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Orkambi is a brand name for Lumacaftor. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Orkambi tablets are indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (see sections 4.2, 4.4, and 5.1).
Verbatim from this product's EMA label. Tap a section to expand.
Orkambi should only be prescribed by physicians with experience in the treatment of CF. If the patient’s genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of the F508del mutation on both alleles of the CFTR gene.
Posology Table 1:
Dosing recommendations in patients aged 6 years and older Age Strength Dose (every 12 hours) Morning Evening 6 to < 12 years lumacaftor 100 mg/ivacaftor 125 mg 2 tablets 2 tablets 12 years and older lumacaftor 200 mg/ivacaftor 125 mg 2 tablets 2 tablets 3 Patients may start treatment on any day of the week.
This medicinal product should be taken with fat-containing food. 2). Missed dose If less than 6 hours have passed since the missed dose, the scheduled dose should be taken with fat- containing food. If more than 6 hours have passed, the patient should be instructed to wait until the next scheduled dose.
A double dose should not be taken to make up for the forgotten dose. Concomitant use of CYP3A inhibitors No dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking Orkambi. However, when initiating treatment in patients taking strong CYP3A inhibitors, the dose should be reduced to one tablet daily for the first week of treatment to allow for the steady-state induction effect of lumacaftor.
Following this period, the recommended daily dose should be continued (see Table 2).
Table 2:
Treatment initiation in patients taking strong CYP3A inhibitors Age Strength Week 1 of treatment Week 2 onwards 6 to < 12 years lumacaftor 100 mg/ivacaftor 125 mg 1 tablet per day From day 8 and thereafter dosing should be at the recommended daily dose 12 years and older lumacaftor 200 mg/ivacaftor 125 mg If treatment is interrupted for more than one week and then re-initiated while taking strong CYP3A inhibitors, the dose should be reduced to one tablet daily for the first week of treatment re-initiation (see Table 2).
5). Special populations Renal impairment No dose adjustment is necessary for patients with mild to moderate renal impairment. 2). Hepatic impairment No dose adjustment is necessary for patients with mild hepatic impairment (Child-Pugh Class A).
2%). 1%). Tabulated list of adverse reactions Table 5 reflects the adverse reactions reported with lumacaftor/ivacaftor and ivacaftor monotherapy from clinical trials, post-authorisation safety studies and spontaneous reporting. 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); and not known (frequency cannot be estimated using the available data).
14 Table 5: Adverse reactions in lumacaftor/ivacaftor-treated patients and in patients treated with ivacaftor alone System organ class Frequency Adverse reactions Infections and infestations very common Nasopharyngitis* common Upper respiratory tract infection, rhinitis Psychiatric disorders not known Depression Vascular disorders uncommon Hypertension Nervous system disorders very common Headache, dizziness* uncommon Hepatic encephalopathy† Ear and labyrinth disorders common Ear pain*, ear discomfort*, tinnitus*, tympanic membrane hyperaemia*, vestibular disorder* uncommon Ear congestion* Respiratory, thoracic and mediastinal disorders very common Nasal congestion, dyspnoea, productive cough, sputum increased common Respiration abnormal, oropharyngeal pain, sinus congestion*, rhinorrhoea, pharyngeal erythema*, bronchospasm Gastrointestinal disorders very common Abdominal pain*, abdominal pain upper, diarrhoea, nausea common Flatulence, vomiting Hepatobiliary disorders common Transaminase elevations uncommon Cholestatic hepatitis‡ Skin and subcutaneous tissue disorders common Rash Reproductive system and breast disorders common Menstruation irregular, dysmenorrhoea, metrorrhagia, breast mass* uncommon Menorrhagia, amenorrhoea, polymenorrhoea, breast inflammation*, gynaecomastia*, nipple disorder*, nipple pain*, oligomenorrhoea Investigations very common Bacteria in sputum* common Blood creatine phosphokinase increased uncommon Blood pressure increased * Adverse reactions and frequencies observed in patients in clinical studies with ivacaftor monotherapy.
1). Patients with CF who have a gating (Class III) mutation in the CFTR gene Lumacaftor/ivacaftor has not been studied in patients with CF who have a gating (Class III) mutation in the CFTR gene on one allele, with or without the F508del mutation on the other allele.
Since the exposure of ivacaftor is very significantly reduced when dosed in combination with lumacaftor, lumacaftor/ivacaftor should not be used in these patients. , chest discomfort, dyspnoea, bronchospasm, and respiration abnormal) were more common during initiation of lumacaftor/ivacaftor therapy.
Serious respiratory events were seen more frequently in patients with percent predicted forced expiratory volume in 1 second (ppFEV1) < 40, and may lead to discontinuation of the medicinal product. 8). A transient decline in FEV1 has also been observed in some patients following initiation of lumacaftor/ivacaftor.
