Kalydeco 150 mg film-coated tablets

  • Name:

    Kalydeco 150 mg film-coated tablets

  • Company:
    info
  • Active Ingredients:

    Ivacaftor

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 25/08/20

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Summary of Product Characteristics last updated on medicines.ie: 25/8/2020

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Vertex Pharmaceuticals (Ireland) Limited

Vertex Pharmaceuticals (Europe) Limited

Company Products

Medicine NameActive Ingredients
Medicine Name Kaftrio 75 mg, 50 mg, 100 mg film coated tablets Active Ingredients Ivacaftor, Tezacaftor, Elexacaftor
Medicine Name Kalydeco 150 mg film-coated tablets Active Ingredients Ivacaftor
Medicine Name Kalydeco 25mg, 50mg and 75mg granules sachets Active Ingredients Ivacaftor
Medicine Name Orkambi 100 mg/125 mg granules and 150 mg/188 mg granules Active Ingredients Ivacaftor, Lumacaftor
Medicine Name Orkambi 200 mg/125 mg tablets and 100mg/125mg tablets Active Ingredients Ivacaftor, Lumacaftor
Medicine Name Symkevi 100 mg/150 mg film coated tablets Active Ingredients Tezacaftor 100mg, Ivacaftor 150mg
1 - 0 of 6 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 25 August 2020 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

SmPC – Kalydeco tablets

Update to Section 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

  • Revised excipient with known effect text to remove “as” to “lactose monohydrate”.

Update to Section 4.1  Therapeutic indications

  • Text revised to clarify Kalydeco monotherapy indication as well as Kalydeco use in combination with tezacaftor 100 mg/ivacaftor 150 mg.
  • Addition of indication for Kalydeco to be used in combination with ivacaftor 75 mg, tezacaftor 50 mg, elexacaftor 100 mg.

Updated text:

In a combination regimen with ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets for the treatment of adults and adolescents aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation in the CFTR gene or heterozygous for F508del in the CFTR gene with a minimal function (MF) mutation.

Updates to Section 4.2 Posology and method of administration

  • Dosing recommendations table included with posology for ivacaftor as monotherapy, in combination with tezacaftor 100 mg/ivacaftor 150 mg and ivacaftor in combination with ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg

Table 1: Dosing recommendations

 

Morning

Evening

Ivacaftor as monotherapy

6 years and older, ≥25 kg

One ivacaftor 150 mg tablet

One ivacaftor 150 mg tablet

Ivacaftor in combination with tezacaftor/ivacaftor

12 years and older

One tezacaftor 100 mg/ivacaftor 150 mg tablet

One ivacaftor 150 mg tablet

Ivacaftor in combination with ivacaftor/tezacaftor/elexacaftor

12 years and older

Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets

One ivacaftor 150 mg tablet

The morning and evening dose should be taken approximately 12 hours apart with fat-containing food (see Method of administration).

Updates to “Missed dose” section to add clarifying text around existing language and also to account for missed dose instructions where Kalydeco is used in a combination regimen.

Updated text:

Missed dose

If 6 hours or less have passed since the missed morning or evening dose, the patient should take it as soon as possible and continue on the original schedule. If more than 6 hours have passed since the time the dose is usually taken, the patient should be told to wait until the next scheduled dose.

Patients receiving ivacaftor in a combination regimen should not take more than one dose of either medicine at the same time.

Update to Concomitant use of CYP3A inhibitors section to include dosing recommendations table for ivacaftor as monotherapy, in combination with tezacaftor 100 mg/ivacaftor 150 mg and ivacaftor in combination with ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg

“Elderly” section updated to summarise language around dose adjustment

Updated text:

Elderly

Very limited data are available for elderly patients treated with ivacaftor (administered as monotherapy or in a combination regimen). No dose adjustment specific to this patient population is required (see section 5.2).

“Hepatic impairment” section updated to include the combination regimen in addition to the monotherapy. Text has been summarised and table updated.

Paediatric population

  • Administrative edits and updated to include ivacaftor/tezacaftor/elexacaftor combination regimen.

Method of administration

  • Information related to tablets not being chewed, crushed or broken before swallowing updated to confirm there is no clinical data to support other methods of administration, therefore tablets should be swallowed whole.

