Co-Altria/Co-Altria Ped

Co-Altria: Montelukast sodium, levocetirizine hydrochloride.
Co-Altria Ped: Montelukast sodium, levocetirizine hydrochloride.

Co-Altria: Each uncoated bilayered tablet contains: Montelukast (as sodium), USP 10 mg; Levocetirizine hydrochloride, USP 5 mg.
Co-Altria Ped: Each chewable tablet contains: Montelukast (as sodium), USP 5 mg; Levocetirizine hydrochloride, USP 2.5 mg.
Montelukast (as sodium), USP 5 mg; Levocetirizine hydrochloride, USP 5 mg.

Leukotriene Receptor Antagonist/Antihistamine.
Pharmacology: Pharmacodynamics: Montelukast: 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.
Binding studies revealed that levocetirizine has high affinity for human H1-receptors (Ki = 3.2 nmol/l). Levocetirizine has an affinity 2-fold higher than that of cetirizine (Ki = 6.3 nmol/l). Levocetirizine dissociates from H1-receptors with a half-life of 115 ± 38 min.
After single administration, levocetirizine shows a receptor occupancy of 90% at 4 hours and 57% at 24 hours.
Pharmacodynamic studies in healthy volunteers demonstrate that, at half the dose, levocetirizine has comparable activity to cetirizine, both in the skin and in the nose.
Co-Altria Ped: The onset of action of Levocetirizine 5 mg in controlling pollen-induced symptoms has been observed at 1 hour post drug intake in placebo controlled trials in the model of the allergen challenge chamber.
In vitro studies (Boyden chambers and cell layers techniques) show that Levocetirizine inhibits eotaxin-induced eosinophil transendothelial migration through both dermal and lung cells. A pharmacodynamic experimental study in vivo (skin chamber technique) showed three main inhibitory effects of Levocetirizine 5 mg in the first 6 hours of pollen-induced reaction, compared with placebo in 14 adult patients: Inhibition of VCAM-1 release, modulation of vascular permeability, and a decrease in eosinophil recruitment.
Pharmacodynamic studies in healthy volunteers demonstrate that, at half the dose, Levocetirizine has comparable activity to cetirizine, both in the skin and in the nose.
Pharmacokinetic/pharmacodynamic relationship: 5 mg Levocetirizine provide a similar pattern of inhibition of histamine-induced wheal and flare than 10 mg cetirizine. As for cetirizine, the action on histamine-induced skin reactions was out of phase with the plasma concentrations. ECGs did not show relevant effects of Levocetirizine on QT interval.
Pharmacokinetics: Montelukast: Absorption: Montelukast is rapidly absorbed following oral administration. For the 10 mg film-coated tablet, the mean peak plasma concentration (Cmax) is achieved 3 hours (Tmax) after administration in adults in the fasted state. The mean oral bioavailability is 64%. The oral bioavailability and Cmax are not influenced by a standard meal. Safety and efficacy were demonstrated in clinical trials where the 10 mg film-coated tablet was administered without regard to the timing of food ingestion.
For the 5 mg chewable tablet, the Cmax is achieved in 2 hours after administration in adults in the fasted state. The mean oral bioavailability is 73% and is decreased to 63% by a standard meal.
Distribution: Montelukast is more than 99% bound to plasma proteins. The steady-state volume of distribution of montelukast averages 8-11 litres. Studies in rats with radiolabelled montelukast indicate minimal distribution across the blood-brain barrier. In addition, concentrations of radiolabelled material at 24 hours post-dose were minimal in all other tissues.
Biotransformation: Montelukast is extensively metabolised. In studies with therapeutic doses, plasma concentrations of metabolites of montelukast are undetectable at steady state in adults and children.
Cytochrome P450 2C8 is the major enzyme in the metabolism of montelukast. Additionally CYP 3A4 and 2C9 may have a minor contribution, although itraconazole, an inhibitor of CYP 3A4, was shown not to change pharmacokinetic variables of montelukast in healthy subjects that received 10 mg montelukast daily. Based on in vitro results in human liver microsomes, therapeutic plasma concentrations of montelukast do not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19, or 2D6. The contribution of metabolites to the therapeutic effect of montelukast is minimal.
Co-Altria: 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 urine. Coupled with estimates of montelukast oral bioavailability, this indicates that montelukast and its metabolites are excreted almost exclusively via the bile.
Co-Altria Ped: Metabolism: Montelukast is extensively metabolized. In studies with therapeutic doses, plasma concentrations of metabolites of Montelukast are undetectable at steady state in adults and pediatric patients.
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 urine. Coupled with estimates of montelukast oral bioavailability, this indicates that montelukast and its metabolites are excreted almost exclusively via the bile.
In several studies, the mean plasma half-life of Montelukast ranged from 2.7 to 5.5 hours in healthy young adults. The pharmacokinetics of Montelukast is nearly linear for oral doses up to 50 mg. During once-daily dosing with 10 mg Montelukast, there is little accumulation of the parent drug in plasma (14%).
Levocetirizine: The pharmacokinetics of levocetirizine are linear with dose- and time-independent with low inter-subject variability. The pharmacokinetic profile is the same when given as the single enantiomer or when given as cetirizine. No chiral inversion occurs during the process of absorption and elimination.
Absorption: Levocetirizine is rapidly and extensively absorbed following oral administration. In adults, peak plasma concentrations are achieved 0.9 h after dosing. Steady state is achieved after two days. Peak concentrations are typically 270 ng/ml and 308 ng/ml following a single and a repeated 5 mg o.d. dose, respectively. The extent of absorption is dose-independent and is not altered by food, but the peak concentration is reduced and delayed.
Distribution: No tissue distribution data are available in humans, neither concerning the passage of levocetirizine through the blood-brain-barrier. In rats and dogs, the highest tissue levels are found in liver and kidneys, the lowest in the CNS compartment.
In humans, levocetirizine is 90% bound to plasma proteins. The distribution of levocetirizine is restrictive, as the volume of distribution is 0.4 l/kg.
Biotransformation: The extent of metabolism of levocetirizine in humans is less than 14% of the dose and therefore differences resulting from genetic polymorphism or concomitant intake of enzyme inhibitors are expected to be negligible. Metabolic pathways include aromatic oxidation, N- and O-dealkylation and taurine conjugation. Dealkylation pathways are primarily mediated by CYP 3A4 while aromatic oxidation involved multiple and/or unidentified CYP isoforms. Levocetirizine had no effect on the activities of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 at concentrations well above peak concentrations achieved following a 5 mg oral dose.
Due to its low metabolism and absence of metabolic inhibition potential, the interaction of levocetirizine with other substances, or vice-versa, is unlikely.
Elimination: The plasma half-life in adults is 7.9 ± 1.9 hours. The half-life is shorter in small children.
The mean apparent total body clearance in adults is 0.63 ml/min/kg. The major route of excretion of levocetirizine and metabolites is via urine, accounting for a mean of 85.4% of the dose. Excretion via faeces accounts for only 12.9% of the dose. Levocetirizine is excreted both by glomerular filtration and active tubular secretion.

