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KAFTRIO is a brand name for Elexacaftor. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Kaftrio granules are indicated in a combination regimen with ivacaftor for the treatment of cystic fibrosis (CF) in paediatric patients aged 2 to less than 6 years who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (see section 5.1).
Verbatim from this product's MHRA label. Tap a section to expand.
Kaftrio should only be prescribed by healthcare professionals with experience in the treatment of CF. 1). Posology Paediatric patients aged 2 to less than 6 years should be dosed according to Table 1. 5 mg granules 2 to less than 6 years ≥14 kg One sachet of ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg granules One sachet of ivacaftor 75 mg granules The morning and evening dose should be taken approximately 12 hours apart, with fat-containing food (see Method of administration).
Missed dose If 6 hours or less have passed since the missed morning or evening dose, the patient should take the missed dose as soon as possible and continue on the original schedule. If more than 6 hours have passed since: • the missed morning dose, the patient should take the missed dose as soon as possible and should not take the evening dose.
The next scheduled morning dose should be taken at the usual time. OR • the missed evening dose, the patient should not take the missed dose. The next scheduled morning dose should be taken at the usual time. Morning and evening doses should not be taken at the same time.
5). 5).
Table 2:
Dosing schedule for concomitant use with moderate and strong CYP3A inhibitors Moderate CYP3A Inhibitors Strong CYP3A Inhibitors Alternate each day: • One sachet of ivacaftor/tezacaftor/elexacaftor (IVA/TEZ/ELX) granules on the first day • One sachet of ivacaftor (IVA) granules on the next day No evening sachet of IVA granules.
One sachet of IVA/TEZ/ELX granules twice a week, approximately 3 to 4 days apart. No evening sachet of IVA granules. Special populations Hepatic impairment Treatment of patients aged 2 to less than 6 years with moderate hepatic impairment (Child-Pugh Class B) is not recommended.
For patients aged 2 to less than 6 years with moderate hepatic impairment, the use of Kaftrio 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 (see Table 3).
Studies have not been conducted in patients with severe hepatic impairment (Child-Pugh Class C), but the exposure is expected to be higher than in patients with moderate hepatic impairment. Patients with severe hepatic impairment should not be treated with Kaftrio.
9%). 5%) in placebo. Tabulated list of adverse reactions Table 4 reflects adverse reactions observed with IVA/TEZ/ELX in combination with IVA, TEZ/IVA in combination with IVA, and IVA monotherapy. Adverse reactions are listed by MedDRA system organ class and frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 4:
Adverse reactions MedDRA System Organ Class Adverse Reactions Frequency Infections and infestations Upper respiratory tract infection*, Nasopharyngitis very common Table 4: Adverse reactions MedDRA System Organ Class Adverse Reactions Frequency Rhinitis*, Influenza* common Metabolism and nutrition disorders Hypoglycaemia* common Psychiatric disorders Low mood not known Nervous system disorders Headache*, Dizziness* very common Ear pain, Ear discomfort, Tinnitus, Tympanic membrane hyperaemia, Vestibular disorder common Ear and labyrinth disorders Ear congestion uncommon Oropharyngeal pain, Nasal congestion* very common Rhinorrhoea*, Sinus congestion, Pharyngeal erythema, Abnormal breathing* common Respiratory, thoracic and mediastinal disorders Wheezing* uncommon Diarrhoea*, Abdominal pain* very common Gastrointestinal disorders Nausea, Abdominal pain upper*, Flatulence* common Transaminase elevations very common Alanine aminotransferase increased*, Aspartate aminotransferase increased* common Hepatobiliary disorders Liver injury†, Total bilirubin elevations† not known Rash* very commonSkin and subcutaneous tissue disorders Acne*, Pruritus* common Breast mass common Reproductive system and breast disorders Breast inflammation, Gynaecomastia, Nipple disorder, Nipple pain uncommon Bacteria in sputum very common Blood creatine phosphokinase increased* very commonInvestigations Blood pressure increased* uncommon *Adverse reactions observed during clinical studies with IVA/TEZ/ELX in combination with IVA.
Elevated transaminases and hepatic injury In a patient with cirrhosis and portal hypertension liver failure leading to transplantation has been reported while receiving IVA/TEZ/ELX in combination with ivacaftor. , cirrhosis, portal hypertension) and only if the benefits are expected to outweigh the risks.
2). Elevated transaminases are common in patients with CF and have been observed in some patients treated with IVA/TEZ/ELX in combination with IVA. In patients taking IVA/TEZ/ELX in combination with IVA, these elevations have sometimes been associated with concomitant elevations in total bilirubin.
Assessments of transaminases (ALT and AST) and total bilirubin are recommended for all patients prior to initiating treatment, every 3 months during the first year of treatment and annually thereafter. For patients with a history of liver disease or transaminase elevations, more frequent monitoring should be considered.
In the event of ALT or AST >5 x the upper limit of normal (ULN), or ALT or AST >3 x ULN with bilirubin >2 x ULN, dosing should be interrupted, and laboratory tests closely followed until the abnormalities resolve. 2). Hepatic impairment Treatment of patients with moderate hepatic impairment is not recommended.
