Combolin

Uses

Ipratropium Nebuliser Solution is used for a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema.

Levosalbutamol tablet is used for the treatment or prevention of bronchospasm in adults, adolescents, and children 6 years of age and older with reversible obstructive airway disease.

Levosalbutamol Nebuliser Solution or Inhaler is used for the treatment or prevention of bronchospasm in adults, adolescents, and children with reversible obstructive airway disease.

Combolin is also used to associated treatment for these conditions: Acute Exacerbation of Asthma, Asthma, Bronchospasm, Chronic Obstructive Pulmonary Disease (COPD), Nasal Congestion Associated With the Common Cold, Non-Allergic Rhinitis, Perennial Allergic Rhinitis (PAR), RhinitisBronchospasm

How Combolin works

Ipratropium acts as an antagonist of the muscarinic acetylcholine receptor. This effect produces the inhibition of the parasympathetic nervous system in the airways and hence, inhibit their function. The function of the parasympathetic system in the airway is to generate bronchial secretions and constriction and hence, the inhibition of this action can lead to bronchodilation and fewer secretions.

At the cellular level, the diameter of the airways is controlled by the release of acetylcholine into the muscle cells causing them to contract and producing a narrow airway. Thus administration of ipratropium stops the activity of acetylcholine in the smooth muscle preventing the contraction and producing relaxed airways.

β2 adrenergic receptors on airway smooth muscle are Gs coupled and their activation by levosalbutamol leads to activation of adenylate cyclase and to an increase in the intracellular concentration of 3',5'-cyclic adenosine monophosphate (cyclic AMP). Increased cyclic AMP activates protein kinase A which itself inhibits the phosphorylation of myosin produces lower intracellular ionic calcium concentrations, inducing muscle relaxation. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways, potentially contributing to its benefit in asthma attacks.

Dosage

Combolin dosage

Children over 3 years: The usual dose is 0.4-2.0 ml Ipratropium Bromide Solution (100-500 micrograms) up to three times daily.

Adults (including elderly and adolescents) over 12 years of age: The usual dose is 0.4-2.0 ml Ipratropium Bromide Solution (100-500 micrograms) up to four times daily.

Levosalbutamol Tablet-

• Adults and children above 12 years: 1-2 mg three times daily.
• Children (6 -11 years): 1 mg three times daily.

Syrup-

• Adults and children above 12 years: 5-10 ml three times daily.
• Children (6 -11 years): 5 ml three times daily.

Levosalbutamol Nebuliser Solution-

This Nebuliser Solutionis supplied in unit-dose ampoules and requires no dilution before administration by nebulization.

• Children (6 months-11 years): The recommended dosage is 0.31 mg administered three times a day, by nebulization. Routine dosing should not exceed 0.63 mg three times a day.
• Adults and Adolescents above 12 years old: The recommended starting dosage is 0.63 mg administered three to four times a day, every 6 to 8 hours, by nebulization.
• Patients 12 years of age and older with more severe asthma or patients who do not respond adequately: 0.63 mg of Levosalbutamol Nebuliser Solution may benefit from a dosage of 1.25 mg three times a day.

Levosalbutamol Inhaler-

You should take your Levosalbutamol Inhaler as needed for an asthma attack at any time of day, with or without food, by taking 1-2 puffs up to 4 times daily and no more than 8 puffs in 24 hours. If you are using your Levosalbutamol Inhaler more than 3-4 times a week this may indicate that your asthma is not well controlled and you may need to review your medication. You can also use your Levosalbutamol Inhaler to prevent allergy or exercise induced asthma by taking 2 puffs 15 minutes before exercise or exposure to a known allergen.

Side Effects

Allergic-type reactions such as skin rash, angio-oedema of the tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reactions have been reported, with positive rechallenge in some cases.

Potentially serious side effects like hypokalamia may result from ß-2 agonist therapy. This effect may be potentiated by hypoxia. The other likely side effects are gastrointestinal disturbances such as nausea, vomiting, burning substernal or epigastric pain and diarrhoea. In some cases nervousness, headache, dizziness, fatigue and sleeplessness may occur.

