BREATHEZY L 10/5MG TABLET

Indications

• Prophylaxis of asthma
• Management of seasonal allergic rhinitis
• Symptomatic relief of seasonal allergic rhinitis in patients with asthma

Dosage

Adults: 10 mg once daily, taken in the evening.

Mechanism of action

Montelukast binds with high affinity and selectivity to the cysteinyl leukotriene receptor type-1 (CysLT1). This action inhibits the physiological effects of cysteinyl leukotrienes (like LTC4, LTD4, and LTE4), which include bronchoconstriction, mucus secretion, and eosinophil recruitment. By blocking these receptors, montelukast effectively reduces the bronchoconstriction and other symptoms associated with asthma and allergic rhinitis.

Pharmacodynamics

Montelukast exhibits significant affinity for the CysLT1 receptor, preferentially blocking the effects of leukotriene LTD4 at doses as low as 5 mg. Clinical studies have shown that montelukast can inhibit both early and late phase bronchoconstriction due to antigen exposure by approximately 75% and 57%, respectively. The onset of bronchodilation can occur within 2 hours of oral administration, and its effects can be additive when used with beta agonists. However, doses above 10 mg daily do not provide additional clinical benefits in adults.

Pharmacokinetics

Montelukast is well absorbed following oral administration, with peak plasma concentrations occurring within 3 to 4 hours. It is extensively metabolized in the liver, primarily via cytochrome P450 enzymes. The half-life of montelukast is approximately 2.7 to 5.5 hours, allowing for once-daily dosing. It is eliminated via bile, with a small percentage excreted unchanged in urine. Special populations, such as those with hepatic impairment, may require caution, although specific dosage adjustments have not been established.

Adverse effects

• Headache
• Abdominal pain
• Dizziness
• Fatigue
• Nausea
• Rash
• Changes in mood or behavior
• Sleep disturbances

Interactions

• Opicapone: Severe (increases exposure)
• Selpercatinib: Severe (increases exposure)
• Deferasirox: Unknown (increases exposure)
• Leflunomide: Unknown (increases exposure)
• Mifepristone: Unknown (increases exposure)
• Mitotane: Unknown (decreases exposure)
• Teriflunomide: Unknown (increases exposure)
• Rifampicin: Unknown (decreases exposure)

Precautions

• Caution in patients with hepatic impairment
• Use with caution in patients with renal impairment
• Consider risk of mood changes and behavioral side effects

Pregnancy

Manufacturer advises to avoid use during pregnancy due to limited information available.

Breast-feeding

Manufacturer advises to avoid during breastfeeding, especially in the first few days after birth due to potential transfer of antibodies to the infant.

Storage

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

Formulations

• Tablets: 10 mg (adults and children over 15 years)
• Chewable tablets: 5 mg (children 6–14 years)
• Granules: 4 mg (children 6 months–5 years)

Indications

• Allergic rhinitis
• Chronic urticaria (hives)
• Seasonal allergic rhinitis

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Refer to the BNF for specific dosing guidance.

Mechanism of action

Levocetirizine is a selective antagonist of the H1 histamine receptor. It competes with histamine for binding at these receptors, thereby inhibiting the physiological effects of histamine including vasodilation, increased vascular permeability, and stimulation of sensory nerves, which contribute to allergic symptoms.

Pharmacodynamics

Levocetirizine demonstrates a rapid onset of action, typically within one hour of administration. It has a long duration of action, allowing for once-daily dosing. The drug is less likely to cross the blood-brain barrier compared to first-generation antihistamines, resulting in a lower incidence of sedation and central nervous system side effects.

Pharmacokinetics

Levocetirizine is well absorbed after oral administration, with peak plasma concentrations reached within approximately 0.9 hours. It has a bioavailability of around 100%. The drug undergoes limited metabolism, primarily through conjugation, and is excreted predominantly unchanged in the urine. The elimination half-life is approximately 7 to 10 hours, allowing for once-daily dosing. Renal impairment may necessitate dosage adjustments.

Contra-indications

• Hypersensitivity to levocetirizine, cetirizine, or any of the excipients.
• Severe renal impairment (creatinine clearance less than 10 mL/min).

Adverse effects

• Drowsiness
• Fatigue
• Dry mouth
• Headache
• Nausea
• Gastrointestinal disturbances

Interactions

• Alcohol may increase the sedative effects.
• Other CNS depressants may enhance drowsiness.
• Concurrent use with theophylline can reduce clearance of levocetirizine.

Precautions

• Caution in patients with a history of seizure disorders.
• Use with caution in elderly patients, as they may be more sensitive to the effects.
• Avoid in patients with significant renal impairment.

Pregnancy

Levocetirizine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Levocetirizine is excreted in human milk, and caution is advised when administered to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat, in a tightly closed container.

Formulations

• Tablets
• Oral solution

Indications

• Hyponatremia
• Hypovolemia
• Electrolyte replacement
• Fluid resuscitation

Dosage

Children: Pediatric dosing should be determined based on the child's condition, age, weight, and clinical guidelines. Refer to the BNF for Children for specific dosing information.

Adults: Sodium replacement therapy and dosage depend on the clinical condition and are usually administered in a controlled medical setting. It is crucial to refer to specific guidelines or protocols for dosing recommendations.

Mechanism of action

Sodium functions mainly by maintaining the electrochemical gradient across cell membranes, which is crucial for the propagation of action potentials in neurons and muscle cells. It is actively transported into cells via sodium-potassium ATPase pumps, and it influences the movement of water across cell membranes through osmosis.

Pharmacodynamics

Sodium ions are vital for various physiological processes, including the regulation of blood pressure, the conduction of electrical impulses in nerves and muscles, and the maintenance of acid-base balance. Changes in sodium levels can significantly affect cellular functions and overall homeostasis.

