Febuxostat

Febuxostat comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take febuxostat at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take febuxostat exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may increase your dose of febuxostat after 2 weeks if a laboratory test shows that you still have too much uric acid in your blood.

It may take several months before febuxostat begins to prevent gout attacks. Febuxostat may increase the number of gout attacks during the first few months of your treatment. Your doctor may prescribe another medication such as colchicine or a nonsteroidal anti-inflammatory drug (NSAID) to prevent gout attacks during the first 6 months of your treatment. Continue to take febuxostat even if you have gout attacks during your early treatment.

Febuxostat controls gout but does not cure it. Continue to take febuxostat even if you feel well. Do not stop taking febuxostat without talking to your doctor.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Unless your doctor tells you otherwise, continue your normal diet.

Febuxostat may cause side effects. Tell your doctor if either of these symptoms is severe or does not go away:

• nausea
• joint pain

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• rash
• chest pain
• shortness of breath
• slow or difficult speech
• dizziness or faintness
• weakness or numbness of an arm or leg

Febuxostat may cause you to have high levels of liver enzymes in your blood. This may be a sign of liver damage. Your doctor will monitor you carefully during your treatment.

Febuxostat may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

• Uloric^®

Yes

Uloric comes as a tablet to take by mouth. It's typically taken once a day, with or without food.

The usual dose is 40 milligrams (mg) or 80 mg daily.

Your doctor may start you on a lower dose of Uloric and then increase it.

Try to take this medicine around the same time each day.

You can take antacids along with Uloric.

Follow the instructions on your prescription label carefully. Don't take more or less Uloric than is recommended.

Uloric Overdose

An overdose of Uloric isn't believed to be life-threatening.

But if you suspect an overdose, seek medical care. You can get in touch with a poison control center at 800-222-1222.

Missed Dose of Uloric

If you miss a dose of Uloric, take it as soon as you remember.

But skip the missed dose if it's almost time for your next scheduled dose.

Don't take extra medicine to make up for a missed dose.

>1%

Arthralgia

Elevated liver function test (LFT) results

Liver function abnormalities

Nausea

Rash

Postmarketing Reports

Immunologic: Anaphylaxis, anaphylactic reaction

Musculoskeletal: Rhabdomyolysis

Hepatobiliary: Hepatic failure (some fatal), jaundice, serious cases of abnormal LFT results, liver disorders

Psychiatric: Psychotic behavior, including aggressive thoughts

Renal and urinary: Tubulointerstitial nephritis

Dermatologic: Generalized rash, Stevens-Johnson syndrome, hypersensitivity skin reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN)

Mechanism of Action

Xanthine oxidase inhibitor; inhibits conversion of hypoxanthine to xanthine to uric acid; at therapeutic dosages, decreases production of uric acid without disrupting synthesis of vital purines and pyrimidines

Absorption

Bioavailability: 49%

Peak plasma time: 1-1.5 hr

Distribution

Protein bound: 99.2%

Vd: 50 L

Metabolism

Metabolized by UGT1A1, UGT1A3, UGT1A9, and UGT2B7; oxidized by CYP1A2, CYP2C8, and CYP2C9; also metabolized by non-CYP450 enzymes

Elimination

Half-life: 5-8 hr

Excretion: Feces (45%; 12% unchanged), urine (49%; 3% unchanged)

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Febuxostat does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2C9, 2C19, or 3A4; febuxostat is a weak inhibitor of CYP2D6.1 Febuxostat does not induce CYP1A2, 2B6, 2C9, 2C19, 3A4.1

Febuxostat is metabolized by conjugation by glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate β-D-glucuronosyltransferase [acceptor-unspecific], UGT) enzymes, including UGT1A1, UGT1A3, UGT1A9, and UGT2B7, as well as by oxidation by CYP isoenzymes, including CYP1A2, 2C8, and 2C9, and non-CYP enzymes.1 Relative contribution of each enzyme isoform to the drug’s metabolism is not clear.1

Drugs Affecting Hepatic Microsomal or Other Enzymes

Drug interactions generally are not expected between febuxostat and inhibitors or inducers of particular enzyme isoforms.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions are unlikely between febuxostat and substrates of these isoenzymes.1

Drugs Metabolized by Xanthine Oxidase

Inhibition of xanthine oxidase by febuxostat may increase plasma concentrations of drugs metabolized by the enzyme if administered concomitantly, resulting in toxicity.1 (See Contraindications.)

