Febuxostatum
Febuxostatum Uses, Dosage, Side Effects, Food Interaction and all others data.
Febuxostatum is a non-purine, selective xanthine oxidase (XO) inhibitor. It decreases serum uric acid level by inhibiting xanthine oxidase, which is responsible for uric acid production. Xanthine oxidase breaks down hypoxanthine to xanthine and thus to uric acid. Febuxostatum is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.
Febuxostatum is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion. Febuxostatum at daily doses of 40-80 mg reduced the 24-hour mean serum uric acid concentrations by 40 to 55%. Closely related to the drug-induced reduction of serum uric acid levels and mobilization of urate crystals in tissue deposits, febuxostat is associated with gout flares.
Unlike allopurinol and oxypurinol, febuxostat has no inhibitory actions against other enzymes involved in purine and pyrimidine synthesis and metabolism, because it does not structurally resemble purines or pyrimidines.
| Trade Name | Febuxostatum |
| Availability | Prescription only |
| Generic | Febuxostat |
| Febuxostat Other Names | Fébuxostat, Febuxostat, Febuxostatum |
| Related Drugs | allopurinol, Zyloprim, probenecid, Uloric, Krystexxa |
| Type | |
| Formula | C16H16N2O3S |
| Weight | Average: 316.375 Monoisotopic: 316.088163078 |
| Protein binding | Febuxostat is approximately 99.2% bound to plasma proteins, primarily to albumin. Plasma protein binding is constant over the concentration range achieved with 40 mg and 80 mg doses. |
| Groups | Approved |
| Therapeutic Class | Drugs used in Gout |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Febuxostatum is used for the long-term management of Hyperuricemia in patients with gout. It is not recommended for use in the treatment of asymptomatic Hyperuricemia.
Febuxostatum is also used to associated treatment for these conditions: Chronic, symptomatic Hyperuricemia
How Febuxostatum works
Gout is a form of acute arthritis that is characterized by the accumulation of crystals of monosodium urate and urate crystals in or around a joint, leading to inflammation and persistent urate crystal deposition in bones, joints, tissues, and other organs that may exacerbate over time. Hyperuricemia is closely related to gout, whereby it may exist for many years before the first clinical attack of gout; thus, aberrated serum uric acid levels and hyperuricemia are believed to be the biochemical aberration involved in the pathogenesis of gout. Xanthine oxidoreductase (XOR) can act as a xanthine oxidase or xanthine dehydrogenase. In humans, it is a critical enzyme for uric acid production as it catalyzes the oxidation reaction steps from hypoxanthine to xanthine and from xanthine to uric acid in the pathway of purine metabolism. Febuxostatum potently inhibits XOR, blocking both its oxidase and dehydrogenase activities. With high affinity, febuxostat binds to XOR in a molecular channel leading to the molybdenum-pterin active site, where allopurinol demonstrates relatively weak competitive inhibition.
XOR is mainly found in the dehydrogenase form under normal physiological conditions; however, in inflammatory conditions, XOR can be converted into the xanthine oxidase form, which catalyzes reactions that produce reactive oxygen species (ROS), such as peroxynitrite. ROS contribute to vascular inflammation and alterations in vascular function. As febuxostat can inhibit both forms of XOR, it can inhibit ROS formation, oxidative stress, and inflammation. In a rat model, febuxostat suppressed renal ischemia-reperfusion injury by attenuating oxidative stress.
Dosage
Febuxostatum dosage
The recommended starting dosage of Febuxostatum is 40 mg once daily. For patients who do not achieve a serum uric acid concentration of less than 6 mg/dL after 2 weeks at the 40 mg dose, Febuxostatum 80 mg once daily is recommended. Febuxostatum can be administered without regard to food or antacid use.
Side Effects
The most common adverse events associated with the use of Febuxostatum may include liver function abnormalities, nausea, arthralgia, and rash.
Toxicity
Oral lowest published toxic dose (TDLO) in humans is 1.82 mg/kg/14D (intermittent). Oral LD50 is 300 mg/kg in mice, 3200 mg/kg in rabbits, and 980 mg/kg in rats.