Update to Section 4.4 Special warnings and precautions for use

Minor administrative edits and references made to use of Kalydeco with combination regimens.

Hepatic impairment section updated to include information on use of ivacaftor in a combination regimen for patients with severe and moderate hepatic impairment.

Addition of text:

Hepatic impairment

Use of ivacaftor, either as monotherapy or in a combination regimen with tezacaftor/ivacaftor, is not recommended in patients with severe hepatic impairment unless the benefits are expected to outweigh the risks. Patients with severe hepatic impairment should not be treated with ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor.

For patients with moderate hepatic impairment, use of ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor is not recommended. Treatment should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks. If used, it should be used with caution at a reduced dose.

Renal impairment section updated with minor edits to include information on use of ivacaftor in a combination regimen.

Patients after organ transplantation section updated with minor edits to include information on use of ivacaftor in a combination regimen.

Addition of Rash events section to SmPC

Updated text:

Rash events

The incidence of rash events with ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor was higher in females than in males, particularly in females taking hormonal contraceptives. A role for hormonal contraceptives in the occurrence of rash cannot be excluded. For patients taking hormonal contraceptives who develop rash, interrupting treatment with ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor and hormonal contraceptives should be considered. Following the resolution of rash, it should be considered if resuming ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor without hormonal contraceptives is appropriate. If rash does not recur, resumption of hormonal contraceptives can be considered (see section 4.8).

Updates to Interactions with medicinal products related to the exposure to ivacaftor and tezacaftor, elexacaftor respectively when concomitantly used with CYP3A inducers and CYP3A inihibitors, either as monotherapy or as part of a combination regimen.

Header of sub-section amended to “Paediatric population” instead of “Cataracts” and text updated to refer to ivacaftor monotherapy and as part of a combination regimen.

 

Update to Section 4.5 Interaction with other medicinal products and other forms of interaction

Minor administrative edits to text to reflect ivacaftor as monotherapy and combination regimens throughout this section.

Addition of “verapamil” in the example of moderate CYP3A inhibitors where a reduction in ivacaftor dose is required if concomitantly used (either when used with ivacaftor as monotherapy or as part of a combination regimen).

Subsection related to ivacaftor to interact with transporters has moved position within this section of the SmPC.

 

Administrative edits to section 4.6, 4.7 of SmPC

 

Update to Section 4.8 Undesirable effects

Update adverse events table to include additional adverse effects observed with ivacaftor in a combination regimen with either tezacaftor/ivacaftor and/or ivacaftor/tezacaftor/elexacaftor.

Footnote of table updated to differentiate  adverse effects seen in clinical studies where ivacaftor used in combination with tezacaftor/ivacaftor and/or in combination with ivacaftor/tezacaftor/elexacaftor.

Additional information related to transaminase elevations updated, in addition to new subsections related to “Rash events” and “Increased creatine phosphokinase” and “Increased blood pressure”.

Clinical studies in paediatric population section updated to include data for transaminase elevations in patients 6 months to <12 years treated with ivacaftor as monotherapy.

 

Updates to section 5.1 Pharmacodynamic properties

Minor administrative edits throughout section.

Addition of sweat chloride data for ivacaftor used in combination regimen with ivacaftor/elexacaftor/tezacaftor.

Addition of clinical data for two Phase 3 studies conducted in patients 12 years and older when ivacaftor was used in combination regimen with ivacaftor/tezacaftor/elexacaftor where efficacy and safety were demonstrated.

 

Updates to section 5.2 Pharmacokinetic properties

Minor administrative edits throughout section.

Updates to the Absorption, Distribution, Biotransformation and Elimination subsections.

Updates to special populations ( hepatic impairment and renal impairment subsections) to include information related to combination regimens.

Elderly subsection updated to clarify around PK parameters in patients over 65.

Table in Paediatric population subsection updated to include data on ivacaftor exposure when used in combination with tezacaftor and in combination with tezacaftor/elexacaftor.

Updated on 25 August 2020 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects

Free text change information supplied by the pharmaceutical company

Section 1. What Kalydeco is and what it is used for

  • Update to PIL text to clarify indication for Kalydeco used as monotherapy and in combination regimen.