MONTELUKAST PLUS LEVOCETIRIZINE is indicated for relief of symptoms associated with seasonal and perennial allergic rhinitis.

Co-Altria: Adults: One tablet containing Montelukast 10mg plus Levocetirizine 5mg once daily. Or as prescribed by the physician.
Elderly: Dosages in the elderly should be adjusted in accordance with their renal function (see Patients with Renal Impairment as follows).
Patients with Renal Impairment: In adults and children 12 years of age and older with: Mild renal impairment (CrCl 50-80 mL/min): One tablet containing Montelukast 10mg plus Levocetirizine 2.5mg once daily.
Moderate renal impairment (CrCl 30-50 mL/min): One tablet containing Montelukast 10mg plus Levocetirizine 2.5mg once daily, every other day.
Patients with hepatic disease: No dosages adjustment is needed in patients solely with mild to moderate hepatic impairment. Usage is not recommended in patients with severe hepatic impairment.
Children and Adolescent: Children aged 15+: One tablet containing 10mg Montelukast and Levocetirizine 5mg once daily. Or as prescribed by the physician.
Co-Altria Ped: Patients with hepatic disease: No dosage adjustment is needed in patients solely with mild to moderate hepatic impairment. Usage is not recommended in patients with severe hepatic impairment.
Children and Adolescents: Children aged 6-14: One chewable tablet containing 5mg Montelukast and 2.5mg Levocetirizine or 5mg Montelukast and 5mg Levocetirizine once daily. OR as prescribed by the physician.

