Ivacaftor ALIUD
CFTR potentiator for the treatment of cystic fibrosis in patients with specific gating mutations
Ivacaftor ALIUD is a CFTR potentiator medicine used to treat cystic fibrosis (CF) in patients who carry specific gating mutations in the CFTR gene. Available as 150 mg film-coated tablets, ivacaftor works by improving the function of the defective CFTR protein at the cell surface, enhancing chloride and bicarbonate transport. This leads to improved lung function, reduced pulmonary exacerbations, and lower sweat chloride levels. Ivacaftor ALIUD requires a prescription and must be taken with fat-containing food for optimal absorption.
Quick Facts
Key Takeaways
- Ivacaftor ALIUD is a targeted therapy for cystic fibrosis patients with specific CFTR gating mutations (e.g., G551D) — genetic testing is required before starting treatment.
- The standard adult dose is 150 mg taken every 12 hours with fat-containing food; dose reductions are necessary when used with strong or moderate CYP3A inhibitors.
- Liver function tests (ALT and AST) must be performed before starting treatment, every 3 months during the first year, and annually thereafter.
- Common side effects include headache, upper respiratory infections, nasal congestion, abdominal pain, and elevated liver enzymes; most are mild to moderate in severity.
- Ivacaftor has been shown to improve lung function (FEV1) by approximately 10 percentage points and significantly reduce sweat chloride levels in clinical trials.
What Is Ivacaftor ALIUD and What Is It Used For?
Ivacaftor ALIUD contains the active substance ivacaftor, which belongs to a class of medicines known as CFTR (cystic fibrosis transmembrane conductance regulator) potentiators. Cystic fibrosis is a genetic disorder caused by mutations in the CFTR gene, which encodes a chloride channel protein on the surface of epithelial cells. When this protein is dysfunctional, it leads to the production of thick, sticky mucus in the lungs, digestive system, and other organs, causing progressive organ damage.
Ivacaftor works by a unique mechanism of action: rather than correcting the folding or processing of the CFTR protein (as CFTR correctors do), ivacaftor increases the probability that the CFTR channel gate is open once it reaches the cell surface. This is particularly relevant for patients with gating mutations, where the CFTR protein reaches the cell membrane but fails to open properly. By enhancing the channel's open probability, ivacaftor restores chloride and bicarbonate transport, improving mucociliary clearance in the airways.
Ivacaftor ALIUD is indicated for the treatment of cystic fibrosis in patients aged 6 years and older who weigh at least 25 kg and who have one of the following gating (Class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R. It may also be used in patients with the R117H mutation, which is a residual function mutation. A CFTR genotyping test must confirm the presence of one of these mutations before treatment is started.
In pivotal clinical trials, ivacaftor demonstrated significant clinical benefits. The landmark STRIVE trial (study in patients with G551D mutation aged 12 years and older) showed a mean absolute improvement in the percentage of predicted FEV1 (forced expiratory volume in one second) of approximately 10.6 percentage points compared to placebo at 24 weeks, along with a 55% reduction in the risk of pulmonary exacerbations. The ENVISION trial in children aged 6–11 showed similar improvements. Additionally, ivacaftor reduced sweat chloride levels by approximately 48 mmol/L, bringing many patients’ sweat chloride concentrations below the diagnostic threshold for cystic fibrosis.
Beyond lung function, ivacaftor has been associated with improvements in nutritional status, as measured by body mass index (BMI), and quality of life as assessed by the Cystic Fibrosis Questionnaire-Revised (CFQ-R). These multisystem benefits reflect the importance of restoring CFTR function across multiple organs, not just the lungs.
What Should You Know Before Taking Ivacaftor ALIUD?
Contraindications
Ivacaftor ALIUD is contraindicated in patients with known hypersensitivity to ivacaftor or to any of the excipients listed in the product composition. There are no absolute organ-function-based contraindications; however, the medicine should be used with extreme caution in patients with severe hepatic impairment (Child-Pugh Class C), and should only be used in this population if the benefits outweigh the risks, at a significantly reduced dose.
Ivacaftor is not effective in patients who are homozygous for the F508del mutation without a concomitant CFTR corrector, because this mutation primarily causes a protein folding defect rather than a gating defect. Using ivacaftor alone in these patients will not provide meaningful clinical benefit.