Warnings and Precautions

  • Addition of ivacaftor/tezacaftor/elexacaftor combination regimen to warning related to increased liver enzymes already in the PIL
  • Addition of precaution to inform your doctor if you are using hormonal contraception such as the contraceptive pill with clarification that some patients may experience rash whilst taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor.
  • Addition of ivacaftor/tezacaftor/elexacaftor combination regimen to cataracts precautions already in the PIL.
  • Reformatting of “other medicines and Kalydeco” section to include medicines in alphabetical order, simplify descriptors and amend subheaders to “Antibiotic medicines” instead of antibacterial agents and Epilepsy medicines from “anticonvulsant medicines”.
  • Addition of verapamil (Medicine for lowering blood pressure) to PIL

Section 3. How to take Kalydeco

  • Addition of dosing recommendation table with minor text amends due to introduction of the table.

Section 4. Possible side effects

  • Minor administrative edits.
  • Subsection “Possible signs of liver problems” included.
  • Updated side effects to also include those possibly experienced when Kalydeco is used in a combination regimen.

Updated on 25 August 2020 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Minor update to Section 5.1 Pharmacodynamic properties

Reference to Completion of Study 661-110 (Study 6)

Previous text:

Kalydeco in a combination regimen with tezacaftor/ivacaftor

The efficacy and safety of Kalydeco in a combination regimen with tezacaftor/ivacaftor in patients with CF was assessed in two clinical studies; a 24 week, randomized, double‑blind, placebo‑controlled study with 504 patients aged 12 years and older who were homozygous for the F508del mutation; and a randomized, double‑blind, placebo‑controlled and ivacaftor controlled, 2 period, 3 treatment, 8‑week crossover study with 244 patients aged 12 years and older who were heterozygous for the F508del mutation and a second mutation associated with residual CFTR activity. An open‑label, rollover, 96-week study is on‑going to evaluate the long‑term safety and efficacy of the combination regimen in both patient populations. Refer to the Summary of Product Characteristics of tezacaftor/ivacaftor for additional data.

Updated text:

Kalydeco in a combination regimen with tezacaftor/ivacaftor

The efficacy and safety of Kalydeco in a combination regimen with tezacaftor/ivacaftor in patients with CF was assessed in two clinical studies; a 24 week, randomized, double‑blind, placebo‑controlled study with 504 patients aged 12 years and older who were homozygous for the F508del mutation; and a randomized, double‑blind, placebo‑controlled and ivacaftor controlled, 2 period, 3 treatment, 8‑week crossover study with 244 patients aged 12 years and older who were heterozygous for the F508del mutation and a second mutation associated with residual CFTR activity. The long-term safety and efficacy of the combination regimen was also assessed in both patient populations in a 96-week open-label, rollover, long-term extension study. Refer to the Summary of Product Characteristics of tezacaftor/ivacaftor for additional data.

Updated on 24 June 2020 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

  • Updates associated to sections 4.1, 4.2 associated with changed to indication stating that Kalydeco tablets can be used for treatment of adults, adolescents and children aged 6 years and older who have an R117H mutation.
  • Updates to sections 4.4 and 5.1 associated with the indication expansion described in section 4.1 and corresponding study data (Study 6) which has been updated/added to the SmPC.

Updated on 24 June 2020 PIL

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - use in children and adolescents

Free text change information supplied by the pharmaceutical company

Updates associated with use of Kalydeco in patients who are 6 years and older with R117H mutation

Previous text:

  1. What Kalydeco is and what it is used for

 

Kalydeco contains the active ingredient ivacaftor. Ivacaftor acts at the level of the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that forms a channel at the cell surface that allows the movement of particles such as chloride in and out of the cell. Due to mutations in the CFTR gene (see below), chloride movement is reduced in those with cystic fibrosis (CF). Ivacaftor helps certain abnormal CFTR proteins open more often to improve chloride movement in and out of the cell.

 

Kalydeco tablets are indicated for the treatment of adults, adolescents and children aged 6 years and older and weighing 25 kg or more with cystic fibrosis (CF) who have one of the following gating mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

 

Kalydeco tablets are also indicated for the treatment of adults aged 18 years and older with CF who have an R117H mutation in the CFTR gene.

