Xuriden

1 INDICATIONS AND USAGE XURIDEN ® is indicated in adult and pediatric patients for the treatment of hereditary orotic aciduria. XURIDEN is a pyrimidine analog for uridine replacement indicated in adult and pediatric patients for the treatment of hereditary orotic aciduria.

Recommended Dosage: The starting dosage is 60 mg/kg once daily; the dose may be increased to120 mg/kg (not to exceed 8 grams) once daily for insufficient efficacy. See the full prescribing information for 60 mg/kg and 120 mg/kg weight-based dosing tables. Preparation and Administration Measure the dose using either a scale accurate to at least 0.1 gram, or a graduated teaspoon, accurate to the fraction of the dose to be administered. Administer the dose with food (applesauce, pudding or yogurt) or in milk or infant formula. See full prescribing information for preparation and administration instructions.

2.1Recommended Dosage The

recommended starting dosage of oral XURIDEN is 60 mg/kg once daily. Increase the dosage of XURIDEN to 120 mg/kg (not to exceed 8 grams) once daily for insufficient efficacy, such as occurrence of one of the following: Levels of orotic acid in urine remain above normal or increase above the usual or expected range for the patient Laboratory values (e.g., red blood cell or white blood cell indices) affected by hereditary orotic aciduria show evidence of worsening Worsening of other signs or symptoms of the disease The XURIDEN dose to be administered at the 60 mg/kg and 120 mg/kg dose levels by body-weight is presented in Tables 1 and 2. A 2 gram packet of XURIDEN contains approximately ¾ teaspoon of XURIDEN. Therefore, in the tables below for patients requiring doses in multiples of 2 grams (¾ teaspoon) an entire packet(s) may be administered without weighing or measuring.

XURIDEN Daily Dose Based on Body Weight (kg) Patient Weight Table 1: XURIDEN 60 mg/kg total daily dose by weight category in the tables was rounded to achieve the approximate dose level Dose Level Kilograms Dose to be Administered Using a Scale (grams) Dose in Teaspoons up to 5 0.4 ⅛ 6-10 0.4 to 0.6 ¼ 11-15 0.7 to 0.9 ½ 16-20 1 to 1.2 21-25 1.3 to 1.5 26-30 1.6 to 1.8 ¾ 31-35 1.9 to 2.1 may use 1 entire 2 gram packet without weighing or measuring 36-40 2.2 to 2.4 1 41-45 2.5 to 2.7 46-50 2.8 to 3 51-55 3.1 to 3.3 1 ¼ 56-60 3.4 to 3.6 61-65 3.7 to 3.9 may use 2 entire 2 gram packets without weighing or measuring 1 ½ 66-70 4 to 4.2 71-75 4.3 to

4.5Above

75 6 may use 3 entire 2 gram packets without weighing or measuring 2 Patient Weight Table 2: XURIDEN 120 mg/kg total daily dose by weight category in the tables was rounded to achieve the approximate dose level Dose Level Kilograms Dose to be Administered Using a Scale (grams) Dose in Teaspoons up to 5 0.8 ¼ 6-10 0.8 to 1.2 ½ 11-15 1.4 to 1.8 ¾ 16-20 2 to 2.4 1 21-25 2.6 to 3 26-30 3.2 to 3.6 1 ¼ 31-35 3.8 to 4.2 may use 2 entire 2 gram packets without weighing or measuring 1 ½ 36-40 4.4 to 4.8 1 ¾ 41-45 5 to 5.4 2 may use 3 entire 2 gram packets without weighing or measuring 46-50 5.6 to 6 51-55 6.2 to 6.6 2 ¼ 56-60 6.8 to 7.2 2 ½ 61-65 7.4 to 7.8 66-70 8 2 ¾ may use 4 entire 2 gram packets without weighing or measuring 71-75 8 Above 75 8

2.2Preparation and Administration Preparation Measure the

dose using either a scale accurate to at least 0.1 gram, or a graduated teaspoon, accurate to the fraction of the dose to be administered. Once the measured dose has been removed from the XURIDEN packet, discard the unused portion of granules. Do not use any granules left in the open packet.

Administration with Food Place 3 to 4 ounces of applesauce, pudding or yogurt in a small clean container. Mix the measured amount of granules in the applesauce, pudding or yogurt Swallow applesauce/pudding/yogurt immediately. Do not chew the granules. Do not save the applesauce/pudding/yogurt for later use.

Drink at least 4 ounces of water. Administration in Milk or Infant Formula XURIDEN can be mixed with milk or infant formula instead of the soft foods described above for patients receiving up to 3/4 teaspoon (2 grams) of XURIDEN. After weighing the dose of XURIDEN: Pour 5 mL of milk or infant formula into a 30 mL medicine cup. Insert the tip of the oral syringe into the medicine cup and draw up 5 mL of milk/infant formula into the syringe.

Hold the syringe with the tip pointing upward. Pull down on the plunger until the plunger reaches 10 mL. This will add air to the syringe. Place the cap over the tip of the syringe. Then invert the syringe so the syringe tip is pointing down, and remove the plunger. Pour the measured amount of XURIDEN granules into the syringe barrel and reinsert the syringe plunger.

Do not push up on the plunger. Gently swirl the syringe to mix the XURIDEN granules with the liquid. Turn the syringe so the syringe tip is pointing up. Then remove the syringe cap and push up on the plunger until the plunger reaches the 5 mL mark. This will remove air from the syringe.

Place the tip of the syringe in the patient's mouth between the cheek and gum at the back of the mouth. Gently push the plunger all the way down. Refill the syringe with another 5 mL of milk/infant formula. Gently swirl the syringe to rinse any remaining XURIDEN granules from the syringe barrel.

Place the tip of the syringe in the patient's mouth between the cheek and gum at the back of the mouth. Gently push the plunger all the way down. Follow with a bottle of milk or infant formula, if desired.

None

None None

8.1Pregnancy Risk Summary There

are no available data on XURIDEN use in pregnant women to inform a drug-associated risk. When administered orally to pregnant rats during the period of organogenesis, uridine triacetate at doses similar to the maximum recommended human dose (MRHD) of 120 mg/kg per day was not teratogenic and did not produce adverse effects on embryo-fetal development . The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data Animal Data In an embryo-fetal development study, uridine triacetate was administered orally to pregnant rats during the period of organogenesis at doses up to 2000 mg/kg per day (about 2.7 times the maximum recommended human dose (MRHD) of 120 mg/kg per day on a body surface area basis). There was no evidence of teratogenicity or harm to the fetus and no effect on maternal body weight and overall health.

No adverse reactions were reported in clinical trials with XURIDEN in patients with hereditary orotic aciduria. To report SUSPECTED ADVERSE REACTIONS, contact BTG International Inc. at (1-877-377-3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because

clinical trials are conducted under widely varying conditions and using a wide range of doses, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of XURIDEN was assessed in 4 patients with hereditary orotic aciduria ranging in age from 3 to 19 years (3 male, 1 female) who received 60 mg/kg of XURIDEN once daily for six weeks. All patients continued to receive XURIDEN for at least 24 months at dosages of up to 120 mg/kg once daily.

No adverse reactions were reported with XURIDEN.