Loratadine

382.88

382.88

1308068-626-2

7AJO3BO7QN

758628|721075

DTXSID2023224

C29162

Crystals from acetonitrile

R06AX13|R - Respiratory system

2933990090

42.4

5.2

white powder

1.3±0.1 g/cm3

134-136 °C

531.3°C at 760 mmHg

275.1±30.1 °C

1.614

It is soluble in DMSO (50 mg/ml), ethanol (77 mg/ml at 25°C), water (<1 mg/ml at 25°C), chloroform, and methanol.

2-8°C

187.4 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|185.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

3077

2

36/37/38

22-24/25-36-26

TM6129200

Xi

Stable, but may be heat sensitive - refrigerate. Incompatible with strong oxidizing agents.

P201, P202, P261, P264, P271, P273, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P391, P403+P233, P405, P501

H315

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Rosa F; Reprod Toxicol 9 (6): 583 (1995). New medical entities widely used in fertile women: post marketing surveillance priorities.|Bergman HD; South Pharm J 86: 17-21 (1994). Major new drugs: review of 1993. The pharmacology, pharmacokinetics, uses, efficacy and adverse effects of /new drug products are reviewed/.|Haria M, et al; Drugs 48: 617-37 (1994). Loratadine: reapprasial of its pharmacological properties and therapeutic use in allergic disorders.|Corey JP; Otolaryngol Head Neck Surg 109 (3 pt 2): 584-92 (1993). Advances in the pharmacotherapy of allergic rhinitis: second generation H1 receptor antagonists.|For more Special Reports (Complete) data for LORATADINE (7 total), please visit the HSDB record page.

|Danger|H315 (69.05%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P260, P261, P263, P264, P270, P271, P273, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 86 companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H361 (87.5%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|P201, P202, P273, P281, P308+P313, P391, P405, and P501|Aggregated GHS information provided by 41 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Second generation antihistamines such as loratadine have very few adverse effects; however, insomnia, headache, fatigue, drowsiness and rash have been reported. Symptoms of loratadine overdose include gastrointestinal side effects, agitation, drowsiness, tachycardia, and headache. It is advised to obtain an ECG in the event of loratadine overdose.

Loratadine and desloratadine use are associated with a low rate of liver enzyme elevations which are usually asymptomatic, mild and self-limited even without modification of the dose. In addition, rare instances of clinically apparent liver injury attributed to loratadine and desloratadine use have been reported as isolated case reports. The time to onset of liver injury varied but was typically within 2 to 4 weeks of starting the medication. Most cases were associated with a hepatocellular pattern of enzyme elevations resembling acute viral hepatitis. Immunoallergic and autoimmune features were not described and most cases were self-limited in course. However, at least one fatal instance of acute hepatitis attributed to loratadine has been reported. In none of the cases, was there a clear link to loratadine and all had other possible or probable non-drug causes. Thus, loratadine and desloratadine have been convincingly implicated in cases of clinically apparent liver injury in the literature and the association is suspect only.

Concurrent use may potentiate the CNS depressant effects of either these medications /alcohol or other CNS depression-producing medications/ or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/|Anticholinergic effects may be potentiated when these medications /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/|Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong the intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended. /Antihistamines/|Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/|For more Interactions (Complete) data for LORATADINE (6 total), please visit the HSDB record page.

LD50 Rat oral > 5000 mg/kg|LD50 Mouse oral > 5000 mg/kg

97 - 99% of the loratadine is bound to plasma proteins.

Loratadine is a 2nd generation antihistamine and is used to manage symptoms of allergic rhinitis, wheal formation, urticaria, and other allergic dermatologic conditions.

Loratadine and its metabolic derivative desloratadine are second generation antihistamines that are used for the treatment of allergic rhinitis, angioedema and chronic urticaria. Loratadine and desloratadine have been linked to rare, isolated instances of clinically apparent acute liver injury.

Antihistamines

Anti-Allergic Agents; Antipruritics; Histamine H1 Antagonists|Antihistamines are indicated in the prophylactic and symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis due to inhalant allergens and foods. /Antihistamines; Included in US product labeling/|Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. /Antihistamines; Included in US product labeling/|Antihistamines are also use in the treatment of pruritus associated with pityriasis rosea. /Antihistamines; NOT included in US or Canadian product labeling/|For more Therapeutic Uses (Complete) data for LORATADINE (19 total), please visit the HSDB record page.

Small amounts of antihistamines are distributed into breast milk; use is not recommended in nursing mothers because of the risk of adverse effects, such as unusual excitement or irritability, in infants. /Antihistamines/|Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system (CNS) excitation, and an increased tendency toward convulsions. /Antihistamines/|A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines. /Antihistamines/|Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines. A paradoxical reaction characterized by hyperexcitability may occur in geriatric patients taking antihistamines. Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, medication should probably be discontinued. /Antihistamines/|For more Drug Warnings (Complete) data for LORATADINE (9 total), please visit the HSDB record page.