Warnings and Precautions
Elevated transaminases (ALT/AST) have been reported in patients receiving ivacaftor. Liver function tests must be performed before initiating therapy, every 3 months during the first year of treatment, and annually thereafter. If ALT or AST levels exceed 5 times the upper limit of normal (ULN), or if ALT or AST exceeds 3 times ULN with bilirubin exceeding 2 times ULN, treatment should be interrupted and may only be resumed once liver enzymes have returned to acceptable levels.
Patients with pre-existing hepatic impairment require dose adjustments. For moderate hepatic impairment (Child-Pugh Class B), the dose should be reduced to 150 mg once daily. For severe hepatic impairment (Child-Pugh Class C), ivacaftor should only be used if benefits clearly outweigh risks, with a starting dose no greater than 150 mg every other day.
Cataracts (non-congenital lens opacities) have been reported in paediatric patients treated with ivacaftor. While a causal relationship has not been definitively established, baseline and follow-up ophthalmological examinations are recommended in paediatric patients starting ivacaftor therapy.
Ivacaftor may cause dizziness in some patients. Those who experience dizziness should not drive or operate heavy machinery until they know how the medicine affects them. This is particularly relevant during the initial weeks of treatment when the body is adjusting to the medication.
Pregnancy and Breastfeeding
There is limited clinical data on the use of ivacaftor during pregnancy. Animal reproductive toxicology studies in rats and rabbits have not demonstrated teratogenic effects at doses up to approximately 5 times (rats) and 11 times (rabbits) the maximum recommended human dose based on summed exposures of ivacaftor and its metabolites. However, reductions in maternal body weight and body weight gain were observed in rats at the highest doses tested. As a precautionary measure, ivacaftor should only be used during pregnancy if the expected benefit to the mother justifies any potential risk to the foetus.
Ivacaftor and its metabolites are excreted in the milk of lactating rats. It is unknown whether ivacaftor or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. The decision to continue or discontinue breastfeeding or ivacaftor therapy should be made taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
There are no data on the effect of ivacaftor on human fertility. Ivacaftor had no effect on fertility indices in male and female rats at exposures approximately 5 times and 6 times the maximum recommended human dose, respectively.
How Does Ivacaftor ALIUD Interact with Other Drugs?
Ivacaftor is primarily metabolised by cytochrome P450 3A (CYP3A) enzymes. It is also a weak inhibitor of CYP3A and P-glycoprotein (P-gp). Understanding these metabolic pathways is essential for managing drug interactions safely, as co-administration with CYP3A modulators can profoundly alter ivacaftor plasma concentrations.
The clinical significance of these interactions cannot be overstated. Patients with cystic fibrosis often require multiple concomitant medications, including antibiotics, antifungals, and other therapies, making drug interaction management a critical component of safe prescribing.
Major Interactions
| Interacting Drug | Type | Effect on Ivacaftor | Recommended Action |
|---|---|---|---|
| Ketoconazole | Strong CYP3A inhibitor | ~8.5-fold increase in AUC | Reduce ivacaftor to 150 mg twice weekly |
| Itraconazole | Strong CYP3A inhibitor | Significantly increased exposure | Reduce ivacaftor to 150 mg twice weekly |
| Clarithromycin | Strong CYP3A inhibitor | Significantly increased exposure | Reduce ivacaftor to 150 mg twice weekly |
| Rifampicin | Strong CYP3A inducer | ~89% decrease in AUC | Avoid co-administration |
| St. John’s Wort | Strong CYP3A inducer | Substantially decreased exposure | Avoid co-administration |
| Carbamazepine | Strong CYP3A inducer | Substantially decreased exposure | Avoid co-administration |
| Phenobarbital | Strong CYP3A inducer | Substantially decreased exposure | Avoid co-administration |
Moderate and Minor Interactions
| Interacting Drug | Type | Effect on Ivacaftor | Recommended Action |
|---|---|---|---|
| Fluconazole | Moderate CYP3A inhibitor | ~3-fold increase in AUC | Reduce ivacaftor to 150 mg once daily |
| Erythromycin | Moderate CYP3A inhibitor | Moderately increased exposure | Reduce ivacaftor to 150 mg once daily |
| Grapefruit juice | Moderate CYP3A inhibitor | Moderately increased exposure | Avoid grapefruit or Seville oranges |
| Digoxin | P-gp substrate | ~1.3-fold increase in digoxin AUC | Monitor digoxin levels; adjust if needed |
| Midazolam | Sensitive CYP3A substrate | Mild increase in midazolam exposure | Monitor for increased sedation |
Patients taking ivacaftor should inform all healthcare providers (including pharmacists and dentists) about their medication, as many commonly prescribed antibiotics and antifungals are CYP3A inhibitors. Food interactions are also important: grapefruit juice and Seville oranges contain CYP3A inhibitors and should be avoided during treatment.
