Claritin-D® (Loratadine; Pseudoephedrine)
Claritin-D® | Alavert™ Allergy and Sinus D-12 Hour | Allergy and Congestion Relief | Allergy and Sinus Relief | Allergy Relief 12 Hour | Allergy Relief D | Claritin-D® 12 Hour | Claritin-D® 24 Hour | Clear-Atadine™ D
Classification:
Antihistamines
H1-blockers
Autonomic Agents
Sympathomimetics
Respiratory Agents
Adrenergic agonists
Description: Loratadine and pseudoephedrine are used in combination to relieve the nasal and non-nasal symptoms of allergic rhinitis. Loratadine is a non-sedating H1-blocker that does not readily cross the blood-brain barrier. Pseudoephedrine is a sympathomimetic amine which is effective in relieving the symptoms of nasal and sinus congestion. Claritin-D® was first approved by the FDA in November 1994 as a 12-hour formulation; Claritin-D® 24 HOUR was subsequently approved in August 1996. Previously only available by prescription, the FDA approved the non-prescription (OTC) use of Claritin®-D 12 HOUR and 24 HOUR formulations on November 27, 2002. Claritin®-D products became available for OTC sale during December 2002. Generic formulations of Claritin®-D 12 Hour and Claritin®-D 24 Hour formulations were approved during February 2003.
Mechanism of Action: Claritin-D® has combined antihistaminic and sympathomimetic properties due to the components loratadine and pseudoephedrine, respectively.
- Loratadine: Loratadine is a long-acting, competitive, tricyclic antihistamine with selective peripheral histamine H1-receptor antagonistic activity. Loratadine blocks the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. H1-blockers possess anticholinergic properties in varying degrees; however, loratadine does not exert significant anticholinergic effects at therapeutic concentrations. In vitro studies have shown that loratadine has a weak affinity for acetylcholine and alpha-adrenergic receptors.
- Pseudoephedrine: Pseudoephedrine is an agonist at both alpha- and, to a lesser degree, beta-adrenergic receptors. Like ephedrine, pseudoephedrine also has an indirect effect by releasing norepinephrine from its storage sites. By stimulating alpha-adrenergic receptors in the mucosa of the respiratory tract, pseudoephedrine shrinks swollen nasal mucous membranes; reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. Also, drainage of sinus secretions is increased, and obstructed eustachian ostia may be opened. Oral administration of pseudoephedrine usually produces negligible effects on blood pressure. In some patients, especially those with preexisting cardiac disease receiving higher doses, pseudoephedrine may increase blood pressure or irritability of the heart muscle and may affect ventricular conduction.
Claritin-D 12 Hour Extended Release Tablets(Tab ER 5;120 mg;mg)
Pharmacokinetics:
Claritin-D® may be administered orally as a 12-hour formulation containing 5 mg of
loratadine for immediate release combined with 120 mg pseudoephedrine sulfate which is equally distributed between the tablet coating for immediate release and the barrier-coating for extended release; or as the 24-hour tablet which contains 10 mg of
loratadine for immediate release combined with 240 mg pseudoephedrine formulated for extended release. The bioavailability of
loratadine and pseudoephedrine from
Claritin-D® 12-HOUR and 24-HOUR extended-release tablets is similar to that achieved with separate administration of the components. In a single-dose study, food increased the AUC of
loratadine by approximately 125% and Cmax by approximately 80%. However, food did not significantly affect the pharmacokinetics of pseudoephedrine or descarboethoxyloratadine.
- Loratadine: Loratadine is rapidly absorbed and extensively metabolized to an active metabolite (descarboethoxyloratadine). The onset of action of loratadine occurs within 1 - 3 hours, with peak effects in 8 - 12 hours, a duration of action greater than 24 hours, and no evidence of tolerance. Administration with food enhances absorption and increases the AUC of loratadine by approximately 125%, but does not alter the pharmacokinetics of pseudoephedrine. Loratadine is 97% protein-bound and is excreted into breast milk. Loratadine does not affect the plasma protein binding of warfarin and digoxin.
Loratadine has a high first pass effect and is almost completely metabolized in the liver to an active metabolite, descarboethoxyloratadine, predominantly by P450 CYP3A4 and to a lesser extent by P450 CYP2D6. The mean elimination half-lives of loratadine and its metabolite are 8.4 hours (range 3 - 20 hours) and 28 hours, respectively. Elimination occurs through the fecal and renal routes.
The elderly and those with chronic alcoholic liver disease will have prolonged elimination half lives for both the parent drug (18.2 hours and 24 hours, respectively) and its metabolite (17.5 hours and 37 hours, respectively). In elderly subjects, the AUC and peak plasma concentrations of loratadine are roughly 50% greater than those observed in younger subjects. Patients with chronic alcoholic liver disease achieve peak serum concentrations which are approximately double those observed in patients without hepatic disease. Peak loratadine serum concentrations may increase up to 73% in the presence of renal impairment; although patients with renal impairment have similar elimination rates to normal subjects. Hemodialysis does not alter the pharmacokinetics of loratadine or its metabolite.
- Pseudoephedrine: Pseudoephedrine duration of action is dependent upon the dose and the extended release formulation (12 or 24 hours). Pseudoephedrine is presumed to cross the placenta, blood brain barrier, and may be distributed into breast milk. Pseudoephedrine is incompletely metabolized in the liver to norpseudoephedrine, the primary active metabolite of the parent. The drug and metabolite are excreted in the urine; with 55 - 75% excreted as unchanged drug. The elimination half-life of the drug ranges from 9 - 16 hours dependent primarily upon urinary pH. The rate of urinary excretion is accelerated upon urinary acidification to a pH near 5. Upon alkalination of the urine to a pH of approximately 8, some of the drug is reabsorbed into the kidney tubule and the rate of urinary excretion is slowed.
Renal impairment signifcantly reduces pseudoephedrine clearance. The effect of liver disease on pseudoephedrine pharmacokinetics is unknown. The effect of hemodialysis on the removal of pseudoephedrine is unknown.
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[ Revised 4/25/2005 3:21:00 PM ]
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