3.3.2 Leukotriene receptor antagonists (LTRAs)

Patients in whom leukotriene receptor antagonists (LTRAs) may be particularly effective are those with aspirin sensitivity, a large exercise induced component to the symptoms, highly atopic eczema, and rhinitis.

Montelukast

• Tablets 10mg (£1.31)
• Chewable tablets sugar free 4mg, 5mg (£0.94 = 4mg, £1.11 = 5mg)
• Granules sachets sugar free 4mg (£6.33)

Indications and dose:

• Prophylaxis of asthma:
  
  • Child 6 months–5 years: 4mg once daily, dose to be taken in the evening
  • Child 6–14 years: 5mg once daily, dose to be taken in the evening
  • Adults and adolescents 15 years of age and above: 10mg once daily, dose to be taken in the evening

Notes

1. Montelukast is not indicated for treatment of an acute deterioration of asthma and should not be used to relieve an attack of acute severe asthma. Montelukast does not necessarily allow a reduction in the existing corticosteroid treatment.
2. Montelukast may be considered if exercise induced asthma is a specific problem in a patient who is otherwise well controlled.
3. Treatment should be trialled – if no benefit seen after 4 weeks, montelukast should be discontinued and alternative treatment options discussed with the patient.
4. Refer to paediatric and adult asthma guidance for further information on the use of montelukast in the management of asthmatic patients.
5. MHRA Drug Safety Update (April 2024): Montelukast: reminder of the risk of neuropsychiatric reactions
   1. The warnings in the Patient Information Leaflet and SmPC for all montelukast products in the UK have been strengthened and highlighted with a black box for greater emphasis.
   2. Be alert for neuropsychiatric reactions in patients taking montelukast; events have been reported in adults, adolescents, and children.
   3. Neuropsychiatric reactions reported in association with montelukast include:
      1. sleep disturbances, depression and agitation including aggressive behaviour (may affect up to 1 in 100 people taking montelukast)
      2. disturbances of attention or memory (up to 1 in 1,000 people)
      3. very rarely, hallucinations and suicidal thinking and behaviour (up to 1 in 10,000 people).
   4. Discontinue montelukast if patients experience new or worsening symptoms of neuropsychiatric reactions.
   5. Advise patients and their caregivers to carefully read the list of neuropsychiatric reactions in the Patient Information Leaflet and to seek medical advice immediately should they occur.
   6. Refer to the Drug Safety Update for additional advice to give to patients.

3.3.3 Phosphodiesterase type-4 inhibitors

Roflumilast

• Tablets 500micrograms (£35.20)
• Tablets 250micrograms (hospital only) (see note 2)

Indications and dose

• Adjunct to bronchodilators for maintenance treatment of severe COPD in adults with chronic bronchitis in line with NICE TA461 (see note 6).
  • Initially 250micrograms once daily for 28 days, then maintenance 500micrograms once daily
  • Renal impairment: no dose adjustment required
  • Hepatic impairment: use with caution in mild hepatic impairment (Child-Pugh A). Contraindicated in moderate or severe hepatic impairment (Child-Pugh B or C).

Notes

1. Treatment should be started by a specialist in respiratory medicine. Specialist prescribing should continue until the patient is established on the maintenance dose, after which GPs may be asked to continue prescribing.
2. The starting dose (250micrograms once daily) is intended to reduce adverse reactions and patient discontinuation when initiating therapy, but it is a sub-therapeutic dose and should be used only as a starting dose. After 28 days of treatment with the starting dose, patients must be up-titrated to 500micrograms once daily. For this reason, the 250microgram tablets remain hospital only.
3. Body weight loss: Roflumilast can cause weight loss (see SmPC for more details):
   1. Patients should be advised to check their body weight on a regular basis.
   2. Body weight of underweight patients should be checked at each specialist visit.
   3. In the event of an unexplained and clinically concerning loss of weight, roflumilast should be stopped and body weight should be further followed-up.
4. Psychiatric disorders: Roflumilast is associated with an increased risk of psychiatric disorders such as insomnia, anxiety, nervousness and depression, and rare instances of suicidal ideation and behaviour (refer to SmPC for further information)
5. Interactions: The use of strong cytochrome P450 enzyme inducers (e.g. phenobarbital, carbamazepine, phenytoin) may reduce the therapeutic efficacy of roflumilast (concomitant treatment not recommended). Refer to BNF and SmPC for more information and further interactions.
6. NICE TA461: Roflumilast (Daxas), as an add-on to bronchodilator therapy, is recommended as an option for treating severe chronic obstructive pulmonary disease in adults with chronic bronchitis (July 2017), only if:
   1. the disease is severe, defined as a forced expiratory volume in 1 second (FEV1) after a bronchodilator of less than 50% of predicted normal, and
   2. the person has had 2 or more exacerbations in the previous 12 months despite triple inhaled therapy with a long-acting muscarinic antagonist, a long-acting beta-2 agonist and an inhaled corticosteroid.
   3. Treatment with roflumilast should be started by a specialist in respiratory medicine.