Loratadine

FORMULATION
Each tablet contains:
Loratadine … 10mg

PHARMACOLOGY
Loratadine, like other antihistamines acts via competitive blocking of HI-histaminic receptors. Loratadine penetrates very poorly into central nervous system (CNS). Therefore, it is devoid of significant CNS depressant effects. Loratadine is highly selective antagonist of HI-histaminic receptors. Loratadine has very weak affinity for alpha adrenoreceptors or acetylcholine receptors. In animal models, loratadine has very high affinity for HI-histaminic receptors, which is greater than that of the terfenadine or astemizole. The antihistaminic effect persists for 18 to 24 hours. In human subjects, loratadine suppresses wheal response to intradermally injected histamine. This action starts within 1 to 2 hours of oral administration and maximum inhibitory effect evident in 2 to 4 hours. The magnitude and duration of effects are dependent upon loratadine dose. On long term administration the drug retains its effectiveness without developing tachyphylaxis. In animal models, loratadine has also shown anti-serotonin activity. It also suppresses mast cell mediator release. In addition, loratadine also possess anti-allergic activity which has been demonstrated in humans by skin prick and nasal challenge tests. In human volunteers, loratadine did not reduce psychomotor performance as measured by sleep latency, symbol copying, digit symbol substitution, dynamic visual activity test, or driving performance. In addition, loratadine does not potentiate the effects of centrally acting drugs like diazepam, ethanol, and barbiturates.

PHARMACOKINETICS
Absorption: In humans loratadine is rapidly absorbed after oral administration. There is a linear relationship between loratadine dose and both maximum plasma concentration (Cm ax) and area under the plasma concentration time curve  (AUC). The 10, 20 and 40 mg of loratadine produce peak plasma concentrations of 5, 11, 28 microgram per litre, respectively. Time to reach maximum concentration (T max) occurs between 1 to 1.5 hours. After repeated dosing steady state plasma concentrations occur by fifth day. Metabolism: Loratadine is metabolized to descarboethoxyloratadine (DCL) which is pharmacologically active.

Distribution: Loratadine has extensive distribution in the body. The distribution half-lives of loratadine and DCL is 1.02 and 3.8 hours, respectively. Loratadine is 97 to 99% bound to plasma proteins whereas DCL is 73 to 76% bound to plasma proteins. Small amount of both loratadine and DCL is secreted in breast milk, but the amount is minimal. Elimination: Loratadine undergoes extensive biotransformation. The elimination half-life of loratadine after single dose is 8 to 11 hours and that of DCL is 17 to 24 hours. After multiple dosing, elimination half-life of loratadine is 4.4 hours and that of DCL is 8.7 hours. Pharmacokinetics of loratadine and that of DCL is not affected in patients with renal disease and in plasma patients on hemodialysis. In elderly patients too, disposition kinetics of loratadine and DCL is not affected. In patients of alcoholic liver disease, the half-lives of loratadine and that of DCL are longer but still within the range observed in a population of normal subjects.

INDICATIONS
Loratadine is indicated in conditions which respond to antihistaminic therapy such as :

• Seasonal allergic-rhinitis
• Perennial allergic-rhinitis
• Acute Coryza (common colds)

Chronic idiopathic urticaria and similar allergic and dermatological disorders

PRECAUTIONS
Experience with loratadine in pregnant women is inadequate. Therefore, as true with all new drugs, it should not be used in pregnancy unless clinical benefits outweighs possible risks. Similarly, there is insufficient data regarding use of loratadine in children. However, it has been safely used in children older than 5 years. Administer with caution to patients with severe hepatic impairment.

DOSAGE AND ADMINISTRATION
The recommended dose for adults and children over 6 years old is 10 mg once daily. For children in age group of 2 to 5 years old a dose of 5 mg daily or as prescribed by a physician.

Patients with hepatic impairment
Patients with severe liver impairment should be administered a lower initial dose because they may have reduced clearance of loratadine. An initial dose of 10 mg every other day is recommended for adults and children weighing more than 30 kg.

Patients with renal impairment
No dosage adjustments are required in patients with renal insufficiency.

Elderly
No dosage adjustments are required in the elderly.

CONTRAINDICATIONS
Hypersensitivity to loratadine or to any of the excipients in this product.

ADVERSE EFFECTS
Somnoloence, headache, increased appetite, insomnia, anaphylaxis, dizziness, tachycardia, palpitation, nausea, dry mouth, gastritis, abnormal hepatic function, rash, alopecia, and fatigue.

DRUG INTERACTIONS
Loratadine is metabolized with cytochrome P450 isoenzymes CYP3A4 and CYP2D6.
Therefore, concomitant administration of other drugs that inhibit or are metabolized by these hepatic enzymes may result in changes in plasma concentrations of either drug and, possibly, other adverse effects. Drugs known to inhibit one or other one of these enzymes include cimetidine, erythromycin, ketoconazole, quinidine, fluconazole, and
fluoxetine.

STORAGE CONDITION
Store at temperatures not exceeding 300C.

Keep all medicines out of reach of children.

AVAILABILITY
2 Composite AIu/PVC Blister packs 5x I O’S tablets (Box of 1 00’s)

“For suspected adverse drug reaction, report to the FDA: www.fda.gov.ph“.