Ivacaftor STADA Nordic

What Is Ivacaftor STADA Nordic and What Is It Used For?

Cystic fibrosis (CF) is a serious, progressive genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The CFTR protein functions as a chloride and bicarbonate channel on the surface of epithelial cells throughout the body. When this protein is absent, non-functional, or poorly functioning, the transport of chloride ions and water across cell membranes is disrupted, leading to the production of thick, sticky mucus that clogs the lungs and digestive system.

Ivacaftor belongs to a class of drugs known as CFTR potentiators. Unlike CFTR correctors (such as lumacaftor or tezacaftor), which help the misfolded CFTR protein reach the cell surface, ivacaftor works by increasing the probability that the CFTR channel will open once it is at the cell surface. This mechanism is particularly effective in patients who carry gating mutations, where the CFTR protein reaches the cell surface normally but has a defect in channel gating — the process by which the channel opens and closes.

The European Medicines Agency (EMA) has approved ivacaftor for the treatment of cystic fibrosis in patients aged 6 years and older who weigh at least 25 kg and have one of the following gating mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R. Additionally, ivacaftor is approved for patients with an R117H CFTR mutation. The G551D mutation is the most common gating mutation, present in approximately 4–5% of all CF patients worldwide.

In pivotal clinical trials, ivacaftor treatment resulted in rapid and sustained improvements in lung function, as measured by forced expiratory volume in one second (FEV1). In the STRIVE trial involving patients aged 12 years and older with at least one G551D mutation, ivacaftor demonstrated a mean absolute improvement in percent predicted FEV1 of 10.6 percentage points compared with placebo at 24 weeks. Patients also experienced significant improvements in body weight, a reduction in sweat chloride concentrations (a biomarker of CFTR function), and fewer pulmonary exacerbations.

Ivacaftor STADA Nordic is a generic formulation of ivacaftor manufactured by STADA. It contains the same active ingredient at the same strength (150 mg) and has been demonstrated to be bioequivalent to the reference product. As a generic medicine, it offers an important option for improving access to this critical therapy for eligible CF patients.

What Should You Know Before Taking Ivacaftor STADA Nordic?

Contraindications

Ivacaftor STADA Nordic is contraindicated in patients with known hypersensitivity to ivacaftor or any of the excipients contained in the formulation. Although absolute contraindications are limited, there are several important precautions that must be carefully considered before initiating therapy. Patients should undergo CFTR genotyping to confirm the presence of a responsive mutation before starting treatment, as ivacaftor is not effective in all CF genotypes.

Importantly, ivacaftor monotherapy has not been shown to be effective in patients who are homozygous for the F508del mutation. In these patients, the CFTR protein does not reach the cell surface in sufficient quantities, and a potentiator alone cannot restore adequate CFTR function. These patients may benefit from combination therapies that include a CFTR corrector alongside ivacaftor.

Warnings and Precautions

Hepatic impairment requires careful consideration when prescribing ivacaftor. Elevations in transaminases (ALT and AST) have been observed in clinical trials. Some cases of elevated transaminases up to five times the upper limit of normal (ULN) have been reported. The EMA and FDA recommend baseline liver function tests before initiating ivacaftor therapy, with repeat testing every 3 months during the first year and annually thereafter. If transaminases exceed 5 times the ULN, or if elevations are accompanied by elevated bilirubin, the drug should be discontinued and liver function monitored closely until abnormalities resolve.

For patients with moderate hepatic impairment (Child-Pugh Class B), the dose of ivacaftor should be reduced to 150 mg once daily. For patients with severe hepatic impairment (Child-Pugh Class C), a further dose reduction to 150 mg once daily or less frequently may be necessary, and the drug should be used only if the benefits outweigh the risks. No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh Class A).

Cataracts have been reported in pediatric patients treated with ivacaftor. Although a causal relationship has not been established, baseline and follow-up ophthalmological examinations are recommended for pediatric patients initiating ivacaftor therapy. Non-congenital lens opacities or cataracts without impact on vision were observed in some pediatric patients during clinical development.

Patients with renal impairment should be treated with caution. No dose adjustment is necessary for patients with mild to moderate renal impairment. However, caution is advised in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min) or end-stage renal disease, as ivacaftor has not been studied in these populations.

