Lesinurad is a medication used in the management of gout. It works by inhibiting the URAT1 transporter in the kidneys, which helps to increase the excretion of uric acid, ultimately lowering serum uric acid levels. Lesinurad is often prescribed in combination with a xanthine oxidase inhibitor, such as allopurinol or febuxostat, in patients who have not achieved adequate control of their serum uric acid levels with xanthine oxidase inhibitors alone.

Lesinurad (Zurampic) is a medication that lowers urates. It promotes the body's excretion of uric acid by preventing its reabsorption from the renal tubules.

Lesinurad (Zurampic) Uses:

• Hyperuricemia associated with gout:
  • It is suggested for the treatment of gout patients with hyperuricemia who don't respond well to xanthine oxidase inhibitor monotherapy. (Allopurinol).
  • Impediments of use:
    • Asymptomatic hyperuricemia is not a condition for which it is prescribed.
    • It's not advised to use monotherapy.

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:

• For treating high uric acid levels linked to gout, the usual dose of Lesinurad is 200 mg once a day.
• You take it by mouth.
• It's best to take it alongside another medication called a xanthine oxidase inhibitor, like allopurinol or febuxostat.
• The most you should take in a day is 200 mg.

Important to note: If you stop taking the xanthine oxidase inhibitor for any reason, you should also stop taking Lesinurad.

Use in Children:

Not indicated

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

• In studies with animals, no negative effects on reproduction were seen with Lesinurad.
• However, it's important to know that Lesinurad might make hormonal birth control methods like the pill, injection, or patches less effective.
• So, if you're using hormonal birth control while taking Lesinurad, it's smart to also use another form of contraception to prevent pregnancy.

Lesinurad use during breastfeeding:

• It's unclear whether Lesinurad passes into breast milk.
• The manufacturer advises that if you're breastfeeding and considering Lesinurad treatment, you should weigh the benefits of the treatment for you against the potential risks for your baby.

Lesinurad (Zurampic) Dose in Kidney disease:

Preexisting Renal Impairment:

• Estimated CrCl ≥60 mL/minute:
  • No need to adjust the dosage.
• Estimated CrCl 45 to <60 mL/minute:
  • No dosage adjustment required, but monitoring should be more frequent.
• Estimated CrCl 30 to <45 mL/minute:
  • Treatment might be less effective and should not be started due to limited experience.
• Estimated CrCl <30 mL/minute:
  • Use of Lesinurad is not recommended.
• End-stage Renal Disease (ESRD) or Patients on Dialysis:
  • Lesinurad should not be used.

Renal Toxicity During Treatment:

• Estimated CrCl Persistently <45 mL/minute:
  • Treatment should be discontinued.

Lesinurad (Zurampic) Dose in Liver disease:

• Mild to Moderate Impairment (Child-Pugh Class A and B):
  • No need to adjust the dosage.
• Severe Impairment (Child-Pugh Class C):
  • It's not recommended to use Lesinurad as it hasn't been studied in this condition.

The incidence was reported in combination with a xanthine oxidase inhibitor.

Side Effects of Lesinurad (Zurampic):

• Gastrointestinal:
  • Gastroesophageal reflux disease
•  
• Central nervous system:
  • Headache
• Renal:
  • Increased serum creatinine
  • Renal failure
• Infection:
  • Influenza

Uncommon Side effects of Lesinurad (Zurampic):

• Renal:
  • Acute renal failure
• Cardiovascular:
  • Cerebrovascular accident
  • Myocardial infarction

Contraindications to Lesinurad (Zurampic):

• If you have severe kidney problems (with a CrCl less than 30 mL/minute), end-stage kidney disease, are on dialysis, have had a kidney transplant, have tumor lysis syndrome, or Lesch-Nyhan syndrome, Lesinurad might not be suitable for you.

Warnings and precautions

Cardiovascular events

• Major Cardiac Adverse Events: In clinical trials, there were instances of major heart-related issues like cardiovascular deaths, non-fatal heart attacks (MI), or non-fatal strokes. However, it's not confirmed if these events were directly caused by Lesinurad.

