V. IDENTIFICACIÓN, DESCRIPCIÓN Y EVALUACIÓN DE LOS IMPACTOS
V.1. METODOLOGIA PARA IDENTIFICAR Y EVALUAR LOS IMPACTOS
V.1.1. Indicadores de impacto
Description
Axodin (Fexofenadine), a pharmacologically active metabolite of Terfenadine, is a non-sedating antihistamine with selective peripheral H1 receptor antagonist activity.
Fexofenadine Hydrochloride is rapidly absorbed into the body following oral administration, with Tmaxoccurring at approximately 1-3 hours post dose. The mean Cmaxvalue was approximately 427 ng/ml and 494 ng/ml
following the administration of a 120 mg and 180 mg dose (once daily) respectively.
Fexofenadine is 60-70% plasma protein bound. Fexofenadine undergoes negligible metabolism, as it was the only major compound identified in urine and faeces of animal and human. The plasma concentration profiles of Fexofenadine follow a bi-exponential decline with a terminal elimination half-life ranging from 11 to 16 hours after multiple dosing. The single and multiple dose pharmacokinetics of Fexofenadine are linear between 40 mg and 240 mg taken daily. The major route of elimination is believed to be via biliary excretion while up to 10% of ingested dose is excreted unchanged through the urine.
Indications
Axodin is indicated for the relief of symptoms associated with allergic rhinitis and allergic skin conditions e.g. chronic urticaria.
Dosage and Administration ♦Allergic rhinitis
Children 6 to 11 years
The recommended dose of Fexofenadine Hydrochloride is 30 mg twice daily.
Adults and children aged 12 years and over
The recommended dose of Fexofenadine Hydrochloride for adults and children aged 12 years and over is 120 mg once daily.
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♦Allergic skin conditions, e.g. chronic urticaria
Children 6 to 11 years
The recommended dose of Fexofenadine Hydrochloride is 30 mg twice daily.
Adults and children 12 years and over
The recommended dose of Fexofenadine Hydrochloride for adults and children aged 12 years and over is 180 mg once daily.
Children under 6 years of age
The efficacy and safety of Fexofenadine Hydrochloride has not been studied in children under 6.
Use in Special Risk Group
Studies in special risk groups (elderly and patients with renal or hepatic impairment) indicate that it is not necessary to adjust the dose of Fexofenadine Hydrochloride in these patients.
Contraindication
The product is contraindicated in patients with known hypersensitivity to any of its ingredients.
Drug Interactions
Fexofenadine does not undergo hepatic bio-transformation and is therefore unlikely to interact with drugs that rely upon hepatic metabolism. Fexofenadine Hydrochloride at doses of 120 mg twice daily has been safely co-administered with Erythromycin (500 mg three times daily) and Ketoconazole (400 mg once daily) under steady state conditions in healthy volunteers. A two fold increase in the level of plasma Fexofenadine was observed after co-administration of Erythromycin or Ketoconazole but this was not associated with any increase in adverse event or effects on the QT interval, compared to that seen when the drugs were given alone.
Animal studies have shown that the increase in plasma level of Fexofenadine observed after co-administration of Erythromycin or Ketoconazole appears to be due to an increase in gastrointestinal absorption.
Side Effects
In placebo-controlled trials, adverse events were comparable in Fexofenadine and placebo treated patients. Adverse events reported with Fexofenadine include-
Common : headache, Uncommon : fatigue, drowsiness, nausea, tachycardia,
palpitations, dry mouth, dyspepsia and gastrointestinal disturbances (including diarrhoea), Rare : taste, disturbances, anaphylactic reactions,
dyspnoea, chest tightness, increased hair loss/hair thinning, photosensitivity, dysmenorrhoea, menstrual disorders, Others : As with
other non-sedating antihistamines, dizziness, nervousness, agitation, sleep disorders, insomnia or paroniria may infrequently be reported by patients. The incidence of such reports under Fexofenadine was similar to the incidence under placebo.
