近日，美国食品药品监督管理局批准Xuriden上市。Xuriden是第一款由FDA准许的用于治疗遗传性乳清酸尿症的药物。遗传性乳清酸尿症是一种罕见的代谢紊乱疾病，据报道全世界仅有20例左右的遗传性乳清酸尿症的患者。
遗传性乳清酸尿症经由人类隐性基因获得。该病主要是因为机体代谢中存在有错误或有缺陷的酶（乳清酸磷酸核糖转移酶和乳清酸核苷酸脱羧酶），从而导致机体不能够合成正常的尿苷（嘧啶类核苷酸），而尿苷是核糖核酸的重要组成部分。乳清酸不能转变为尿苷酸，就会导致血液和尿液中大量出现乳清酸。遗传性乳清酸尿症的主要标志和病症包括血液异常（贫血、白细胞数量减少、嗜中性粒细胞数量减少）、因乳清酸结晶形成物堵塞尿道引发的尿道堵塞、发育停滞和生长迟缓。在Xuriden被批准用药之前，治疗遗传性乳清酸尿症常用的方案是每天给予1到1.5g的尿嘧啶核苷。
FDA药物评估和研究中心的药物三期评估办公室负责人助理 Amy G. Egan说：“此次批准Xuriden的上市和罕见儿科疾病的优先审查制度均凸显了FDA保证罕见病患者能够获得有效治疗措施的决心。而在Xuriden被批准之前，患有罕见代谢紊乱疾病的病人并没有通过政府认可的可行治疗方案。”
FDA之所以批准Xuriden孤儿药的研发上市主要归因于其能够治疗罕见病。在美国，孤儿药的设计研发将会得到财政方面的激励，像临床试验税收抵免、使用者费用减免以及保证市场独占性资格等，这些措施无疑推动了孤儿药研发的进程。同样地，作为孤儿药的Xuriden 经批准也得到了优先审批。FDA的药物优先审批机制为某类严重疾病或特殊情况的治疗药物的加速审批提供了获得重大突破的便利之门。由于政府鼓励防治罕见儿童疾病治疗的新药和生物制品的研发，Xuriden的研发企业获得了罕见儿科病优先审批的“特权”。
Xuriden是一种旨在代替脲苷的口服类产品。Xuriden作为口服颗粒剂，可与食物、牛奶、婴儿配方奶粉等混合服用，每天口服一次即可。
为了评估Xuriden的安全性和有效性，相关专家对患有4名从3岁到19岁不等的遗传性乳清酸尿症患者进行了无对照的为期六周的开放性标记试验，并根据需要将试验周期延长到六个月之久。此次研究评估了患者在试验期间的各项血液学参数的变化情况。不管是六周还是六个月的评估，四位采用Xuriden进行治疗的遗传性乳清酸尿症患者的各项血液学参数均表现稳定。此项脲苷替代治疗方案已从发表公开的文献资料中得到了进一步的印证和支持。在长达九个月的试验中，服用Xuriden治疗的患者并未出现任何副作用。
批准日期：2015年9月4日 公司：Wellstat生物制药公司上市。
Xuriden(尿苷三乙酸 uridine triacetate)颗粒剂 为口服使用
包装规格
2克/包*30包/盒
存储在控制室温，25°C（77°F）;游览允许15°至30°C（59°至86°F）

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use XURIDEN safely and effectively. See full prescribing information for XURIDEN.
XURIDEN™ (uridine triacetate) oral granules
Initial U.S. Approval: [20XX]
INDICATIONS AND USAGE
XURIDEN is a pyrimidine analog indicated for uridine replacement in patients with hereditary orotic aciduria. (1)
DOSAGE AND ADMINISTRATION
Recommended dosage (2.1):
The starting dosage is 60 mg/kg once daily
Increase the dose by 60 mg/kg increments up to a maximum of 240 mg/kg (not to exceed 8 grams) once daily for insufficient efficacy
Decrease the dose if diarrhea occurs that persists for 3 or more successive days without another identifiable cause.
See the full prescribing information for weight-based dosing tables.
Measure the dose using either a balance accurate to at least 0.1 gram, or a pharmacy-provided graduated teaspoon, accurate to the fraction of the dose to be administered
Administration (2.2)
Administer the dose in applesauce, pudding or yogurt or in milk/infant formula, see full prescribing information.
DOSAGE FORMS AND STRENGTHS
Oral granules: 2 gram packets. (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
None (5)
ADVERSE REACTIONS
No adverse reactions were reported with XURIDEN in patients with hereditary orotic aciduria (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Wellstat Therapeutics Corporation at (1-800-###-####) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 7/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
XURIDEN™ is a pyrimidine analog indicated for uridine replacement in patients with hereditary orotic aciduria.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
The recommended starting dosage of oral XURIDEN is 60 mg/kg once daily.
Increase the dose of XURIDEN by increments of 60 mg/kg up to a maximum of 240 mg/kg (not to exceed 8 grams) once daily for insufficient efficacy such as the following:
Levels of orotic acid in urine remain above normal or increase above the usual or expected range for the patient
Signs or symptoms of hereditary orotic aciduria show evidence of worsening
Laboratory values (e.g., red blood cell or white blood cell indices) affected by hereditary orotic aciduria show evidence of worsening
Decrease the dose of XURIDEN if diarrhea occurs that persists for 3 or more successive days without another identifiable cause.
The XURIDEN dose to be administered at various dose levels is presented in Tables 1 through 4. Measure the dose using either a balance accurate to at least 0.1 gram, or a pharmacy-provided graduated teaspoon, accurate to the fraction of the dose to be administered.
Tables 1 – 4 XURIDEN Daily Dose Based on Body Weight (kg)

