Lesch-Nyhan Disease Medication

Updated: Sep 25, 2019
  • Author: H A Jinnah, MD, PhD; Chief Editor: Amy Kao, MD  more...
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Medication Summary

Allopurinol, which inhibits the metabolism of hypoxanthine and xanthine to uric acid by the enzyme xanthine oxidase, is generally effective in limiting hyperuricemia and its consequences. The dose is titrated with the goal of bringing serum uric acid levels into the normal range.


Hypouricemic Agents

Class Summary

Hypouricemic agents are used to control hyperuricemia, thereby reducing risk for nephrolithiasis, gouty arthritis, and subcutaneous tophi.

Allopurinol (Zyloprim)

Allopurinol controls hyperuricemia by blocking action of xanthine oxidase, which converts xanthine and hypoxanthine into uric acid. The dose is titrated to lower uric acid levels to a normal range.

Febuxostat (Uloric)

Febuxostat is a potential alternative to allopurinol. Like allopurinol, febuxostat is a xanthine oxidase inhibitor that prevents uric acid production and lowers elevated serum uric acid levels. Unlike allopurinol, it is a thiazolecarboxylic acid derivative, not a purine base analog. Febuxostat physically blocks the channel to the molybdenum-pterin active site of xanthine oxidase and is metabolized by liver oxidation and glucuronidation.

Common adverse events include upper respiratory tract infections, arthralgias, diarrhea, headache, and liver function abnormalities. Atrioventricular block or atrial fibrillation in 5% and cholecystitis in 2% have also been reported.



Class Summary

Agents from this class may mitigate the severity of the neurologic features of the disease. Benzodiazepines, such as diazepam or alprazolam, reduce severity and help attenuate anxiety that may indirectly exacerbate the extrapyramidal abnormalities. Additionally, adjunctive medications including benzodiazepines and gabapentin are sometimes useful for attenuating problem behaviors.

Lorazepam (Ativan)

Lorazepam is a sedative-hypnotic of the benzodiazepine class that has a rapid onset of effect and a relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, it may depress all levels of the central nervous system (CNS), including the limbic system and reticular formations. Lorazepam is suitable for patients who need to be sedated for longer than 24 hours.

Diazepam (Valium, Diastat)

Diazepam depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.


Anticonvulsants, Other

Class Summary

Agents from this class may mitigate the severity of the neurologic features of the disease. Adjunctive medications, sometimes useful for attenuating problem behaviors, include gabapentin and benzodiazepines.

Gabapentin (Neurontin)

Gabapentin, a membrane stabilizer, is a structural analogue of the inhibitory neurotransmitter GABA, although, paradoxically, it is thought not to exert an effect on GABA receptors. It appears to exert its action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels. Gabapentin is used to manage pain and provide sedation in neuropathic pain.


Skeletal Muscle Relaxants

Class Summary

Agents from this class may mitigate the severity of the neurologic features of the disease. Muscle relaxants are commonly used to treat muscle pain, but they must be used cautiously because of sedation and because of the addictive potential of some of the medications in this category of drugs.

Baclofen (Lioresal, Gablofen)

Baclofen may induce the hyperpolarization of afferent terminals and inhibit monosynaptic and polysynaptic reflexes at the spinal level.