There is no experience of initiating 5 treatment with lumacaftor/ivacaftor in patients having a pulmonary exacerbation and initiating treatment in patients having a pulmonary exacerbation is not advisable. Effect on blood pressure Increased blood pressure has been observed in some patients treated with lumacaftor/ivacaftor.
8). Elevated transaminases and hepatic injury Abnormalities in liver function, including advanced liver disease, can be present in patients with CF. Worsening of liver function in patients with advanced liver disease has been reported.
Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension receiving lumacaftor/ivacaftor. Cases of liver failure leading to transplantation have been reported within the first 6 months of treatment in patients with and without pre-existing advanced liver disease treated with other CFTR modulators.
Lumacaftor/ivacaftor should be used with caution in patients with advanced liver disease and only if the benefits are expected to outweigh the risks. 2). Elevated transaminases have been commonly reported in patients with CF receiving lumacaftor/ivacaftor.
1.
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For patients with moderate hepatic impairment (Child-Pugh Class B), a dose reduction is recommended. There is no experience of the use of the medicinal product in patients with severe hepatic impairment (Child-Pugh Class C), but exposure is expected to be higher than in patients with moderate hepatic impairment.
2). For dose adjustments for patients with moderate or severe hepatic impairment (see Table 3). 4 Table 3: Dose adjustment recommendations for patients with moderate or severe hepatic impairment Age Strength Total Daily Dose Moderate (Child-Pugh Class B) Severe (Child-Pugh Class C) Morning Evening Morning Evening 6 to < 12 years lumacaftor 100 mg/ivacaftor 125 mg 2 tablets 1 tablet 1 tablet or less frequently* 1 tablet or less frequently* 12 years and older lumacaftor 200 mg/ivacaftor 125 mg * Dosing interval should be modified according to clinical response and tolerability; the frequency may be reduced for both the morning dose and the evening dose.
Paediatric population The safety and efficacy of Orkambi in children aged less than 1 year have not yet been established. No data are available. Method of administration For oral use. Patients should be instructed to swallow the tablets whole.
Patients should not chew, break, or dissolve the tablets.
† 1 patient out of 738 ‡ 2 patients out of 738 The safety data from a 96-week rollover study (809-105) were consistent with the safety data from the phase 3 studies (trials 809-103 and 809-104). 1% in lumacaftor/ivacaftor- and placebo-treated patients, respectively.
6% in lumacaftor/ivacaftor-treated patients and those who received placebo, respectively. Seven patients who received lumacaftor/ivacaftor had liver-related serious adverse reactions with elevated transaminases, including 3 with concurrent elevation in total bilirubin.
4). Among 7 patients with pre-existing cirrhosis and/or portal hypertension who received lumacaftor/ivacaftor in the placebo-controlled, phase 3 studies, worsening liver function with increased ALT, AST, bilirubin, and hepatic encephalopathy was observed in one patient.
4). 4). 0% in patients who received placebo. The incidence of these adverse reactions was more common in patients with lower pre-treatment FEV1. Approximately three-quarters of the events began during the first week of treatment, and in most patients the events resolved without dosing interruption.
4). 2%. 6%. Of the patients who were initiated lumacaftor/ivacaftor at the full dose, one patient had a serious respiratory adverse reaction, three patients subsequently had their dose reduced, and three patients discontinued treatment.
4). 7% in placebo-treated females. These […]
In some instances, these elevations have been associated with concomitant elevations in total serum bilirubin. 8). Because an association with liver injury cannot be excluded, assessments of liver function tests (ALT, AST, and bilirubin) are recommended before initiating lumacaftor/ivacaftor, every 3 months during the first year of treatment, and annually thereafter.
For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered. Treatment should be interrupted and serum transaminases and total bilirubin measured promptly if clinical signs or symptoms of liver injury develop.
Interrupt dosing in the event of ALT or AST > 5 × the upper limit of normal (ULN), or ALT or AST > 3 × ULN with total bilirubin > 2 × ULN and/or clinical jaundice. Closely monitor laboratory tests until the abnormalities resolve. A thorough investigation of potential causes should be conducted and patients should be followed closely for clinical progression.
2). Patients who resume treatment after interruption should be monitored closely. 8). In some cases, symptom improvement was reported after dose reduction or treatment discontinuation. Patients (and caregivers) should be alerted about the need to monitor for depressed mood, suicidal thoughts, unusual changes in behaviour, anxiety, or insomnia and to seek medical advice immediately if these symptoms occur.
Interactions with medicinal products Substrates of CYP3A Lumacaftor is a strong inducer of CYP3A. 5). 5). Strong CYP3A inducers Ivacaftor is a substrate of CYP3A4 and CYP3A5. , rifampicin, St. 5). 2). Cataracts Cases of non-congenital lens opacities without impact on vision have been reported in paediatric patients treated with lumacaftor/ivacaftor and ivacaftor monotherapy.
Although other risk factors were present in some cases (such as corticosteroid use and exposure to radiation), a possible risk attributable to ivacaftor […]