Patient Weight	Table 1: XURIDEN 60 mg/kg Dose Level
Kilograms	Dose to be Administered Using a Balance (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	1.0 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
36-40	2.2 to 2.4	1
41-45	2.5 to 2.7
46-50	2.8 to 3.0
51-55	3.1 to 3.3	1 ¼
56-60	3.4 to 3.6
61-65	3.7 to 3.9	1 ½
66-70	4.0 to 4.2
71-75	4.3 to 4.5
>75	6	2
Patient Weight	Table 2: XURIDEN 120 mg/kg Dose Level
Kilograms	Dose to be Administered Using a Balance (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	2.0 to 2.4	1
21-25	2.6 to 3.0
26-30	3.2 to 3.6	1 ¼
31-35	3.8 to 4.2	1 ½
36-40	4.4 to 4.8	1 ¾
41-45	5.0 to 5.4	2
46-50	5.6 to 6.0
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
71-75	8
>75	8
Patient Weight	Table 3: XURIDEN 180 mg/kg Dose Level
Kilograms	Dose to be Administered Using a Balance (grams)	Dose in Teaspoons
Up to 5	0.9	½
6 to 10	1.1 to 1.8	¾
11 to 15	2.0 to 2.7	1
16 to 20	2.9 to 3.6	1 ¼
21 to 25	3.8 to 4.5	1 ½
26 to 30	4.7 to 5.4	2
31 to 35	5.6 to 6.3
36 to 40	6.5 to 7.2	2 ¼
41 to 44	7.4 to 7.9	2 ½
≥45	8	2 ¾
Patient Weight	Table 4: XURIDEN 240 mg/kg Dose Level
Kilograms	Dose to be Administered Using a Balance (grams)	Dose in Teaspoons
Up to 5	1.2	½
6 to 10	1.5 to 2.4	1
11 to 15	2.7 to 3.6	1 ¼
16 to 20	3.9 to 4.8	1 ¾
21 to 25	5.1 to 6.0	2
26 to 34	6.3 to 7.2	2 ½
≥ 35	8	2 ¾

* total daily dose by weight category in the tables was rounded to achieve the approximate dosage level
may use 1 entire 2 gram packet without weighing or measuring
may use 2 entire 2 gram packets without weighing or measuring
may use 3 entire 2 gram packets without weighing or measuring
may use 4 entire 2 gram packets without weighing or measuring
2.2 Preparation and Administration
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 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 soft foods, as described above.
For infants receiving up to ¼ teaspoon (0.8 grams) of XURIDEN. After weighing the dose of XURIDEN:
Remove the syringe plunger from a pharmacy-provided oral 10 mL syringe.
With a finger under the tip of the syringe, pour the measured amount of XURIDEN granules into the syringe barrel.
Reinsert the syringe plunger.
In a clean container with 10 mL of milk or infant formula, insert the tip of the oral syringe and draw up 5 mL of milk/infant formula into the syringe.
Gently swirl the syringe in order to prevent the granules from settling.
Administer the mixture immediately between the cheek and gum at the back of the mouth. Do not save the milk and granule mixture for later use.
Refill the syringe with the remaining 5 mL of milk/infant formula, swirl gently, and administer.
Follow this with a bottle of milk or infant formula if desired.
For older children (age 3 years and older) and adults:
Pour 3 to 4 ounces of milk into a clean container.
Add the measured amount of granules into the milk and stir briefly
Drink the mixture immediately. Do not chew the granules. Do not save the mixture for later use.
Drink at least 4 more ounces of water or milk.
3 DOSAGE FORMS AND STRENGTHS
Oral granules: 2 grams of orange-flavored oral granules (95% w/w) in single-use packets
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
None.
6 ADVERSE REACTIONS
6.1 Clinical 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 once daily of XURIDEN for six weeks. The patients continued to receive XURIDEN for at least 9 months at dosages of up to 120 mg/kg once daily. No adverse reactions were reported with XURIDEN. In clinical trials evaluating the use of XURIDEN for treatment of indications other than hereditary orotic aciduria, diarrhea was observed in some adult patients who received doses of 4 grams or 8 grams per day or greater [see Dosage and Administration (2.1)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
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 240 mg/kg per day was not teratogenic and did not produce adverse effects on embryo-fetal development [see Data]. 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 1.3 times the maximum recommend human dose (MRHD) of 240 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.
8.2 Lactation
Risk Summary
There are no data on the presence of uridine triacetate in human milk, the effect on the breastfed infant or the effect on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for XURIDEN and any potential adverse effects on the breastfed infant from XURIDEN or from the underlying maternal condition.
8.4 Pediatric Use
The safety and effectiveness of XURIDEN have been established in pediatric patients. Use of XURIDEN is supported by a single open-label clinical trial of uridine triacetate in 4 patients and a retrospective review of the clinical course of 19 patients with hereditary orotic aciduria who were treated with uridine beginning at ages 2 months to 12 years. There are no apparent differences in clinical response between adults and pediatric patients with hereditary orotic aciduria treated with uridine, however, data are limited. [see Clinical Studies (14)]
11 DESCRIPTION
XURIDEN (uridine triacetate) oral granules is a pyrimidine analog containing uridine triacetate. Uridine triacetate has the chemical designation (2',3',5'-tri-O-acetyl-ß-D-ribofuranosyl)-2,4(1H,3H)-pyrimidinedione. The molecular weight is 370.3 and it has an empirical formula of C15H18N2O9. The structural formula is:

