Desloratadine is approved for the treatment of seasonal allergic rhinitis above the age of 2, perennial allergic rhinitis above the age of 6 months, and chronic idiopathic urticaria above the age of 6 months.1,2,3 Desloratadine has a non-FDA labeled indication for acute urticaria.3 See Table 1 for a comparison of the different second-generation H1 selective antihistamines and their indications.
Table 1: Comparison of indications for the different second-generation H1 selective antihistamines1,2,3,4,5,6
Seasonal Allergic Rhinitis
Perennial Allergic Rhinitis
Chronic Idiopathic Urticaria
Desloratadine is a major metabolite of loratadine that is selective to the peripheral H1-receptor, which prevents histamine release from the mast cells in vitro.1,2,3 Desloratadine is a tricyclic antihistamine antagonist and is long-acting in duration.1,2,3
Table 2. Pharmacokinetics of drug and comparators 1,2,3,4,5,6,10
No food effects
Food decreased AUC 40% and delayed Tmax 1 hour
Food delayed Tmax 1.7 hours and decreased Cmax 23%
High fat meal decreased AUC 21% and Cmax 20%
Food decreased Cmax 36% and delayed Tmax 1.25 hours
To 3-hydroxy active metabolite via unidentified enzyme(s)
CYP 3A4 and some 2D6 to descarboethoxy active metabolite
Small amount of first degree metabolism in the liver by unidentified enzyme(s). Limited o-dealkylation to inactive metabolite.
About 5% by hepatic metabolism via unidentified enzyme(s)
About 14% hepatic metabolism via mainly 3A4
THERAPEUTIC/COMPARATIVE EFFICACY (clinical trials) and summary:
A review of three trials of over 1800 patients, ages 15 and older, desloratadine in patients with seasonal allergic rhinitis, persistent allergic rhinitis, or chronic idiopathic urticaria showed it to be efficacious and to have increased efficacy over placebo. In two trials, doses of desloratadine 5 mg showed significant benefits in nasal congestion scores and total symptom scores in persistent allergic rhinitis and seasonal allergic rhinitis respectively. However, when desloratadine 5mg was compared with levocetirizine 5 mg, although both were found to reduce pruritis severity, levocetirizine was more efficacious after 1 and 4 weeks. Table 3 provides a summary overview of the studies reviewed.
Table 3. Summary of Efficacy Studies
Primary End Points
Level of Evidence**
Desloratadine 5 mg
N = 584
Patients had to have a positive skin prick test or radioallergosorbent test of class >2 to house dust mite or cat dander within 24 months prior to screening and had a >2 year history of moderate-to-severe nasal symptoms associated with allergen exposure
Patients were randomized to treatment with desloratadine 5 mg or a matching placebo once daily in the morning.
Change from baseline in a.m. to p.m. nasal congestion score.
Secondary outcomes of change from baseline in total nasal symptom score, individual symptom scores and RQLQ scores.
Primary endpoint was achieved by 64% of those treated with desloratadine 5 mg (p<0.024 vs placebo) and 55% with placebo. There was a significant 28 day reduction in nasal congestion of 0.36 (P = 0.0003). There was a significant 28 day reduction in total nasal symptom score of 1.32 (P = 0.007). There was significant improvement in RQLQ score from 3.0 to 1.9 (P 0.008).
The same percentage of people dropped out of the study equally in both groups due to treatment failure. The side effects were similar between groups and headache was the only side effect noted occurring in greater than 2% of the patients.
It was noted that the placebo effect occurs frequently in rhinitis studies and was strong in this study, however the group receiving desloratadine had a 25% greater effect on the RQLQ score than placebo.
Reduction in am/pm nasal congestion score
Desloratadine 5 mg
N = 331
Patients had to have a 2 years history of seasonal allergic rhinitis and increased asthma signs or symptoms during the fall/winter allergy season. Had to be symptomatic at screening having a total nasal symptom score of 6 or more, a total nonnasal score or 5 or more and mild seasonal allergic asthma exacerbations.
The change from baseline in am/pm reflective total symptom scores.
Secondary outcomes were the change in individual seasonal allergic rhinitis and asthma symptoms.
Desloratadine significantly reduced the am/pm reflective total symptom scores from days 1-15 (-4.90, 31.6% reduction) vs placebo (-2.98, 19.3% reduction; P< 0.001) and continued over the 4 week study. Desloratadine improved the mean am/pm reflective nasal congestion score from days 1-29 (-0.64) vs. placebo (-0.47; P= 0.014). Desloratadine reduced the am/pm reflective total asthma symptom score from days 1-15 (-1.35) vs. placebo (-0.94; P< 0.023).
