Commissioned by Aspire Pharma Ltd 

Information intended for healthcare professionals only.

This formulary decision guide was developed from content supplied by Aspire Pharma Ltd in a format developed by Guidelines in Practice. It has been reviewed by a medicines management professional.

Click here to view prescribing information and adverse event reporting information.

Key points on this medicine

Combisal FDG

  • Combisal® 25/50 mcg, 25/125 mcg, and 25/250 mcg is the only branded generic alternative to Seretide® (salmeterol/fluticasone) that offers all the strengths of the originator product, across all of the indications1
  • Prescribing Combisal® pMDI by brand, in place of current salmeterol/fluticasone combination pMDIs, could offer the NHS cost savings of up to 25%2
  • Combisal® allows for adherence to the BTS/SIGN guidance on asthma prescribing;* enabling patients to be stepped up and down the pathways while being maintained on an alternative, cost-effective, branded option—for the first time3
  • Aspire Pharma offers a price and supply guarantee for Combisal® 25/50 mcg, 25/125 mcg, and 25/250 mcg pMDI.4†

*When LABA/ICS combination inhaler recommended. Maximum licensed dose of fluticasone propionate in children is 100 mcg twice daily.

Click here to download a PDF of the formulary decision guide.

Drug name

Combisal® (salmeterol/fluticasone) pressurised metered dose inhaler (pMDI)

Available strengths

  • 25/50 mcg, 25/125 mcg, and 25/250 mcg salmeterol/fluticasone per metered dose pressurised inhalation, suspension.5

Therapeutic indications

  • Combisal® is indicated in the regular treatment of asthma where use of a combination product (LABA and ICS) is appropriate:5
    • patients not adequately controlled with ICS and ‘as needed’ inhaled SABA or

    • patients already adequately controlled on both ICS and LABA.

Dosage and method of use

  • For inhalation use5
  • Recommended dose:5
    • adults and adolescents 12 years and older—two inhalations twice daily of appropriate dosage for the severity of disease
    • children 4 years and older—two inhalations of 25/50 mcg twice daily
  • Maximum licensed dose of fluticasone propionate in children is 100 mcg twice daily—there are no data in children under 4 years of age5
  • The dose should be titrated to the lowest dose at which effective control of symptoms is maintained5
    • if long-term control is maintained at the lowest dose, consider testing ICS alone, or using the combination once daily
  • Combisal® 25/50 mcg strength is not appropriate for adults and children with severe asthma5
  • Combisal® can be used with an AeroChamber Plus® spacer device—this may increase drug delivery to the lungs, increasing the risk of systemic adverse effects5
  • Patients should be advised to rinse their mouth out with water and spit out and/or brush teeth after each dose to minimise risk of oropharyngeal candidiasis and hoarseness.5

BTS/SIGN recommendations 

Pharmacological management3

  • For adults and children, ICS is the recommended preventer drug for achieving overall treatment goals
  • The first-choice as add-on therapy to ICS:
    • in adults—LABA
    • in children aged 5 years and over—LABA or an LTRA
  • A combination of an ICS and a LABA in a single inhaler is recommended to:
    • guarantee that the LABA is not taken without the ICS
    • improve inhaler adherence.

Stepping up and stepping down treatment3

  • If control remains suboptimal following addition of a LABA, the ICS dose may be increased either from low to medium or medium to high (adults) or from either very low to low or low to medium (children 5–12 years), if not already on these doses
  • Patients should be maintained on the lowest possible dose of ICS; reductions should be considered every 3 months, decreasing the dose by 25–50% each time.

Prescribing devices3

  • The most important factors to consider when prescribing devices are patient preference and local cost
  • Generic prescribing of inhalers should be avoided so that people are not given unfamiliar devices that they are unable to use properly. 

Budgetary implications

  • Prescribing Combisal® pMDI by brand, in place of Seretide® (salmeterol/fluticasone) could offer the NHS cost savings of up to 25%.2
ICS dose3‡Product (salmeterol/fluticasone pMDI)Dose NHS list price2
Low Combisal® 25/50 mcg 2 puffs bd £13.50
Seretide Evohaler 25/50 mcg 2 puffs bd £18.00
Medium       Combisal® 25/125 mcg 2 puffs bd £17.59
Seretide Evohaler 25/125 mcg 2 puffs bd £23.45
Sirdupla 25/125 mcg 2 puffs bd £22.45
AirFluSal 25/125 mcg 2 puffs bd £18.50
Aloflute 25/125 mcg 2 puffs bd £22.45
Sereflo 25/125 mcg 2 puffs bd £18.50
High Combisal® 25/250 mcg 2 puffs bd £29.89
Seretide Evohaler 25/250 mcg 2 puffs bd £39.85
Sirdupla 25/250 mcg 2 puffs bd £38.85
AirFluSal 25/250 mcg 2 puffs bd £29.95 
Aloflute 25/250 mcg 2 puffs bd £38.85
Sereflo 25/250 mcg 2 puffs bd £29.95

