loratadine, Claritin
Assessing satisfaction with desloratadine and fexofenadine in allergy patients who report dissatisfaction with loratadine.

Glass DJ, Harper AS.

Zynx Life Sciences, Cerner Corporation, Beverly Hills, CA, USA. dglass cerner.com

BACKGROUND: The FDA recently moved loratadine (Claritin) from prescription only status to over-the-counter (OTC). In response to the availability of an OTC non-sedating antihistamine, many managed care organizations are reevaluating which if any prescription antihistamines should remain on formulary. From a managed care perspective, determining which of the remaining prescription antihistamines results in the greatest patient satisfaction with allergy treatment would be informative. METHODS: We report on a weighted cross sectional survey (n = 10,023) delivered online to a sample of allergy sufferers in the U.S. during the month of December 2002. Two segments were identified for analysis: patient who were dissatisfied with loratadine and converted to desloratadine (Clarinex; n = 61), and patients who were dissatisfied with loratadine and converted to fexofenadine (Allegra; n = 211). The two segments were compared along a series of measures that the literature suggests are related to treatment satisfaction. RESULTS: The survey found that two of the satisfaction measures differentiated desloratadine converters from fexofenadine converters (p <.05): mean sum of self-reported adverse events and nighttime awakening due to allergy symptoms. For the remainder of satisfaction measures though, patients who were dissatisfied with loratadine reported equal duration of coverage and satisfaction with desloratadine as fexofenadine. When severity of disease was controlled for in the analysis, a pattern emerged suggesting greater levels of satisfaction amongst loratadine dissatisfied patients who converted to desloratadine. Point estimates suggest a consistent pattern favoring desloratadine patient satisfaction, with statistically significant results reported for sum of adverse effects, nighttime awakening due to symptoms, symptom severity just prior to the next dose, and overall satisfaction (p < 0.05). CONCLUSIONS: On average, patients who were dissatisfied with loratadine reported equal or better satisfaction with desloratadine as fexofenadine. Patients with severe allergic rhinitis reported greater satisfaction when converted from loratadine to desloratadine than fexofenadine for select satisfaction measures. These results suggest that if managed care intends to position prescription antihistamines as second line for OTC loratadine treatment dissatisfaction, desloratadine is a useful treatment alternative. These findings, while informative to formulary decision-makers, must be interpreted with caution. Only through head-to-head controlled clinical trials can differences in efficacy and safety be established.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12917016&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Reliable and specific high-performance liquid chromatographic method for simultaneous determination of loratadine and its metabolite in human plasma.

Yin OQ, Shi X, Chow MS.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. qpyin cuhk.edu.hk

A high-performance liquid chromatographic (HPLC) method with fluorescence detection has been developed for the simultaneous determination of loratadine (L) and its metabolite, descarboethoxyloratadine (DCL), in human plasma. Following a two-step liquid-liquid extraction with toluene, the analytes were separated using a gradient mobile phase consisting of methanol-acetonitrile-phosphate buffer. The linearity for L and DCL was within the concentration range of 0.5-16 ng/ml. The coefficient of variation of intra- and inter-day assay was <8.3%, with accuracy ranging from 98.3 to 105.7%. The lower limit of quantification was 0.5 ng/ml for both L and DCL. This method has been demonstrated to be reliable, and is an improvement over existing methods due to its capability for determining L and DCL simultaneously in a single chromatographic run.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14552827&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Effects of perinatal loratadine exposure on male rat reproductive organ development.

McIntyre BS, Vancutsem PM, Treinen KA, Morrissey RE.

Schering-Plough Research Institute, PO Box 32, 144 Route 94, Lafayette, NJ 07848-0032, USA. barry.mcintyre spcorp.com

Normal pre- and postnatal male reproductive development and function is dependent upon testicular androgen production and is sensitive to antiandrogenic perturbations. It was of interest to determine if the H(1) histamine antagonist loratadine had the potential to alter androgen-mediated reproductive development in the rat, a sensitive species for detecting antiandrogenic effects. Loratadine was administered orally by gavage to pregnant Sprague-Dawley rats at doses of 4, 12 or 24 mg/kg from gestation day 7 to postnatal day 4, encompassing the period of androgen-dependent male reproductive development. Vehicle control rats received 0.4% aqueous methylcellulose. Dams were allowed to deliver naturally and rear their offspring until postnatal day 21. On postnatal day 21 male offspring were retained for further evaluation of androgen-dependent endpoints and the female offspring were euthanized and their sex confirmed internally. Males were necropsied from postnatal day 72 to 85. Dams administered 24 mg/kg of loratadine exhibited a transient 45% decrement in maternal body weight gain at the initiation of dosing (gestation days 7-9). Mean pup body weight on postnatal days 1 and 4 were approximately 4% lower than controls. No other effects on offspring growth were observed. Anogenital distance on postnatal day 1 was unaffected by loratadine exposure. Loratadine exposure did not induce the retention of nipples in male rats, affect preputial separation, or induce external malformations, including hypospadias. Seminal vesicle and prostate weights were not decreased by loratadine exposure. These data clearly demonstrate that systemic loratadine exposure, in multiples up to 26 times clinical exposure levels, does not exhibit in vivo antiandrogen activity, as evidenced by the absence of alterations or malformations in androgen-dependent reproductive tissues in male rats exposed to loratadine during the critical period of androgen-dependent development.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14613821&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Simultaneous determination of loratadine and pseudoephedrine sulfate in pharmaceutical formulation by RP-LC and derivative spectrophotometry.