Toxicity

The reported LD50 in mice after oral administration of ipratropium is 1500 mg/kg. However, overdosage is not very likely due to the poor absorption of ipratropium.

Ipratropium was not shown to present carcinogenesis, teratogenesis not mutagenesis potential and it did not present effects on fertility. The only effect after high administration of ipratropium was a reduction in the conception rate.

Precaution

Ipratropium Bromide should be used with caution in patients predisposed to narrow-angle glaucoma, or with prostatic hyperplasia or bladder-neck obstruction.

Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations. Oral Levosalbutamol should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias or hypertension. Levosalbutamol can be used with caution after myocardial infarction.

Levosalbutamol Hydrochloride, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmias; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Levosalbutamol Nebuliser Solution or Inhaler must not be injected.

Interaction

Other short-acting sympathomimetic bronchodilators or epinephrine should be used with caution with Levosalbutamol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

Volume of Distribution

Ipratropium has a volume of distributions of 4.6 L/kg and hence, it is known to be highly distributed in the tissues.

Elimination Route

Ipratropium is a topically active but poorly absorbed agent. The lack of absorption potential in the mucosal surfaces is associated with the presence of a charge in the 5-valent nitrogen. The molecule itself presents very large topic effectiveness however, it does not produce detectable blood levels nor systemic effects.

Serum levels of ipratropium after oral or inhaled administration are very low, corresponding to only 1-2% of the administered dose. These low levels peak after 1-2 hours and it presents a low bioavailability of 2%.

Inhalation delivers the medication directly into the airways and lungs, thereby minimizing side effects because of reduced systemic absorption of the inhaled medications.

Half Life

Ipratropium presents a short half-life of about 1.6 hours.

3.3 - 4 hours

Clearance

The average clearance rate of ipratropium is of 2.3 L/min with a renal clearance of 0.9 L/min.

Elimination Route

About 80-100% of the administered dose of ipratropium is excreted in the urine leaving less than 20% of the dose to be eliminated through the feces. From the urine eliminated portion, almost all the drug is found unchanged.

However, when ipratropium is orally administered, due to its low absorption, most of the dose is recovered in the feces with a very minimal amount found in the urine.

excreted into the urine.

Pregnancy & Breastfeeding use

The safety of Ipratropium Bromide during human pregnancy has not been established. The benefits of using Ipratropium Bromide during a confirmed or suspected pregnancy must be weighed against possible hazards to the unborn child. It is not known whether Ipratropium Bromide is excreted into breast milk.

Use in pregnancy: Use of oral Levosalbutamol in pregnant women should be considered only if the expected benefit to the mother is greater than any possible risk to the foetus or the infant.

Use in lactation: It is not known whether Levosalbutamol is excreted in human milk. Caution should be exercised when oral Levosalbutamol is administered to a nursing woman.

Pregnancy: There are no adequate and well-controlled studies of Levosalbutamol Nebuliser Solution in pregnant women. Levosalbutamol Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether Levosalbutamol is excreted in human milk. Caution should be exercised when Levosalbutamol Nebuliser Solution is administered to a nursing woman.

Contraindication

Ipratropium Bromide solution should not be taken by patients with known hypersensitivity to atropine or its derivatives or to any other component of the product.

Levosalbutamol Nebuliser Solution is contraindicated in patients with a history of hypersensitivity to Levosalbutamol Hydrochloride or racemic salbutamol.

Acute Overdose

The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under side effects e.g., tachycardia, nervousness, headache, tremor, nausea, dizziness, fatigue and sleeplessness. Hypokalaemia also may occur. Treatment consists of discontinuation of oral Levosalbutamol together with appropriate symptomatic therapy. In the event of serious poisoning, the stomach should be emptied and, if necessary, a beta-blocker administered with caution in patients with a history of bronchospasm.

Storage Condition

Should be stored in cool and dry place

Store at cool and dry place. Protected from light and moisture. Keep out of the reach of children.

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