ICS=inhaled corticosteroid; pMDI=pressurised metered dose inhaler; bd=twice daily

Based on BTS/SIGN classification for adults.3

Information for CCGs and prescribers

  • Aspire Pharma offers a price and supply guarantee for Combisal 25/50 mcg, 25/125 mcg, and 25/250 mcg pMDI.4†

Prices unchanged unless material change to Category C of UK Drug tariff or product in 2019 PPRS review.

Bioequivalence

  • The equivalence of Combisal® 25/250 mcg to the reference Seretide Evohaler®, when used with or without the AeroChamber Plus® spacer, has been demonstrated conclusively, based on in vivo pharmacokinetic studies6
    • a biowaiver, supported by in vitro data, has been accepted for the lower strengths (25/50 mcg, 25/125 mcg).

Contraindications and precautions

  • Combisal® is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients5
  • Patients should not be initiated on Combisal®:5
    • during an exacerbation
    • if asthma is significantly worsening or deteriorating
  • Combisal® should not be used to treat acute asthma for which fast- and short-acting bronchodilator use is required5
  • Prolonged use of high doses of ICS may result in adrenal suppression and acute adrenal crisis5
  • Use with caution in patients with pulmonary tuberculosis and fungal, viral, or other infections of the airway; severe cardiovascular disorders or heart rhythm abnormalities; diabetes mellitus; thyrotoxicosis; or hypokalaemia5
  • Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery5
  • Patients transferring from oral steroids should be monitored for impaired adrenal reserve5
  • The safety and efficacy of Combisal® in COPD has not been established5
  • Patients of black African or Afro-Caribbean ancestry should seek medical advice if their asthma is uncontrolled or worsens on Combisal®5
  • Avoid combining with: ritonavir or other potent CYP3A inhibitors; ketoconazole or other potent CYP3A4 inhibitors; non-selective and selective β blockers; xanthine derivatives, steroids, and diuretics in acute severe asthma5
    • other β-adrenergic containing drugs can have an additive effect
  • If treatment in children is prolonged, monitor height.5

Side-effects

  • Very common (≥1/10) side-effects include headache and nasopharyngitis5
  • Common (≥1/100 to <1/10) side-effects include candidiasis of mouth and throat, pneumonia, bronchitis, hypokalaemia, throat irritation, hoarseness/dysphonia, sinusitis, contusions, muscle cramps, traumatic fractures, arthralgia, and myalgia5
  • For a full list of side-effects, refer to the SPC.5

Abbreviations

pMDI=pressurised metered dose inhaler; BTS=British Thoracic Society; SIGN=Scottish Intercollegiate Guidelines Network; LABA=long-acting beta2-agonist; ICS=inhaled corticosteroid; SABA=short-acting beta2-agonist; LTRA=leukotriene receptor antagonist; COPD=chronic obstructive pulmonary disease; SPC=summary of product characteristics

References

  1. Aspire Pharma Ltd. Data on file, 1010422396 v 2.0 June 2018.
  2. NHSBSA. NHS Dictionary of medicines and devices (dm+d). Effective 1st September 2018. www.nhsbsa.nhs.uk/pharmacies-gp-practices-and-appliance-contractors/dictionary-medicines-and-devices-dmd (accessed September 2018).
  3. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. SIGN 153. BTS/SIGN, 2016. Available at: www.brit-thoracic.org.uk/standards-of-care/guidelines/btssign-british-guideline-on-the-management-of-asthma/
  4. Aspire Pharma’s Supply Guarantee, 1010422400 v 2.0 September 2018.
  5. Aspire Pharma Ltd. Combisal® 25/50 μg, 25/125 μg, 25/250 μg—summary of product characteristics. March 2018. Available at www.medicines.org.uk
  6. Aspire Pharma Ltd. Data on file, 1010422379 v 3.0 July 2018.

Job code: 1010422387 v 2.0 September 2018

Date of preparation: September 2018.