Loratadine dosing

Grant JA, Riethuisen JM, Moulaert B, DeVos C A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo sup- 59 pression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects. 

Renal/Hepatic function impairment Use a lower initial dose of loratadine, desloratadine, and cetirizine in patients with renal or hepatic impairment. 

No advantage over loratadine or cetirizine lower doses associated with less sedation and efficacy... 

During the NAC, loratadine was associated with significantly fewer symptoms than placebo at the highest dose of allergen (6250 AUs) (P = 0.04, t = 1.83, df = 19) as well as overall, expressed as the sum of nasal symptom scores experienced over the NAC (P = 0.04, t = 1.83, df = 19). During the NAC, there were no statistically significant differences between Herbal Blend and placebo at any time point (Figure 10.3). 

In healthy volunteers promethazine caused impaired cognitive function and psychomotor performance (64). The test battery consisted of critical flicker fusion, choice reaction time, compensatory tracking task, and assessment of subjective sedation. Cetirizine and loratadine at all doses tested were not significantly different from placebo in any of the tests used. 

In a double-blind, crossover study levocetirizine 5 mg once daily for 4 days was compared with cetirizine 10 mg, loratadine 10 mg, promethazine 30 mg, and placebo in terms of nervous system inhibitory effects in 20 healthy volunteers (456). With the exception of promethazine none of the drugs had disruptive or sedative effects on objective measurements in a comprehensive battery of psychomotor and cognitive tests. These studies suggest that levocetirizine has minimal sedative effects in healthy individuals when given in its recommended dose. 

Loratadine is well absorbed after oral administration, with peak plasma concentrations at approximately 1.5 hours. Clinically significant relief of symptoms is usually obtained within 2 to 4 hours of the first dose. Excretion of loratadine occurs almost equally through the urine and feces.This dual mechanism of secretion provides a measure of safety in patients with liver or kidney disease, but caution should be exercised in both groups. Also, torsades de pointes may occur with the concurrent use of loratadine and amiodarone. Desloratadine is a metabolite of loratadine. 

In a comparison of cetirizine and loratadine, cetirizine 10 mg had acute sedative effects and impaired driving performance (65), whereas loratadine had no sedating potential furthermore, there was an additive effect of alcohol and cetirizine but not alcohol and loratadine. However, in a study using a driving simulator cetirizine 10 mg did not affect driving ability (66). In other studies cetirizine 20 mg caused significant sedation, while in one study there was a dose-dependent sedative effect with 10 mg and 20 mg but not 5 mg (67). Pooling the available data (SEDA-16, 163) shows that cetirizine is little more sedative than loratadine and terfenadine. 

The effects of loratadine 10, 20, and 40 mg on tests of visnomotor coordination, dynamic visnal acnity, shortterm memory, digit symbol snbstitntion, and snbjective assessments of mood have been stndied (68). Triprohdine was used as an active control and impaired performance on all the tasks presented. Loratadine 40 mg caused a significant impairment of the Digit Symbol Substitution Test and the Dynamic Visual Acuity Test, but the 10 and 20 mg doses were without effect. Loratadine did not affect objective sleepiness, as measured by Multiple Sleep Latency Test (69). In other studies of loratadine in the normal 10 mg dose the sedation rate was no different from placebo (SEDA-12, 143) (SEDA-14, 136). 

Ketoconazole affects plasma concentrations of lorata-dine, a non-sedating antihistamine, but appears to be devoid of any electrocardiographic effects (31). In a randomized, single-bhnd, multiple-dose, three-way, crossover study, concomitant administration of loratadine 10 mg qds and ketoconazole 200 mg bd resulted in significantly increased mean loratadine plasma... 

The pharmacokinetics, electrocardiographic effects, and tolerability of loratadine syrup have been studied in 161 children aged 2-5 years (3). A single-dose open study was performed to characterize the pharmacokinetic profiles of loratadine and its metabolite desloratadine, and a randomized, double-bUnd, placebo-controlled, parallel-group study was performed to assess the tolerability of loratadine syrup 5 mg after multiple doses. Electrocardiographic parameters were not altered by loratadine compared with placebo. There were no clinically important changes in other tolerability assessments. 

In healthy adults loratadine 10 mg/day had no effects on the electrocardiogram when co-administered for 10 days with therapeutic doses of ketoconazole or cimetidine (4). 

Nefazodone is a phenylpiperazine antidepressant that is predominantly metabolized by CYP3A. In a randomized, double-blind, double-dummy, parallel-group, multiple-dose study in healthy men and women who were given loratadine 20 mg od or nefazodone 300 mg every 12 hours, the plasma loratadine concentrations were significantly increased by co-administration of nefazodone (7). The mean QT interval was unchanged by loratadine alone, but was markedly prolonged with co-administration of nefazodone, and the extent of prolongation correlated with the plasma loratadine concentration. 

Acrivastine has a rapid onset of action and a short half-life, necessitating more frequent dosing than cetirizine or loratadine, but it may be useful to give rapid relief. 

Loratidine is about 98% bound to plasma protein. The drug does not readily cross the blood-brain barrier. Loratidine is extensively metabolized to an active metabolite called descarboethoxyloratadine. Approximately 80% of the total dose administered can be found equally distributed between urine and feces. The mean elimination half-life is 8.4 hours for loratadine. Loratidine overdosage (40 mg) causes somnolence, tachycardia, and headache. 

The second-generation ( nonsedating ) Hj antagonists e.g., loratadine, cetirizine, and fexofenadine) are largely excluded from the brain when given in therapeutic doses because they do not cross the blood-brain barrier. An interesting and useful property of certain Hj antagonists is the capacity to counter motion sickness see Chapters 7 and 37). This effect was first observed with dimenhydrinate and subsequently with diphenhydramine (the active moiety of dimenhydrinate), various piperazine derivatives, and promethazine. 

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