For patients with moderate hepatic impairment, the use of IVA/TEZ/ELX 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 (see Table 3).
2). 2). Patients after organ transplantation IVA/TEZ/ELX in combination with IVA has not been studied in patients with CF who have undergone organ transplantation. Therefore, use in transplanted patients is not recommended. 5 for interactions with commonly used immunosuppressants.
Rash events The incidence of rash events 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 IVA/TEZ/ELX in combination with IVA and hormonal contraceptives should be considered.
1.
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2).
Table 3:
Recommendation for use in patients aged 2 to less than 6 years with hepatic impairment Mild (Child-Pugh Class A) Moderate (Child-Pugh Class B) Severe (Child-Pugh Class C) No dose adjustment Use not recommended. Treatment of patients with moderate hepatic impairment should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks.
If used, Kaftrio should be used with caution at a reduced dose, as follows: • Days 1-3: one sachet of IVA/TEZ/ELX granules each day • Day 4: no dose • Days 5-6: one sachet of IVA/TEZ/ELX granules each day • Day 7: no dose Repeat above dosing schedule each week.
The evening dose of the IVA granules should not be taken. Should not be used Renal impairment No dose adjustment is recommended for patients with mild and moderate renal impairment. 2). Paediatric population The safety and efficacy of Kaftrio in combination with ivacaftor in children aged less than 2 years have not yet been established.
1). Method of administration For oral use. The entire contents of each sachet of granules should be mixed with one teaspoon (5 mL) of age-appropriate soft food or liquid and the mixture completely consumed. Food or liquid should be at room temperature or below.
Each sachet is for single use only. Once mixed, the product has been shown to be stable for one hour, and therefore should be ingested during this period. Some examples of soft food or liquids include pureed fruits or vegetables, yogurt, water, milk, or juice.
A fat-containing meal or snack should be consumed just before or after dosing. Kaftrio should be taken with fat-containing food. 2). 5).
†Liver injury (ALT and AST and total bilirubin elevations) reported from post-marketing data with IVA/TEZ/ELX in combination with IVA. This also included liver failure leading to transplantation in a patient with pre-existing cirrhosis and portal hypertension.
Frequency cannot be estimated from the available data. Safety data from the following studies were consistent with the safety data observed in study 445-102. • A 4-week, randomised, double-blind, active-controlled study in 107 patients aged 12 years and older (study 445-103).
• A 192-week, open-label safety and efficacy study (study 445-105) in 506 patients rolled over from studies 445-102 and 445-103. • An 8-week, randomised, double-blind, active-controlled study in 258 patients aged 12 years and older (study 445-104).
• A 24-week, open-label study (study 445-106) in 66 patients aged 6 to less than 12 years. • A 192-week, two-part (part A and part B), open-label safety and efficacy study (study 445-107) in patients aged 6 years and older who rolled over from study 445-106.
• A 24-week, open-label study (study 445-111) in 75 patients aged 2 to less than 6 years. 5% in placebo-treated patients. 0% in placebo-treated patients. 4). 5% in placebo-treated patients. The rash events were generally mild to moderate in severity.
3% in females in placebo-treated patients. 4). 0% in placebo-treated patients. The observed creatine phosphokinase elevations were generally transient and asymptomatic and many were preceded by exercise. 5 mmHg, respectively for placebo-treated patients (baseline: 114 mmHg systolic and 70 mmHg diastolic).
5%, respectively in placebo-treated patients. Paediatric population The safety data of IVA/TEZ/ELX in combination with IVA in studies 445-102, 445-103, 445-104, 445-106 and 445-111 was evaluated in 228 patients between 2 to less than 18 years of age.
The safety profile is generally consistent among paediatric and adult patients. During study 445-106 in patients aged 6 to less […]
Following the resolution of rash, it should be considered if resuming IVA/TEZ/ELX in combination with IVA without hormonal contraceptives is appropriate. 8). Mood disturbances Effects on mood and behaviour have been reported in patients treated with IVA/TEZ/ELX, usually occurring within three months of treatment initiation.
Patients (and caregivers) should be alerted about the need to monitor for symptoms including new onset or worsening of anxiety or low mood, sleep disturbance, and forgetfulness. In some children, persistent behavioural changes have been observed while taking IVA/TEZ/ELX.
Inform patients to seek medical advice as soon as possible if these symptoms present. Consider whether treatment discontinuation is appropriate. Elderly Clinical studies of IVA/TEZ/ELX in combination with IVA did not include sufficient number of patients aged 65 years and older to determine whether response in these patients is different from younger adults.
2). 5). CYP3A inhibitors Exposures of ELX, TEZ and IVA are increased when co-administered with strong or moderate CYP3A inhibitors. 2). Cataracts Cases of non-congenital lens opacities without impact on vision have been reported in paediatric patients treated with IVA-containing regimens.
Although other risk factors were present in some cases (such as corticosteroid use, exposure to radiation) a possible risk attributable to treatment with IVA cannot be excluded. 3). Excipients with known effect Lactose This medicinal product contains lactose.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per sachet, that is to say essentially ‘sodium-free’.