Leukotriene Modifiers

Leukotriene modifiers are oral medications that are normally prescribed as adjunctive therapy, to assist in decreasing bronchoconstriction and inflammation, when other anti-inflammatory medications are not able to produce the desired therapeutic effect. They are used in the treatment of allergic rhinitis, asthma, and exercise-induced bronchospasm.

Prototype and Other Medications

The prototype medication that we will use for leukotriene modifiers is montelukast. Other leukotriene modifiers that we’ll cover because of their adverse effects are zileuton and zafirlukast.

Expected Pharmacologic Action

Leukotrienes are mediators within the body’s immune system that cause allergic reactions such as inflammation of the air passages and mucus production. Leukotrienes modifiers work to suppress the effect of leukotrienes. Zileuton, a leukotriene inhibitor, decreases the number of leukotrienes available to cause inflammation. Montelukast and zafirlukast, leukotriene antagonists, decrease inflammation by preventing the activation of leukotrienes.

Adverse Drug Reactions

Two leukotriene modifiers may cause liver damage. These medications are zileuton, and less frequently, zafirlukast. This adverse effect, however, does not occur with montelukast, a medication that doesn’t commonly cause any untoward side effects. All the leukotriene modifiers carry the slight risk of adverse neuropsychiatric manifestations such as suicidal thoughts or behaviors.

Interventions

Leukotriene modifiers are not commonly associated with side effects, except for zileuton and zafirlukast. Because of this, there are fewer interventions the provider must take to ensure safe administration. However, because of the potential for liver damage in clients taking zileuton and zafirlukast, the provider must closely monitor the client’s liver function tests. Mild analgesics may be necessary for clients who experience headaches after administration.

Administration

Give the leukotriene modifier montelukast once daily in the evening. It is available as oral or chewable tablets and oral granules. When using the oral granules, clients can mix them in with applesauce, cooked carrots, rice, or ice cream, or they can place them directly on their tongues. If you give the medication to prevent EIB, make sure it is at least 2 hr before exercising. Also, tell the client not to take it again for 24 hr.

Client Instructions

Instruct clients taking zileuton or zafirlukast to report abdominal pain or tenderness, nausea, or anorexia immediately to their provider. For clients who report headaches after administration, encourage them to use over-the-counter analgesics as needed. Educate clients and family to be aware of any behavioral changes such as anxiety, agitation, insomnia, or irritability which could be indicative of neuropsychiatric adverse effects. Monitor clients for any behavioral changes indicating suicidal ideation or depression.

Safety Alert

Clients taking zileuton and zafirlukast are at risk for developing liver damage. Instruct them to report abdominal pain or tenderness, nausea, or anorexia immediately to their provider. To reduce risk of liver injury, instruct clients to have their liver function laboratory tests checked at regular intervals.

Contraindications and Precautions

Do not give zileuton and zafirlukast to clients who have liver dysfunction. This is not a contraindication for montelukast because it does not cause liver damage. In general, do not give leukotriene modifiers for acute asthma exacerbations or status asthmaticus because of the time it takes for the medication to take effect. Use leukotriene modifiers with caution in clients who have severe asthma because of the higher level of efficacy of other medication options.

Interactions

Leukotriene modifiers can interact with other medications. Clients taking phenobarbital, rifampin, or phenytoin may need higher doses of montelukast. Both zileuton and zafirlukast can increase levels of warfarin. Zileuton can also increase levels of theophylline and propranolol.

Safety Alert

Instruct clients to tell their provider that they are taking zileuton or zafirlukast. These medications interact with several types of other medications, particularly warfarin. Concurrent administration of zileuton and zafirlukast with warfarin can increase the anticoagulant effects of warfarin. This can cause bleeding and hemorrhage.