Lesinurad (Zurampic) is a urate-lowering drug. It inhibits the reabsorption of uric acid from the renal tubules promoting the excretion of uric acid from the body.

Lesinurad (Zurampic) Uses:

• Hyperuricemia associated with gout:

  • It is indicated for the treatment of hyperuricemia associated with gout in patients who have an inadequate response to xanthine oxidase inhibitors monotherapy (Allopurinol).
  • Limitations of use:
    • It is not indicated for the treatment of asymptomatic hyperuricemia.
    • Monotherapy is not recommended.

Lesinurad is available in combination with allopurinol by the brand name of Duzallo.

Lesinurad (Zurampic) Dose in Adults:

Lesinurad (Zurampic) Dose in the treatment of Hyperuricemia associated with gout:

• 200 mg orally once a day in combination with a xanthine oxidase inhibitor such as allopurinol or febuxostat.
• The maximum daily dose is 200 mg once a day.

Note:

• Patients who discontinue or interrupt treatment with a xanthine oxidase inhibitor, should also withhold lesinurad treatment.

Use in Children:

Not indicated

Lesinurad (Zurampic) pregnancy Risk Category: N (not assigned)

• In animal reproduction studies, no adverse fetal events have been observed. The data on human pregnancies are limited.
• All forms of hormonal contraceptives, oral, injectable and topical, are affected by treatment.
• While on treatment, you should consider other nonhormonal methods to contraceptive.

Lesinurad use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• Manufacturer suggests weighing the advantages of treatment for the mother against the potential risks to the infant from drug exposure.

Lesinurad (Zurampic) Dose in Kidney disease:

• Patients with a preexisting renal impairment:

  • Estimated CrCl ≥60 mL/minute:
    • Adjustment in the dose is not necessary.
  • Estimated CrCl 45 to <60 mL/minute:
    • Adjustment is not necessary, however, frequent monitoring of renal function should be done.
  • Estimated CrCl 30 to <45 mL/minute:
    • Treatment should not be initiated as it may be less effective.
  • Estimated CrCl <30 mL/minute:
    • The drug is contraindicated in patients with a CrCl of less than 30 ml/minute.
  • End-stage renal disease (ESRD) or patients on dialysis:
    • The drug is contraindicated in patients on dialysis and ESRD.

• Patients who develop renal toxicity during treatment:

  • Estimated CrCl persistently <45 mL/minute:
    • Discontinue treatment if the creatinine clearance drops to less than 45 ml/minute.

Lesinurad (Zurampic) Dose in Liver disease:

• Mild to moderate impairment (Child-Pugh class A and B):
  • Adjustment in the dose is not necessary.
• Severe impairment (Child-Pugh class C):
  • Avoid using the drug in patients with advanced liver disease.

Incidence reported in combination with a xanthine oxidase inhibitor.

Side Effects of Lesinurad (Zurampic):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Gastroesophageal reflux disease

• Infection:

  • Influenza

• Renal:

  • Increased serum creatinine
  • Renal failure

Uncommon Side effects of Lesinurad (Zurampic):

• Cardiovascular:

  • Cerebrovascular accident
  • Myocardial infarction

• Renal:

  • Acute renal failure

Contraindications to Lesinurad (Zurampic):

• Patients with severe renal impairment (CrCl 30 mL/minute), end stage renal disease (ESRD) and/or dialysis
• Kidney transplant recipients
• Tumor lysis syndrome (or)
• Lesch-Nyhan syndrome

Warnings and precautions

• Cardiovascular events

  • Patients receiving lesinurad treatment were found to have MACE (major adverse cardiovascular events), which included deaths due to a cardiovascular cause, non-fatal myocardial injury, and strokes.
  • However, it was not possible to establish a clear causal relationship.

• Gout flare

  • Gout can flare up due to the mobilization of uric acids from the tissues.
  • Before you start treatment, it is a good idea to prevent acute flare-ups of goutyarthritis.
  • The treatment with lesinurad can be continued during a gouty attack or while you manage the flare-up of gouty arthritis.

• Nephrotoxicity:

  • A combination therapy with a xanthine oxide inhibitor can lead to an increase in serum creatinine levels. Treatment discontinuation will usually reverse the effect.
  • [US Boxed Warning]: Monotherapy can lead to acute renal failure.
  • Patients taking concomitant xanthine oxide inhibitors have been known to be at risk for acute and chronic kidney failure, as well as the development of nephrolithiasis.
  • Nephrotoxicity is more common when the drug was taken in a higher dose than recommended.

• Renal impairment

  • It is important to evaluate the renal function before starting treatment and then periodically thereafter, if clinically indicated.
  • People with a CrCl less than 60 ml/minute, or elevated creatinine levels 1.5 to 2 times the baseline level, should have their renal functions monitored more often.
  • Patients with an eGFR below 45 ml/minute should not receive treatment. Treatment is also contraindicated for patients with a CrCl lower than 30 ml/minute.
  • Treatment may not work for those who have a CrCl below 30 ml/minute or those on dialysis.
  • Patients with serum creatinine levels greater than 2x the baseline level must be stopped from receiving treatment.
  • Patients with acute urate neuropathy, such as nausea, vomiting, flank pain or nausea, should be treated immediately.

• Secondary hyperuricemia

  • Patients with secondary hyperuricemia, such as transplant recipients, have not been treated with the drug.
  • Patients with cancer, tumor lysis syndrome, or Lesch-Nyhan syndrome should avoid it.

Lesinurad: Drug Interaction

Monitoring parameters:

• Serum creatinine and estimated CrCl before the start of therapy and periodically thereafter as clinically indicated.
• Serum creatinine and estimated CrCl should be more frequently monitored in patients with a baseline creatinine of 1.5 to 2 times the upper limits of normal or a CrCl of less than 60 ml/minute.
• Monitor serum uric acid levels at 2 to 5 weeks intervals while titrating the dose and then every 6 monthly.

How to administer Lesinurad (Zurampic)?

• It is administered orally, preferably in the morning with food and water.
• The drug should be taken at the same time each morning.
• Patients should be advised to maintain hydration.
• A minimum of 2 litres of fluid intake is recommended daily.

Mechanism of action of Lesinurad (Zurampic):

• Lesinurad (Zurampic), is a uricosuric medication.
• It inhibits uric acid absorption and promotes its excretion. It prevents the absorption uric acids by blocking two important transporter proteins (uric Acid Transporter 1 [URAT1]) and Organic Anion Transporter 4 [OAT4]), which are involved in the reabsorption uric acid from your kidneys.

Absorption:

• Rapid

Protein binding:

• >98% (It is bound primarily to albumin)

Metabolism:

• It is primarily metabolized oxidatively via CYP2C9
• Metabolites of the drug do not contribute to the drug activity and their plasma exposure is minimal.

Bioavailability:

• ~100%

Half-life elimination:

• ~5 hours

Time to peak:

• Within 1 to 4 hours

Excretion:

• Urine (63%; ~30% as unchanged drug);
• feces (32%)

International Brand Names of Lesinurad:

• Zurampic

Lesinurad Brand Names in Pakistan:

No Brands Available in Pakistan.