Co-Altria: There is no data reported on the overdosage of this combination. However, overdosage has been reported with individual molecules.
Montelukast: In chronic asthma studies, montelukast has been administered at doses up to 200 mg/day to adult patients for 22 weeks and in short term studies, up to 900 mg/day to patients for approximately one week without clinically important adverse experiences.
There have been reports of acute overdose in post-marketing experience and clinical studies with montelukast. These include reports in adults and children with a dose as high as 1,000 mg (approximately 61 mg/kg in a 42-month old child). The clinical and laboratory findings observed were consistent with the safety profile in adults and paediatric patients. There were no adverse experiences in the majority of overdose reports.
Symptoms of overdose: 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.
Management of overdose: No specific information is available on the treatment of overdose with montelukast. It is not known whether montelukast is dialyzable by peritoneal- or haemodialysis.
Levocetirizine: Symptoms: Symptoms of overdose may include drowsiness in adults. In children, agitation and restlessness may initially occur, followed by drowsiness.
Management of overdoses: There is no known specific antidote to levocetirizine.
Should overdose occur, symptomatic or supportive treatment is recommended. Gastric lavage may be considered shortly after ingestion of the drug. Levocetirizine is not effectively removed by haemodialysis.
Co-Altria Ped: There is no data reported on the overdosage of this combination. However, overdosage has been reported with individual molecules.
Montelukast: There have been reports of acute overdosage 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 consistent with the safety profile in adults and pediatric patients. There were no adverse experiences in the majority of overdosage 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. There is no known specific antidote to Levocetirizine. Should 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.

Co-Altria: Co-Altria Tablets are contraindicated in patients with known hypersensitivity to montelukast, levocetirizine, to other piperazine derivatives or to any of the excipients. Also, contraindicated in patients with severe renal impairment at less than 10 ml/min creatinine clearance, and patients undergoing haemodialysis.
Co-Altria Ped: It is 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 contraindicated in patients with severe renal impairment at less than 10 mL/min creatinine clearance.

Co-Altria: Montelukast: Patients should be advised never to use oral montelukast to treat acute asthma attacks and to keep their usual appropriate rescue medication for this purpose readily available. If an acute attack occurs, a short-acting inhaled beta-agonist should be used. Patients should seek their doctor's advice as soon as possible if they need more inhalations of short-acting beta-agonists than usual.
Montelukast should not be substituted abruptly for inhaled or oral corticosteroids.
There are no data demonstrating that oral corticosteroids can be reduced when montelukast is given concomitantly.
In rare cases, patients on therapy with anti-asthma agents including 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 cases have been sometimes associated with the reduction or withdrawal of oral corticosteroid therapy. Although a causal relationship with leukotriene receptor antagonism has not been established, physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. Patients who develop these symptoms should be reassessed and their treatment regimens evaluated.
Treatment with montelukast does not alter the need for patients with aspirin-sensitive asthma to avoid taking aspirin and other non-steroidal anti-inflammatory drugs.
Levocetirizine: Precaution is recommended with concurrent intake of alcohol.
Caution should be taken in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as levocetirizine may increase the risk of urinary retention.
Caution should be taken in patients with epilepsy and patients at risk of convulsion as levocetirizine may cause seizure aggravation.
Response to allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pruritus may occur when levocetirizine is stopped even if those symptoms were not present before treatment initiation.
The symptoms may resolve spontaneously. In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.
Co-Altria Ped: 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, 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.
Neuropsychiatric events have been reported in adults, adolescents, and children.
Levocetirizine: Caution should be taken in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as levocetirizine may increase the risk of urinary retention.
Caution should be taken in patients with epilepsy and patients at risk of convulsion as levocetirizine may cause seizure aggravation.
Response to allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.
Pruritus may occur when levocetirizine is stopped even if those symptoms were not present before treatment initiation. The symptoms may resolve spontaneously. In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted. Avoid concurrent use of alcohol with Levocetirizine.

