Zofran Relieves Fatigue of Hepatitis C in One Patient

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Zofran Relieves Fatigue of Hepatitis C in One Patient

Without any anti-HCV therapy, daily Zofran alleviated fatigue and itching

by Harvey S. Bartnof, MD

8/23/99

<http://www.hivandhepatitis.com/hepc/c08239902.html>

A common debilitating symptom that occurs with chronic hepatitis infection

is fatigue. This prevents many patients with HCV from maintaining gainful

employment and decreases quality-of-life. In a letter to the editor in this

week's issue of The Lancet, E. , MD, describes a 35-year old

woman with chronic hepatitis C. With six interrupted courses of Zofran

(ondansetron) pills during 9 months, she had clear resolution of her fatigue

while taking the medication. Moreover, she was able to work more efficiently

and for longer hours. Her fatigue returned within 24 hours after stopping

the medication.

The author suggests that the results indicate that fatigue from hepatitis C

is due to effects in the brain. Zofran is an FDA-approved drug to treat

nausea and vomiting from cancer chemotherapy, radiation treatments or while

recovering from anesthesia after surgery. It is available as a pill, liquid

or by injection and is manufactured by Glaxo Wellcome. Zofran selectively

blocks brain receptors of serotonin (natural brain chemical) 5-HT type 3.

The woman had acquired HCV infection from a blood transfusion. Her HCV RNA

viral load was positive by PCR (polymerase chain reaction). Her liver biopsy

showed portal hepatitis. A decision was made not to start anti-HCV therapy.

However, she did have significant fatigue and itching.

She was originally enrolled in a double-blind (medication or placebo not

known by the patient or physician), placebo trial. The original dose was

Zofran 8 mg or placebo every 8 hours for one month, followed by one month

with the opposite randomized therapy for the second month. During the first

month, she noticed no changes in symptoms. However, 4 days into the second

month, her itching went away. Due to constipation, a common side effect from

Zofran, the dose was decreased to twice daily. She also had some mild double

vision, another side effect that resolved after a few days. The woman noted

in the second month that her fatigue had been " substantially less. "

At the end of the second month, after unblinding, it was determined that

indeed Zofran and not placebo was the medication during that time. Within 6

days after stopping the Zofran, her fatigue returned, and she requested to

be started on the medication again. During the ensuing 9 months, she had

taken 6 courses of Zofran, ranging from several weeks to a few months. She

interrupted the medication due to reasons not related to the medication

itself.

The woman found that the optimal dose for her was 4 mg twice daily. This

lowered dose, her " energy level was normal " and side effects were nil.

Constipation was avoided by increasing the roughage ( " bulk " ) in her diet and

by increasing fluid intake. A once daily dose of 4 mg was insufficient in

relieving her fatigue, and a 3-times-daily dose caused constipation. At the

time the letter to the editor was written, the woman had been taking Zofran

daily for four months regularly, without symptoms or side effects.

Dr. believes that the findings in his patient " support the hypothesis

that altered central [brain] serotoninergic [natural chemical]

neurotransmission [nerve tissue functioning] contributes to the profound

fatigue that complicates chronic liver disease. " He points out that the

hypothesis is supported by 2 previous studies. In the first one, rats who

were fatigued after extended exercise " correlated directly with the indices

of central serotoninergic transmission. " In the second study, the exercise

endurance time of athletes was significantly reduced after taking Paxil

(paroxetine, antidepressant medication), a selective inhibitor of serotonin

reuptake. (The athletes were not emotionally depressed.)

Dr. concludes that the findings " are compatible with altered

transmission in neural pathways...contributing to fatigue of central origin,

and support the hypothesis that excessive fatigue associated with chronic

liver disease may be of central origin. "

This report represents only one patient. No conclusions can be drawn.

However, the results easily could be confirmed in a standard

placebo-controlled, double-blinded trial. Such trials should begin

immediately. Until then, there are certain to be patients with fatigue from

chronic hepatitis C who will request that their physicians write a

prescription. It should also be noted that fatigue and other symptoms from

hepatitis C are also improved in patients whose HCV viral loads respond to

standard therapies. These include one of the type 1 interferons alone or

with Rebetol (ribavirin).

Zofran does have other side effects not reported in the letter. In addition

to constipation and temporary blurred vision, the following have been

reported at the dose of 8 mg three times daily. Side effects include

headache, temporary malaise and weakness, dizziness, abdominal pain,

retained urine and dry mouth. Rash occurs in 1% of patients.

Rarely, the rash is associated with life-threatening anaphylactic shock (low

blood pressure, weakness, sometimes with itchy hives rash and lung wheezing

due to bronchial spasms and causing breathing difficulties. There are also

rare reports of low blood potassium, angina (heart pain due to low oxygen),

blood vessel occlusion and seizures ( " fit " or convulsions).

Zofran comes in 4 and 8 milligram tablets, a strawberry oral solution with

an equivalent of 4 mg per 5 milliliters (approximately 1 teaspoon) and as

injection with 2 milligrams per milliliter. The cost of Zofran is high, and

this may be a barrier to its usage for many patients.

References:

SP, JM, Ahlborn EN. Neuroendocrine and substrate responses to

altered brain 5-HT activity during prolonged exercise to fatigue. Journal of

Applied Physiology 1993; 74: 3006-12.

EA. Relief from profound fatigue associated with chronic liver disease

by long-term ondansetron therapy. The Lancet July 31, 1999;254(9176): 31.

EA, Yurdaydin C. Is fatigue associated with cholestasis mediated by

altered central neurotransmission? Hepatology 1997; 25: 492-94.

WM, Maughan RJ. Evidence for a possible role of 5-hydroxytryptamine

in the genesis of fatigue in man: administration of paroxetine, a 5-HT

re-uptake inhibitor, reduces the capacity to perform prolonged exercise.

Experimental Physiology 1992; 77: 921-24.

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