Montelukast

The CysLTs (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released from various cells, including mast cells and eosinophils. These important pro-asthmatic mediators bind to the CysLT receptors. The 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 the symptoms of allergic rhinitis. The 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 the physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity.

Fexofenadine

Fexofenadine hydrochloride is a non-sedating H1 antihistamine. Fexofenadine is a pharmacologically active metabolite of terfenadine.

Human histamine wheal and flare studies following single and twice-daily doses of fexofenadine hydrochloride demonstrate that the drug exhibits an antihistaminic effect beginning within 1 hour, achieving maximum effect at 6 hours, and lasting for 24 hours. Clinical studies conducted in seasonal allergic rhinitis have shown that a dose of 120 mg is sufficient for 24-hour efficacy.

In seasonal allergic rhinitis patients who were given fexofenadine hydrochloride up to 240 mg twice daily for 2 weeks, no significant differences in the QTc intervals were observed when compared to placebo. Also, no significant change in the QTc intervals was observed in healthy subjects given fexofenadine hydrochloride up to 60 mg twice daily for 6 months, 400 mg twice daily for 6.5 days, and 240 mg once daily for 1 year, when compared to placebo.

Montelukast

Absorption: After administration of a 10 mg film-coated tablet to fasted adults, the mean peak montelukast plasma concentration (Cmax) is achieved in 3 to 4 hours (Tmax). The mean oral bioavailability is 64%. The oral bioavailability and Cmax are not influenced by a standard meal in the morning.
Distribution: Montelukast is more than 99% bound to plasma proteins. The steady-state volume of distribution of montelukast averages 8 to 11 litres.

Metabolism: Montelukast is extensively metabolized. In studies with therapeutic doses, plasma concentrations of the metabolites of montelukast are undetectable at the steady state in adults and paediatric patients. In vitro studies using human liver microsomes indicate that cytochromes P450 3A4 and 2C9 are involved in the metabolism of montelukast.

Elimination: The plasma clearance of montelukast averages 45 mL/min in healthy adults. Following an oral dose of radiolabelled montelukast, 86% of the radioactivity was recovered in 5-day faecal collections and <0.2% was recovered in the urine. Coupled with estimates of montelukast oral bioavailability, this indicates that montelukast and its metabolites are excreted almost exclusively via the bile.

Fexofenadine

The single- and multiple-dose pharmacokinetics of fexofenadine are linear for oral doses up to 120 mg b.i.d. A dose of 240 mg b.i.d. produced a slightly greater than proportional increase (8.8%) in the steady-state area under the curve (AUC), indicating that fexofenadine pharmacokinetics are practically linear at doses between 40 mg and 240 mg taken daily.

Absorption: Fexofenadine hydrochloride is rapidly absorbed into the body following oral administration, with the Tmax occurring at approximately 1–3 hours post-dose. The mean Cmax value was approximately 427 ng/ml following the administration of a 120 mg dose once daily.

Distribution: Fexofenadine is 60–70% plasma protein-bound.

Elimination: The major route of elimination is believed to be via biliary excretion, while up to 10% of the ingested dose is excreted unchanged through the urine.

Sufemon Tablets are indicated for the relief of symptoms of allergic rhinitis (seasonal and perennial) whenever a combination is indicated.

Adults (>15 years of age)
One tablet once daily

Sufemon Tablets are contraindicated in patients with a known hypersensitivity to montelukast, fexofenadine or to any of the excipients.

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/ethinylestradiol 35 mcg), terfenadine, digoxin and warfarin.

Fexofenadine
Fexofenadine does not undergo hepatic biotransformation and, therefore, will not interact with other drugs through hepatic mechanisms. Co-administration of fexofenadine hydrochloride with erythromycin or ketoconazole has been found to result in an increase by two to three times in the level of fexofenadine in plasma.

Fruit juices such as grapefruit, orange and apple may reduce the bioavailability and exposure of fexofenadine.

Renal Impairment
As with most new drugs, there is only limited data in renally impaired patients. Fexofenadine hydrochloride should be administered with care in these special groups.

Hepatic Impairment
As with most new drugs, there is only limited data in hepatically impaired patients. Fexofenadine hydrochloride should be administered with care in these special groups.

Pregnancy
There are no adequate and well-controlled studies of either montelukast or fexofenadine in pregnant women. Limited animal studies do not indicate the direct or indirect harmful outcomes with respect to the effects on pregnancy, embryonal/foetal development, parturition, or postnatal development. Because animal reproduction studies are not always predictive of human response, Sufemon Tablets should 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. There are no data on the content of human milk after administering fexofenadine hydrochloride. However, when terfenadine was administered to nursing mothers, fexofenadine was found to cross into human breast milk. Therefore, Sufemon Tablets are not recommended for nursing mothers.

Sufemon Tablets – Strip pack of 10 tablets