Levocetirizine Dihydrochloride (Page 5 of 6)

14.2 Chronic Idiopathic Urticaria

Adult Patients 18 Years of Age and Older

The efficacy of levocetirizine dihydrochloride for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria was evaluated in two multi-center, randomized, placebo-controlled, double-blind clinical trials of 4 weeks duration in adult patients 18 to 85 years of age with chronic idiopathic urticaria. The two trials included one 4-week dose-ranging trial and one 4 week single-dose level efficacy trial. These trials included 423 patients (139 males and 284 females). Most patients (>90%) were Caucasian and the mean age was 41. Of these patients, 146 received levocetirizine dihydrochloride 5 mg once daily in the evening. Efficacy was assessed based on patient recording of pruritus severity on a severity score of 0 to 3 (0 = none to 3 = severe). The primary efficacy endpoint was the mean reflective pruritus severity score over the first week and over the entire treatment period. Additional efficacy variables were the instantaneous pruritus severity score, the number and size of wheals, and duration of pruritus.

The dose-ranging trial was conducted to evaluate the efficacy of levocetirizine dihydrochloride 2.5, 5, and 10 mg once daily in the evening. In this trial, each of the three doses of levocetirizine dihydrochloride demonstrated greater decrease in the reflective pruritus severity score than placebo and the difference was statistically significant for all three doses (see Table 6).

The single dose level trial evaluated the efficacy of levocetirizine dihydrochloride 5 mg once daily in the evening compared to placebo in patients with chronic idiopathic urticaria over a 4 week treatment period. Levocetirizine dihydrochloride 5 mg demonstrated a greater decrease from baseline in the reflective pruritus severity score than placebo and the difference from placebo was statistically significant.

Duration of pruritus, number and size of wheals, and instantaneous pruritus severity score also showed significant improvement over placebo. The significant improvement in the instantaneous pruritus severity score over placebo confirmed end of dosing interval efficacy (see Table 6).

Table 6: Mean Reflective Pruritus Severity Score in Chronic Idiopathic Urticaria Trials

Treatment	N	Baseline	On Treatment Adjusted Mean	Difference From Placebo
				Estimate	95% CI		p-value
Dose Ranging Trial – Reflective pruritus severity score
Levocetirizine Dihydrochloride 2.5 mg	69	2.08	1.02	0.82	(0.58, 1.06)	<0.001
Levocetirizine Dihydrochloride 5 mg	62	2.07	0.92	0.91	(0.66, 1.16)	<0.001
Levocetirizine Dihydrochloride 10 mg	55	2.04	0.73	1.11	(0.85, 1.37)	<0.001
Placebo	60	2.25	1.84
Chronic Idiopathic Urticaria Trial – Reflective pruritus severity score
Levocetirizine Dihydrochloride 5 mg	80	2.07	0.94	0.62	(0.38, 0.86)	<0.001
Placebo	82	2.06	1.56

Pediatric Patients

There are no clinical efficacy trials in pediatric patients with chronic idiopathic urticaria [see Use in Specific Populations (8.4)].

16 HOW SUPPLIED/STORAGE AND HANDLING

Levocetirizine Dihydrochloride Tablets USP are available as follows:

5 mg — white to off-white, film-coated, oval-shaped, scored tablets. One side of the tablet is scored in half and debossed with the number “9” on one side of the score and “3” on the other. The other side of the tablet debossed with the number “7701”. They are available in bottles of 90 (NDC 0093-7701-98).

Storage:

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

17 PATIENT COUNSELING INFORMATION

Somnolence

Caution patients against engaging in hazardous occupations requiring complete mental alertness, and motor coordination such as operating machinery or driving a motor vehicle after ingestion of levocetirizine dihydrochloride tablets.

Concomitant Use of Alcohol and other Central Nervous System Depressants

Instruct patients to avoid concurrent use of levocetirizine dihydrochloride tablets with alcohol or other central nervous system depressants because additional reduction in mental alertness may occur.

Dosing of Levocetirizine Dihydrochloride Tablets

Do not exceed the recommended daily dose in adults and adolescents 12 years of age and older of 5 mg once daily in the evening. In children 6 to 11 years of age the recommended dose is 2.5 mg once daily in the evening. In children 6 months to 5 years of age, the recommended dose is 1.25 mg once daily in the evening. Advise patients to not ingest more than the recommended dose of levocetirizine dihydrochloride tablets because of the increased risk of somnolence at higher doses.

Manufactured In Croatia By:
Pliva Hrvatska d.o.o.
Zagreb, Croatia
Manufactured For:
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454

Rev. S 4/2019