Monteral-LC 15

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

Administration of Monteral-LC 15mg (Levocetirizine 5mg and Montelukast 10mg) once a day in the evening.

For Prophylaxis of exercise-induced asthma (Adults):

Administration of Monteral-LC 15mg (Montelukast 10mg + Levocetirizine 5mg), at least two hours before exercise.

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.

The clinically relevant drug interactions of Monteral-LC 15 which contains Montelukast 10mg+ Levocetirizine 5mg are briefly summarized here:

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 by 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 levocetirizine 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 levocetirizine. 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 physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Monteral-LC 15.

There is no data to prove the overdosage of this combination. However, overdosage has 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 levocetirizine. Should an overdose occur, symptomatic or supportive treatment is recommended. Levocetirizine is not effectively removed by dialysis and dialysis will be ineffective unless a dialyzable agent has been concomitantly ingested.

Monteral-LC 15 contains Montelukast 10mg + Levocetirizine 5mg.

Pharmacodynamics

Levocetirizine:

Levocetirizine is an antihistamine and is an active enantiomer of cetirizine. Its binding affinity to H1-receptor is twice that of 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) receptors 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 feces (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%); feces (12.9%). Elimination half-life: Approx 8-9 hours.

• Therapeutic benefits of Montelukast +Levocetirizine:

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.