Updated text:

  1. What Kalydeco is and what it is used for

 

Kalydeco contains the active ingredient ivacaftor. Ivacaftor acts at the level of the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that forms a channel at the cell surface that allows the movement of particles such as chloride in and out of the cell. Due to mutations in the CFTR gene (see below), chloride movement is reduced in those with cystic fibrosis (CF). Ivacaftor helps certain abnormal CFTR proteins open more often to improve chloride movement in and out of the cell.

 

Kalydeco tablets are indicated for the treatment of adults, adolescents and children aged 6 years and older and weighing 25 kg or more with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

 

Previous text:

Children and adolescents

Do not give this medicine to children under 6 months of age with gating mutations as it is not known if ivacaftor is safe and effective in these children, or in patients under 18 years of age with an R117H mutation as ivacaftor may not work in them.

Do not give this medicine in combination with tezacaftor/ivacaftor to children under 12 years of age as it is not known if they are safe and effective for them.

 

Updated text:

Children and adolescents

Do not give this medicine to children under 6 months of age as it is not known if ivacaftor is safe and effective in these children.

Do not give this medicine in combination with tezacaftor/ivacaftor to children under 12 years of age as it is not known if they are safe and effective for them.

 

 

 

 

 

 

 

 

 

 

 

Updated on 24 February 2020 PIL

Reasons for updating

  • Change to Section 1 - what the product is

Free text change information supplied by the pharmaceutical company

Wording in PIL updated to reflect reference to adults, adolescents and children

Updated on 24 February 2020 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.1 updated wording to reflect adults, adolescents, and children rather than "Cf patients"

Section 4.2 updated wording to reflect license expansion to lower age group

 

Updated on 6 December 2018

Updated on 6 December 2018 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 7 - Marketing authorisation holder

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Removal of black triangle.

Section 4.8: Addition of paediatric data and details of paediatric trial During the 24‑week, open‑label, Phase 3 clinical study in patients aged 12 months to less than 24 months (Study 8), the incidence of patients experiencing transaminase elevations (ALT or AST) >3, >5, and >8 x ULN was 27.8% (5/18), 11.1% (2/18) and 11.1% (2/18), respectively. No patients had elevations in total bilirubin. No patients discontinued ivacaftor treatment due to transaminase elevations. The two patients with elevations of ALT or AST >8 x ULN interrupted treatment and subsequently resumed ivacaftor successfully (see section 4.4 for management of elevated transaminases)."

Section 5.2 updates to Table 7

Section 7 MAH address change

 

Updated on 6 December 2018 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 7 - Marketing authorisation holder

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Note inverted black triangle now removed.

Section 4.8 paediatric population data added, "The safety data of ivacaftor monotherapy were evaluated in 19 patients between 12 months to less than 24 months of age" and data on paediatric trial added "During the 24‑week, open‑label, Phase 3 clinical study in patients aged 12 months to less than 24 months (Study 8), the incidence of patients experiencing transaminase elevations (ALT or AST) >3, >5, and >8 x ULN was 27.8% (5/18), 11.1% (2/18) and 11.1% (2/18), respectively. No patients had elevations in total bilirubin. No patients discontinued ivacaftor treatment due to transaminase elevations. The two patients with elevations of ALT or AST >8 x ULN interrupted treatment and subsequently resumed ivacaftor successfully (see section 4.4 for management of elevated transaminases).

Section 5.2 Table 7 updated with new paediatric data

section 8 Marketing Authorisation Holder address changed

 

 

 

Updated on 8 November 2018 PIL

Reasons for updating

  • Change to Section 1 - what the product is

Updated on 7 November 2018 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - Marketing authorisation number(s)

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

New wording added to sections to reflect updated SmPC

 

Updated on 2 June 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 2 June 2017 SmPC

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.5 - Nature and contents of container
  • Change to section 9 - Date of first authorisation/renewal of the authorisation

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

In section 3: minor editorial changes

In section 4.1: minor editorial changes

In section 4.2: minor editorial changes

In section 4.4: Removal of the warning regarding limited data in patients with FEV1 <40%. Other minor editorial changes

In section 4.5: Removal of the drug-drug interaction information for CYP2C8 substrates. Other minor editorial changes