Pregnancy and Breastfeeding

There are limited data on the use of ivacaftor in pregnant women. Animal reproductive studies have not shown evidence of teratogenicity or adverse effects on fertility at clinically relevant exposures. However, as a precautionary measure, ivacaftor should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should discuss family planning with their healthcare provider.

It is not known whether ivacaftor or its metabolites are excreted in human breast milk. Animal studies have shown that ivacaftor is present in the milk of lactating rats. A decision should be made whether to discontinue breastfeeding or discontinue ivacaftor therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. Given the chronic nature of CF and the importance of ongoing CFTR modulator therapy, this decision should be made in close consultation with the treating physician.

How Does Ivacaftor STADA Nordic Interact with Other Drugs?

Ivacaftor is extensively metabolised by the cytochrome P450 enzyme CYP3A, and to a lesser extent by CYP3A5. It is also a substrate of P-glycoprotein (P-gp). Understanding these metabolic pathways is crucial for managing drug interactions, as co-administration with drugs that affect CYP3A activity can significantly alter ivacaftor plasma concentrations and potentially lead to either toxicity or reduced efficacy.

Major Interactions

Co-administration with strong CYP3A inhibitors dramatically increases ivacaftor exposure. For example, ketoconazole (400 mg once daily) increased ivacaftor AUC by approximately 8.5-fold. When ivacaftor must be co-administered with a strong CYP3A inhibitor, the dose should be reduced to 150 mg twice weekly (i.e., approximately one dose every 3–4 days). Similar considerations apply to other strong CYP3A inhibitors including itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin.

Strong CYP3A inducers substantially reduce ivacaftor plasma concentrations. Rifampicin (600 mg once daily) decreased ivacaftor AUC by approximately 89%. Co-administration with strong CYP3A inducers such as rifampicin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John's wort (Hypericum perforatum) is not recommended, as the resulting reduction in ivacaftor exposure may diminish therapeutic effectiveness to a clinically insignificant level.

Minor Interactions

Ivacaftor is a weak inhibitor of CYP3A and P-glycoprotein. Co-administration of ivacaftor with sensitive CYP3A substrates or P-gp substrates with a narrow therapeutic index (such as digoxin, ciclosporin, or tacrolimus) may increase the plasma concentrations of these drugs. Appropriate monitoring and dose adjustments should be considered when these drugs are co-administered with ivacaftor.

Ivacaftor may also have minor effects on CYP2C9 substrates such as warfarin. Although no clinically significant interaction has been definitively established, patients on warfarin therapy should have their INR monitored more frequently when initiating or discontinuing ivacaftor. Hormonal contraceptives are not expected to have significant interactions with ivacaftor based on the available data, but patients should be advised to report any changes in menstrual pattern to their healthcare provider.

Food has a significant effect on ivacaftor absorption. Ivacaftor should always be taken with fat-containing food, as this increases drug exposure by approximately 2–4 fold compared to the fasting state. Consistent use with fat-containing meals helps maintain stable drug levels and optimal therapeutic efficacy.

What Is the Correct Dosage of Ivacaftor STADA Nordic?

Ivacaftor STADA Nordic should only be prescribed by physicians experienced in the treatment of cystic fibrosis. Prior to initiation, the patient's CFTR genotype must be confirmed to ensure the presence of a responsive gating mutation. Treatment should be initiated and monitored under the supervision of a specialist centre experienced in cystic fibrosis management.

Adults

If a dose is taken without fat-containing food, drug absorption is significantly reduced, which may compromise therapeutic effectiveness. Patients should be counselled on the importance of consistent dietary habits when taking this medication. The tablet should be swallowed whole and should not be chewed, broken, or dissolved.

Children

The 150 mg film-coated tablet formulation is approved for children aged 6 years and older who weigh at least 25 kg. The dose is the same as for adults: 150 mg every 12 hours with fat-containing food. For younger children (aged 4 months to less than 6 years), or children weighing less than 25 kg, alternative formulations such as oral granules are available in certain markets. The prescribing physician will select the appropriate formulation and dose based on the child's age, weight, and CFTR mutation status.

Pediatric patients should undergo baseline ophthalmological examination before initiating ivacaftor therapy, with follow-up examinations at regular intervals. This recommendation stems from the observation of lens opacities in some pediatric patients during clinical development programmes, although a direct causal link with ivacaftor has not been conclusively established.