No dose-limiting toxicities were observed with febuxostat administered at doses up to 300 mg daily for seven days in healthy subjects. There are no reports of overdose of febuxostat in clinical studies and there is no known antidote. Overdose should be managed by symptomatic and supportive care.
Precaution
Gout Flare: An increase in gout flares is frequently observed during initiation of anti-hyperuricemic agents, including Febuxostatum. If a gout flare occurs during treatment, Febuxostatum need not be discontinued. Prophylactic therapy (i.e., non-steroidal anti-inflammatory drug (NSAID) or colchicine upon initiation of treatment) may be beneficial for up to six months.
Cardiovascular Events: A higher rate of cardiovascular thromboembolic events was observed in patients treated with febuxostat than allopurinol in clinical trials. Monitor for signs and symptoms of MI and stroke.
Liver Enzyme Elevation: Transaminase elevations have been observed in febuxostat -treated patients. Monitor liver function tests periodically.
Interaction
Concomitant administration of Febuxostatum with azathioprine, mercaptopurine or theophylline could increase plasma concentrations of these drugs resulting in severe toxicity.
Food Interaction
- Take with or without food. A high fat meal decreases Cmax and AUC in a clinically insignificant way.
Febuxostatum Drug Interaction
Unknown: aspirin, aspirin, rosuvastatin, apixaban, omega-3 polyunsaturated fatty acids, furosemide, atorvastatin, metoprolol, metoprolol, esomeprazole, amlodipine, omega-3 polyunsaturated fatty acids, acetaminophen, clopidogrel, acetaminophen, multivitamin, cyanocobalamin, ascorbic acid, cholecalciferol, rivaroxaban
Febuxostatum Disease Interaction
Major: secondary hyperuricemiaModerate: CV disease, renal dysfunction, hepatic impairment
Volume of Distribution
The apparent steady-state volume of distribution (Vss/F) of febuxostat ranges from 29 to 75 L, indicating a low to medium volume of distribution.
Elimination Route
After oral administration, about 85% of febuxostat is absorbed rapidly. Tmax ranges from 1 to 1.5 hours. Following once-daily oral administration, Cmax was approximately 1.6 ± 0.6 mcg/mL at a dose of 40 mg febuxostat and 2.6 ± 1.7 mcg/mL at a dose of 80 mg febuxostat.
A high-fat meal decreased Cmax by 49% and AUC by 18%, but there were no clinically significant changes in the ability of febuxostat to decrease serum uric acid concentrations.
Half Life
The apparent mean terminal elimination half-life of approximately 5 to 8 hours.
Clearance
Following oral administration of single doses of 10 to 240 mg, the mean apparent total clearance ranged from 10 to 12 L/h.
Elimination Route
Febuxostatum is eliminated via both hepatic and renal pathways. Following oral administration of 80 mg radiolabeled febuxostat, approximately 49% of the dose was recovered in the urine. In urine, about 3% of the recovered dose accounted for unchanged febuxostat, 30% accounted for the acyl glucuronide metabolite, 13% accounted for oxidative metabolites and their conjugates, and 3% accounted for unidentified metabolites.
Approximately 45% of the total dose was recovered in the feces, where 12% of the dose accounted for the unchanged parent drug. About 1% accounted for the acyl glucuronide metabolite, 25% accounted for oxidative metabolites and their conjugates, and 7% accounted for unidentified metabolites.
Pregnancy & Breastfeeding use
Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Febuxostatum should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: It is not known whether this drug is excreted in human milk. Caution should be exercised when Febuxostatum is administered to a nursing woman.
Contraindication
Febuxostatum is contraindicated in patients being treated with azathioprine, mercaptopurine, or theophylline.
Special Warning
Pediatric Use: Safety and effectiveness in pediatric patients under 18 years of age have not been established
Acute Overdose
Febustat was studied in healthy subjects in doses up to 300 mg daily for seven days without evidence of dose-limiting toxicities.
