Drug Interactions- summary

CYP3A4 agents eg calcium blockers, cisapride, cyclosporine, ketoconazole +
Zileuton
use caution and careful monitoring when these agents are coadministered with zileuton

Zileuton + Pimozide -
Zileuton may inhibit pimozide metabolism whic may increase  the risk of life-threatening
cardiac arrhthmias

Zileuton + propranolol -
Coadministration   results in elevated propranolol concentration. Avoid coadministration.
Adjust dose of propranolol as needed

Zileuton + Terfenadine-
coadmin results in terfenadine concentration. Coadministration not recommended

Zileuton + theophyline-
coadmin results in increased theophylline concentration. Reduce dose of theophylline by
50% amd monitor theophylline comcentration

Zileuton + Warfarin-
coadmin results in clincaaly significant increase in prothrombin concentration.
Adjust warfarin dose.

Asthma

Adverse reactions-

Nausea  4% 

Pharyngolaryngeal pain  4%   

Siniusitis  6%

Acute liver disease or persistent transaminase elevations

Special precautions-

Acute asthma attacks-  Zileton is not indicated for reversal of bronchospasm in acute asthma attacks. Therapy can be continued during acute exacerbations of asthma

Hepatic effects- if clinical signs of liver dysfunction (eg. fatigue, flu like symptoms, jaundice,lethargy, nausea, pruritus, upper quadrant pain ) develop or transaminase levels of 5 or more X the ULN  occur, discontinue zileuton and follow levels until they return to normal. 

Pregnancy- zileuton should be used during pregnancy only if the potential benefit benefit
justifies the potential risk to fetus

Lactation- decide to discontinue breast feeding or the drug depending upon the importance
of the drug to the mother.

Children- safety and efficacy for use in children below 12 years of age have not been established

Elderly- older patients  appear to be at risk of ALT elevations

Monitoring- it is recommended that hepatic tansaminase be evaluated at initiation of treatment,
and during therapy with zileton .
Monitor serum ALT  before treatment begins , once  a month for the first 3 months,
every 2 o 3 times for the reminder of the year and periodically thereafter for patients
receiving long term therapy.

Indication-
Asthma

Dosage-
Two extended release tablets twice daily within 1 hour of morning and evening meals, for
a total daily dose of 2400mg 

Zileuton extended release tablets should not be chewed
If the dose is missed the next dose should be taken at the scheduled time and not double
the dose.

1. Inform patients that zileuton used for  chronic asthma  treatment, should be taken regularly

2. Inform patients that zileuton is not bronchodilator and should not be used to treat  episodes    of asthma

3. Advice patients if  the dose is missed the next dose should be taken at the scheduled time   and not double the dose.

4. Advice patients that zileuton extended release should be taken within 1 hour of morning and   evening meals

5.Advice patients not to cut or chew sustained release  formulation

6.Advice patients to seek medical attention if short acting bronchodilators are needed
   more often than usual or if more than the maximum number of short acting inhaltions
   prescribed for 24 hours are needed during treatment

7. Inform patients the most serious side effect of zileuton is elevation of liver enzymes tests
    and that while taking zileuton they must return to their health care provider  for liver                enzyme test  montoring on a regular basis.

8. Inform patients they must inform their Doctor if they experience signs andsymptoms of
    liver dysfunction  ( eg fatigue, lethargy, jaundice, nausea, pruritus, right upper quadrant         pain)

It is recommended that zileuton extended release be adminstered with food.

Pregnancy-
Zileuton should be used during pregnancy only if the potential benefit benefit
justifies the potential risk to fetus

Lactation-
Decide to discontinue breast feeding or the drug depending upon the importance
of the drug to the mother.

Children-
Safety and efficacy for use in children below 12 years of age have not been established

Elderly-
Older patients  appear to be at risk of ALT elevations