Mabrouk MM, el-Fatatry HM, Hammad S, Wahbi AA.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt. mokhtar_mabrouk yahoo.com

Highly sensitive, simple and accurate reversed phase liquid chromatographic and first derivative spectrophotometric methods for determination of antihistaminic drug loratadine [I] and nasal decongestant drug pseudoephedrine sulfate [II] are described. The HPLC method involves separation of [I] and [II] on micro-BondaPak C18 column using mixture of (methanol:H(2)O:phosphoric acid:ammonium dihydrogen phosphate) (220:300:2:3 g) (V/V/V/W), 60 and 40% acetonitrile as mobile phase flowing at 2 ml/min with ultraviolet detection at 247 nm. The calibration graphs are linear from 5 to 100 microg/ml for [I] and from 120 to 1200 microg/ml for [II] the detection limits are 0.5 microg/ml for [I] and 60 microg/ml for [II]. The spectrophotometric method is based on recording the first derivative spectra for [I] and [II] at 307, 266 nm, respectively, of their solutions in 0.1 M hydrochloric acid using the acid as blank. The calibration graphs are linear in the range of 5-25 microg/ml for [I] and 240-720 microg/ml for [II]; the limits of detection are 0.16 microg/ml for [I] and 10 microg/ml for [II]. The mean percentage recoveries obtained for different synthetic mixtures by using this method are 97.6% with coefficient of variation 1.79 for [I] and 101.6% with coefficient of variation 1.95 for [II]. The two methods have been applied successfully for the determination of [I] in its combination with [II] Clarinase tablets and [I] alone in different pharmaceutical dosage forms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14623585&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Determination of loratadine in human plasma by liquid chromatography electrospray ionization ion-trap tandem mass spectrometry.

Salem II, Idrees J, Al Tamimi JI.

ACDIMA Center for Bioequivalence and Pharmaceutical Studies, PO Box 925161, Amman 11190, Jordan. dr.salem acdima.com

A sensitive and specific liquid chromatography electrospray ionization ion-trap mass spectrometry (LC-ESI-IT-MS/MS) method has been developed and validated for the identification and quantitation of loratadine in human plasma. After the addition of the internal standard (IS), plasma samples were extracted using isooctane:isoamyl alcohol mixture. The compounds were separated on a prepacked Zorbax phenyl column using a mixture of acetonitrile, 0.20% formic acid as mobile phase. A Finnigan LCQ(DUO) ion-trap mass spectrometer connected to a Waters Alliance high performance liquid chromatography (HPLC) was used to develop and validate the method. The results were within the accepted criteria as stated in the FDA bioanalytical method validation guidance. The method was proved to be sensitive and specific by testing six different plasma batches. Linearity was established for the range of concentrations 0.10-10.0 ng/ml with a coefficient of determination (r(2)) of 0.9998. Accuracy for loratadine ranged from 105.00 to 109.50% at low, mid and high levels. The intra-day precision was better than 10.86%. The lower limit of quantitation (LLOQ) was identifiable and reproducible at 0.10 ng/ml with a precision of 9.84%. The proposed method enables the unambiguous identification and quantitation of loratadine for pharmacokinetic, bioavailability or bioequivalence studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14738928&dopt=Abstract loratadine, Claritin



loratadine, Claritin
The risk of esophageal obstruction associated with an anti-allergy medication (Claritin-D 24-Hour--original formulation).

Manda B, Drinkard CR, Shatin D, Graham DJ.

Center for Health Care Policy and Evaluation, UnitedHealth Group, 12125 Technology Drive, MN002-0260, Minneapolis, MN 55344-7302, USA. bharati_s_manda uhc.com

PURPOSE: To investigate a possible increased risk of esophageal obstruction among users of loratadine and pseudoephedrine (Claritin-D 24-Hour [C-D 24], the original, round, extended-release formulation) compared to two other tablet formulations of loratadine. METHODS: Pharmacy data of 12 managed care plans were screened to identify users in the three groups from 1 September 1996 to 31 December 1998. Users with a medical claim following their first loratadine prescription (Index prescription) indicating an esophageal obstruction or endoscopic procedure were considered claims-identified cases. Medical records were reviewed to validate case status. RESULTS: There were 233,901 users (61% female) and 245 claims-identified cases occurring within 30 days after the first prescription. The incidence rate per 10,000 users of claims-identified cases occurring on the Index prescription date was higher among C-D 24 users (IR = 1.4) than Claritin Regular (C-R) users (IR = 0.07; p < 0.002) or Claritin-D 12-Hour (C-D 12) users (IR = 0.3; p > 0.05). Medical record review of 15 claims-identified cases confirmed two cases of acute esophageal obstruction, both among C-D 24 users. CONCLUSIONS: Claims-based analysis suggested an increased risk of endoscopic procedures on the Index date among C-D 24 users compared to C-R users. However, after medical record review, the study did not provide conclusive evidence of an association between C-D 24 use and esophageal obstruction. This study highlights the importance of validating findings from claims data using medical records.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14971120&dopt=Abstract loratadine, Claritin