Pharmacokinetics

Sodium is absorbed primarily in the gastrointestinal tract, with the kidneys playing a key role in regulating sodium excretion. The balance of sodium is tightly controlled by hormones such as aldosterone, which promotes sodium reabsorption in the renal tubules. The plasma half-life of sodium is variable but is generally related to dietary intake and renal function.

Contra-indications

• Hypersensitivity to sodium or any component of the formulation
• Severe renal impairment
• Hypernatremia
• Heart failure
• Edema associated with renal failure

Adverse effects

• Fluid retention
• Hypertension
• Edema
• Hypernatremia
• Nausea
• Vomiting
• Muscle spasms
• Confusion
• Seizures (in severe cases)

Interactions

• Diuretics (particularly thiazide and loop diuretics)
• ACE inhibitors
• Angiotensin II receptor antagonists
• Lithium (sodium can affect lithium levels)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)

Precautions

• Monitor serum sodium levels regularly
• Use with caution in patients with cardiovascular disease
• Caution in patients with liver disease
• Assess fluid balance in patients receiving sodium supplementation

Pregnancy

Sodium is generally considered safe during pregnancy, but excessive intake should be avoided to prevent fluid retention and hypertension.

Breast-feeding

Sodium is excreted in breast milk, but dietary intake is usually safe; excessive supplementation should be avoided.

Storage

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

Formulations

• Sodium chloride injection
• Sodium bicarbonate tablets
• Sodium acetate solution
• Sodium citrate oral solution

Mechanism of action

Cysteinyl leukotrienes (CysLT) like LTC4, LTD4, and LTE4, among others, are eicosanoids released by a variety of cells like mast cells and eosinophils. When such CysLT bind to corresponding CysLT receptors like CysLT type-1 receptors located on respiratory airway smooth muscle cells, airway macrophages, and on various pro-inflammatory cells like eosinophils and some specific myeloid stem cells activities that facilitate the pathophysiology of asthma and allergic rhinitis are stimulated. In particular, CysLT-mediated airway bronchoconstriction, occluding mucous secretion, vascular permeability, and eosinophil recruitment are all types of effects that facilitate asthma. Alternatively, in allergic rhinitis, CysLTs are released by the nasal mucosa when exposed to allergens during both early and late phase reactions and participate in eliciting symptoms of allergic rhinitis like a congested nose and airway. Subsequently, montelukast is a leukotriene receptor antagonist that binds with high affinity and selectivity to the CysLT type 1 receptor, which consequently assists in inhibiting any physiological actions of CysLTs like LTC4, LTD4, and LTE4 at the receptor that may facilitate asthma or allergic rhinitis. Montelukast inhibits bronchoconstriction due to antigen challenge. Montelukast is a selective leukotriene receptor antagonist of the cysteinyl leukotriene CysLT1 receptor. The cysteinyl leukotrienes (LTC4 , LTD4, LTE4) are products of arachidonic acid metabolism that are released from various cells, including mast cells and eosinophils. They bind to cysteinyl leukotriene receptors (CysLT) found in the human airway. Binding of cysteinyl leukotrienes to leukotriene receptors has been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, factors that contribute to the signs and symptoms of asthma. Montelukast binding to the CysLT1, receptor is high-affinity and selective, preferring the CysLT1 receptor to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or beta-adrenergic receptor. Montelukcast inhibits physiologic actions of LTD4 at the CysLT1 receptors, without any agonist activity. Because of the role of leukotrienes in the pathogenesis of asthma, modification of leukotriene activity may be used to reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control. Inhibition of leukotriene-mediated effects may be achieved by drugs that interrupt 5-lipoxygenase activity and prevent formation of leukotrienes (e.g., zileuton) or by antagonism of leukotriene activity at specific receptor sites in the airway (e.g., montelukast, zafirlukast). The antagonist activity of montelukast is selective, competitive, and reversible. Montelukast competitively inhibits the action of LTD4 at a subgroup of CysLT receptors (CysLT1) in airway smooth muscle. In vitro, montelukast possesses affinity for the CysLT1 receptor that is similar to that of LTD4. In in vitro studies, montelukast antagonized contraction of isolated animal smooth muscle produced by LTD4, but did not antagonize contraction produced by LTC4. In animal studies, montelukast antagonized contraction of airway smooth muscle produced by LTD4 or antigen.

Pharmacodynamics

Montelukast is a leukotriene receptor antagonist that demonstrates a marked affinity and selectivity to the cysteinyl leukotriene receptor type-1 in preference to many other crucial airway receptors like the prostanoid, cholinergic, or beta-adrenergic receptors. As a consequence, the agent can elicit substantial blockage of LTD4 leukotriene-mediated bronchoconstriction with doses as low as 5 mg. Moreover, a placebo-controlled, crossover study (n=12) demonstrated that montelukast is capable of inhibiting early and late phase bronchoconstriction caused by antigen challenge by 75% and 57% respectively. In particular, it has been documented that montelukast can cause bronchodilation as soon as within 2 hours of oral administration. This action can also be additive to the bronchodilation caused by the concomitant use of a beta agonist. Nevertheless, clinical investigations performed with adults 15 years of age and older revealed that no additional clinical benefit is obtained when doses of montelukast greater than 10 mg a day are used. Additionally, in clinical trials with adults and pediatric asthmatic patients aged 6 to 14 years, it was also determined that montelukast can reduce mean peripheral blood eosinophils by about 13% to 15% from baseline in comparison to placebo during double-blind treatment periods. At the same time, in patients aged 15 years and older who were experiencing seasonal allergic rhinitis, the use of montelukast caused a median reduction of 13% in peripheral blood eosinophil counts when compared to placebo as well.