Medications for Allergy

Drug Approvals

(BANM, US Adopted Name, rINNM)

Note. Nedocromil Calcium is also USAN.

Adverse Effects and Precautions

Inhaled nedocromil sodium may cause headache, gastrointestinal disturbances (nausea, vomiting, dyspepsia, and abdominal discomfort). An unusual or unpleasant taste is reported rarely. Paradoxical bronchospasm may occur. Eye drops may cause transient burning and stinging.

It should not be used for the treatment of acute asthma attacks. The general cautions described under sodium cromoglicate also apply.

Incidence of adverse effects. A review of nedocromil sodium noted that adverse effects were infrequent, mild, and shortlived. The most common effect appeared to be an unpleasant or bitter taste, which was experienced by 12 to 13% of patients, although less than 1 % of patients stopped treatment because of it. Other adverse effects included cough (in 7%), headache (6%), sore throat (5.7%), nausea (4%), and vomiting (1.7%).

Pharmacokinetics

Nedocromil sodium is poorly absorbed from the gastrointestinal tract about 10% of the inhaled dose is absorbed from the lungs. Absorption is also poor after topical ophthalmic use, and occurs mainly through the nasal mucosa. Nedocromil sodium is excreted unchanged in the urine and faeces. The half-life is stated to range from about 1 to 3.3 hours.

The extent of absorption or bioavailability of nedocromil sodium after inhalation in healthy subjects was 7 to 9% of the dose, including 2 to 3% oral absorption and 5 to 6% absorption from the respiratory tract. After inhalation of nedocromil sodium 4 mg the mean peak plasma concentration was 3.3 nanograms/mL in healthy subjects and 2.8 nanograms/mL in asthmatic patients, with peak values being reached at about 20 and 40 minutes respectively. The mean total urinary excretion 24 hours after a single dose was 5.4% of the dose in healthy subjects and 2.3% in asthmatics.

Uses and Administration

Nedocromil sodium has a stabilising action on mast cells resembling that of sodium cromoglicate and is used similarly in the management of chronic asthma. It should not be used to treat an acute attack of asthma.

For asthma, nedocromil sodium is inhaled from a metered-dose aerosol. The usual dose for adults and children from 6 years of age is 4 mg inhaled four times daily which may be decreased to 4 mg twice daily after control of symptoms is achieved. Clinical improvement may not be obtained for 1 week or longer after beginning therapy.

Nedocromil sodium is also used topically in the treatment of allergic conjunctivitis and allergic rhinitis. For seasonal and perennial allergic conjunctivitis it is given as a 2% solution, instilled into each eye twice daily. This may be increased to 4 times daily if necessary, which is the usual dose in vernal keratoconjunctivitis. In seasonal allergic conjunctivitis, treatment is usually given for no more than 12 weeks. In allergic rhinitis nedocromil sodium is used as a 1 % nasal spray: one spray is given into each nostril 4 times daily. For details of doses in children, see Administration in Children, below.

Administration in children. Nedocromil sodium is given by metered-dose aerosol inhalation for the treatment of asthma in children from 6 years of age at the adult dose, see above. Although unlicensed in the UK for younger children, the BNFC recommends the same dose from 5 years of age. Similarly, for the topical treatment of seasonal allergic conjunctivitis and vernal keratoconjunctivitis, the adult dose may be given to children from 6 years of age, see above. Treatment of perennial allergic conjunctivitis with nedocromil sodium is not licensed in children in the UK, but the BNFC recommends adult doses from 6 years of age.

Asthma. Nedocromil sodium is generally considered to be an alternative to sodium cromoglicate in the management of asthma. Nedocromil has been shown to improve symptoms and reduce bronchodilator intake in adults and children with chronic asthma. However, a systematic review of nedocromil for chronic asthma in children subsequently found that although a number of small studies have shown that nedocromil improves airflow limitation, reduces symptoms, and reduces bronchial hyperresponsiveness, this has not been confirmed in a larger long-term study of children with milder asthma. Its place in relation to other asthma therapies for children is also unclear. It may be used before exercise to reduce exercise-induced bronchoconstriction, and appears to be as effective as sodium cromoglicate for this indication.

Cough. For references indicating a positive response to sodium cromoglicate but not to nedocromil sodium in the management of cough induced by ACE inhibitor therapy, see Cough.

Rhinitis and conjunctivitis. Nedocromil has been used in the management of allergic rhinitis and conjunctivitis. In the management of seasonal allergic rhinitis, there is some evidence that prophylactic mometasone furoate reduces symptoms more effectively than nedocromil. In vernal keratoconjunctivitis nedocromil may be more effective than cromoglicate, but is less effective than fluorometholone.

Preparations

Proprietary Preparations

Australia: Tilade

Austria: Tilade Tilarin Tilavist

Brazil: Tilade

Canada: Alocril Tilade

Czech Republic: Tilade Tilarin Tilavist

Denmark: Tilade Tilavist

Finland: Tilade Tilarin Tilavist †

France: Tilavist

Germany: Halamid † Irtan Tilade

Greece: Tilade

Hong Kong: Tilade

Hungary: Tilade

Ireland: Tilade Tilavist †

Israel: Tilade Tilavist

Italy: Kovilen Kovinal Tilade Tilarin Tilavist

Mexico: Irtan

The Netherlands: Tilade Tilavist

Norway: Tilavist

New Zealand: Tilade

Portugal: Tilavist

Russia: Tilade

Spain: Brionil Cetimil Tilad Tilavist

Sweden: Tilavist

Switzerland: Tilade Tilarin Tilavist

Turkey: Tilade

UK: Rapitil Tilade

USA: Alocril Tilade

Multi-ingredient

Italy: Zarent

1. How useful is nedocromil sodium (Tilarin) to people who suffer from year-round allergic rhinitis?

Nedocromil sodium nasal spray has proven efficacy against seasonal bouts of allergic rhinitis and is most effective when dosed regularly throughout the pollen seasons. People who are allergic to several pollens (birch, grass, ragweed, etc.) may suffer more than one bout of seasonal allergic rhinitis during the year and on each occasion nedocromil sodium nasal spray can be used with confidence throughout the period of exposure to pollen allergens. There is no evidence of any loss of activity with continued use, or of any accumulation of the drug in the body tissues. Information regarding the use of the nasal spray in non-seasonal (house dust) allergic rhinitis is limited at the present time.

2. Which symptoms are most and least affected by nedocromil sodium (Tilarin)?

In general, itching and running of the nose and sneezing are most rapidly improved by nedocromil sodium nasal spray; stuffy nose may be less readily affected in some patients.

3. Is nedocromil sodium more effective in milder cases of rhinitis, or can it help even the worst sufferers?

Our clinical trials were carried out in patients with mild or moderate allergic rhinitis, and nasal corticosteroids are recommended to control more severe symptoms. However, nedocromil sodium nasal spray used in combination with antihistamine tablets can be a very effective additive therapy for allergic rhinitis.

4. Is this primarily an asthma drug that’s also useful for allergic rhinitis, or is it a rhinitis drug that’s also useful for asthma?

Nedocromil sodium reduces the allergic inflammatory reaction which occurs after sensitive tissues are exposed to allergens such as pollen, but it is also effective against inflammatory reactions to non-specific stimuli such as chemical air pollutants. Because of its anti-inflammatory properties when applied to the surface of the affected tissue, whether in the lung, the nose or the eye, nedocromil sodium is useful in asthma, allergic rhinitis and allergic conjunctivitis.

It is important that a topical medication for the relief of allergy symptoms be well tolerated by patients, and not remain in circulation within the body for extended periods of time, where it might accumulate at harmful levels with repeated doses. The antiinflammatory drug Tilarin meets these requirements handsomely, and appears to also offer greater relief than the old standby sodium cromoglycate.

Tilarin is a solution of 1% nedocromil sodium, which is highly water-soluble but barely fat-soluble, making it ideally suited to topical use on mucous-covered surfaces such as nasal passages. Less than 8% of the nasal spray is absorbed into the system from the nasal mucosa, and even that is rapidly eliminated from the bloodstream.

The elimination of drugs from the circulation is measured by half-life in the same way as radiation. Nedocromil sodium has an elimination half-life of about five minutes, which means that when that time has elapsed any amount of the compound introduced in the bloodstream will have been reduced to half. After a further five minutes it will have been reduced again to a quarter of the original dose and so on. Most of it is then eliminated from the body in urine, and the remainder in bile, without being metabolized. This means that unless it is wildly overused, there is no danger of nedocromil sodium lingering in the blood and creating a cumulative systemic overdose.

Nedocromil sodium is also very unlikely to cause serious adverse reactions. It has no known human metabolite, meaning that it does not break down or transform into any other substance in the human body. A comparison of side-effects reported by Tilarin users showed that no significant differences existed between the drug and a harmless placebo, except in one category: it produced a distinctive taste in the mouth in about 7% of patients.

Twenty-eight studies have measured the efficacy of nedocromil sodium in treating SAR, mostly with similar results. The drug was found to reduce aggravating symptoms and nasal discharge, to score higher than placebo in patient and clinician appraisals of treatment outcomes, and to reduce the tendency of SAR sufferers to reach for antihistamines as a last line of defence.

Tilarin has been found effective by North American ragweed sufferers, Finnish birch pollen sufferers, and Italian grass pollen sufferers. Canadian and U.S. studies that sought to monitor Tilarin groups as they progressed from the beginning through the peak of the ragweed pollen season found great reductions in nasal discharge and antihistamine use

compared with placebo users, and an absolute reduction in sleep loss, even though pollen levels quadrupled during the study. A U.S. ragweed study compared Tilarin with sodium cromoglycate and found that it produced slightly lower symptom severity scores in all five categories: stuffy nose, runny nose, itchy nose, sneezing and sleep disturbance. Patient satisfaction was also higher in the Tilarin group. Sodium cromoglycate users, however, had less recourse to antihistamine rescue therapy.

An Italian study of the efficacy of Tilarin in treating grass pollen SAR found that symptom severity scores of Tilarin users during the four-week peak pollen period consistently fell while those of placebo users rose slightly. The Tilarin group, which had slightly worse average symptom scores when the study began, ended the trial period with severity scores less than half that of their placebo counterparts.

In conclusion, Tilarin has been shown to be a safe topical remedy for SAR symptoms both in adults and small children, without any of the potential side effects of topical steroids. It can be used regularly from the first day of the pollen season, but will also prove useful to patients who are already suffering. It reduces the need for antihistamines in most users, but if symptoms are not alleviated by Tilarin alone, it is safe to use in conjunction with any other SAR medication.