FEXET-D TABLETS

Indications

• Nasal congestion
• Sinusitis affecting the maxillary antrum

Dosage

Children: For children aged 6-11 years, the recommended dose is 30 mg 3-4 times a day. For children aged 12-17 years, the dose is 60 mg 3-4 times a day. Caution is advised in children under 6 years.

Adults: The typical adult dose is 60 mg every 4-6 hours, not exceeding 240 mg per day.

Mechanism of action

Pseudoephedrine acts primarily as a selective agonist of alpha-adrenergic receptors, which causes vasoconstriction of the nasal mucosa. This leads to a decrease in mucosal edema and congestion. It may also have some beta-adrenergic activity, contributing to bronchodilation.

Pharmacodynamics

The pharmacodynamic effects of pseudoephedrine include reduced nasal congestion and increased airflow through the nasal passages. Its action is dose-dependent, with higher doses leading to more pronounced effects. Side effects may include increased heart rate, hypertension, and CNS stimulation such as anxiety and insomnia.

Pharmacokinetics

Pseudoephedrine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is metabolized primarily in the liver and has a half-life of approximately 5-8 hours. The drug is excreted mainly in the urine, with a portion being unchanged.

Contra-indications

• Severe hypertension
• Severe renal impairment
• Severe hepatic impairment
• Hyperthyroidism
• Angle closure glaucoma
• Use in children under 6 years of age is not recommended due to safety concerns

Adverse effects

• Anxiety
• Headache
• Insomnia
• Nausea
• Dizziness
• Dry mouth
• Increased heart rate (tachycardia)
• Hypertension
• Palpitations
• Rebound congestion
• Irritability
• Tremors
• Hallucinations
• Dermatitis
• Muscle weakness
• Vomiting
• Piloerection

Interactions

• Monoamine oxidase inhibitors (MAOIs) may enhance the hypertensive effects
• Other sympathomimetics may increase the risk of cardiovascular effects
• Caution with antihypertensive medications as pseudoephedrine may counteract their effectiveness

Precautions

• Use with caution in individuals with cardiovascular disease
• Caution in patients with diabetes due to potential hyperglycemia
• Monitor patients with a history of psychiatric disorders as it may exacerbate symptoms
• Use with caution in patients with a history of seizures

Pregnancy

Manufacturer advises avoidance due to potential risks such as defective closure of the abdominal wall in newborns after first trimester exposure.

Breast-feeding

Present in breast milk; manufacturer advises avoidance due to the potential for irritability and disturbed sleep in infants.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Oral solution (e.g., Sudafed Decongestant 30mg/5ml liquid)
• Nasal drops (e.g., Galpseud 0.5% drops)

Indications

• Allergic rhinitis
• Seasonal allergic rhinitis
• Chronic idiopathic urticaria

Dosage

Children: For children aged 6 to 12 years, the recommended dosage for allergic rhinitis is 30 mg twice daily. For children aged

Adults: The usual adult dosage for allergic rhinitis is 120 mg once daily or 60 mg twice daily. For chronic idiopathic urticaria, the recommended dose is 180 mg once daily.

Mechanism of action

Fexofenadine acts as an inverse agonist of the H1 histamine receptor, binding to and stabilizing the inactive form of the receptor. This prevents the activation of the receptor and the subsequent release of pro-inflammatory cytokines, such as interleukins, which are responsible for various allergic symptoms. By antagonizing the effects of histamine, fexofenadine effectively mitigates allergic reactions without crossing the blood-brain barrier, thus minimizing central nervous system effects.

Pharmacodynamics

Fexofenadine alleviates allergy symptoms by blocking the actions of histamine, a key mediator in allergic responses. Its long duration of action-approximately 24 hours-facilitates once or twice daily dosing. The onset of action occurs within 1-3 hours following administration. Notably, fexofenadine should not be taken with fruit juice, as it may impair absorption and efficacy.

Pharmacokinetics

Fexofenadine exhibits rapid absorption following oral administration, with a peak plasma concentration typically reached within 1-3 hours. It has a bioavailability of approximately 33% and is primarily excreted unchanged in the feces and urine. The drug does not undergo significant metabolism and has a half-life ranging from 14.4 to 15.4 hours, allowing for effective once-daily dosing in most patients.

Adverse effects

• Headache
• Dizziness
• Nausea
• Fatigue
• Dry mouth

Interactions

• Antacids containing aluminum or magnesium may reduce the absorption of fexofenadine
• Fruit juices (like grapefruit, orange, and apple juice) can significantly decrease the bioavailability of fexofenadine

Precautions

• Use with caution in patients with renal impairment
• Monitor for possible allergic reactions

Pregnancy

Fexofenadine should be used during pregnancy only if clearly needed. Consult with a healthcare provider for guidance.

Breast-feeding

Fexofenadine is excreted in breast milk, caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Indications

• Nasal congestion due to cold
• Allergic rhinitis
• Sinusitis
• Eustachian tube dysfunction

Dosage

Children: For children aged 6 to 12 years, the recommended dose is 30 mg every 6 hours, not exceeding 120 mg per day. For children aged 2 to 6 years

Adults: The typical adult dose is 60 mg every 4 to 6 hours, not exceeding 240 mg per day.

Mechanism of action

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors. The agonism produces vasoconstriction in the mucosa of the respiratory tract, leading to decreased nasal congestion. It also inhibits norepinephrine, dopamine, and serotonin transporters, which may contribute to its sympathomimetic effects such as increased arterial pressure and heart rate. Additionally, pseudoephedrine has anti-inflammatory actions through the inhibition of NF-kappa-B and other transcription factors.

