M Cold Plus Cz

Uses

Cetirizine is used for the treatment of seasonal allergic rhinitis and conjunctivitis, perennial allergic rhinitis, pruritus and urticaria. It is also used in allergen induced asthma.

Levocetirizine Dihydrochloride is used for the treatment of symptoms associated with allergic conditions such as seasonal allergic rhinitis, perennial allergic rhinitis and chronic idiopathic urticaria.

Phenylephrine is an alpha-1 adrenergic agonist used in the management of hypotension, generally in the surgical setting associated with the use of anesthetics.

Phenylephrine injections are indicated to treat hypotension caused by shock or anesthesia, an ophthalmic formulation is indicated to dilate pupils and induce vasoconstriction, an intranasal formulation is used to treat congestion, and a topical formulation is used to treat hemorrhoids. Off-label uses include situations that require local blood flow restriction such as the treatment of priapism.

M Cold Plus Cz is also used to associated treatment for these conditions: Chronic Idiopathic Urticaria, Flu caused by Influenza, Perennial Allergic Rhinitis (PAR), Pollen Allergy, Respiratory Allergy, Seasonal Allergic RhinitisAllergic Rhinitis (AR), Chronic Idiopathic Urticaria, Common Cold, Nasal Congestion, Perennial Allergic Rhinitis (PAR), Seasonal Allergic RhinitisAllergic Rhinitis (AR), Anorectal discomfort, Cold, Common Cold, Common Cold/Flu, Congestion of the Conjunctivas, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Eye allergy, Eye redness, Fever, Flu caused by Influenza, Headache, Headache caused by Allergies, Headache caused by Common Cold, Headache caused by Pollen Allergy, Hemorrhoids, Hypotension, Irritative cough, Itching of the nose, Itching of the throat, Laryngotracheitis, Nasal Congestion, Nose discomfort, Ocular Inflammation, Ocular Irritation, Paroxysmal Supraventricular Tachycardia, Pollen Allergy, Respiratory tract congestion, Respiratory tract irritation, Rhinopharyngitis, Rhinorrhoea, Seasonal Allergies, Shock, Cardiogenic, Sinus Congestion, Sinus pressure, Sinusitis, Sneezing, Sore Throat, Tracheobronchitis, Upper respiratory tract hypersensitivity reaction, site unspecified, Vasomotor Rhinitis, Aching caused by Flu caused by Influenza, Bronchial congestion, Itchy throat, Minor aches and pains, Watery itchy eyes, Airway secretion clearance therapy, Antihistamine, Dilatation of the pupil, Vasoconstrictor in regional analgesia therapy

How M Cold Plus Cz works

Cetirizine, a metabolite of hydroxyzine, is an antihistamine drug. Its main effects are achieved through selective inhibition of peripheral H1 receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models. In vivo and ex vivo animal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors other than the H1 receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain. Ex vivo studies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H1 receptors significantly .

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.

Phenylephrine is an alpha-1 adrenergic agonist that mediates vasoconstriction and mydriasis depending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha-1 adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance. Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia.

Dosage

M Cold Plus Cz dosage

Tablet:

• Adults and children over 6 years: 1 tablet (10 mg) once daily or ½ tablet twice daily.
• Children 2-6 years: ½ tablet once daily.

Syrup:

• Adults and children over 6 years: 2 teaspoonful (10 mg) once daily or 1 teaspoon (5 mg) twice daily.
• Children 2-6 years: 1 teaspoonful once daily or ½ teaspoon twice daily.

Adults and children 12 years of age and older: 5 mg once daily in the evening

Children 6 to 11 years of age: 2.5 mg once daily in the evening

Children 6 months to 5 years of age: 1.25 mg (1/2 teaspoon oral solution) once daily in the evening

Renal Impairment: Adjust the dose in patients 12 years of age and older with decreased renal function

Side Effects

Cetirizine dihydrochloride is well tolerated. Lower incidence of sedation, headache, dry mouth, and gastrointestinal disturbances may occur. It does not produce anticholinergic effects.

The most common adverse reactions (rate ≥2% and > placebo) were somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis in subjects 12 years of age and older, and pyrexia, somnolence, cough, and epistaxis in children 6 to 12 years of age. In subjects 1 to 5 years of age, the most common adverse reactions (rate ≥2% and > placebo) were pyrexia, diarrhea, vomiting, and otitis media. In subjects 6 to 11 months of age, the most common adverse reactions (rate ≥3% and > placebo) were diarrhea and constipation.

Toxicity

Oral LD50 (rat): 365 mg/kg; Intraperitoneal LDLO (mouse): 138 mg/kg; Oral TDLO (rat): 50 mg/kg; Oral TDLO (mouse): 0.1 mg/kg .

Carcinogenesis and mutagenesis: In a 2-year carcinogenicity study in rats, cetirizine was not shown to be carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults). In a 2-year carcinogenicity study in mice, cetirizine administration lead to an incidence of benign liver tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults). The clinical significance of these findings during long-term use of cetirizine is unknown at this time .

Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and in vivo micronucleus test in rats .

Impairment of fertility

In a fertility and reproduction study in mice, cetirizine did not negatively impact fertility at an oral dose of 64 mg/kg (approximately 25 times the maximum recommended daily oral dose in adults) .

Pregnancy Category B:

In mice, rats, and rabbits, cetirizine was not teratogenic at oral doses up to 96, 225, and 135 mg/kg, respectively (approximately 40, 180 and 220 times the maximum recommended daily oral dose in adults). There are no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, cetirizine should be used in pregnancy only if clearly needed .

