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Zyflo CR Side Effects

Generic Name: zileuton

Note: This page contains side effects data for the generic drug zileuton. It is possible that some of the dosage forms included below may not apply to the brand name Zyflo CR.

More frequent side effects include dyspepsia. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to zileuton: oral tablet, oral tablet extended release

As well as its needed effects, zileuton (the active ingredient contained in Zyflo CR) may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking zileuton, check with your doctor immediately:

  • Flu-like symptoms
  • itching
  • right upper stomach pain
  • unusual tiredness or weakness
  • yellow eyes or skin
Incidence not known
  • Attack, assault, or force
  • attempts at killing oneself
  • discouragement
  • dry mouth
  • fear or nervousness
  • feeling sad or empty
  • hyperventilation
  • irregular heartbeats
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • restlessness
  • seeing, hearing, or feeling things that are not there
  • shakiness in the legs, arms, hands, or feet
  • shortness of breath
  • sleeplessness
  • tiredness
  • trembling or shaking of the hands or feet
  • trouble with concentrating
  • trouble with sleeping
  • unable to sleep

Some zileuton side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Cough
  • fever
  • headache
  • nausea
  • pain or tenderness around the eyes and cheekbones
  • stuffy or runny nose
  • tightness of the chest or wheezing
  • troubled breathing
  • upset stomach
Less common
  • Abdominal or stomach pain
  • sore throat
  • weakness

For Healthcare Professionals

Applies to zileuton: oral tablet, oral tablet extended release

Nervous system

Nervous system side effects have included headache (up to 24.6%), dizziness (greater than 1%), and somnolence (greater than 1%).[Ref]


Gastrointestinal side effects have included dyspepsia (up to 8.2%), nausea (up to 5.5%), diarrhea (up to 5%), abdominal pain (up to 4.6%), constipation (greater than 1%), flatulence (greater than 1%), upper abdominal pain (1% or greater), and vomiting (1% or greater).[Ref]


Hepatic side effects have included elevated ALT (greater than or equal to 3 times ULN; up to 4.6%), hepatotoxicity (1% or greater), at least one case of symptomatic hepatitis with jaundice, and at least three cases of mild hyperbilirubinemia (less than 3 times ULN) in patients with transaminase elevations. Elevations of one or more hepatic function enzymes and bilirubin have been reported. Cases of severe hepatic injury (including death, life-threatening liver injury with recovery, symptomatic jaundice, hyperbilirubinemia, and elevations of ALT greater than 8 times ULN) have been reported during postmarketing experience with the immediate-release tablets.[Ref]

In subset analyses, females over the age of 65 appeared to be at an increased risk for ALT elevations.

With continued zileuton therapy, 52% of patients with ALT elevations between 3 to 5 times ULN had ALT levels drop below 2 times ULN, while 34% continued to demonstrate rising levels to greater than or equal to 5 times ULN. In patients in whom zileuton was discontinued, ALT levels dropped below 2 times ULN in approximately one month.[Ref]


Respiratory side effects have included upper respiratory tract infection (9%), sinusitis (6.5%), and pharyngolaryngeal pain (5%).


Other side effects have included pain (unspecified; 7.8%), asthenia (3.8%), accidental injury (3.4%), chest pain (greater than 1%), fever (greater than 1%), and malaise (greater than 1%).


Musculoskeletal side effects have included myalgia (up to 7%), arthralgia (greater than 1%), hypertonia (greater than 1%), and neck pain/rigidity (greater than 1%).[Ref]


Hematologic side effects have included lymphadenopathy (greater than 1%) and low white blood cell count [less than 3 x 10(9)/L: 2.6%; less than or equal to 2.8 x 10(9)/L: 1%].[Ref]

Most cases of low white blood cell count were either transient or reversed upon discontinuation of zileuton.[Ref]


Psychiatric side effects have included insomnia and nervousness in greater than 1% of patients. Sleep disorders and behavior changes have been reported during postmarketing experience.


Dermatologic side effects have included pruritus (greater than 1%) and rash (1% or greater).


Genitourinary side effects have included urinary tract infection and vaginitis in greater than 1% of patients.


Hypersensitivity side effects have included hypersensitivity (1% or greater).


Ocular side effects have included conjunctivitis (greater than 1%).


1. "Product Information. Zylo Filmtab (zileuton)." Abbott Pharmaceutical, Abbott Park, IL.

2. Hackshaw KV, Shi Y, Brandwein SR, Jones K, Westcott JY "A pilot study of zileuton, a novel selective 5-lipoxygenase inhibitor, in patients with systemic lupus erythematosus." J Rheumatol 22 (1995): 462-8

3. Weinblatt ME, Kremer JM, Coblyn JS, Helfgott S, Maier AL, Petrillo G, Henson B, Rubin P, Sperling R "Zileuton, a 5-lipoxygenase inhibitor in rheumatoid arthritis." J Rheumatol 19 (1992): 1537-41

4. Israel E, Rubin P, Kemp JP, Grossman J, Pierson W, Siegel SC, Tinkelman D, Murray JJ, Busse W, Segal AT, et al "The effect of inhibition of 5-lipoxygenase by zileuton in mild-to- moderate asthma." Ann Intern Med 119 (1993): 1059-66

5. Israel E, Cohn J, Dube L, Drazen JM "Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial. Zileuton Clinical Trial Group." JAMA 275 (1996): 931-6

It is possible that some side effects of Zyflo CR may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

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