Adverse effects were similar in both groups and headache was the most commonly reported side effect at 3% and 3.7% treatment vs. placebo groups respectively.
Reduction in am/pm total symptom scores
NNT = 8
Desloratadine 5 mg
Levocetirizine 5 mg
N = 886
Ages: 18 - 81
Patients had to have a clinical history of chronic idiopathic urticaria (CIU) for a period of at least 6 weeks in the last 3 months without an identifiable cause. Patients also had to have a pruritis severity score greater than 2 over the previous 24 hours and the number of wheal score greater than 1 for at least 3 days in the last week.
Comparing the efficacy of desloratadine and levocetirizine on the mean pruritis severity score after 1 week of treatment.
Secondary outcomes were the mean pruritis severity score over 4 weeks, pruritis duration score, number and size of wheals, mean CIU composite score, quality of life and the satisfaction with treatment.
Both levocetirizine and desloratadine reduced the severity of pruritis in the first week (-1.17 vs. -1.04 respectively), however there was a significant difference between the two groups with the adjusted mean difference [95% CI = 0.16 (0.07; 0.26) P< 0.001]. This carried through the full 4 week study (P = 0.004). In the first week and entire study the patients reporting a pruritis severity score of none/mild was greater in the levocetirizine group over the desloratadine group (56% week 1, 67% week 4; 47% week 1, 57% week 4 respectively). After treatment week 1 48.8% of patients in the levocetirizine group reported their sleep was unaffected by CIU vs. 41.4% of the desloratadine group. After the entire treatment it was 66.8% vs. 63.2% respectively.
Reduction in pruritis severity score after 1 week:
levocetirizine versus desloratadine
NNT = 11
*Study design abbreviations: DB=double blind; RCT=randomized trial; PC=placebo-controlled; PG=parallel group; XO=crossover
**Level of evidence: Grade 1=RCT; Grade 2=nonrandomized concurrent studies; Grade 3=historical cohort & case-control studies; Grade 4=case series; Grade 5=expert opinion.
The main adverse effects that were found in clinical trials occurring in more than two percent of the patients were pharyngitis (4.1%), dry mouth (3.0%), myalgia (2.1%), fatigue (2.1%), somnolence (2.1%), and dysmenorrhea (2.1%).1 Adverse effects seen in desloratadine were generally similar to placebo and other second-generation H1selective antihistamines.1,2,4,5,6
Desloratadine reported very few drug interactions, and no drug interactions that affected the safety of desloratadine.1 There were studies done with giving desloratadine with erythromycin, ketoconazole, azithromycin, fluoxetine, and cimetidine.1 All of the studies showed increased Cmax and AUC, with the exception of fluoxetine where the AUC was not increased.1
Loratadine also was studied against erythromycin, ketoconazole and cimetidine and there was also increased AUC that was shown to not affect the safety.11
Cetirizine was studied against theophylline, azithromycin, pseudoephedrine, ketoconazole and erythromycin and found to not have any drug interactions with the listed drugs.6 There was a slight decrease in clearance from a 400 mg dose of theophylline so it is proposed that a larger dose could affect the clearance of Cetirizine, however it has not been proven.6 Ritonavir was shown to increase the AUC and elimination half-life of cetirizine by 42% and 53% respectively.5 Ritonavir also decreased the clearance of cetirizine by 29%.5 Conversely, ritonavir was not affected by cetirizine.5 Levocetirizine drug interactions were studied using cetirizine.5
Fexofenadine was studied against erythromycin and ketoconazole and also showed an increase in Cmax and AUC, and the safety was not affected.4
CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS:
Desloratadine is contraindicated in patients with a hypersensitivity to desloratadine or loratadine. 1,2
Desloratadine orally disintegrating tablets contain phenylalanine, therefore it should be avoided in patients with phenylketonuria.1,2
Desloratadine is pregnancy category C because no adequate studies have been performed on pregnant women, only in rats and rabbits.1,2 Therefore, pregnant women should only use if it is needed and if directed by their physician.1,2 Cetirizine and Levocetirizine are both second-generation H1 selective antihistamines that are in pregnancy category B.5,6
Desloratadine does enter into the breast milk.1,2 This is similar to the other second-generation H1 selective antihistamines, with the exception of Fexofenadine, where it is unknown yet if it is excreted in breast milk.2,4,5,6
MONITORING: no special monitoring required.1,2
AVAILABILITY AND DOSING:
Recommended dosing for adults and children 12 years or older for all indications: 5 mg once daily.1
Dose adjustment for children 6-11 years old: 2.5 mg (5 ml syrup or 2.5 mg orally disintegrating tablet) once daily.1
Dose adjustment for children 12 months to 5 years old: 1.25 mg (2.5ml syrup) once daily.1
Dose adjustment for children 6-11 months old: 1 mg (2ml syrup) once daily.1
Dose adjustment for adults with renal or liver impairment: 5 mg every other day.1
Dose adjustment for children with renal or liver impairment has not been studied.1
Table 4: Availability1,2
bottles of 100, 500 tablets
unit of use package of 30
unit dose back of 100
orally disintegrating tablet
2.5 mg, 5 mg
unit of use package of 30
4 oz, 16 oz amber bottle
Administration of orally disintegrating tablets: place on the tongue and it will disintegrate immediately. Can take with or without water.1,2
Administration of syrup: use with a dropper or syringe.2
Administration of all dosage forms may be take with or without regards to food.1,2
Table 5: Failure Modes and Effects Analysis (FMEA)1,2
Information is limited, however there were no death in moneys in doses up to 250 mg/kg. If overdose occurs treat the symptoms that occur. Desloratadine cannot be removed from hemodialysis.