Effects on ability to Drive and Use Machines
On the basis of the pharmacodynamics profile and reported adverse events it is unlikely that Fexofenadine Hydrochloride will produce an effect on the ability to drive or use machines. In objective tests, Fexofenadine Hydrochloride has been shown to have no significant effects on central nervous system function. This means that patients may drive or perform tasks that require concentration.
Overdosage
Most reports of Fexofenadine Hydrochloride overdose contain limited information. However, dizziness, drowsiness and dry mouth have been reported. Single doses up to 800 mg and doses up to 690 mg bid for 1 month or 240 mg qid for 1 year were studied in healthy subjects without the development of clinically significant adverse events as compared to placebo.
Use in Pregnancy and Lactation
Fexofenadine should be used in pregnancy only if the potential benefit outweighs the potential risk to the foetus. 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 Fexofenadine is not recommended for mothers breast feeding their babies.
73 Pharmaceutical Precautions
Store in cool and dry place. Keep away from children. Commercial Pack
Axodin 60 Tablet : Each tablet contains Fexofenadine Hydrochloride 60 mg in 10 x 5 blister strips.
Axodin 120 Tablet : Each tablet contains Fexofenadine Hydrochloride 120 mg in 10 x 5 blister strips.
Axodin 180 Tablet : Each tablet contains Fexofenadine Hydrochloride 180 mg in 10 x 3 blister strips.
Azithrocin
®Capsule/Tablet/Suspension
Description
Azithrocin contains Azithromycin USP. It is an azalide antibiotic active against Gram-positive and Gram-negative organisms. Azithromycin interferes with ribosome function in susceptible bacteria by inhibiting the translocation of peptides.
Indications
Azithrocin (Azithromycin) is indicated for infections caused by susceptible organisms, in upper respiratory tract infections including sinusitis, pharyngitis and tonsillitis, in lower respiratory tract infections including bronchitis and pneumonia, skin and soft tissue infections, and otitis media.
Azithrocin is indicated in the treatment of uncomplicated genital infections due to Chlamydia trachomatis.
Dosage and Administration
Adult : Azithrocin should be given as 500 mg once-daily orally for 3 days or as an alternative, given over 5 days with 500 mg on day 1, then 250 mg on days 2-5.
For sexually transmitted diseases caused by Chlamydia trachomatis in adults,
the dose is 1 g given as a single dose.
Normal adult dose is recommended for elderly patients.
For children over 6 months recommended dose is 10 mg/kg once daily for 3 days; or if body weight is 15-25 kg : 200 mg once daily for 3 days, if body weight is 26-35 kg : 300 mg once daily for 3 days, if body weight is 36-45 kg : 400 mg once daily for 3 days.
As common with many other antibiotics, Azithrocin should be taken at least 1 hour before or 2 hours after meal and antacid.
75 Contraindication
Azithromycin is contraindicated in patients hypersensitive to Azithromycin or any other macrolide antibiotic. Co-administration of ergot derivatives and Azithromycin is contraindicated. Azithromycin is contraindicated in patients with hepatic diseases.
Side Effects
Azithromycin is well tolerated with a low incidence of side effects. Majority of the side effects were mild to moderate in nature and of gastrointestinal in origin with nausea, abdominal discomfort, vomiting, flatulence and diarrhoea. Allergic reactions such as rash have occurred and there have also been rare reports of serious hypersensitivity reactions. Reversible elevations in liver transaminases have been seen with a frequency similar to the comparative macrolides and penicillins used in clinical trials. Transient mild reductions in neutrophil counts have occasionally been observed in clinical trials, although a causal relationship to Azithromycin has not been established.
Precautions
As with any antibiotic, observation for signs of superinfection with non- susceptible organisms, including fungi, is recommended. No dose adjustment is needed in patients with renal impairment.