In section 4.6: minor editorial changes

In section 4.7: minor editorial changes

In section 4.8: minor editorial changes

In section 4.9: minor editorial changes

In section 5.1: minor editorial changes

In section 5.2: minor editorial changes

In section 6.5: minor editorial changes

In section 9: minor editorial changes

Updated on 30 May 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 30 May 2017 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - driving and using machines
  • Change to section 3 - how to take/use
  • Change to section 3 - overdose, missed or forgotten doses
  • Change to section 4 - possible side effects
  • Change to section 5 - how to store or dispose
  • Change to section 6 - what the product contains

Updated on 5 December 2016 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 2: minor editorial changes
Section 4.2: minor editorial changes
Section 4.4: minor editorial changes
Section 4.5: minor editorial changes
Section 4.6: changes in relation to pre-clinical pregnancy, breast-feeding and fertility data
Section 5.1: minor editorial changes
Section 5.2: minor editorial changes
Section 5.3: changes to pre-clinical data on teratogenicity, carcinogenicity and findings of cataracts

Updated on 1 December 2016 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects
  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - manufacturer

Updated on 27 June 2016 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



In section 6.3 of the Tablets SmPC – the shelf life has been changed from ‘30 months’ to ‘4 years’

Updated on 16 January 2016 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



Changes made to Sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 to support introduction of a new indication for the treatment of cystic fibrosis in patients aged 18 years and older who have a R117H mutation in the CFTR gene.

Changes made to Sections 4.1, 4.2, 4.4, 4.8 and 5.2 to support revised dosing recommendations for cystic fibrosis patients aged 6 years and older and weighing 25 kg or more; as well as to align with introduction of the new Kalydeco strengths and pharmaceutical form (Kalydeco granules in sachet).

Additional editorial changes and alignment with QRD templates have been made to Sections 2, 4.5, 4.6, 4.7, 4.8, 5.3, 6.1, 6.5 and 6.6.

Updated on 11 January 2016 PIL

Reasons for updating

  • Change to, or new use for medicine

Updated on 18 September 2015 SmPC

Reasons for updating

  • Change to marketing authorisation holder

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Marketing Authorisation Holder address changed to

Vertex Pharmaceuticals (Europe) Limited

2 Kingdom Street

London W2 6BD

United Kingdom

Tel: +44 (0) 1923 437672

Updated on 17 September 2015 PIL

Reasons for updating

  • Change to MA holder contact details

Updated on 22 June 2015 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



Section 4.8, editorial changes that address the inclusion of Study 111 part 2. (Study 111 part 1 is already in the SmPC)
Section 5.1, detailed explanation of Study 111 part 2

Updated on 9 June 2015 PIL

Reasons for updating

  • Correction of spelling/typing errors

Updated on 4 February 2015 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



Section 4.5: CYP3A inhibitors: Modifications to the wording in the first 2 paragraphs

Section 4.5: CYP3A inducers: Modifications to wording in first paragraph

Section 5.2: Distribution: Deletion of the sentence, “The apparent volume of distribution (Vz/F) of ivacaftor after a single dose of 275 mg in the fed state was similar for healthy subjects and patients with CF.”

Section 5.2: Elimination: change “the 150 md dose” to a single 150 mg dose, and delete the words, “at steady state”

Section 5.2: Paediatric population: Replaced entire paragraph, and added Table 6 just under the new paragraph. New paragraph states:

Non-compartmental analysis of sparse PK samples collected in Phase 3 studies demonstrate an apparent (oral) clearance (CL/F) that was lower in children than in adults and resulted in approximately 47% to 58% higher AUC0-12  and 35% to 46% higher Ctrough in children 6 to <12 years old relative to adults (Table 6). Due to sparse PK sampling ivacaftor volume of distribution and half-life cannot be calculated.


Section 5.3: Changed the number 0.12 to 0.22, and added the clause, “; exposures were obtained by non-compartmental analysis (NCA) of plasma concentrations of all subjects in Study 5”

Updated on 18 December 2014 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Addition of paragraph for Ciprofloxacin stating that ciprofloxacin did not affect exposure of ivacaftor when co-administered, and therefore no dose adjustment is required.