Storage Condition
Keep out of the reach of children. Keep in a cool & dry place, protected from light.
Innovators Monograph
You find simplified version here Febuxostatum
Febuxostatum contains Febuxostat see full prescribing information from innovator Febuxostatum Monograph, Febuxostatum MSDS, Febuxostatum FDA label
FAQ
How safe is Febuxostatum?
Febuxostatum is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol.
How safe is Febuxostatum?
Take one tablet each day. There have been a few reports of Febuxostatum causing a serious allergic reaction. Although this is rare, if you experience any of these symptoms, you should stop taking Febuxostatum and contact your doctor straightaway.
How does Febuxostatum work?
Febuxostatum works by decreasing the amount of uric acid that is made in the body.
What are the common side effects of Febuxostatum?
Common side effects of Febuxostatum are include:
- Arm, back, or jaw pain
- black, tarry stools
- bloody nose
- blurred vision
- chest pain or discomfort
- chills
- cloudy urine
- confusion
- cough
- dark urine
- decreased frequency or amount of urine
- diarrhea
- difficult or labored breathing
- difficulty with moving
- dizziness
- dry mouth
- fainting
- fast, irregular, pounding, or racing heartbeat or pulse
- feeling of fullness
- fever
Is Febuxostatum safe during pregnancy?
Some experts advise against use during pregnancy as the potential risk for humans is unknown.
Is Febuxostatum safe during breastfeeding?
There are no data on the effects of this drug on the breastfed infant or its effects on milk production. Some experts advise against breastfeeding as a risk to the breastfeeding infant cannot be excluded.
Can I drink alcohol with Febuxostatum?
Alcohol doesn't interact significantly with Febuxostatum, but it does increase the level of urate in the blood.
Can I drive after taking Febuxostatum ?
Be aware that you may experience dizziness, sleepiness, blurred vision and numbness or tingling sensation during treatment and should not drive or operate machines, if affected.
When is the best time to take Febuxostatum?
It is best taken in the morning. If you do shift work or want to take your medicine at night, talk to your doctor, nurse or pharmacist.
Can I take Febuxostatum on an empty stomach?
You can take Febuxostatum with or without food.
How long does Febuxostatum take to work?
Febuxostatum should be taken every day to prevent a gout attack. It can take six months to become fully effective. It does not have any effect during a gout attack, although you should continue to take it regularly every day even if this happens.
Does Febuxostatum affect the liver?
No instances of acute liver failure or chronic liver injury have been reported due to Febuxostatum, but the clinical experience with this agent is limited.
Can I take Febuxostatum for a long time?
Treatment with Febuxostatum is usually long-term unless you experience an adverse effect. Continue to take the tablets unless you are advised otherwise by a doctor.
Is Febuxostatum bad for my heart?
Febuxostatum does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death.
Is Febuxostatum bad for kidney?
Febuxostatum has shown to be safe and effective in patients with moderate to severe renal impairment, and dose adjustment is not required in these patients.
Can Febuxostatum be stopped?
You should not stop using Febuxostatum suddenly.
What happen If I stop taking Febuxostatum?
If Febuxostatum treatment is stopped there is a high risk that your gout may worsen. You should continue to take it even if you do not have symptoms.
Who should not take Febuxostatum?
Taking Febuxostatum may increase your risk of serious or fatal heart problems. Seek medical attention if you have chest pain, trouble breathing, fast heartbeats, sudden severe headache, numbness or weakness on one side of your body, or problems with vision or speech. You should not use Febuxostatum if you also use azathioprine or mercaptopurine.
What happens if I miss a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
What happen if I take too much Febuxostatum?
If you take too much Febuxostatum, call your healthcare provider or local Poison Control Center or seek emergency medical attention right away. If Febuxostatum is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if an overdose is suspected, seek emergency medical attention.
Will Febuxostatum affect my fertility?
The effects of Febuxostatum on fertility are not currently known, but it's unlikely to be harmful.