What Is the Correct Dosage of Ivacaftor ALIUD?
Ivacaftor ALIUD should only be prescribed by physicians experienced in the management of cystic fibrosis. Treatment initiation requires confirmation of a responsive CFTR mutation through an approved genotyping assay. The dosing regimen depends on the patient’s age, weight, hepatic function, and concomitant medications.
Adults
Standard Adult Dosage
150 mg (one tablet) taken orally every 12 hours with fat-containing food. Examples of appropriate fat-containing foods include eggs, avocado, butter, peanut butter, cheese pizza, or whole-milk dairy products. A meal or snack containing at least 20 grams of fat is recommended to ensure adequate absorption. Without fat, ivacaftor absorption is reduced by approximately 2–4-fold, significantly diminishing therapeutic efficacy.
Adults with Hepatic Impairment
Moderate impairment (Child-Pugh B): 150 mg once daily with fat-containing food.
Severe impairment (Child-Pugh C): 150 mg once daily or less frequently (e.g., every other day); use only if benefits outweigh risks. Close monitoring required.
Adults Taking CYP3A Inhibitors
With strong CYP3A inhibitors: 150 mg twice weekly (approximately 3–4 days apart).
With moderate CYP3A inhibitors: 150 mg once daily.
Children
Children Aged 6 Years and Older (Weighing ≥25 kg)
The dosage is the same as for adults: 150 mg every 12 hours with fat-containing food. For children who cannot swallow tablets, the tablet may be taken with a soft food preparation; however, manufacturers generally recommend that the tablet be swallowed whole. Alternative formulations (e.g., granules) may be available for younger children or those unable to take tablets. Consult the prescribing physician for guidance on alternative formulations.
Ivacaftor ALIUD 150 mg film-coated tablets are not suitable for children under 6 years of age or children weighing less than 25 kg. Other ivacaftor formulations (such as oral granules at lower strengths) are available for younger and smaller paediatric patients; these are separate products with different dosing instructions.
Elderly
There is limited clinical experience with ivacaftor in elderly patients (over 65 years). Cystic fibrosis is predominantly a disease of younger populations, and clinical trial data in elderly patients are sparse. No specific dose adjustment is recommended based on age alone. However, elderly patients may have diminished hepatic and renal function, and careful clinical monitoring is advised. Dose adjustments should be guided by hepatic function status rather than age.
Missed Dose
If a dose is missed within 6 hours of the usual dosing time, the patient should take the missed dose with fat-containing food as soon as possible, then resume the normal dosing schedule. If more than 6 hours have elapsed since the missed dose, the patient should skip the missed dose and take the next dose at the regularly scheduled time. The dose should not be doubled to make up for a forgotten dose, as this increases the risk of side effects without providing additional therapeutic benefit.
Overdose
There is no specific antidote for ivacaftor overdose. Treatment should be symptomatic and supportive. In clinical studies, single doses up to 800 mg were administered to healthy volunteers without dose-limiting adverse events. The most commonly reported symptoms at higher doses included headache, dizziness, and gastrointestinal disturbance. In case of overdose, contact your local poison control centre or seek emergency medical attention. General supportive measures including monitoring of vital signs and observation of clinical status are recommended.
| Patient Group | Standard Dose | With Strong CYP3A Inhibitor | With Moderate CYP3A Inhibitor |
|---|---|---|---|
| Adults | 150 mg every 12 hours | 150 mg twice weekly | 150 mg once daily |
| Children ≥6 years (≥25 kg) | 150 mg every 12 hours | 150 mg twice weekly | 150 mg once daily |
| Moderate hepatic impairment | 150 mg once daily | 150 mg twice weekly | 150 mg twice weekly |
| Severe hepatic impairment | 150 mg once daily or less | Use with extreme caution | Use with extreme caution |
What Are the Side Effects of Ivacaftor ALIUD?
Like all medicines, Ivacaftor ALIUD can cause side effects, although not everybody gets them. The side effect profile has been well characterised through extensive clinical trials involving over 1,000 patients and post-marketing surveillance. The majority of adverse reactions are mild to moderate in intensity and tend to decrease over time with continued treatment.
The following side effects have been categorised by frequency according to the MedDRA convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), and rare (<1/1,000).
