defonase

Uses

Loratadine & Pseudoephedrine tablet is used for the relief of symptoms of seasonal and perennial allergic rhinitis, temporarily relieves runny nose, sneezing, itching, watery eyes, nasal congestion, itching of the nose or throat due to allergic rhinitis or other upper respiratory allergies, symptoms of common cold, nasal congestion & sinus pressure associated with sinusitis.

defonase is also used to associated treatment for these conditions: Allergic Dermatologic Disorders, Allergic Rhinitis (AR), Allergies, Chronic Urticaria, Common Cold, Eye pruritus, Fever, Nasal Congestion, Nasal Itching, Pain, Perennial Allergic Rhinitis (PAR), Perennial Rhinitis, Pollen Allergy, Pruritus, Rhinorrhoea, Seasonal Allergic Rhinitis, Sneezing, Sensation of burning in the eyes, Watery eyes, Watery itchy eyesAllergic Rhinitis (AR), Allergies, Common Cold, Common Cold Associated With Cough, Common Cold/Flu, Cough, Cough caused by Common Cold, Eye allergy, Fever, Flu caused by Influenza, Headache, Irritative cough, Nasal Allergies, Nasal Congestion, Nasal Congestion caused by Common Cold, Pain, Perennial Allergy, Priapism, Respiratory Allergy, Rhinorrhoea, Seasonal Allergic Rhinitis, Seasonal Allergies, Sinus Congestion, Sinusitis, Sneezing, Sore Throat, Symptoms of Acute Bronchitis Accompanied by Coughing, Throat irritation, Upper Respiratory Tract Infection, Upper respiratory tract congestion, Upper respiratory tract signs and symptoms, Dry cough, Minor aches and pains, Sinus pain, Watery itchy eyes, Airway secretion clearance therapy

How defonase works

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.

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors.[A10896] This agonism of adrenergic receptors produces vasoconstriction which is used as a decongestant and as a treatment of priapism. Pseudoephedrine is also an inhibitor of norepinephrine, dopamine, and serotonin transporters.

The sympathomimetic effects of pseudoephedrine include an increase in mean arterial pressure, heart rate, and chronotropic response of the right atria. Pseudoephedrine is also a partial agonist of the anococcygeal muscle. Pseudoephedrine also inhibits NF-kappa-B, NFAT, and AP-1.

Dosage

defonase dosage

Adults and Children 12 years of age and over:

• Loratadine 5 mg and Pseudoephedrine 120 mg: One tablet twice a day (every 12 hours).
• Loratadine 10 mg and Pseudoephedrine 240 mg: One tablet once daily.

Safety and effectiveness of this drug in children below the age of 12 years have not been established.

Loratadine & Pseudoephedrine tablet should be administered when both the antihistaminic properties of Loratadine and the nasal decongestant activity of Pseudoephedrine Sulfate are desired in patients 12 years of age and older.

Side Effects

Pregnancy Category B. There was no evidence of animal teratogenicity in reproduction studies. Loratadine and pseudoephedrine sulfate combination tablet should be used during pregnancy only if clearly needed.

Lactation: It is not known if this combination product is excreted in human milk. However, both loratadine and pseudoephedrine sulfate when administered alone passes into breast milk, therefore, a decision should be made whether to discontinue lactation or to discontinue loratadine and pseudoephedrine sulfate combination tablet, taking into account the importance of the drug to the mother.

Toxicity

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.

The oral LD₅₀ of pseudoephedrine is 2206mg/kg in rats and 726mg/kg in mice.

Patients experiencing an overdose of pseudoephedrine may present with giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty urinating, muscle weakness, muscle tension, anxiety, restlessness, insomnia, toxic psychosis, cardiac arrhythmias, circulatory collapse, convulsions, coma, and respiratory failure. Treat overdose with symptomatic and supportive treatment including removal of unabsorbed drug.

Precaution

Loratadine and pseudoephedrine sulfate combination tablet should be used with caution in patients with hypertension, diabetes mellitus, ischemic heart disease, increased intraocular pressure, hyperthyroidism, renal impairment or prostatic hypertrophy. Central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension may be produced by sympathomimetic amines.

Interaction

No specific interaction studies have been conducted with loratadine and pseudoephedrine sulfate extended release tablets. However, loratadine (10 mg once daily) has been safely coadministered with therapeutic doses of erythromycin, cimetidine, and Ketoconazole in controlled clinical pharmacology studies.

Loratadine and pseudoephedrine sulfate combination tablet is contraindicated in patients taking monoamine oxidase inhibitors and for 2 weeks after stopping use of an MAO inhibitor. The antihypertensive effects of beta- adrenergic blocking agents, methyldopa, reserpine and veratrum alkaloids may be reduced by sympathomimetics. Increased ectopic pacemaker activity can occur when Pseudoephedrine is used concomitantly with digitalis.

Volume of Distribution

The volume of distribution of loratadine is 120 L/Kg.

The apparent volume of distribution of pseudoephedrin is 2.6-3.3L/kg.

Elimination Route

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

A 240mg oral dose of pseudoephedrine reaches a C_max of 246.3±10.5ng/mL fed and 272.5±13.4ng/mL fasted, with a T_max of 6.60±1.38h fed and 11.87±0.72h fasted, with an AUC of 6862.0±334.1ng*h/mL fed and 7535.1±333.0ng*h/mL fasted.

Half Life

The elimination half life is approximately 10 hours for loratadine and 20 hours for descarboethoxyloratadine.

The mean elimination half life of pseudoephedrine is 6.0h.

Clearance

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.

A 60mg oral dose of pseudoephedrine has a clearance of 5.9±1.7mL/min/kg.

Elimination Route

Over a 10 day period, 40% of loratadine is excreted in the urine, and 42% is eliminated in the faeces.

55-75% of an oral dose is detected in the urine as unchanged pseudoephedrine.

Pregnancy & Breastfeeding use

Use in pregnancy: There is no experience of the use of Loratadine in human pregnancy, hence it should not be used during pregnancy.

Use in lactation: Loratadine is excreted in breast milk, so it should not be administered to lactating mother.

Contraindication

Loratadine & Pseudoephedrine tablet is contraindicated in patients who are hypersensitive to this medication or any of its ingredients. It is also contraindicated in patients with narrow-angle glaucoma or urinary retention, and in patients receiving monoamine oxidase (MAO) inhibitor therapy or within fourteen (14) days of stopping such treatment. It is also contraindicated in patients with severe hypertension, severe coronary artery disease, and in those who have shown hypersensitivity to its components, to adrenergic agents, or to other drugs of similar chemical structures.

Special Warning

Use in patients Approximately 60 years age and older: The safety and efficacy in patients greater than 60 years old have not been investigated in placebo-controlled clinical trials. The elderly are more likely to have adverse reactions to sympathomimetic amines.

Use in children: Safety and effectiveness in children below the age of 12 years have not been established.

Acute Overdose

In the event of overdosage, general symptomatic and supportive, measures should be instituted promptly and maintained for as long as necessary. 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.

Storage Condition

Store at a cool and dry place, away from light. Keep out of the reach of children.

Innovators Monograph

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