Use in breastfeeding/nursing

Cetirizine has been reported to be excreted in human breast milk. The use of cetirizine in nursing mothers is not recommended .

Patients experiencing an overdose may present with drowsiness. Children may become agitated and restless before drowsiness. Patients should be treated with supportive measures. Dialysis will not assist in removing the drug from the body.

The maximal nonlethal dose in mice and rats is 240mg/kg.

Patients experiencing and overdose may present with headache, hypertension, reflex bradycardia, tingling limbs, cardiac arrhythmias, and a feeling of fullness in the head. Overdose may be treated by supportive care and discontinuing phenylephrine, chronotropic medications, and vasodilators. Subcutaneous phentolamine may be used to treat tissue extravasation.

Precaution

Caution should be exercised when driving a car or operating a heavy machinery. Concurrent use of cetirizine with alcohol or other CNS depressants should be avoided because additional reduction in alertness and CNS performance may occur.

Epileptic patients and patients at risk of convulsions. Renal impairment. Pregnancy and lactation.

Interaction

No clinically significant drug interactions have been found with theophylline, azithromycin, pseudoephedrine, ketoconazole or erythromycin and with some other drugs.

Volume of Distribution

Apparent volume of distribution: 0.44 +/- 0.19 L/kg .

The volume of distribution of levocetirizine is 0.33±0.02L/kg.

The volume of distribution of phenylephrine is 340L.

Elimination Route

Cetirizine was rapidly absorbed with a time to maximum concentration (Tmax) of about 1 hour after oral administration of tablets or syrup formulation in adult volunteers . Bioavailability was found to be similar between the tablet and syrup dosage forms. When healthy study volunteers were given several doses of cetirizine (10 mg tablets once daily for 10 days), a mean peak plasma concentration (Cmax) of 311 ng/mL was measured .

Effect of food on absorption

Food had no effect on cetirizine exposure (AUC), however, Tmax was delayed by 1.7 hours and Cmax was decreased by 23% in the fed state .

Following a 5mg oral dose of levocetirizine, a C_max of 0.27±0.04µg/mL with a T_max of 0.75±0.50h. The AUC of levocetirizine is 2.31±0.50µg*h/mL. Taking levocetirizine with food does not affect the AUC but delays T_max by 1.25 hours and lowers C_max by 36%.

Phenylephrine is 38% orally bioavailable. Clinically significant systemic absorption of ophthalmic formulations is possible, especially at higher strengths and when the cornea is damaged.

Half Life

Plasma elimination half-life is 8.3 hours .

The average half life of levocetirizine is 7.05±1.54 hours.

Intravenous phenylephrine has an effective half life of 5 minutes and an elimination half life of 2.5 hours.

Clearance

Apparent total body clearance: approximately 53 mL/min .

Cetirizine is mainly eliminated by the kidneys , . Dose adjustment is required for patients with moderate to severe renal impairment and in patients on hemodialysis .

The average clearance of levocetirizine is 0.57±0.18mL/min/kg.

Phenylephrine has an average clearance of 2100mL/min.

Elimination Route

Mainly eliminated in the urine , .

Between 70 – 85% of an orally administered dose can be found in the urine and 10 – 13% in the feces .

168 hours post dose an average of 85.4% of a radiolabeled dose was recovered with an average of 80.8% in the urine and 9.5% in the feces. In the urine, 77% of the dose was recovered as unchanged drug, 0.5% as the M8 and M9 metabolites, 0.4% as the M10a metabolite, 0.4% as the M10b metabolite, 0.3% as the M3 metabolite, 0.3% as the M4 and M5 metabolite, 0.2% as the M2 metabolite, and 0.1% as the M1 metabolite. In the feces, 9.0% of the dose was recovered as unchanged drug, 1.0% as the M4 and M5 metabolite, and 0.1% as the M1 metabolite.

86% of a dose of phenylephrine is recovered in the urine with 16% as the unmetabolized drug, 57% as the inactive meta-hydroxymendelic acid, and 8% as inactive sulfate conjugates.

Pregnancy & Breastfeeding use

Pregnancy category B. There are no adequate and well controlled studies in pregnant women. Cetirizine should be used during pregnancy only if clearly needed. Cetirizine has been reported to be excreted in human breast milk. As large amount of drugs are excreted in human milk, use of Cetirizine in nursing mother is not recommended.

Pregnancy: The safety of Levocetirizine in pregnancy has not been established. Therefore, it should be used with caution during pregnancy and only if the potential benefits to the mother outweigh any risks to the foetus.

Lactation: Levocetirizine passes into breast milk. So, it should be used with caution in nursing mothers and only if the expected benefit to the mother is greater than the risk to the nursing infant.

Contraindication

Cetirizine Dihydrochloride is contraindicated in those patients with a known hypersensitivity to it or any of its ingredients or hydroxyzine.

It is contraindicated in patients who are hypersensitive to this medication or to any of its ingredients.

Special Warning

Paediatric use: Not recommended for use in children less than 6 years of age.

Acute Overdose

Symptoms: Confusion, dizziness, fatigue, headache, malaise, restlessness, sedation, somnolence, diarrhoea, mydriasis, pruritus, stupor, tachycardia, tremor, and urinary retention.

Management: Symptomatic and supportive treatment. Gastric lavage may be done shortly following ingestion.

Symptoms: Drowsiness, agitation, restlessness, confusion, diarrhoea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, sedation, somnolence, stupor, tachycardia, tremor and urinary retention.

Management: Symptomatic and supportive treatment. Gastric lavage must be considered shortly following ingestion.

Storage Condition

Store between 20-25°C. Syrup: Store between 2-8°C.

Store between 20-25°C.

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