Elderly

There is limited clinical experience with ivacaftor in patients aged 65 years and older. No specific dose adjustment is recommended solely based on age. However, elderly patients are more likely to have decreased hepatic or renal function and may be taking concomitant medications that interact with ivacaftor. Therefore, dose selection for elderly patients should be made cautiously, generally starting at the lower end of the dosage range and with more frequent monitoring of organ function and drug interactions.

Missed Dose

If a dose is missed and less than 6 hours have passed since the scheduled time, the missed dose should be taken as soon as possible with fat-containing food. If more than 6 hours have passed, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time. Patients should not take two doses at the same time to make up for a missed dose. Maintaining consistent dosing intervals is important for achieving optimal therapeutic outcomes.

Overdose

There is no specific antidote for ivacaftor overdose. In the event of an overdose, symptomatic and supportive measures should be employed. In clinical trials, healthy volunteers who received single doses up to 800 mg showed no dose-limiting adverse effects. The most common symptoms reported at higher doses were consistent with the known side-effect profile, including headache, dizziness, and gastrointestinal disturbances. Given that ivacaftor is highly protein-bound (approximately 99%), haemodialysis is unlikely to be effective in removing the drug from the circulation.

What Are the Side Effects of Ivacaftor STADA Nordic?

Like all medicines, Ivacaftor STADA Nordic can cause side effects, although not everybody gets them. The safety profile of ivacaftor has been well characterised through extensive clinical trial programmes and post-marketing surveillance. Most side effects are mild to moderate in severity and tend to diminish over time as the body adjusts to the medication. However, some adverse effects, particularly hepatic events, require careful monitoring.

The following side effect frequencies are based on pooled data from clinical trials and post-marketing experience. It is important to note that some symptoms commonly attributed to ivacaftor may also be manifestations of the underlying cystic fibrosis disease or concurrent infections.

Patients should be advised to report any new or worsening symptoms to their healthcare provider promptly. In particular, signs of liver dysfunction such as unexplained right upper abdominal pain, jaundice (yellowing of the skin or eyes), dark urine, or unusual fatigue should prompt immediate medical evaluation. Changes in vision or any eye-related concerns should also be reported, especially in pediatric patients.

Post-marketing pharmacovigilance has not identified any significant new safety signals beyond those characterised in clinical trials. The overall safety profile of ivacaftor is considered favourable relative to the substantial clinical benefits observed in patients with responsive CFTR mutations. However, long-term data continue to be collected and monitored to ensure the ongoing safety of this therapy.

How Should You Store Ivacaftor STADA Nordic?

Ivacaftor STADA Nordic 150 mg film-coated tablets should be stored at temperatures not exceeding 30°C. The tablets should be kept in the original blister packaging to protect them from moisture. Exposure to high humidity can affect the stability and integrity of the film coating, potentially altering the drug's release characteristics and bioavailability.

As with all medicines, Ivacaftor STADA Nordic should be kept out of the sight and reach of children. This is particularly important in households where the medication is used by an adult or older child with cystic fibrosis, as younger children in the household may inadvertently access the medication.

Do not use this medicine after the expiry date stated on the carton and blister after "EXP". 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 responsible pharmaceutical waste management.

If you notice any change in the appearance of the tablets (e.g., discolouration, crumbling, or unusual odour), do not use the medication and consult your pharmacist for a replacement. Proper storage is essential to maintain the medication's full efficacy throughout its shelf life.

What Does Ivacaftor STADA Nordic Contain?

The active substance is ivacaftor. Each film-coated tablet contains 150 mg of ivacaftor (as ivacaftor). The excipients used in the tablet core and film coating are standard pharmaceutical ingredients selected to ensure optimal drug stability, bioavailability, and patient acceptability.

The tablet core typically contains excipients such as microcrystalline cellulose, lactose monohydrate, hypromellose acetate succinate, croscarmellose sodium, sodium lauryl sulfate, colloidal anhydrous silica, and magnesium stearate. The film coating contains hypromellose, titanium dioxide (E171), polyethylene glycol (macrogol), and may contain iron oxide colourants for product identification purposes.

Patients with known lactose intolerance should be aware that the tablet formulation contains lactose monohydrate. Although the amount of lactose per tablet is relatively small, patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine without consulting their physician.

The film-coated tablets are designed to be swallowed whole. The film coating serves to protect the active ingredient from degradation in the acidic environment of the stomach, to mask any unpleasant taste, and to facilitate easy swallowing. Patients should not crush, break, or chew the tablets, as this may affect the drug's release profile and absorption characteristics.