Use in Pregnancy and Lactation
Animal reproduction studies have demonstrated that Azithromycin crosses the placenta, but have revealed no evidence of harm to the foetus. There are no adequate and well controlled studies in pregnant women. Since animal reproduction studies are not always predictive of human response, Azithromycin should be used during pregnancy only if adequate alternatives are not available. No data on secretion of Azithromycin in breast milk is available, so, Azithromycin should only be used in lactating mothers where adequate alternatives are not available. Drug Interactions
Azithromycin absorption is reduced in presence of food and antacid. So, Azithromycin should be administered 1 hour before or 2 hours after taking food or antacid. In patients receiving ergot alkaloids, Azithromycin should be avoided concurrently because of the possibility of ergotism resulting from interaction of Azithromycin with the cytochrome P450
system. However, no cases of such interaction have been reported. Macrolides have been known to increase the plasma concentration of Digoxin and Cyclosporin. Therefore, if co-administration is necessary, caution should be exercised and serum level of Digoxin and Cyclosporin should be checked. There have been no pharmacokinetic drug interactions between Azithromycin and Warfarin, Theophylline, Carbamazepine, Methylprednisolone and Cimetidine.
Overdosage
There is no data on overdosage with Azithromycin. Typical symptoms of overdosage with macrolide antibiotics include hearing loss, severe nausea, vomiting and diarrhoea. Gastric lavage and general supportive measures are indicated.
Commercial Pack
Azithrocin Capsule : Box containing 1 x 10’s blister strip, each capsule contains Azithromycin USP equivalent to 250 mg anhydrous Azithromycin.
Azithrocin 500 Tablet : Box containing 1 x 3’s blister strip, each film coated tablet contains Azithromycin USP equivalent to 500 mg anhydrous Azithromycin.
Azithrocin Suspension : Dry powder in glass bottle for reconstitution into 15 ml of suspension. After reconstitution each 5 ml contains Azithromycin USP equivalent to 200 mg anhydrous Azithromycin.
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Azmasol
®Inhaler
Description
Salbutamol BP, the active ingredient of Azmasol Inhaler, is a ß2-
adrenoceptor agonist used in the treatment of asthma and other forms of diffuse reversible airways obstruction.
Indications
Azmasol (Salbutamol) inhaler is indicated for the treatment and prophylaxis of bronchial asthma and for the treatment of reversible airways obstruction associated with bronchitis and emphysema. Azmasol inhaler may be used to relieve attacks of acute dyspnoea and may also be taken prophylactically before exertion or to prevent exercise-induced- asthma. It is suitable for treating bronchospasm in patients with coexisting heart disease or hypertension, including those taking β- blockers, because of its selective action on the bronchial receptors and lack of effects on the cardiovascular system. Salbutamol is a sympathomimetic agent which has a highly selective action on β- adrenergic receptors in bronchial muscle. At therapeutic levels, it has little effect on cardiac receptors.
Dosage and Administration Adults
i) For the relief of acute bronchospasm and for managing intermittent episodes of asthma : one or two inhalation as a single dose
ii) For chronic maintenance or prophylactic therapy : two inhalations three or four times daily
iii) For prevention of exercise induced bronchospasm : two inhalations before exertion.
Children
For relief of acute bronchospasm, management of episodic asthma and for prevention of exercise induced bronchospasm : one inhalation; for routine maintenance and prophylaxis : one inhalation three or four times daily, increasing if necessary to two inhalations three or four times daily.
Elderly
The dosage is the same as that for adults. Contraindication
Although intravenous Salbutamol, and occasionally Salbutamol tablets, are used in the management of premature labour uncomplicated by conditions such as placenta praevia, ante-partum haemorrhage or toxaemia of pregnancy, Salbutamol inhaler preparations are not appropriate for managing premature labour. Salbutamol preparation should not be used for threatened abortion during the first or second trimesters of pregnancy. Salbutamol inhaler is contraindicated in patients with a history of hypersensitivity to any of its components.
Precautions
In the event of previously effective dose of Salbutamol inhaler failing to give relief for at least three hours, the patient should be advised to seek medical advice in order that any necessary additional steps may be taken. Salbutamol should be administered cautiously to patients suffering from thyrotoxicosis.
As with other inhalation therapy, the potential for paradoxical bronchospasm should be kept in mind. If it occurs, the preparation should be discontinued immediately and alternative therapy should be instituted.