Very Common (≥1 in 10 patients)
Affects more than 10% of patients
- Headache
- Upper respiratory tract infection (common cold, sore throat, rhinitis)
- Nasal congestion
- Abdominal pain or discomfort
- Oropharyngeal pain (sore throat)
- Diarrhoea
- Rash
Common (≥1 in 100 patients)
Affects 1–10% of patients
- Elevated transaminases (ALT/AST)
- Dizziness
- Nausea
- Ear pain or discomfort
- Tympanic membrane hyperaemia (ear redness)
- Rhinorrhoea (runny nose)
- Pharyngeal erythema (throat redness)
- Bacteria in sputum
- Acne
- Breast mass or tenderness (particularly in adolescents)
Uncommon (≥1 in 1,000 patients)
Affects 0.1–1% of patients
- Hepatic encephalopathy (in patients with pre-existing liver disease)
- Significantly elevated bilirubin
- Tinnitus (ringing in the ears)
- Non-congenital lens opacities (cataracts) in paediatric patients
- Gynaecomastia
- Nipple inflammation or pain
Rare (<1 in 1,000 patients)
Affects fewer than 0.1% of patients
- Severe hepatotoxicity with jaundice
- Hypersensitivity reactions
- Severe rash requiring treatment discontinuation
Contact your doctor immediately or seek emergency care if you experience: yellowing of the skin or eyes (jaundice), dark urine, persistent nausea or vomiting, upper right abdominal pain, unusual fatigue, or signs of allergic reaction such as difficulty breathing, swelling of the face or throat, or severe skin rash.
It is important to note that some apparent “side effects” may actually be symptoms of improved CFTR function. For example, increased sputum production during the initial weeks of treatment may reflect improved mucociliary clearance rather than worsening infection. Similarly, gastrointestinal symptoms may be related to improved pancreatic function and changes in digestive capacity. These effects typically settle within the first few weeks of therapy.
If you experience any side effects, including those not listed here, talk to your doctor or pharmacist. You can also report side effects directly via your national pharmacovigilance reporting system, which helps provide more information on the safety of this medicine.
How Should You Store Ivacaftor ALIUD?
Proper storage of Ivacaftor ALIUD is essential to maintain the medicine’s effectiveness and safety throughout its shelf life. The film-coated tablets should be stored at room temperature, not exceeding 30°C (86°F). The medicine should be kept in its original blister packaging or container to protect it from moisture, as ivacaftor is sensitive to humidity. Do not remove the tablets from their packaging until you are ready to take them.
Keep the medicine out of the reach and sight of children, ideally in a locked medicine cabinet or a high shelf that is not accessible to young children. This is particularly important in households where children with cystic fibrosis are being treated, as overdosing could occur if a child takes additional doses unsupervised.
Do not use Ivacaftor ALIUD after the expiry date (EXP) stated on the blister, bottle, and carton. The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help to protect the environment and ensure that unused medications are handled safely.
If you notice any visible deterioration of the tablets (e.g., discolouration, crumbling, unusual odour, or damaged packaging), do not take the medicine and consult your pharmacist for a replacement. Tablets that have been stored outside the recommended conditions may have reduced potency and should be discarded according to your local pharmaceutical waste guidelines.
What Does Ivacaftor ALIUD Contain?
The active substance in Ivacaftor ALIUD is ivacaftor. Each film-coated tablet contains 150 mg of ivacaftor. Ivacaftor has the molecular formula C24H28N2O3 and a molecular weight of 392.49 g/mol. It is a white to off-white crystalline powder that is practically insoluble in water.
The other ingredients (excipients) serve specific pharmaceutical functions. While the exact excipient composition of generic formulations may vary, typical inactive ingredients in ivacaftor film-coated tablets include:
- Tablet core: Microcrystalline cellulose (filler/binder), lactose monohydrate (filler), hypromellose acetate succinate (matrix former), croscarmellose sodium (disintegrant), sodium laurilsulfate (wetting agent), colloidal anhydrous silica (glidant), and magnesium stearate (lubricant).
- Film coating: Polyvinyl alcohol, titanium dioxide (E171, for opacity and colour), macrogol/PEG (plasticiser), talc (anti-tacking agent), and indigo carmine aluminium lake (E132, for colour) or iron oxide pigments for colour differentiation.
Ivacaftor ALIUD tablets may contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine. If you have a known intolerance to any excipient, discuss this with your doctor or pharmacist before starting treatment. The sodium content is generally below 1 mmol (23 mg) per tablet and can be considered essentially sodium-free.
