Author: Olivia Schwaller, PharmD Candidate 2016
Clinical Review: Kelly Cochran, PharmD, BCPS
When reviewing a patient’s medication list I noticed the Singulair (montelukast) prescription instructed her to take one tablet by mouth in the evening. I knew this was the proper way to take this medication because I had seen it come through the pharmacy many times, but I always wondered why it had to be taken in the evening.
What is montelukast? Montelukast is a medication that can be used for the treatment of asthma, allergic rhinitis, and exercise-induced bronchoconstriction in the pill form. It is an anti-inflammatory agent that inhibits the leukotriene pathway by blocking receptors located in the cell walls of the lungs, preventing smooth muscle contraction, respiratory inflammation, and edema.1 These leukotrienes are also released from the nasal mucosa after allergen exposure, and montelukast may inhibit symptoms associated with allergic rhinitis.1
Upon a little research I found that the prescribing information states, “There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing… Efficacy has been demonstrated for asthma when montelukast was administered in the evening…”2 From this information I gathered that most of the trials that were treating asthma patients with montelukast included evening administration in their trial protocols and the efficacy morning administration has not been studied. For those that would use montelukast for seasonal allergic rhinitis or perennial allergic rhinitis, a specific time to take the dose was not recommended.
A study from 2006, Pajaron-Fernandez et al, compared the response children with exercise induce bronchoconstriction (EIB) had to a morning or evening dose of montelukast over a two week period.3 Children enrolled were between the ages of 6-14 years old and were only taking an inhaled beta-2 agonist as needed for asthma symptoms.3 Following two weeks of treatment with montelukast in the morning or evening each treatment group underwent a one week washout period where they did not take any doses of montelukast. Then the groups switched to the opposite treatment time, for example from morning previously now to evening for an additional two weeks of treatment.3 Of 48 children enrolled, 24 completed the trial and their response to therapy was analyzed The main outcome variable interpreted was the maximum percent fall in the forced expired volume in 1 second (FEV1) after 3, 5, 10, 15, and 20 minutes of exercise. The secondary outcome measured was the maximum percent fall in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%). When interpreting these variables we look to see which treatment option has the least amount of decline in FEV1 and FEF25-75%to consider them the more viable option when treating asthma. A more pronounced decrease in these variables means asthma symptoms are worse, decreasing the outflow of air from the lungs. The results showed there was not statistical significance in maximum percent decline in FEV1 or in the area under the curve of FEV1 (AUCFEV1) between montelukast either given in the morning or the evening; meaning results did not show a difference in correlation to the time of day montelukast was given. There was a difference shown in the maximum percent fall of FEF25-75% while the morning dose showed a slight decrease compared to the evening dose, but it was not statistically significant. The authors of this trial concluded that montelukast exerts an increased action at night, either because of higher plasma concentration at the moment of the challenge test, or because of anti-inflammatory effect during the first hours of the morning, or both.3 Since this study observed the effects of montelukast in children with EIB, it cannot be accurately compared to adults with asthma due to the human lungs continuing to develop throughout one’s lifetime.5
In the Rumor vs. Truth section of the Pharmacists Letter evaluating when montelukast should be dosed, they concluded asthma symptoms tend to be worse during the night and early morning hours and that montelukast has a short half-life of about 4-7 hours with blood levels peaking 3-4 hours after a dose.4 For these reasons, they concluded that this is why healthcare providers and the prescribing information for montelukast recommends taking it at night in order to match peak drug levels with symptom onset.4 A comment was added by a pharmacist from Maryland that leukotriene synthesis occurs more at night than during the day. This would argue that evening dosing would have the most significant benefit on asthma symptoms both during sleep and the next day4. No clinical data could be found supporting this comment. Since the publication from the Pharmacist Letter, there has not been any additional studies or trials conducted to compare morning versus evening dosing of montelukast.
With the question still slightly up in the air, I would still recommend the use of montelukast in the evening, despite there being no clinical evidence in comparing morning doses versus evening doses in adults with asthma. I say this because from clinical trials comparing placebo versus montelukast, montelukast was always given in the evening showing statistical significant results in reducing asthma symptoms in children and adults.2
- Leukotriene modifiers pathway, Pharmacodynamics. PharmDKB. Accessed July 27, 2015. https://www.pharmgkb.org/pathway/PA165947317
- Singulair – Full Prescribing Information. Merck & Co., Inc. 2012. Accessed July 17, 2015. https://www.merck.com/product/usa/pi_circulars/s/singulair/singulair_pi.pdf
- Pajaron-Fernandez M, Garcia-Rubia S, Sanchez-Solis M, Garcia-Marcos L. Montelukast Administration in the Morning or Evening to Prevent Exercise-Induced Bronchoconstriction in Children. Pediatr Pulmonol. 2006 41: 222-227. Accessed July 17, 2015. http://onlinelibrary.wiley.com/doi/10.1002/ppul.20377/pdf
- Rumor vs. Truth; Singulair MUST be taken in the evening for asthma. Pharmacists Letter. Published September 9, 2008. Accessed July 17, 2015. http://pharmacistsletter.therapeuticresearch.com/pl/Rumor.aspx?cs=student&s=PL&fpt=56&rtid=242
- Narayanan M, Owers-Bradley J, Beardsmore CS, et al. Alveolarization Continues during Childhood and Adolescence. Am J Respir Crit Care Med. 2012;185(2): 186-191. Accesses July 27, 2015. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410735/