Levocetirizine+ Montelukast

Levocetirizine is a Second-generation antihistamines, and Montelukast is a Leukotriene receptor antagonist.

Levocetirizine+ Montelukast is used in treating Allergic rhinitis and Urticaria, chronic spontaneous. It is also used to treat Angioedema, acute allergic or recurrent idiopathic; Urticaria, new onset; Urticaria, nonsteroidal anti-inflammatory drug associated (prophylaxis).

Levocetirizine+ Montelukast shows common side effects like Drowsiness or sedation, Dry mouth , Headache, Fatigue, Dizziness, Nausea, Abdominal pain, Dysgeusia (distortion or alteration of the sense of taste)

Levocetirizine+ Montelukast is available in the form of tablets.

Levocetirizine+ Montelukast is available in India, Germany, Canada, Italy, USA

Levocetirizine selectively inhibits histamine H1 receptors. This action prevents histamine from activating this receptor and causing effects like smooth muscle contraction, increased permeability of vascular endothelium, histidine uptake in basophils, stimulation of cough receptors, and stimulation of flare responses in the nervous system

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.

Levocetirizine+ Montelukast is available in the form of tablets.

Levocetirizine+ Montelukast is used in the treatment of asthma, including prevention of exercise-induced bronchoconstriction, and for the relief of symptoms of allergic rhinitis, such as sneezing, stuffy nose, and itching of the nose, seasonal and perennial allergic rhinitis, including hay fever, and for the treatment of chronic idiopathic urticaria, which is a type of hives that occurs without a known cause.

Montelukast selectively antagonizes leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Montelukast inhibits the actions of LTD4 at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus. Levocetirizine is an inverse agonist that decreases activity at histamine H1 receptors. This in turn prevents the release of other allergy chemicals and increased blood supply to the area, and provides relief from the typical symptoms associated with seasonal and perennial allergic rhinitis. It does not prevent the actual release of histamine from mast cells.

Levocetirizine+ Montelukast is approved for use in the following clinical indications

• Montelukast is indicated for the treatment of asthma, including prevention of exercise-induced bronchoconstriction, and for the relief of symptoms of allergic rhinitis, such as sneezing, stuffy nose, and itching of the nose.
• Levocetirizine is indicated for the treatment of seasonal and perennial allergic rhinitis, including hay fever, and for the treatment of chronic idiopathic urticaria, which is a type of hives that occurs without a known cause.

For treatment of allergic rhinitis and chronic asthma (Adults):

Consider administration of 10 mg once a day in the evening.

For Prophylaxis of exercise-induced asthma (Adults):

Consider administration of 10 mg of Montelukast + Levocetirizine, at least two hours before exercise.

Levocetirizine+ Montelukast is available in various strengths as 5mg + 10 mg.

Levocetirizine+ Montelukast is available in the form of tablets.

Montelukast + Levocetirizine is contraindicated in patients with an allergy to either or both drugs, hepatic impairment, NSAID allergy, Churg-Strauss syndrome.

Common Adverse effects:

Headache, Dizziness, abdominal pain, diarrhea, and nausea.

Less Common Adverse effects:

Rapid or irregular heartbeat Confusion and memory problems Difficulty urinating or urinary retention Blurred vision and eye pain Seizures Depression and other psychiatric symptoms.

Rare Common Adverse effects:

Aggressive behavior and hostility Movement disorders, such as dystonia and tremors Hypersensitivity reactions, such as angioedema and anaphylaxis Acute generalized exanthematous pustulosis, which is a rare skin reaction characterized by widespread redness and pustules Hepatitis and other liver problems

MONTELUKAST

In drug-interaction studies, the recommended clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (norethindrone 1 mg/ethinyl estradiol 35 mcg), terfenadine, digoxin, and warfarin. Although additional specific interaction studies were not performed, montelukast was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without evidence of clinical adverse interactions. These medications included thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, and decongestants. Phenobarbital, which induces hepatic metabolism, decreased the AUC of montelukast approximately 40% following a single 10-mg dose of montelukast. No dosage adjustment for montelukast is recommended. It is reasonable to employ appropriate clinical monitoring when potent cytochrome P450 enzyme inducers, such as phenobarbital or rifampin, are co-administered with montelukast.