Updated on 4 December 2014 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use

Legal category: Product subject to medical prescription which may be renewed (B)

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Addition of reported cases of non-congenital cataracts without impact on vision in paediatric patients up to 12 years old

Updated on 26 November 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 19 August 2014 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties

Legal category: Product subject to medical prescription which may be renewed (B)

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Overview: Addition of Study 4 (open-label extension study) and associated changes to ADRs in Tables 1 and 2, and addition of new Table 4; and Study 5 (study in patients with non-G551D gating mutations): Extension of Indication to include additional gating (class III) mutations in the CFTR gene: G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N and S549R and associated data.

Section 4.1 (therapeutic indications): added new class III gating mutations; indicated mutations are G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, and S549R

Section 4.2 (posology and method of administration) Updated to note that genotyping should be performed to confirm the presence of one of the indicated class III mutations

Section 4.4: (special warnings and precautions for use) Added information for Study 5

Section 4.8 (undesirable effects):

·        updated summary of the safety profile to include study 5;

·        updated Table 1: changed AR frequency status of dizziness, vestibular disorder, and breast mass; changed N’s to cover study 5

·        updated Table 2: changed AR frequency status of dizziness, diarrhea, and investigations; added tinnitus, sinus congestion, and breast mass as new ARs based on new study 5 data; changed N’s to cover Study 5

Section 5.1 (pharmacodynamics properties):

·        reworded the Mechanism of action description;

·        added efficacy data from Study 5 including new Table 4; added description of Study 5

·        changed description of Study 4 and added new Table 5 to cover efficacy from open-label extension study

Section 5.2 (pharmacokinetic properties): deleted paragraph on pharmacokinetic/pharmacodynamic relationships; changed Paediatric population paragraphs to cover Study 5 PK parameters in this population

Updated on 18 August 2014 PIL

Reasons for updating

  • Change to further information section

Updated on 15 May 2014 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

New text shown in red, deleted text shown by strikethrough

Section 4.2: Concomitant use of CYP3A inhibitors:
When co-administered with potent strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin and clarithromycin), Kalydeco should be administered at a dose of 150 mg twice a week (see sections 4.4 and 4.5).

Section 4.4: Interactions with medicinal products:
Ivacaftor is a substrate of CYP3A4 and CYP3A5 isoenzymes. Medicinal products that inhibit or induce CYP3A activity, may impact the pharmacokinetics of ivacaftor (see section 4.5). The dose of Kalydeco must be adjusted when concomitantly used with strong or moderate CYP3A inhibitors. Exposure to ivacaftor may be reduced by the concomitant use of CYP3A inducers, potentially resulting in loss of Kalydeco efficacy (see sections 4.2 and 4.5).

Ivacaftor is a weak CYP3A inhibitor and may modify the pharmacokinetics of medicinal products metabolised through the CYP3A system. In vitro studies indicated that ivacaftor has the potential to inhibit P-glycoprotein (P-gp) and CYP2C9. Ivacaftor is a weak inhibitor of P-glycoprotein (P-gp) and may increase the exposure of medicinal products that are substrates for P-gp The dose of Kalydeco must be adjusted when concomitantly used with potent and moderate CYP3A inhibitors. Exposure to ivacaftor is reduced by the concomitant use of CYP3A inducers, therefore potentiallyl resulting in loss of efficacy of Kalydeco (see sections 4.2 and 4.5).

Section 4.5: Interaction with other medicinal products and other forms of interaction
Ivacaftor is a substrate of CYP3A4 and CYP3A5. It is a weak inhibitor of CYP3A and P-gp and a potential inhibitor of P-gp and CYP2C9.

Section 4.5: CYP3A, P-gp or CYP2C9 substrates
Based on in vitro results, iIvacaftor and its M1 metabolite have the potential to inhibit CYP3A and P-gp. Co-administration with (oral) midazolam, a sensitive CYP3A substrate, increased midazolam exposure 1.5-fold, consistent with weak inhibition of CYP3A by ivacaftor. Co-administration with digoxin, a sensitive P-gp substrate, increased digoxin exposure by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor.

Updated on 14 March 2014 SmPC

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.8

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to the IMB (see www.imb.ie or e-mail imbpharmacovigilance@imb.ie).

Updated on 21 December 2013 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

None provided

Updated on 20 December 2013 PIL

Reasons for updating

  • New PIL for medicines.ie