Specific Drugs

Storage

Oral

25°C (may be exposed to 15–30°C).1

Take febuxostat only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

febuxostat comes with a patient information insert. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

You may take febuxostat with or without food. It may also be taken with antacids.

At first, when you start using febuxostat you may have more gout attacks. Keep using febuxostat even if this happens. Your doctor may give you other medicines (such as colchicine or pain medicines [NSAIDs]) to help prevent these gout attacks.

Dosing

The dose of febuxostat will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of febuxostat. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For treatment of hyperuricemia:
    • Adults—At first, 40 milligrams (mg) once a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 80 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of febuxostat, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check your progress at regular visits to make sure that febuxostat is working properly. Blood tests may be needed to check for unwanted effects.

Do not use azathioprine (Azasan®, Imuran®) or mercaptopurine (Purinethol®) while you are taking febuxostat. Using these medicines together can cause serious medical problems.

febuxostat may increase your risk of having serious heart and blood vessel problems such as heart attack or stroke. Check with your doctor right away if start having chest pain, trouble with breathing, sudden or severe headache, or problems with vision, speech, or walking.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abdominal or stomach fullness or pain
• 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
• gaseous abdominal or stomach pain
• general tiredness and weakness
• headache
• heavier menstrual periods
• inability to speak
• increase in heart rate
• increased thirst
• itching
• joint pain, stiffness, or swelling
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• lightheadedness
• loss of appetite
• loss of bladder control
• muscle aching or cramping
• nausea and vomiting
• nervousness
• pain, swelling, or redness in the joints
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• pounding in the ears
• rapid breathing
• rash
• redness of the skin
• right upper abdominal or stomach pain and fullness
• runny nose
• seizures
• severe or sudden headache
• shivering
• shortness of breath
• slow or fast heartbeat
• slurred speech
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• sunken eyes
• sweating
• swelling
• temporary blindness
• thirst
• tightness in the chest
• trouble sleeping
• troubled breathing or swallowing
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds
• weakness in the arm or leg on one side of the body, sudden and severe
• weight gain
• wheezing
• wrinkled skin
• yellow eyes and skin

• Blistering, peeling, or loosening of the skin
• diarrhea
• difficulty with swallowing
• hives
• muscle cramps or spasms
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• anxiety
• bad, unusual, or unpleasant (after) taste
• blistering, crusting, irritation, itching, or reddening of the skin
• body aches or pain
• breast pain
• bruising
• burning feeling in the chest or stomach
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in taste
• changes in hair color
• constipation
• continuing ringing or buzzing or other unexplained noise in the ears
• cough producing mucus
• cracked, dry, or scaly skin
• decrease in smell
• decreased interest in sexual intercourse
• depression
• ear congestion
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• fruit-like breath odor
• gum pain
• hair loss or thinning of the hair
• hearing loss
• heartburn
• hyperventilation
• inability to have or keep an erection
• inability to move the arms and legs
• increased or decreased appetite
• increased sensitivity of the skin to sunlight
• increased sweating
• increased urination
• irritability
• large, flat, blue, or purplish patches in the skin
• loss in sexual ability, desire, drive, or performance
• loss of appetite
• loss of consciousness
• loss of voice
• muscle or bone pain or stiffness
• muscle spasm, tightness, or weakness
• muscle twitching
• nasal congestion
• painful blisters on the trunk of the body
• pains in the stomach, side, or abdomen, possibly radiating to the back
• sensation of spinning
• severe or continuing stomach pain
• severe sunburn
• shakiness in the legs, arms, hands, or feet
• skin rash, encrusted, scaly, and oozing
• sleepiness or unusual drowsiness
• small red or purple spots on the skin
• sneezing
• stomach discomfort, upset, or pain
• sudden numbness and weakness in the arms and legs
• sweating
• swelling of the breasts or breast soreness in both females and males
• throat irritation
• trembling or shaking of the hands or feet
• trouble sleeping
• unexplained weight loss
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• weight loss

• Aggressive thoughts
• delusions
• hallucinations

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Antigout Agent
• Xanthine Oxidase Inhibitor

Take with or without meals or antacids.

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Liver function tests at baseline and then periodically, serum uric acid levels (as early as 2 weeks after initiation); signs/symptoms of MI or stroke, signs/symptoms of hypersensitivity or severe skin reactions

Mild and Moderate Renal Impairment (CrCl 30 to 89 mL/min) No adjustment recommended.
Severe Renal Impairment (CrCl less than 30 mL/min): Use with caution.
End-Stage Renal Impairment on Dialysis: Data not available