 6 to less than 18 years who are homozygous for the F508del mutation or who have at least one mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor.

What should I know about storage and disposal of this medication?

Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C).

• Dailymed label info on Tezacaftor and ivacaftor
• FDA Tezacaftor and ivacaftor

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