Co-Altria: Pregnancy: Montelukast: Animal studies do not indicate harmful effects with respect to effects on pregnancy or embryonal/foetal development.
Available data from published prospective and retrospective cohort studies with montelukast use in pregnant women evaluating major birth defects have not established a drug-associated risk. Available studies have methodologic limitations, including small sample size, in some cases retrospective data collection, and inconsistent comparator groups.
Montelukast may be used during pregnancy only if it is considered to be clearly essential.
Levocetirizine: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of levocetirizine in pregnant women. However, for cetirizine, the racemate of levocetirizine, a large amount of data (more than 1000 pregnancy outcomes) on pregnant women indicate no malformative or feto/neonatal toxicity. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition or postnatal development.
The use of levocetirizine may be considered during pregnancy, if necessary.
Breast-feeding: Montelukast: Studies in rats have shown that montelukast is excreted in milk. It is unknown whether montelukast/metabolites are excreted in human milk.
Montelukast may be used in breast-feeding only if it is considered to be clearly essential.
Levocetirizine: Cetirizine, the racemate of levocetirizine, has been shown to be excreted in human. Therefore, the excretion of levocetirizine in human milk is likely. Adverse reactions associated with levocetirizine may be observed in breastfed infants. Therefore, caution should be exercised when prescribing levocetirizine to lactating women.

Co-Altria: There is no data available on undesirable effects of this combination. However, side effects have been reported with individual molecules.
Montelukast: Montelukast has been evaluated in clinical studies as follows: 10 mg film-coated tablets in approximately 4,000 adult and adolescent asthmatic patients 15 years of age and older.
10 mg film-coated tablets in approximately 400 adult and adolescent asthmatic patients with seasonal allergic rhinitis 15 years of age and older.
The following drug-related adverse reactions in clinical studies were reported commonly ≥1/100 to <1/10) in asthmatic patients treated with montelukast and at a greater incidence than in patients treated with placebo: See Table 1.

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Tabulated list of Adverse Reactions: Adverse reactions reported in post-marketing use are listed, by System Organ Class and specific Adverse Reactions, in the table as follows. Frequency Categories were estimated based on relevant clinical trials. (See Table 2.)

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Levocetirizine: Clinical studies: Adults and adolescents above 12 years of age: In therapeutic studies in women and men aged 12 to 71 years, 15.1% of the patients in the levocetirizine 5 mg group had at least one adverse drug reaction compared to 11.3% in the placebo group. 91.6% of these adverse drug reactions were mild to moderate.
In therapeutic trials, the dropout rate due to adverse events was 1.0% (9/935) with levocetirizine 5 mg and 1.8% (14/771) with placebo.
Clinical therapeutic trials with levocetirizine included 935 subjects exposed to the medicinal product at the recommended dose of 5 mg daily. From this pooling, following incidence of adverse drug reactions were reported at rates of 1% or greater (common: ≥1/100 to <1/10) under levocetirizine 5 mg or placebo: See Table 3.