LEVOCETIRIZINE

In vitro data indicate that levocetrizine is unlikely to produce pharmacokinetic interactions through inhibition or induction of liver drug-metabolizing enzymes. No in vivo drug-drug interaction studies have been performed with levocetrizine. Drug interaction studies have been performed with racemic cetirizine. Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole and cimetidine. There was a small decrease (~16%) in the clearance of cetirizine caused by a 400 mg dose of theophylline. It is possible that higher theophylline doses could have a greater effect.

The common side effects of Levocetirizine+ Montelukast include the following headache, dizziness, abdominal pain, diarrhea, and nausea.

There is no data to prove the over dosage of this combination. However, over dosage have been reported with individual molecules. Montelukast: There have been reports of acute over-dosage in post-marketing experience and clinical studies with montelukast. These include reports in adults and children with a dose as high as 1000 mg. The clinical and laboratory findings observed were 6 consistent with the safety profile in adults and pediatric patients. There were no adverse experiences in the majority of over-dosage reports. The most frequently occurring adverse experiences were consistent with the safety profile of montelukast and included abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity. It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis. Levocetirizine: Symptoms of overdose may include drowsiness in adults and initially agitation and restlessness followed by drowsiness, in children. There is no known specific antidote to levocetrizine. Should overdose occur, symptomatic or supportive treatment is recommended. Levocetrizine is not effectively removed by dialysis and dialysis will be ineffective unless a dialyzable agent has been concomitantly ingested.

Pharmacodynamic

Levocetirizine:

Levocetirizine, an antihistamine and is an active enantiomer of cetirizine. Its binding affinity to H₁-receptor is twice than cetirizine. It selectively competes for H₁-receptor sites on effector cells in the gastrointestinal tract, blood vessels and respiratory tract.

Montelukast:

Montelukast is a selective leukotriene receptor antagonist. It inhibits cysteinyl leukotriene type-1 (CysLT₁) receptor found in the human airway and on other pro-inflammatory cells. The binding of CysLTs in leukotriene receptors is involved in the pathophysiology of asthma, including bronchoconstriction, mucous secretion, vascular permeability, and eosinophil recruitment. Additionally, CysLTs are released from the nasal mucosa after allergen exposure which is associated with symptoms of allergic rhinitis.

Pharmacokinetics

Montelukast:

• Absorption: Rapidly absorbed. Bioavailability: 64% (conventional tab); 73% (5 mg chewable tab). Time to peak plasma concentration: 3-4 hours (conventional tab); 2 hours (chewable tab).
• Distribution: Volume of distribution: 8-11 L. Plasma protein binding: >99%.
• Metabolism: Extensively metabolised in the liver, mainly by CYP2C8, and to a lesser extent by CYP3A4 and CYP2C9 enzymes.
• Excretion: Mainly via faeces (86%); urine (<0.2%). Elimination half-life: 2.7-5.5 hours.

Levocetirizine:

• Absorption: Rapid and extensive oral absorption. Time to peak plasma concentration: 0.9 hours.
• Distribution: Volume of distribution: Approx 0.4 L/kg. Plasma protein binding: 91-92%.
• Metabolism: Metabolised by aromatic oxidation, N- and O-dealkylation (via CYPA4) and taurine conjugation.
• Excretion: Mainly via urine (85.4%); faeces (12.9%). Elimination half-life: Approx 8-9 hours.

• Therapeutic benefits of Levocetirizine + Montelukast :

Improved asthma control: Montelukast can help to prevent asthma symptoms such as wheezing, coughing, and shortness of breath, while levocetirizine can help to relieve symptoms such as itching and runny nose that can trigger asthma attacks.

Relief from allergic rhinitis: Levocetirizine can provide relief from symptoms of allergic rhinitis, such as sneezing, runny nose, and nasal congestion, while montelukast can help to reduce inflammation in the nasal passages.

Reduction in hives: Montelukast and levocetirizine can be effective in reducing symptoms of urticaria (hives), such as itching and redness.

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Levocetirizine+Montelukast?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/