Indications And Dose
Cystic fibrosis (in combination with ivacaftor) (specialist use only) ▶BY MOUTH ▶Adult: 100/150 mg, to be taken in the morning and, Ivacaftor 150 mg to be taken in the evening
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Drug reference
Cystic fibrosis (in combination with ivacaftor) (specialist use only) ▶BY MOUTH ▶Adult: 100/150 mg, to be taken in the morning and, Ivacaftor 150 mg to be taken in the evening
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DUE TO INTERACTIONS ▶With concurrent use of potent CYP3A4 inhibitors, manufacturer advises reduce dose to 100/150 mg tezacaftor/ivacaftor twice a week, taken approximately 3–4 days apart; the evening dose of ivacaftor should not be taken. ▶With concurrent use of moderate CYP3A4 inhibitors, manufacturer advises reduce dose to 100/150 mg tezacaftor/ivacaftor every other morning, with ivacaftor 150 mg taken in the mornings alternate to tezacaftor/ivacaftor; the evening dose of ivacaftor should not be taken. DOSE EQUIVALENCE AND CONVERSION ▶Combination dose expressed as x/y mg of tezacaftor/ivacaftor.
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Scottish Medicines Consortium (SMC) decisions SMC No. SMC2183 The Scottish Medicines Consortium has advised (August 2019) that tezacaftor with ivacaftor (Symkevi ®) is not recommended for use within NHS Scotland for the treatment of cystic fibrosis in patients aged 12 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A?G, S945L, S977F, R1070W, D1152H, 2789+5G?A, 3272-26A?G, and 3849+10kbC?T, as the clinical and economic case was not demonstrated.
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→Appendix 1: ivacaftor. tezacaftor
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▶Common or very common Abdominal pain. breast abnormalities. diarrhoea. dizziness. ear discomfort. headache. nausea. ototoxicity. rash. tympanic membrane hyperaemia ▶Uncommon Gynaecomastia ▶Frequency not known Hepatic function abnormal SIDE-EFFECTS, FURTHER INFORMATION Manufacturer advises interrupt treatment if transaminase levels more than 5 times the upper limit of normal or transaminase levels more than 3 times the upper limit of normal and blood bilirubin more than twice the upper limit of normal—consult product literature.
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Manufacturer advises caution in moderate to severe impairment (risk of increased exposure). Dose adjustments Manufacturer advises omit evening dose of ivacaftor in moderate to severe impairment; in severe impairment, adjust dosing interval according to clinical response and tolerability.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 25 ▶Symkevi (Vertex Pharmaceuticals (UK) Ltd) A Tezacaftor 100 mg, Ivacaftor 150 mg Symkevi 100mg/150mg tablets | 28 tablet P £6,293.91 (Hospital only) Cough and congestion Aromatic inhalations, cough preparations and systemic nasal decongestants Aromatic inhalations in adults Inhalations containing volatile substances such as eucalyptus oil are traditionally used and although the vapour may contain little of the additive it encourages deliberate inspiration of warm moist air which is often comforting in bronchitis; boiling water should not be used owing to the risk of scalding. In practice, inhalations are also used for the relief of nasal obstruction in acute rhinitis or sinusitis. Respiratory system Cough preparations in adults 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 a side-effect of another drug, such as an ACE inhibitor, or it can be associated with smoking or environmental pollutants. Cough can also have a significant habit component. When there is no identifiable cause, cough suppressants may be useful, for example if sleep is disturbed. They may cause sputum retention and this may be harmful in patients with chronic bronchitis and bronchiectasis. There is some evidence to suggest that codeine phosphate p. 475 provides no benefit for symptoms of acute cough. Codeine phosphate is also constipating and can cause dependence; dextromethorphan and pholcodine p. 312 have fewer side-effects. Sedating antihistamines are 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. Palliative care Diamorphine hydrochloride p. 477 and methadone hydrochloride p. 524 have been used to control distressing cough in terminal lung cancer although morphine p. 484 is now preferred. In other circumstances they are contra- indicated because they induce sputum retention and ventilatory failure as well as causing opioid dependence. Methadone hydrochloride linctus should be avoided because it has a long duration of action and tends to accumulate. Demulcent and expectorant cough preparations Demulcent cough preparations contain soothing substances such as syrup or glycerol and some patients believe that such preparations relieve a dry irritating cough. Preparations such as simple linctus have the advantage of being harmless and inexpensive; paediatric simple linctus is particularly useful in children. Expectorants are claimed to promote expulsion of bronchial secretions, but there is no evidence that any drug can specifically facilitate expectoration. g An over-the-counter cough medicine containing the expectorant guaifenesin may be used for acute cough; there is some evidence to suggest it may reduce symptoms. h Compound preparations are on sale to the public for the treatment of cough and colds but should not be used in children under 6 years; the rationale for some is dubious. Care should be taken to give the correct dose and to not use more than one preparation at a time. Nasal decongestants, systemic Nasal decongestants for administration by mouth may not be as effective as preparations for local application but they do not give rise to rebound nasal congestion on withdrawal. Pseudoephedrine hydrochloride p. 1267 is available over the counter; it has few sympathomimetic effects. Aromatic inhalations in children The use of strong aromatic decongestants (applied as rubs or to pillows) is not advised for infants under the age of 3 months. Carers of young infants in whom nasal obstruction with mucus is a problem can readily be taught appropriate techniques of suction aspiration but sodium chloride 0.9% p. 1101 given as nasal drops is preferred; administration before feeds may ease feeding difficulties caused by nasal congestion. Cough preparations in children The use of over-the-counter cough suppressants containing codeine phosphate should be avoided in children under 12 years and in children of any age known to be CYP2D6 ultra-rapid metabolisers. Cough suppressants containing Respiratory system similar opioid analgesics such as dextromethorphan and pholcodine are not generally recommended in children and should be avoided in children under 6 years; dextromethorphan should be avoided in children under 12 years. MHRA/CHM advice (March 2008 and February 2009) Children under 6 years should not be given over-the-counter cough and cold medicines containing the following ingredients: . brompheniramine, chlorphenamine maleate p. 297, diphenhydramine, doxylamine, promethazine, or triprolidine (antihistamines); . dextromethorphan or pholcodine (cough suppressants); . guaifenesin or ipecacuanha (expectorants); . Phenylephrine hydrochloride p. 201, pseudoephedrine hydrochloride, ephedrine hydrochloride p. 1266, oxymetazoline, or xylometazoline hydrochloride p. 1267 (decongestants). Over-the-counter cough and cold medicines can be considered for children aged 6–12 years after basic principles of best care have been tried, but treatment should be restricted to five days or less. Children should not be given more than 1 cough or cold preparation at a time because different brands may contain the same active ingredient; care should be taken to give the correct dose. COUGH AND COLD PREPARATIONS › COUGH SUPPRESSANTS
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Missed doses Manufacturer 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.
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100/150 mg, to be taken in the morning and,
First-line fragment. Read the complete Indications and Dose section above.
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