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Further uncommon incidences of adverse reactions (uncommon ≥1/1,000 to <1/100) like asthenia or abdominal pain were observed.
The incidence of sedating adverse drug reactions such as somnolence, fatigue, and asthenia was altogether more common (8.1%) under levocetirizine 5 mg than under placebo (3.1%).
Post-marketing experience: Adverse reactions from post-marketing experience are per System Organ Class and per frequency. The frequency is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Immune system disorders: Not known: hypersensitivity including anaphylaxis.
Metabolism and nutrition disorders: Not known: increased appetite.
Psychiatric disorders: Not known: aggression, agitation, hallucination, depression, insomnia, suicidal ideation, nightmare.
Nervous system disorders: Not known: convulsion, paraesthesia, dizziness, syncope, tremor, dysgeusia.
Ear and labyrinth disorders: Not known: vertigo.
Eye disorders: Not known: visual disturbances, blurred vision, occulogyration.
Cardiac disorders: Not known: palpitations, tachycardia.
Respiratory, thoracic and mediastinal disorders: Not known: dyspnoea.
Gastrointestinal disorders: Not known: nausea, vomiting, diarrhoea.
Hepatobiliary disorders: Not known: hepatitis.
Renal and urinary disorders: Not known: dysuria, urinary retention.
Skin and subcutaneous tissue disorders: Not known: angioneurotic oedema, fixed drug eruption, pruritus, rash, urticaria.
Musculoskeletal, connective tissues, and bone disorders: Not known: myalgia, arthralgia.
General disorders and administration site conditions: Not known: oedema.
Investigations: Not known: weight increased, abnormal liver function tests.
Description of selected adverse reactions: After levocetirizine discontinuation, pruritus has been reported.
Co-Altria Ped: Montelukast: Montelukast has been evaluated for clinical studies in approximately 4,000 adult and adolescent patients 15 years of age and older for 10 mg and approximately 1,750 paediatric patients and adolescents 6 to 14 years of age for 5 mg.
The following drug-related adverse reactions in clinical studies were reported commonly (≥1/100 to <1/10) in asthmatic patients treated with montelukast and at a greater incidence than in patients treated with placebo: Adult and Adolescent Patients 15 years and older (two 12-week studies; n=795) (A), Paediatric Patients 6 to 14 years old (one 8-week study; n=201) (two 56-week studies; n=615) (P), Nervous system disorders: (A) headache, (P) headache, Gastrointestinal disorders: (A) abdominal pain.
Tabulated list of Adverse Reactions: Adverse reactions reported in post-marketing use are listed, by System Organ Class and specific Adverse Experience Term, in the table as follows. Frequency Categories were estimated based on relevant clinical trials. (See Table 4.)

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Levocetirizine: Adults and adolescents above 12 years of age: In therapeutic studies in women and men aged 12 to 71 years, 15.1% of the patients in the Levocetirizine 5 mg group had at least one adverse drug reaction compared to 11.3% in the placebo group. 91.6% of these adverse drug reactions were mild to moderate. In therapeutic trials, the dropout rate due to adverse events was 1.0% (9/935) with Levocetirizine 5 mg and 1.8% (14/771) with placebo. Clinical therapeutic trials with Levocetirizine included 935 subjects exposed to the drug at the recommended dose of 5 mg daily. From this data, the following adverse drug reactions were reported at rates of 1% or greater during treatment with Levocetirizine 5 mg (L) or placebo (P); Headache: L (2.6%), P (3.2%). Somnolence: L (5.2%), P (1.4%). Dry Mouth: L (2.6%), P (1.6%). Fatigue: L (2.5%), P (1.2%).
Pediatric population: In two placebo-controlled studies in pediatric patients aged 6-11 months and aged 1 year to less than 6 years, 159 subjects were exposed to levocetirizine at the dose of 1.25 mg daily for 2 weeks and 1.25 mg twice daily respectively. The following incidence of adverse drug reactions was reported at rates of 1% or greater under levocetirizine or placebo (L) or placebo (P); Diarrhoea: L (1.9%), Vomiting: L (0.6%), P (1.2%). Constipation: L (1.3%), Somnolence: L (1.9%), P (2.4%), Sleep disorder: L (1.3%).
In children aged 6-12 years double blind placebo controlled studies were performed where 243 children were exposed to 5 mg levocetirizine daily for variable periods ranging from less than 1 week to 13 weeks. The following incidence of adverse drug reactions was reported at rates of 1% or greater under levocetirizine or placebo. (L) or placebo (P); Headache: L (0.8%), P (2.1%), Somnolence: L (2.9%), P (0.4%).
List of Adverse Reactions: Adverse reactions from post-marketing experience are per System Organ Class and per frequency. The frequency is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Immune system disorders: Not known: hypersensitivity including anaphylaxis.
Metabolism and nutrition disorders: Not known: increased appetite.
Psychiatric disorders: Not known: aggression, agitation, hallucination, depression, insomnia, suicidal ideation, nightmare.
Nervous system disorders: Not known: convulsion, paraesthesia, dizziness, syncope, tremor, dysgeusia.
Ear and labyrinth disorders: Not known: vertigo.
Eye disorders: Not known: visual disturbances, blurred vision, occulogyration.
Cardiac disorders: Not known: palpitations, tachycardia.
Respiratory, thoracic and mediastinal disorders: Not known: dyspnoea.
Gastrointestinal disorders: Not known: nausea, vomiting, diarrhoea.
Hepatobiliary disorders: Not known: hepatitis.
Renal and urinary disorders: Not known: dysuria, urinary retention.
Skin and subcutaneous tissue disorders: Not known: angioneurotic oedema, fixed drug eruption, pruritus, rash, urticaria.
Musculoskeletal, connective tissues, and bone disorders: Not known: myalgia, arthralgia.
General disorders and administration site conditions: Not known: oedema.
Investigations: Not known: weight increased, abnormal liver function tests.
After levocetirizine discontinuation, pruritus has been reported.

