MONTEBASTO 5/5

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
• Seasonal allergies

Dosage

Children: For children aged 6 to 12 years, the recommended dose is 5 mg once daily. For children over 12 years, the adult dose may be used.

Adults: The typical adult dose is 10 mg once daily.

Mechanism of action

Ebastine acts as a selective antagonist of the histamine H1 receptor. By binding to these receptors, it prevents the action of histamine, a substance in the body that is responsible for allergy symptoms such as itching, sneezing, and runny nose. This selective action contributes to its efficacy in treating allergic reactions while minimizing sedation.

Pharmacodynamics

Ebastine shows a rapid onset of action, typically within 1 to 3 hours of administration, and its effects can last for up to 24 hours. This allows for once-daily dosing in most cases. The drug is primarily effective in reducing symptoms such as nasal congestion, sneezing, and itching associated with allergic reactions.

Pharmacokinetics

Ebastine is well absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes, resulting in the formation of an active metabolite, carebastine. The elimination half-life of ebastine is approximately 15 hours, allowing for prolonged therapeutic effects. It is excreted mainly in the urine, with a small percentage eliminated in the feces.

Pregnancy

The safety of ebastine during pregnancy has not been established. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Ebastine is excreted in breast milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat.

Indications

• Allergic rhinitis
• Chronic urticaria
• Allergic conjunctivitis

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information as it varies based on age and weight.

Adults: Refer to specific clinical guidelines or the BNF for details on adult dosing. Generally, once-daily dosing is common for effective symptom control.

Mechanism of action

Ebastinedium acts as a selective antagonist of the H1 histamine receptor. By blocking the action of histamine, a chemical released during allergic reactions, it prevents the associated symptoms such as vasodilation, increased vascular permeability, and sensory nerve stimulation. Additionally, it may exert antiallergic effects through inhibition of mast cell degranulation.

Pharmacodynamics

The pharmacodynamic profile of ebastinedium includes its ability to mitigate symptoms of allergic reactions without significant sedative effects, which is a common drawback of first-generation antihistamines. It has a rapid onset of action, typically within hours of administration, and provides long-lasting relief, allowing for once-daily dosing in most cases.

Pharmacokinetics

Ebastinedium is well absorbed following oral administration, with peak plasma concentrations occurring within a few hours. It undergoes extensive hepatic metabolism, primarily through cytochrome P450 enzymes, resulting in various metabolites. The elimination half-life is generally in the range of 15 to 20 hours, allowing for sustained therapeutic effects. The drug is primarily excreted in the urine, both as unchanged drug and metabolites.

Contra-indications

• Hypersensitivity to ebastinedium or any of its excipients
• Severe hepatic impairment

Adverse effects

• Drowsiness
• Headache
• Dry mouth
• Nausea
• Fatigue
• Dizziness

Interactions

• CYP3A4 inhibitors may increase plasma levels of ebastinedium
• CYP3A4 inducers may decrease plasma levels of ebastinedium
• Concurrent use with other antihistamines can increase the risk of sedation

Precautions

• Use with caution in patients with renal impairment
• Caution is advised when driving or operating machinery until the individual response to the drug is known
• Elderly patients may be more sensitive to the sedative effects

Pregnancy

The safety of ebastinedium in pregnancy has not been established. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether ebastinedium is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Formulations

• Tablets
• Oral solution

Indications

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Somontelukast selectively binds to the cysteinyl leukotriene receptor 1 (CysLT1), inhibiting the effects of leukotrienes, such as LTC4, LTD4, and LTE4. This action leads to bronchial smooth muscle relaxation and decreased vascular permeability, which reduces airway edema and mucus secretion.

Pharmacodynamics

The pharmacodynamics of somontelukast involve the modulation of the leukotriene pathway, leading to reduced inflammation, decreased bronchoconstriction, and improved airflow. The drug is effective in preventing exercise-induced bronchoconstriction and alleviating symptoms associated with allergic rhinitis, including nasal congestion, sneezing, and runny nose.

Pharmacokinetics

Somontelukast is well absorbed following oral administration, with peak plasma concentrations occurring within 3 to 4 hours. It has high protein binding (approximately 99%) and is extensively metabolized in the liver, primarily by cytochrome P450 enzymes. The elimination half-life is approximately 2.7 to 5.5 hours, and the drug is excreted mainly in the feces, with a small amount eliminated in urine.

Contra-indications

• Hypersensitivity to somontelukast or any component of the formulation

Adverse effects

• Headache
• Gastrointestinal disturbances (e.g., abdominal pain, nausea, diarrhea)
• Dizziness
• Fatigue
• Sleep disturbances (e.g., insomnia)
• Mood changes (e.g., aggression, anxiety, depression)
• Skin reactions (e.g., rash, pruritus)

Interactions

• May interact with other medications that affect liver enzymes, particularly CYP450 isoenzymes, though specific interactions are not well-established
• Not recommended to be used concurrently with other leukotriene receptor antagonists

Precautions

• Use with caution in patients with a history of psychiatric illness
• Monitor for changes in mood or behavior
• Not indicated for acute asthma attacks; patients should have a rescue inhaler available

Pregnancy

Limited data available; use only if clearly needed and the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Excreted in human milk; caution should be exercised when administered to a nursing woman.

Storage

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

Formulations

• Tablets
• Chewable tablets
• Granules

Mechanism of action

Ebastine is a second-generation antihistamine that acts as a selective histamine H1-receptor antagonist to relieve allergic symptoms.

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.