Gout flare

• When starting treatment to lower uric acid levels, gout may temporarily worsen due to the release of uric acid from tissue deposits.
• It's recommended to take preventive measures against gout flare-ups when beginning Lesinurad treatment.
• Even during a gout flare-up, Lesinurad treatment can continue, and the flare-up can be managed.

Nephrotoxicity:

• When Lesinurad is used with a xanthine oxidase inhibitor, there's a higher chance of temporary increases in serum creatinine levels, which typically reverse.
• However, acute renal failure has been seen with Lesinurad, especially when used alone.
• Renal failure and kidney stone formation have also been reported when Lesinurad is combined with a xanthine oxidase inhibitor.
• Higher doses of Lesinurad may increase the risk of kidney-related issues.

Renal impairment

• Doctors should assess kidney function before starting Lesinurad and regularly afterward, especially for patients with estimated CrCl (creatinine clearance) less than 60 mL/minute or if serum creatinine levels are 1.5 to 2 times higher than usual.
• Lesinurad isn't recommended for patients with estimated CrCl less than 45 mL/minute and is not to be used in those with estimated CrCl less than 30 mL/minute, end-stage renal disease (ESRD), or on dialysis.
• Treatment should be halted if serum creatinine levels rise to more than twice the baseline.
• If symptoms of acute uric acid nephropathy appear, like flank pain or nausea, Lesinurad should be paused and serum creatinine levels checked before restarting.

Secondary hyperuricemia

• Lesinurad hasn't been tested in patients with secondary hyperuricemia, such as organ transplant recipients.
• It's not to be used in patients with tumor lysis syndrome or Lesch-Nyhan syndrome, where uric acid production is markedly increased.

Lesinurad: Drug Interaction

Monitoring parameters:

Monitoring before to Treatment and Periodically Thereafter:

• Doctors should check serum creatinine and estimated CrCl levels before starting Lesinurad treatment and regularly afterward, especially if the estimated CrCl is less than 60 mL/minute or if serum creatinine levels are elevated by 1.5 to 2 times compared to baseline.

Serum Uric Acid Levels:

• During the adjustment of uric acid lowering therapy, serum uric acid levels should be monitored every 2 to 5 weeks. After the titration period, monitoring should continue every 6 months. (Reference: Khanna 2012)

How to administer Lesinurad (Zurampic)?

• Lesinurad should be taken orally in the morning, alongside food and water.
• It's best to take it at the same time in the morning as the dose of the xanthine oxidase inhibitor.
• Patients should be advised to drink plenty of fluids, aiming for at least 2 liters per day to stay well hydrated.

Mechanism of action of Lesinurad (Zurampic):

• Lesinurad works by blocking certain transporter proteins in the kidneys, specifically URAT1 (uric acid transporter 1) and OAT4 (organic anion transporter 4).
• These proteins are responsible for reabsorbing uric acid in the kidneys.
• By inhibiting these proteins, Lesinurad helps lower levels of uric acid in the blood.
• Additionally, it increases the clearance of uric acid from the kidneys and boosts the amount of uric acid excreted in the urine.
• This mechanism of action helps in managing gout by reducing elevated levels of uric acid in the body.

Absorption:

• Lesinurad is absorbed quickly after oral administration.

Distribution:

• It spreads widely throughout the body, with a volume of distribution of around 20 liters.

Protein Binding:

• Over 98% of Lesinurad binds to proteins in the blood, mainly to albumin.

Metabolism:

• The drug is primarily broken down through oxidative processes, mainly by the enzyme CYP2C9.
• The metabolites formed are not significant contributors to the drug's effects.

Bioavailability:

• Nearly all of the administered dose is absorbed into the bloodstream, making its bioavailability close to 100%.

Half-life Elimination:

• Lesinurad has a relatively short elimination half-life of about 5 hours.

Time to Peak:

• It reaches peak concentration in the bloodstream within 1 to 4 hours after administration.

Excretion:

• Lesinurad and its metabolites are eliminated primarily through the urine, with about 63% of the dose excreted this way (around 30% as unchanged drug).
• A significant portion is also excreted through feces (about 32%).

International Brand Names of Lesinurad:

• Zurampic

Lesinurad Brand Names in Pakistan:

No Brands Available in Pakistan.