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ORKAMBI is a brand name for Ivacaftor. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Orkambi granules are indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year 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 MHRA 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 1 year and older Orkambi dose (every 12 hours)Age Weight Dose per sachet Morning Evening 7 kg to <9 kg lumacaftor 75 mg/ivacaftor 94 mg 1 to <2 years 9 kg to <14 kg lumacaftor 100 mg/ ivacaftor 125 mg 1 sachet 1 sachet ≥14 kg lumacaftor 150 mg/ ivacaftor 188 mg <14 kg lumacaftor 100 mg/ivacaftor 125 mg2 to 5 years ≥ 14 kg lumacaftor 150 mg/ivacaftor 188 mg 6 years and older See Orkambi tablets SmPC for further details 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, reduce the dose to one sachet every other day 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. , Day 1, 3, 5, 7. On day 8 dosing should be at the recommended full daily dose 6 years and older See Orkambi tablets SmPC for further details If treatment is interrupted for more than one week and then re-initiated while taking strong CYP3A inhibitors, reduce the dose to one sachet every other day 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).
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.
6% on placebo). , transaminase elevations, cholestatic hepatitis, and hepatic encephalopathy. 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 from the available data).
Table 5:
Adverse reactions in lumacaftor/ivacaftor-treated patients and in patients treated with ivacaftor alone System organ class Frequency Adverse reactions very common Nasopharyngitis* Infections and infestations common Upper respiratory tract infection, rhinitis Vascular disorders uncommon Hypertension very common Headache, dizziness* Nervous system disorders uncommon Hepatic encephalopathy† common Ear pain*, ear discomfort*, tinnitus*, tympanic membrane hyperaemia*, vestibular disorder* Ear and labyrinth disorders uncommon Ear congestion* very common Nasal congestion, dyspnoea, productive cough, sputum increased Respiratory, thoracic, and mediastinal disorders common Respiration abnormal, oropharyngeal pain, sinus congestion*, rhinorrhoea, pharyngeal erythema*, bronchospasm very common Abdominal pain*, abdominal pain upper, diarrhoea, nausea Gastrointestinal disorders common Flatulence, vomiting common Transaminase elevationsHepatobiliary disorders uncommon Cholestatic hepatitis‡ Skin and subcutaneous tissue disorders common Rash common Menstruation irregular, dysmenorrhoea, metrorrhagia, breast mass* Reproductive system and breast disorders uncommon Menorrhagia, amenorrhoea, polymenorrhoea, breast inflammation*, gynaecomastia*, nipple disorder*, nipple pain*, oligomenorrhoea very common Bacteria in sputum* common Blood creatine phosphokinase increased Investigations 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 the 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 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). Patients with advanced liver disease 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.
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). Hepatobiliary adverse reactions Elevated transaminases have been commonly reported in patients with CF receiving lumacaftor/ivacaftor.
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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2). For dose adjustments for patients with moderate or severe hepatic impairment see Table 3.
Table 3:
Dose adjustment recommendations for patients with moderate or severe hepatic impairment Moderate (Child-Pugh Class B) Severe (Child-Pugh Class C) Age Wei ght Dose per sachet Morning Evening Morning Evening 7 kg to <9 k g lumacaftor 75 mg/ ivacaftor 94 mg 9 kg to <14 kg lumacaftor 100 mg/ ivacaftor 125 mg 1 to <2 years ≥14 kg lumacaftor 150 mg/ ivacaftor 188 mg <14 kg lumacaftor 100 mg/ ivacaftor 125 mg2 to 5 years ≥14 kg lumacaftor 150 mg/ ivacaftor 188 mg 1 sachet of oral granules 1 sachet of oral granules every other day 1 sachet of oral granules or less frequently No dose Paediatric population The safety and efficacy of Orkambi in children aged less than 1 year have not yet been established.
1). Method of administration For oral use. Each sachet is for single use only. The entire content 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.
Some examples of soft foods or liquids include puréed fruits or vegetables, flavoured yogurt, applesauce, water, milk, breast milk, infant food or juice. Food or liquid should be at room temperature or below. Once mixed, the product has been shown to be stable for one hour, and therefore should be ingested during this period.
† 1 patient out of 738 ‡ 2 patients out of 738 The safety data from a 96-week rollover study (trial 3) were consistent with the safety data from the phase 3 studies (trials 1 and 2). 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 seven 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 adverse reactions 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. […]
In some instances, these elevations have been associated with concomitant elevations in total serum bilirubin. Transaminase elevations have been observed more frequently in paediatric patients than in adult patients. 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. In the event of significant elevation of ALT or AST, with or without elevated bilirubin (either ALT or AST > 5 x the upper limit of normal [ULN], or ALT or AST > 3 x ULN with bilirubin > 2 x ULN and/or clinical jaundice), dosing with lumacaftor/ivacaftor should be discontinued and laboratory tests closely followed until the abnormalities resolve.
A thorough investigation of potential causes should be conducted and patients should be followed closely for clinical progression. 2). 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.
3). Baseline and follow-up ophthalmological examinations are recommended in paediatric patients initiating treatment with lumacaftor/ivacaftor. Patients after organ transplantation Lumacaftor/ivacaftor 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 immunosuppressants. Sodium content This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.