Lumacaftor with ivacaftor 22-Nov-2016
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, ivacaftor p. 186.
lINDICATIONS AND DOSE
Treatment of cystic fibrosis in patients who are
homozygous for the F 508 del mutation in the cystic
fibrosis transmembrane conductance regulator (CFTR)
gene (under expert supervision)
▶BY MOUTH
▶Child 12–17 years: 400 / 250 mg every 12 hours
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶Manufacturer advises reduce initial dose to 200 / 125 mg
daily for thefirst week in those also taking a potent
inhibitor of CYP 3 A 4.
DOSE EQUIVALENCE AND CONVERSION
▶Dose expressed as x/y mg of lumacaftor/ivacaftor.lCAUTIONSForced expiratory volume in 1 second (FEV 1 )
less than 40 % of the predicted normal value—additional
monitoring required at initiation of treatment.pulmonary
exacerbation—no information available
lINTERACTIONS→Appendix 1 : ivacaftor.lumacaftor
lSIDE-EFFECTS
▶Common or very commonBreast abnormalities.diarrhoea.
dizziness.ear discomfort.flatulence.headache.hearing
impairment.menstrual cycle irregularities.nausea.rash.
tympanic membrane hyperaemia.vomiting
▶UncommonGynaecomastia.hepatic encephalopathy.
hepatitis cholestatic.hypertension
▶Frequency not knownCataract.chest pain
lBREAST FEEDINGManufacturer advises avoid—present in
milk inanimalstudies.
lHEPATIC IMPAIRMENTManufacturer advises use with
caution in severe impairment.
Dose adjustmentsManufacturer advises reduce dose to
400 / 250 mg in the morning and 200 / 125 mg in the evening
( 600 / 375 mg total daily dose) in moderate impairment;
reduce dose to 200 / 125 mg every 12 hours ( 400 / 250 mg
total daily dose) in severe impairment.
lPRE-TREATMENT SCREENINGIf the patient’s genotype is
unknown, a validated genotyping method should be
performed to confirm the presence of the F 508 del
mutation on both alleles of the CFTR gene before starting
treatment.
lMONITORING REQUIREMENTSManufacturer advises
monitor blood pressure periodically during treatment.
lDIRECTIONS FOR ADMINISTRATIONTablets should be
taken with fat-containing food.
lPATIENT AND CARER ADVICEPatients or carers should be
given advice on how to administer tablets.
Missed dosesManufacturer advises if a dose is more than
6 hours late, the missed dose should not be taken and the
next dose should be taken at the normal time.
lNATIONAL FUNDING/ACCESS DECISIONS
NICE decisions
▶Lumacaftor with ivacaftor for treating cystic fibrosis
homozygous for the F 508 del mutation (July 2016 )NICE TA398
Lumacaftor with ivacaftor isnotrecommended, within its
marketing authorisation, for treating cysticfibrosis in
patients who are homozygous for the F 508 del mutation in
the cysticfibrosis transmembrane conductance regulator
(CFTR) gene.
Patients whose treatment was started before this
guidance was published may continue treatment until they
(or their carers) and their clinician consider it appropriate
to stop.
http://www.nice.org.uk/TA398
Scottish Medicines Consortium (SMC) Decisions
TheScottish Medicines Consortiumhas advised (May 2016 )
that lumacaftor with ivacaftor (Orkambi®)isnot
recommended within NHS Scotland for the treatment of
cysticfibrosis in patients who are homozygous for the
F 508 del mutation in the cysticfibrosis transmembrane
conductance regulator (CFTR) gene.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Tablet
CAUTIONARY AND ADVISORY LABELS 25
EXCIPIENTS:May contain Propylene glycol
▶Orkambi(Vertex Pharmaceuticals (UK) Ltd)A
Ivacaftor 125 mg, Lumacaftor 200 mgOrkambi 200 mg/ 125 mg
tablets| 112 tabletP£ 8 , 000. 004 Cough and congestion
Aromatic inhalations, cough
preparations and systemic nasal
decongestants
Aromatic inhalations
Inhalations containing volatile substances such as
eucalyptus oil are traditionally used to relieve congestion
and ease breathing. Although the vapour may contain little
of the additive it encourages deliberate inspiration of warm
moist air which is often comforting. Boiling water should not
be used owing to the risk of scalding.
Strong aromatic decongestants (applied as rubs or to
pillows) are not recommended for infants under the age of
3 months. Sodium chloride 0. 9 % solution p. 589 given as
nasal drops can be used to liquefy mucous secretions and
relieve nasal congestion in infants and young children;
administration before feeds may ease feeding difficulties
caused by nasal congestion.Cough preparations
Cough suppressants
Cough may be a symptom of an underlying disorder such as
asthma, gastro-oesophageal reflux disease, or rhinitis, which
should be addressed before prescribing cough suppressants.
Cough may be associated with smoking or environmental
pollutants. Cough can also result from bronchiectasis
including that associated with cysticfibrosis; cough can also
have a significant habit component. There is little evidence
of any significant benefit from the use of cough suppressants
in children with acute cough in ambulatory settings. Cough
suppressants may cause sputum retention and this can be
harmful in children with bronchiectasis.
The use of cough suppressants containing pholcodine
p. 188 or similar opioid analgesics is not generally
recommended in children and should be avoided in children
under 6 years; the use of over-the-counter cough
suppressants containing codeine phosphate p. 276 should be
avoided in children under 12 years and in children of any age
known to be CYP 2 D 6 ultra-rapid metabolisers.
Sedating antihistaminesare used as the cough
suppressant component of many compound cough
preparations on sale to the public; all tend to cause
drowsiness which may reflect their main mode of action.
Demulcent and expectorant cough preparations
Simple linctusand other demulcent cough preparations
containing soothing substances, such as syrup or glycerol,
may temporarily relieve a dry irritating cough. These
preparations have the advantage of being harmless and
inexpensive and sugar-free versions are available.BNFC 2018 – 2019 Cough and congestion 187
Respiratory system3