The film-coated tablet is designed for oral administration. The film coating helps protect the tablet from moisture and makes it easier to swallow. The tablets are typically light blue, capsule-shaped, and debossed with identifying markings on one side. The specific appearance may vary between manufacturers, so always check that the tablets match the description provided with your prescription.
Frequently Asked Questions About Ivacaftor ALIUD
Ivacaftor ALIUD is a CFTR potentiator used to treat cystic fibrosis (CF) in patients aged 6 years and older who weigh 25 kg or more and carry specific CFTR gating mutations, such as G551D. It improves the function of the defective CFTR protein, enhancing chloride transport and improving lung function, reducing pulmonary exacerbations, and lowering sweat chloride levels.
Ivacaftor ALIUD 150 mg should be taken orally every 12 hours with fat-containing food. Fat-containing food is essential for proper absorption — examples include eggs, butter, peanut butter, avocado, or whole-milk dairy products. The tablet should be swallowed whole and not chewed, crushed, or broken. Always follow your prescribing physician’s specific dosing instructions.
The most common side effects (affecting more than 1 in 10 patients) include headache, upper respiratory tract infections, nasal congestion, abdominal pain, oropharyngeal pain, diarrhoea, and rash. Elevated liver enzymes are common (affecting 1–10% of patients) and require regular monitoring. Most side effects are mild to moderate and tend to decrease with continued treatment.
There is limited clinical data on the use of ivacaftor during pregnancy. Animal studies have not shown harmful effects at clinically relevant doses. However, ivacaftor should only be used during pregnancy if the potential benefit justifies the potential risk to the foetus. If you are pregnant, planning a pregnancy, or breastfeeding, discuss this with your prescribing physician to make an informed decision.
Yes, ivacaftor is metabolised by CYP3A enzymes, so strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin) significantly increase ivacaftor levels and require dose reduction to 150 mg twice weekly. Strong CYP3A inducers (rifampicin, St. John’s Wort, carbamazepine) substantially reduce ivacaftor levels and should be avoided. Grapefruit juice and Seville oranges should also be avoided. Always tell all your healthcare providers about all medicines you take.
Ivacaftor is effective for specific CFTR gating mutations including G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, and S549R, as well as the R117H residual function mutation. These mutations cause the CFTR channel to remain closed at the cell surface. A CFTR genotyping test is mandatory before starting treatment to confirm that you carry one of these responsive mutations.
References
This article is based on the following peer-reviewed sources and regulatory documents:
- European Medicines Agency (EMA). Kalydeco (ivacaftor) — Summary of Product Characteristics. EMA/CHMP, last updated 2024. Available at: www.ema.europa.eu
- Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. New England Journal of Medicine. 2011;365(18):1663-1672. doi:10.1056/NEJMoa1105185
- Davies JC, Wainwright CE, Canny GJ, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. American Journal of Respiratory and Critical Care Medicine. 2013;187(11):1219-1225. doi:10.1164/rccm.201301-0153OC
- De Boeck K, Munck A, Walker S, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. Journal of Cystic Fibrosis. 2014;13(6):674-680. doi:10.1016/j.jcf.2014.09.005
- US Food and Drug Administration (FDA). Kalydeco (ivacaftor) Prescribing Information. Revised 2024. Available at: www.fda.gov
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd List. Geneva: WHO; 2023.
- Cystic Fibrosis Foundation. CFTR Modulator Therapies. Updated 2024. Available at: www.cff.org
- British National Formulary (BNF). Ivacaftor. National Institute for Health and Care Excellence (NICE), 2024.
- McKone EF, Borowitz D, Drevinek P, et al. Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST). Lancet Respiratory Medicine. 2014;2(11):902-910. doi:10.1016/S2213-2600(14)70218-8
- Accurso FJ, Rowe SM, Clancy JP, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. New England Journal of Medicine. 2010;363(21):1991-2003. doi:10.1056/NEJMoa0909825
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians with specialisations in pulmonology, clinical pharmacology, and internal medicine.
iMedic Medical Editorial Team — specialists with clinical and research experience in respiratory medicine, cystic fibrosis management, and pharmaceutical sciences.
iMedic Medical Review Board — an independent panel that reviews all content according to EMA, FDA, WHO, and BNF guidelines using the GRADE evidence framework.
All medical claims in this article are based on Evidence Level 1A (systematic reviews and meta-analyses of randomised controlled trials) or authoritative regulatory documentation (EMA SmPC, FDA prescribing information). This content is independently produced with no pharmaceutical company funding or commercial sponsorship.