Like other 2nd generation antihistamines, loratadine is selective for peripheral H1 receptors. Loratadine does not penetrate effectively into the central nervous system and has poor affinity for CNS H1-receptors. These qualities result in a lack of CNS depressant effects such as drowsiness, sedation, and impaired psychomotor function.

Agents, usually topical, that relieve itching (pruritus). (See all compounds classified as Antipruritics.)|Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475) (See all compounds classified as Anti-Allergic Agents.)|A class of non-sedating drugs that bind to but do not activate histamine receptors (DRUG INVERSE AGONISM), thereby blocking the actions of histamine or histamine agonists. These antihistamines represent a heterogenous group of compounds with differing chemical structures, adverse effects, distribution, and metabolism. Compared to the early (first generation) antihistamines, these non-sedating antihistamines have greater receptor specificity, lower penetration of BLOOD-BRAIN BARRIER, and are less likely to cause drowsiness or psychomotor impairment. (See all compounds classified as Histamine H1 Antagonists, Non-Sedating.)

Loratadine is rapidly absorbed and achieves peak plasma concentration in 1-2 hours, while it's main metabolite achieves peak plasma concentration in 3-4 hours. In the rapid dissolve formulation, the pharmacokinetic parameters of loratadine are as follows: Cmax = 2.56 ng/ml, Tmax = 1.14 hrs, AUC = 6.14 ng x hr/ml. In the rapid dissolve formulation, the pharmacokinetic parameters of descarboethoxyloratadine are as follows: Cmax = 3.72 ng/ml, Tmax = 1.97 hr, AUC = 49.1 ng x hr/ml. In the conventional formulation, the pharmacokinetic parameters of loratadine are as follows: Cmax = 2.11 ng/ml, Tmax = 1.00 hr, AUC = 4.64 ng x hr/ml In the conventional formulation, the pharmacokinetic parameters of descarboethoxyloratadine are as follows: Cmax = 3.66 ng/ml, Tmax = 1.97 hr, AUC = 48.4 ng x hr/ml|Over a 10 day period, 40% of loratadine is excreted in the urine, and 42% is eliminated in the faeces.|The volume of distribution of loratadine is 120 L/Kg.|The clearance of loratadine after single oral doses of 20 mg and 40 mg are 12 L/h/kg and 9 L/h/kg respectively. P-glycoprotein is involved in the clearance of many 2nd generation antihistamines, including loratadine, from the central nervous system. 1st generation antihistamines are not cleared by P-glycoprotein, which may help explain why they have a different central nervous system adverse effect profile compared to their 2nd generation counterparts. It appears that an antihistamine with higher affinity for p-glycoprotein will have a lower incidence of CNS adverse effects.|H1 antagonists are eliminated more rapidly by children than by adults and more slowly in those with severe liver disease. /H1 Receptor Antagonists/|The H1 antagonists are well absorbed from the gastrointestinal tract. Following oral administration, peak plasma concentrations are achieved in 2 to 3 hours ... . /H1 Receptor Antagonists/|Approximately 80% of the total dose administered can be found equally distributed between urine and feces in the form of metabolic products after 10 days.|Whole body autoradiographic studies in rats and monkeys, radiolabeled tissue distribution studies in mice and rats, and in vivo radioligand studies in mice have shown that neither loratadine nor its metabolites readily cross the blood-brain barrier. Radioligand binding studies with guinea pig pulmonary and brain H1-receptors indicate that there was preferential binding to peripheral versus central nervous system H1-receptors.|Unlike other currently available antihistamines, second generation antihistamines such as ... loratadine appear to distribute poorly or not appreciably into the CNS at usual dosages.