Co-Altria: Montelukast: Montelukast may be administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma. 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.
The area under the plasma concentration curve (AUC) for montelukast was decreased approximately 40% in subjects with co-administration of phenobarbital. Since montelukast is metabolised by CYP 3A4, caution should be exercised, particularly in children, when montelukast is co-administered with inducers of CYP 3A4, such as phenytoin, phenobarbital and rifampicin.
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.
In vitro studies have shown that montelukast is a potent inhibitor of CYP 2C8. However, data from a clinical drug-drug interaction study involving montelukast and rosiglitazone (a probe substrate representative of medicinal products primarily metabolised by CYP 2C8) demonstrated that montelukast does not inhibit CYP 2C8 in vivo. Therefore, montelukast is not anticipated to markedly alter the metabolism of medicinal products metabolised by this enzyme (e.g., paclitaxel, rosiglitazone, and repaglinide).
In vitro studies have shown that montelukast is a substrate of CYP 2C8, and to a less significant extent, of 2C9, and 3A4. In a clinical drug-drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9) gemfibrozil increased the systemic exposure of montelukast by 4.4-fold. No routine dosage adjustment of montelukast is required upon co-administration with gemfibrozil or other potent inhibitors of CYP 2C8, but the physician should be aware of the potential for an increase in adverse reactions.
Based on in vitro data, clinically important drug interactions with less potent inhibitors of CYP 2C8 (e.g., trimethoprim) are not anticipated. Co-administration of montelukast with itraconazole, a strong inhibitor of CYP 3A4, resulted in no significant increase in the systemic exposure of montelukast.
Levocetirizine: No interaction studies have been performed with levocetirizine (including no studies with CYP3A4 inducers); studies with the racemate compound cetirizine demonstrated that there were no clinically relevant adverse interactions (with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole and pseudoephedrine). A small decrease in the clearance of cetirizine (16%) was observed in a multiple dose study with theophylline (400 mg once a day); while the disposition of theophylline was not altered by concomitant cetirizine administration.
In a multiple dose study of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), the extent of exposure to cetirizine was increased by about 40% while the disposition of ritonavir was slightly altered (-11%) further to concomitant cetirizine administration.
The extent of absorption of levocetirizine is not reduced with food, although the rate of absorption is decreased.
In sensitive patients, the concurrent administration of cetirizine or levocetirizine and alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.
Co-Altria Ped: 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, 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 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.

Store at temperatures not exceeding 30°C. Protect from light and moisture.

Antihistamines & Antiallergics

R03DC53 - montelukast, combinations ; Belongs to the class of leukotriene receptor antagonists. Used in the systemic treatment of obstructive airway diseases.

Rx