Store at room temperature - between 15°C to 30°C (59°F to 86°F)
Efficacy and adverse effects
Table 6: comparative cost information10,12
5 mg daily
5-10 mg daily
$12.38 - $24.75
5-10 mg daily
$37.43 - $74.85
180 mg daily
5 mg daily
SUMMARY AND RECOMMENDATIONS:
Final summary of findings: Briefly highlight the key points pertaining to your drug. This paragraph is the lead-in to your recommendation, so be sure to include the most appropriate key points to support your recommendation.
In a separate paragraph, indicate whether or not the drug should be added to the Drug Formulary of your institution, assuming it has patients that will be treated for illnesses where this drug might be used. Include information related to the comparisons made in your monograph. Make sure to briefly (but clearly) state why you are making these recommendations. Recommendations may be one of the following: 1. Non-formulary (do not add to the current fomulary) OR 2. Formulary (add to the current formulary)
References: (Use AMA Referencing)
1. Clarinex package insert page. DailyMed Web site. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=8630#nlm34069-5. Accessed February 20, 2010.
2. Lexi-Comp. Lexi-Comp Web site. Available at: http://online.lexi.com/crlsql/servlet/crlonline?siteid=20. Accessed February 20, 2010.
3. Micromedex Healthcare Series Web site. Available at: http://www.thomsonhc.com/hcs/librarian. Accessed February 20, 2010.
4. Allegra package insert page. DailyMed Web site. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=8870#nlm34069-5. Accessed February 20, 2010.
5. Xyzal package insert page. DailyMed Web site. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=7522#section-9. Accessed February 20, 2010.
6. Zyrtec package insert page. DailyMed Web site. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=2115#nlm34070-3. Accessed February 20, 2010.
7. Holmberg K, Tonnel A, Dreyfus I, et al. Desloratadine relieves nasal congestion and improves quality-of-life in persistent allergic rhinitis. Allergy [serial online]. November 2009;64(11):1663-1670. Available from: MEDLINE, Ipswich, MA. Accessed February 20, 2010.
8. Berger W, Schenkel E, Mansfield L. Safety and efficacy of desloratadine 5 mg in asthma patients with seasonal allergic rhinitis and nasal congestion. Annals Of Allergy, Asthma & Immunology: Official Publication Of The American College Of Allergy, Asthma, & Immunology [serial online]. November 2002;89(5):485-491. Available from: MEDLINE, Ipswich, MA. Accessed February 20, 2010.
9. Potter P, Kapp A, Maurer M, et al. Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients. Allergy [serial online]. April 2009;64(4):596-604. Available from: MEDLINE, Ipswich, MA. Accessed February 20, 2010.
10. Lehman J, Blaiss M. Selecting the optimal oral antihistamine for patients with allergic rhinitis. Drugs [serial online]. 2006;66(18):2309-2319. Available from: MEDLINE, Ipswich, MA. Accessed February 20, 2010.
11. Clinical pharmacology Web site. Available at: http://www.clinicalpharmacology-ip.com/Default.aspx. Accessed February 20, 2010.
12. Amerisource Bergen Web site. Available at: http://www.amerisourcebergen.com/cp/1/. Accessed February 18, 2010.