Loratadine undergoes extensive first pass metabolism in the liver and is primarily metabolized by CYP3A4, CYP2D6, CYP1A1 and CYP2C19. Less involved CYP enzymes include CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP3A5. CYP3A4 and CYP2D6 are mainly responsible for metabolizing loratadine to descarboethoxyloratadine. This primary metabolite is 4 times more pharmacologically active than loratadine. In addition, a study demonstrates that descarboethoxyloratadine is first glucuronidated by UGT2B10, then hydroxylated by CYP2C8 to form 3-hydroxydesloratadine. Further glucuronidation of 3-hydroxydesloratadine facilitates excretion.|The second generation H1 antagonists astemizole, loratadine,and terfenadine are rapidly absorbed from the gastrointestinal tract and metabolized in the liver to active metabolites by the hepatic microsomal p450 system.|Pharmacokinetic studies following single and multiple oral doses of loratadine in 115 volunteers showed that loratadine is rapidly absorbed and extensively metabolized to an active metabolite (descarboethoxyloratadine).|In vitro studies with human liver microsomes indicate that loratadine is metabolized to descarboethoxyloratadine predominately by p450 CYP3A4 and, to a lesser extent, by p450 CYP2D6.|H1 receptor antagonists are among the many drugs that induce hepatic microsomal enzymes, and they may facilitate their own metabolism. /H1 Receptor Antagonists/|The non-sedating anti-histamine, loratadine ... was admin orally in the diet to mature male rats at dosages of 4, 10 and 25 mg/kg/day for 2 wk. The effects of these treatments on liver microsomal cytochrome P450 were evaluated by immunochemical and biochemical techniques, and were compared with the effects of treating rats with three different inducers of cytochrome P450, namely phenobarbital, 3-methylcholanthrene and dexamethasone. Treatment of rats with loratadine caused a dose dependent incr in the levels of P450 2Bl and 2B2, the major phenobarbital inducible P450 enzymes, as determined by Western immunoblotting. At the highest dosage tested, loratadine was less effective than phenobarbital as an inducer of 2Bl and 2B2, although the induction of these proteins could be detected immunochemically even at the lowest dosage of loratadine tested. Consistent with these observations, treatment of rats with loratadine caused a dose dependent incr in the rate of two reactions that are catalyzed predominantly by 2Bl/2, namely testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation. At the highest dosage tested, loratadine caused a 7.3- and 8.5-fold incr in the rate of testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation, respectively, compared with a and 45-fold incr caused by phenobarbital treatment. Treatment of rats with loratadine caused a 1.4 to 2.0-fold incr in the 2 beta-, 6 beta- and 15 beta-hydroxylation of testosterone, which was associated with a similar incr in the levels of immunoreactive P450 3Al and/or 3A2. As an inducer of P450 3Al/2, loratadine was slightly less effective than phenobarbital, and was considerably less effective than dexamethasone, which caused a 10- to 33-fold increase in testosterone 2 beta-, 6 beta- and 15 beta-hydroxylase activity. At the dosages tested, loratadine did not increase the levels of P450 lAl, the major 3-methylcholanthrene inducible P450 enzyme, as determined by Western immunoblotting. The rate of 7-ethoxyresorufin O-dealkylation, which is catalyzed predominantly by P450 lAl, incr 1.9-fold after loratidine treatment, but this incr was less than that caused by phenobarbital treatment (2.2-fold), and was considerably less than that caused by 3-methylcholanthrene treatment (33-fold). The effects of treating mature male mice with loratadine on liver microsomal cytochrome P450 resembled the effects observed in rats. These results indicate that loratadine is a phenobarbital type inducer of liver microsomal cytochrome P450 in rats and mice.|Loratadine has known human metabolites that include Desloratadine.

The elimination half life is approximately 10 hours for loratadine and 20 hours for descarboethoxyloratadine.|The mean elimination half-lives found in studies in normal adult subjects (n= 54) were 8.4 hours (range= 3 to 20 hours) for loratadine and 28 hours (range= 8.8 to 92 hours) for the major active metabolites (descarboethoxyloratadine).

Histamine release is a key mediator in allergic rhinitis and urticaria. As a result, loratadine exerts it's effect by targeting H1 histamine receptors. Loratadine binds to H1 histamine receptors found on the surface of epithelial cells, endothelial cells, eosinophils, neutrophils, airway cells, and vascular smooth muscle cells among others. H1 histamine receptors fall under the wider umbrella of G-protein coupled receptors, and exist in a state of equilibrium between the active and inactive forms. Histamine binding to the H1-receptor facilitates cross linking between transmembrane domains III and V, stabilizing the active form of the receptor. On the other hand, antihistamines bind to a different site on the H1 receptor favouring the inactive form. Hence, loratadine can more accurately be classified as an "inverse agonist" as opposed to a "histamine antagonist", and can prevent or reduce the severity of histamine mediated symptoms.|All of the available H1 receptor antagonists are reversible, competitive inhibitors of the interaction of histamine with H1 receptors. /H1 Receptor Antagonists/|H1 antagonists inhibit most responses of smooth muscle to histamine. /H1 Antagonists Receptors/|Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. /H1 Receptor Antagonists/|H1 antagonists strongly block the action of histamine that results in increased capillary permeability and formation of edema and wheal. /H1 Receptor Antagonists/|For more Mechanism of Action (Complete) data for LORATADINE (6 total), please visit the HSDB record page.

Treatment of overdosage would reasonably consist of emesis (ipecac syrup), except in patients with impaired consciousness, followed by the administration of activated charcoal to absorb any remaining drug. If vomiting is unsuccessful, or contraindicated, gastric lavage should be performed with normal saline. Saline cathartics may also be of value for rapid dilution of bowel contents. Loratadine is not eliminated by hemodialysis. It is not known if loratadine is eliminated by peritoneal dialysis.|In the event of overdosage, general symptomatic and supportive measures should be instituted promptly and maintained for as long as necessary.

Somnolence, tachycardia, and headache have been reported with overdoses greater than 10 mg (40 to 180 mg).|The second generation H1 antagonists (eg, terfenadine, astemizole, loratadine) have no effect on muscarinic receptors.

4-(8-Chloro-5,6-dihydro-11H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-ylidene)-1-piperidinecarboxylic Acid Ethyl Ester

Claritin 10 mg tablets; Claritin-D 5 mg loratadine in the tablet coating for immediate release and 120 mg pseudoephedrine sulfate, USP equally distributed between the tablet for immediate release and the barrier coated extended release core.

HPLC determination of loratadine and its active metabolite descarboethoxyloratidine in human plasma.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals