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In many of the respiratory diseases including asthma, Immunoglobulin E is the one which plays a major role in mediating an inflammatory process. Omalizumab a recombinant humanised monoclonal antibody that is developed for the treatment of these disorders and given to patients suffering with severe or persistent asthma. The type of dosage form available for the drug is 150mg of powder and also available in solvent for solution for injection. The recommended dose for xolair is 600mg and is administered subcutaneously for every two to four weeks. Omalizumab should be given to a patient tested for positive skin test, or in-vitro reactivity to an aero allergen, whose symptoms were inadequately controlled with inhaled corticosteroids, also who have a reduced lung function. The cost of the medication is high compared to other drugs used for asthma.
MECHANISM OF ACTION:
Omalizumab is a recombinant DNA derived humanised monoclonal antibody containing 5% murine sequence and 95% human sequence which selectively binds to human immunoglobulin (IgE). IgE plays an important role in allergic diseases by releasing histamine and other mediators from mast cells. It acts by inhibiting the immunoglobulin binding to a high affinity cepsilon 3 receptor present on mast cells and basophils which acts by binding to an epitope. The epitope to which it binds is sterically hindered by a receptor preventing an inadvertent anaphylactic reaction. The decrease in surface bound IgE results in decrease of release of mediators of allergic response. The structure of IgE molecule has three domains- CH2, CH3, CH4; binding site for cepsilon3 receptor is located in CH3 domain.
THERAPEUTIC INDICATIONS, POSOLOGY:
It is indicated in adolescents, children (6-11yrs of age), and adults. Omalizumab is given to the patients with severe asthma. The barrier to prevalent use is the injectable form which requires a physician's assistance and visiting the clinic every time. The frequency and appropriate dose is estimated by baseline IgE (IU/ml) before starting of therapy. Before starting of therapy the patients should be tested for IgE level. The xolair shows it effectiveness at least after 12-16 weeks of administration. The discontinuation of xolair treatment in middle results in rapid increase of free IgE levels and associated symptoms. The doses should be adjusted according to the body weight of the individual.
It should not be given to patients who have hypersensitivity reactions. The treatment is not usually recommended in environments where the presence of parasites is prevalent. Clinical studies have indicated a small increased risk of cancer when taking Omalizumab. Omalizumab may cause in increased risk of parasitic infections, like reportings of laryngeal oedema and angioedema have been occurred. Xolair is not preferred for treating acute bronchospasm or status asthmaticus, patients having hyper immunoglobulin E syndrome, or the allergic aspergillosis. Including those annoyed by allergic rhinitis, atopic dermatitis, food allergy, immune complex reactions, hepatic impairment. The other immune system disorders which are contraindicated are anaphylactic shock. Most of the allergic type 1 reactions occur within 2hours after the first and subsequent usage of xolair injections.
The special warnings related to xolair are allergic type3 reactions likes serum sickness etc. The preferred pathophysiology mechanism comprises of immune complex reactions and the average onset for this maximum of 5 days. The symptoms that are involved with serum sickness are urticarial, arthritis, fever, rash and lymphadenopathy. In addition to serum sickness some of the patients associated with severe asthma may also contain churg-strauss syndrome (allergic eosinophilic granulomatous vasculitis of which majorly the treatment done with systemic corticosteroids. For the above mentioned cases the physicians should check the development for rashes, cardiac complications, neuropathy, and Para nasal sinus abnormalities, etc.
During clinical trials few cases has reported for malignancies, and there was an imbalance in cancers related to xolair (0.5%). Malignancies found to be uncommon (<1/100) in both control and active group whereas the IgE is involved in the immunological response of some helminthic infections.
There has been reported a little possibility for drug-drug interactions, because cytochrome P450 enzymes, protein building mechanisms are not involved during clearance of Omalizumab. So far no vaccine interactions have been reported with Omalizumab. During clinical trials it was used along with inhaled and oral corticosteroids, antihistamines, long-acting beta agonists and theophylline modifiers. No specific data available for the use of Omalizumab during pregnancy, in case of animal trials no harmful effects has been observed during pregnancy or during post natal development. It causes the placental barrier but the harm to foetus is not known. During the xolair therapy woman should not breast feed child. No genotoxicity or impairment of fertility has been noticed.
The most commonly reported undesirable effects with Omalizumab in adults and older people are swelling, injection site reactions, injection site pains, pruritus, erythema and headache. In children with less than 12 years of age the most commonly reported adverse effects were abdominal pain, headache. The effects associated with Omalizumab are classified into common, very common, rare and unknown. Some of the diseases which fall under
Rare cases - Parasitic reaction, anaphylactic reaction, angioedema.
Unknown - Idiopathic severe thrombocytopenia, alopecia, arthralgia, myalgia, joint swelling, Churg-Strauss syndrome.
Common - Headache, upper abdominal pain.
Uncommon -Coughing, photosensitivity, nausea, allergic bronchospasm, postural hypotension, flushing, syncope, somnolence.
The maximum tolerated dose administered to patients was 44,000mg for a period of 20 weeks and this did not resulted in any untoward side effects.
Pharmacodynamics - The 28 week double-blind placebo study was demonstrated for safety and efficacy of xolair involving severe allergic asthmatics and reduced lung function patients. The rate of asthma exacerbations was reduced by Omalizumab up to 19%. Placebo controlled supportive studies have been conducted for a period of 28-52 weeks duration, the difference between treatment of two groups found to be 50%.
Pharmacokinetics - xolair is absorbed with a bioavailability of 62%. It was absorbed slowly after subcutaneous injection reaching peak serum concentration after an intermediate of 7-8 days. The apparent volume of distribution was found to be 78.32 ml/kg. It involves the specific IgG clearance through specific binding and complex formation with its target ligand. Serum elimination half-life was found to be 26 days.
ï¿½ Omalizumab powder
ï¿½ Histidine hydrochloride monohydrate
ï¿½ Polysorbate 20
ï¿½ Water for injections
SHELF-LIFE, STORAGE, CONTAINER HANDLING:
Shelf-life of Omalizumab was found to be 4 years. Do not freeze, should be store in refrigerator at (20C - 80C). It is available in form of powder in a colourless type 1 glass vial with blue flip-off seal. There are precautions for disposal and handling of Omalizumab, in general lyophilised medicinal product takes 15-20 minutes to dissolve. It may be slightly clear or opaque with small few bubbles or foam around the neck of vial. Xolair 150 mg powder for solution for injection is supplied in a single-use vial.
In conclusion, Omalizumab is a humanised monoclonal antibody important for the treatment of asthma. It plays a key role in obstructing the binding of IgE to mast cell and thus antedates the firing of immune mediators. When related to other drugs used for treatment of asthma, Omalizumab is more costly.