Pharmacodynamics

Pseudoephedrine causes vasoconstriction resulting in a decongestant effect. Its sympathomimetic properties can lead to increased heart rate and blood pressure. The duration of action is typically short unless formulated as an extended-release product. Patients may experience central nervous system stimulation, which should be considered when prescribing.

Pharmacokinetics

Pseudoephedrine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 2 hours after oral administration. The drug is metabolized in the liver, primarily by the cytochrome P450 system, and has a half-life of about 6 hours. It is excreted mainly through the kidneys, with about 55-70% of the dose eliminated unchanged in the urine.

Adverse effects

• Increased blood pressure
• Centrally mediated side effects such as insomnia
• Nervousness
• Dizziness
• Headache
• Dry mouth

Interactions

• pseudoephedrine + linezolid: Severe (increases risk of elevated blood pressure)
• volatile halogenated anesthetics + pseudoephedrine: Unknown (additive effect)

Precautions

• Use with caution in patients with hypertension
• Use with caution in patients with cardiovascular disease
• May exacerbate conditions like hyperthyroidism or diabetes

Pregnancy

Use only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Use with caution; small amounts may pass into breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral tablets
• Extended-release oral tablets
• Liquid formulations

Mechanism of action

The H₁ histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H₁ receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes. Fexofenadine is considered an “inverse agonist” of the H₁ receptor because it binds to and stabilizes the inactive form of the receptor, preventing its activation and subsequent downstream effects. It has a potent and selective affinity for H₁ receptors, and there is no evidence that it carries antidopaminergic, antiserotonergic, anticholinergic, sedative, or adrenergic blocking activity. Fexofenadine does not cross the blood-brain barrier and thus is unlikely to cause significant CNS effects. Fexofenadine is a specific, selective, histamine H1-receptor antagonist. ... Fexofenadine has been shown to inhibit histamine release from peritoneal mast cells in rats. Unlike terfenadine, fexofenadine does not block the potassium channel involved in repolarization of cardiac cells (i.e., blockade of the delayed rectifier potassium current IK). As a result, fexofenadine lacks the cardiotoxic potential of terfenadine. Fexofenadine also does not possess appreciable anticholinergic, antidopaminergic, or alpha- or beta-adrenergic blocking effects at usual antihistaminic doses in pharmacologic studies. It has been suggested that the increased safety profile of fexofenadine compared with the parent drug results from the lack of fexofenadine-induced cardiotoxicity in addition to only minimal metabolism of fexofenadine in the liver by the cytochrome P-450 microsomal enzyme system. Evidence from animal models using fexofenadine have suggested that the apparent lack of cardiotoxic effects of the drug may have resulted at least in part from lack of blockade of the potassium channel involved in repolarization of cardiac cells (ie, blockade of the delayed rectifier potassium current IK). Prolongations in the QTc interval were not reported in dogs receiving oral fexofenadine hydrochloride dosages of 10 mg/kg daily for 5 days or in rabbits receiving an IV fexofenadine hydrochloride dose of 10 mg/kg (resulting in plasma fexofenadine concentrations 28 or 63 times the therapeutic plasma concentrations in humans, respectively, based on a dosage of 60 mg of fexofenadine hydrochloride given twice daily). In addition, no effect was observed on calcium-channel current, delayed potassium-channel current, or action potential duration in guinea pig myocytes, sodium current in rat neonatal myocytes, or on the delayed rectifier potassium channel cloned from human heart at fexofenadine concentrations up to 1.0 X10-5 M (approximately equivalent to 32 times the therapeutic plasma concentrations in humans, based on a dosage of 60 mg of fexofenadine hydrochloride given twice daily). In vitro, terfenadine exhibits a similar affinity for histamine H1-receptors from brain and peripheral tissues; however, in vivo, unlike first generation antihistamines, terfenadine and fexofenadine do not readily cross the blood-brain barrier and therefore do not appear to interact appreciably with H1-receptors within the CNS at usual doses.

Pharmacodynamics

Fexofenadine relieves allergy symptoms by antagonizing the actions of histamine, an endogenous compound predominantly responsible for allergic symptomatology. The relatively long duration of action of fexofenadine (approximately 24 hours) allows for once or twice daily dosing, and its rapid absorption allows for an onset of action within 1-3 hours. Fexofenadine should not be taken with fruit juice, as this may impair its absorption.

Mechanism of action

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors. 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. THESE AGENTS /BRONCHODILATORS/ ACT ON BETA-2 RECEPTORS TO RELAX BRONCHIAL SMOOTH MUSCLE & PERIPHERAL VASCULATURE, APPARENTLY BY STIMULATING PRODN OF CYCLIC ADENOSINE-3.5-MONOPHOSPHATE (CAMP)... Pseudoephedrine acts on alpha-adrenergic receptors in the mucosa of the respiratory tract, producing vasoconstriction. The medication shrinks swollen nasal mucous membranes; reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. Also, drainage of sinus secretions may be increased and obstructed eustachian ostia may be opened. The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg/kg 2 hr after injection. Immunocytochemical studies confirmed that the majority of the signal was detectable in the nucleus accumbens and striatum. Pre-injection with the D1 dopamine receptor antagonist SCH23390 partially and completely blocked pseudoephedrine-induced Fos-like immunoreactivity in the striatum and nucleus accumbens, respectively, suggesting that the action of pseudoephedrine is mediated via dopamine release and results in the activation of D1 dopamine receptors. With the exception of the higher doses required, the actions of pseudoephedrine were similar to those previously described for the psychostimulant amphetamine.

Pharmacodynamics

Pseudoephedrine causes vasoconstriction which leads to a decongestant effect. It has a short duration of action unless formulated as an extended release product. Patients should be counselled regarding the risk of central nervous system stimulation.