Side Effects
Mild tremor and headache have been rarely reported. These usually disappear with continuous treatment. There have been very rare reports of transient muscle cramp. Hypersensitivity reactions including angioedema, urticaria, bronchospasm, hypotension and collapse have been reported very rarely.
Pharmaceutical Precaution
Pressurized canister, do not puncture, break or incinerate even when apparently empty.
Avoid storage in direct sunlight or heat. Store below 30°C. Keep away from eyes. Keep away from children.
79 Commercial Pack
Azmasol Inhaler : Each canister contains 200 measured doses, each containing 100 µg of Salbutamol BP.
Azmasol Refill Can : Each canister contains 200 measured doses, each containing 100 µg of Salbutamol BP.
Bexidal
®Tablet
Description
Each tablet contains Mebhydrolin 50 mg as Mebhydrolin Napadisylate BPC.
Indications
Allergic diseases or symptoms, such as urticaria, pruritus of various origin, eczema, drug rash, allergic conjunctivitis, dermatitis of nutritional origin, hay fever, vasomotor rhinitis, allergic asthma.
Dosage and Administration
Unless otherwise prescribed, the following doses are recommended: Adults and children over 10 years ... 2-6 tablets daily Children from 5-10 years ... 2-4 tablets daily Children from 2-5 years ... 1-3 tablets daily Children up to 2 years ... 1-2 tablets daily
Treatment should be given in several single doses daily. Bexidal may be swallowed during or shortly after meals. For children, the tablets may be crushed and mixed with food.
Bexidal is essentially free from secondary sedative-hypnotic effects. It does not impair psycho-physical efficiency to any appreciable degree. Contraindication
♦Caution is required while driving or operating heavy machinery ♦Concomitant use of CNS depressant or alcohol
♦Patients to whom Mebhydrolin has previously been suspected to have agranulocytosis or neutropenia
♦First trimester of pregnancy Commercial Pack
Bexidal Tablet : Box containing 20 aluminium strips of 10 tablets. Each tablet contains Mebhydrolin 50 mg as Mebhydrolin Napadisylate BPC.
81
Bexitrol-F
®Inhaler
Description
Bexitrol-F metered dose inhaler is a combination of Salmeterol Xinafoate INN and Fluticasone Propionate BP. Salmeterol Xinafoate is a selective, long acting β2agonist used in the treatment of asthma and other forms of diffuse airways obstruction. Fluticasone Propionate is a corticosteroid with mainly glucocorticoid activity. Fluticasone Propionate is stated to exert a topical effect on the lungs without systematic effects at usual dose. Indications
Bexitrol-F is indicated in the regular treatment of asthma where use of a combination product (long-acting β2agonist and inhaled corticosteroid)
is appropriate. Other indication of Bexitrol-F is patients with frequent asthmatic episodes requiring bronchodilators or those with asthmatic episodes at night.
Pharmacodynamic Properties
Mechanism of action : Bexitrol-F contains Salmeterol and Fluticasone Propionate, which have different modes of action. Salmeterol protects against symptoms, Fluticasone Propionate improves lung function and prevents exacerbations of the condition. Bexitrol-F can offer a more convenient regime for patients on concurrent β-agonist and inhaled corticosteroid therapy. The mechanisms of action of both drugs are discussed below:
Salmeterol : Salmeterol is a selective long-acting (12 hour) β2-
adrenoceptor agonist with a long side chain which binds to the exo-site of the receptor.
Fluticasone Propionate : Fluticasone Propionate given by inhalation at recommended doses has a potent glucocorticoid anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma, without the adverse effects observed when corticosteroids are administered systemically.
Recommended Doses
Adults and adolescents 12 years and older-
The recommended dose is two puffs of Bexitrol-F twice daily or as prescribed by the physicians.
Contraindication
Bexitrol-F is contraindicated in patients with a history of hypersensitivity to any of the ingredients of the product.
Special Warning and Precautions
Consideration should be given to additional corticosteroid therapies, and administration of antibiotics if an infection is present. As with all inhaled medication containing corticosteroids, Bexitrol-F should be administered with caution in patients with active or quiescent pulmonary tuberculosis. Bexitrol-F should be administered with caution in patients with thyrotoxicosis. Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to paediatric patients. The long-term effects of this reduction including the impact of final adult height are unknown.
