MONTELIX LC

(Montelukast sodium 10mg & Levocetirizine dihydrochloride 5 mg tablets)

MONTELIX LC TABLETS

COMPOSITION:

Each uncoated tablet contains: Montelukast sodium equivalent toMontelukast: 10 mg & Levocetirizine dihydrochloride.....5 mg

MONTELIX LC Tablets is a combination of Montelukast Sodium & Levocetirizine

Dihydrochloride.

Montelukast sodium :

The cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released from various cells including mast cells and eosinophils. These important pro-asthmatic mediators bind to cysteinyl leukotriene (CysLT) receptors. The CysLT type-1 (CysLT1) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells).

CysLTs have been correlated with the pathophysiology of asthma and allergic rhinitis. In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen exposure during both early- and late-phase reactions and are associated with symptoms of allergic rhinitis. Intranasal challenge with CysLTs has been shown to increase nasal airway resistance and symptoms of nasal obstruction. Montelukast is an orally active compound that binds with high affinity and selectivity to the CysLT1 receptor. Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity.

Levocetirizine

Levocetirizine, the R-enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receptors. It has been demonstrated by recent studies that the treatment of AR with concomitant administration of an antileukotriene (montelukast) and an antihistamine (levocetirizine), shows significantly better symptom relief compared with the modest improvement of rhinitis symptomatology with each of the treatments alone.

PHARMACOLOGY

As MONTELIX LC is a combination of Montelukast and Levocetirizine, the pharmacological properties of both the molecules are given separately:

Pharmacodynamics:

MONTELIX LC Tablets are indicated for relief of symptoms of allergic rhinitis (seasonal and perennial).

DOSAGE AND ADMINISTRATION

Adults (>15 years): 1 tablet once daily

CONTRAINDICATIONS

MONTELIX LC Tablets are contraindicated in patients with known hypersensitivity to Montelukast, levocetirizine, to other piperazine derivatives, or
to any of the excipients. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
should not take this medicine. Also contradicted in patients with severe renal impairment at less than 10 ml/min creatinine clearance.

WARNINGS AND PRECAUTIONS

Montelukast :

Eosinophilic Conditions: In rare cases, patients on therapy with montelukast may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition, which is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, and worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between Montelukast and these underlying conditions has not been established. Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking Montelukast.

Levocetirizine :

Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery when taking levocetirizine. Avoid concurrent use of alcohol or other central nervous system depressants with levocetirizine.

Drug Interactions

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, and non-steroidal anti-inflammatory agents, benzodiazepines, and decongestants. Penobarbital, which induces hepatic metabolism, decreased the AUC ofmontelukast 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 extent of absorption of levocetirizine is not reduced with food, although the rate of absorption is decreased. Ritonavir increased the plasma AUC of cetirizine by about 42% accompanied by an increase in half-life (53%) and a decrease in clearance (29%) of cetirizine. The disposition of ritonavir was not altered by concomitant cetirizine administration. In sensitive patients the simultaneous administration of cetirizine or levocetirizine and alcohol or other CNS depressants may have effects on the central nervous system, although it has been shown that the racemate cetirizine does not potentiate the effect of alcohol.

Renal Impairment

Levocetirizine is known to be substantially excreted by the kidneys and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Dosage adjustment may be required in patients with impaired renal function. Hence, this combination should be used with caution in such patients.

Hepatic Impairment

As levocetirizine is mainly excreted unchanged by the kidneys, it is unlikely that the clearance of levocetirizine is significantly decreased in patients with solely hepatic impairment. But montelukast is mainly excreted through bile; caution is to be exercised while prescribing this combination in patients with impaired hepatic function.

Pregnancy :

There are no adequate and well controlled studies of either montelukast or levocetirizine in pregnant women. Because animal reproduction studies are not always predictive of human response, this combination should not be used during pregnancy only if it is considered to be clearly essential.

Lactation

It is not known if montelukast is excreted in human milk. Cetirizine has been reported to be excreted in human breast milk. Because levocetirizine is also expected to be excreted in human milk this combination is not recommended during lactation.

Geriatric Use

Montelukast :

No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Levocetirizine :

Clinical studies of levocetirizine for each approved indication did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.