Drug Interactions
Both non-selective and selective β-blockers should be avoided in patients with asthma, unless there are compelling reasons for their use. Due to the very low plasma concentrations achieved after inhaled dosing clinically significant drug interactions are unlikely. Care should be taken when co- administering known strong CYP3A4 (cytocrome P450 3A4) inhibitors (e.g. Ketoconazole, Ritonavir), as there is potential for increased systemic exposure to Fluticasone Propionate.
Use in Pregnancy and Lactation
There is insufficient experience of the use of Salmeterol Xinafoate and Fluticasone Propionate in human pregnancy and lactation. There are no data available for human breast milk.
Administration of drugs during pregnancy and lactation should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus or child.
83 Side Effects
As Bexitrol-F contains Salmeterol and Fluticasone Propionate, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no incidence of additional adverse events following concurrent administration of the two compounds. Adverse events, which have been associated with Salmeterol or Fluticasone Propionate, are given below.
Salmeterol : The pharmacological side effects of β2agonist treatment, such as tremor, subjective palpitations and headache, have been reported, but tend to be transient and reduced with regular therapy. Cardiac arrhythmia (including atrial fibrillation, supraventricular tachycardia and extra systoles) may occur, usually in susceptible patients. There have been reports of oropharyngeal irritation, arthralgia and hypersensitivity reactions, including rash, oedema and angioedema. There have been rare reports of muscle cramps.
Fluticasone Propionate : Hoarseness and candidiasis (thrush) of the mouth
and throat can occur in some patients. Both hoarseness and incidence of candidiasis may be relieved by gargling with water after use of Bexitrol-F Inhaler. Cutaneous hypersensitivity reactions have been reported. Rare cases of facial and oropharyngeal oedema have been reported.
Overdosage
There are no data available from clinical trials on overdosage with this combination drug.
Pharmaceutical Precaution
Pressurized canister, do not puncture, break or incinerate even when apparently empty. Avoid storage in direct sunlight or heat.
Store below 30oC. Keep away from eyes. Keep away from children. Commercial Pack
Bexitrol-F Inhaler : Each canister contains 120 metered doses, each containing Salmeterol Xinafoate INN equivalent to 25 µg Salmeterol and Fluticasone Propionate BP 250 µg.
Bexitrol
®Inhaler
Description
Salmeterol Xinafoate INN, the active ingredient of Bexitrol Inhaler, is a selective, long acting ß2-agonist used in the treatment of asthma and other forms of diffuse airways obstruction. Bexitrol Inhaler is a metered dose aerosol unit containing a micro-crystalline suspension of Salmeterol in a mixture of propellant with lecithin.
Indications
Bexitrol (Salmeterol) is a long-acting ß2-agonist which is considerably more potent, selective and long-acting compared with traditionally used bronchodilators. Bexitrol protects against asthma induced by histamine or methacholine for a period of at least 12 hours in adults and children. Furthermore, long-acting ß2-agonist show a more than 4-fold greater potency than short-acting agents (for example, Salbutamol) against histamine-induced bronchoconstriction. Bexitrol has the potential to improve the treatment of patients with asthma; the drug provides prolonged bronchodilation and decrease asthma symptoms and the need for short acting ß2-agonist, independently of concomitant steroid use.
Studies have consistently reported improved control of nocturnal asthma with long-acting ß2-agonist compared with other anti-asthma drugs. Bexitrol is indicated for the long term regular treatment of reversible airways obstruction (including nocturnal and exercise-induced asthma) and chronic bronchitis. In paediatric asthma, the use of Bexitrol may avoid exposure of children to Theophylline or high-dose corticosteroids, with their attendant risks.
Dosage and Administration
The recommended dose is 50 µg (2 puffs) twice daily, although in severe disease the dose may be increased to 100 µg twice daily. The drug should not be used on an ‘as required’ basis, although on account of its efficacy