Each single-use 2 gram packet of XURIDEN orange-flavored oral granules (95% w/w) contains 2 grams of uridine triacetate and the following inactive ingredients: ethylcellulose (0.062 grams), Opadry Clear [proprietary dispersion of hydroxypropylmethylcellulose and Macrogol] (0.015 grams), and natural orange juice flavor (0.026 grams).
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Uridine triacetate is an acetylated pro-drug of uridine. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation (Figure 1).
Figure 1: Uridine Triacetate Conversion to Uridine

XURIDEN provides uridine in the systemic circulation of patients with hereditary orotic aciduria who cannot synthesize adequate quantities of uridine due to a genetic defect in uridine nucleotide synthesis.
12.2 Pharmacodynamics
Hereditary orotic aciduria (uridine monophosphate synthase deficiency) is a rare congenital autosomal recessive disorder of pyrimidine metabolism caused by a defect in uridine monophosphate synthase (UMPS). The UMPS gene encodes uridine 5'monophosphate synthase, a bifunctional enzyme that catalyzes the final two steps of the de novo pyrimidine biosynthetic pathway in mammalian cells.
The defect in UMP synthase in hereditary orotic aciduria has two primary biochemical consequences. First, the blockade of de novo UMP synthesis results in a systemic deficiency of pyrimidine nucleotides, accounting for most clinical consequences of the disease. Second, orotic acid from the de novo pyrimidine pathway that cannot be converted to UMP is excreted in the urine, accounting for the common name of the disorder, orotic aciduria. Orotic acid crystals in the urine can cause episodes of obstructive uropathy.
XURIDEN delivers uridine into the circulation, where it can be used by essentially all cells to make uridine nucleotides, compensating for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced.
12.3 Pharmacokinetics
Absorption
Following oral administration, uridine triacetate is deacetylated by nonspecific esterases, yielding uridine in the circulation (Figure 1)
XURIDEN delivers 4- to 6-fold more uridine into the systemic circulation compared to equimolar doses of uridine itself. Maximum concentrations of uridine in plasma following oral XURIDEN are generally achieved within 2 to 3 hours, and the half-life ranges from approximately 2 to 2.5 hours.
A study in patients with hereditary orotic aciduria included an assessment of plasma uridine pharmacokinetics in 4 patients. Three of the patients were previously treated with oral uridine. On Day 0 (baseline), these three patients received their usual daily dose of oral uridine as a single dose (150 to 200 mg/kg once daily) and on Day 1, initiated oral XURIDEN treatment (60 mg/kg once daily). A fourth patient was enrolled who was naïve to uridine replacement therapy. The dose of XURIDEN was increased on Day 116 to 120 mg/kg once daily in two patients (Patients 1 and 2) and plasma uridine concentrations were assessed on Day 160 (44 days after the dose increase).
Plasma uridine levels in all four patients are depicted in Figure 2. Pharmacokinetic parameters are summarized in Table 5. Mean exposure to plasma uridine as assessed by Cmax and AUC was greater after oral XURIDEN than after oral uridine (approximately 4-fold on an equiweight basis, and 6-fold on an equimolar basis), although individual differences in relative bioavailability were noted. Plasma concentrations of the uridine catabolite uracil were generally below the limit of quantitation in all patients.
Figure 2 Plasma Uridine Following Oral Administration of Uridine (Day 0) or XURIDEN (Days 1, 28 and 160) in Patients with Hereditary Orotic Aciduria

Table 5: Pharmacokinetic Parameters for Plasma Uridine

Pharmacokinetic Parameters (Plasma Uridine)	Day 0 (Baseline) (Oral Uridine, 150 to 200 mg/kg once daily) N = 3 *	Day 1 (Oral XURIDEN, 60 mg/kg once daily) N = 4	Day 28 (Oral XURIDEN, 60 mg/kg once daily) N = 4	Day 160 (Oral XURIDEN, 120 mg/kg once daily) N = 2 †
Cmax (μM) mean ± SD	55.97  16.65	91.32  32.15	88.68  43.19	80.88 ± 19.98
Tmax (hours) median (range)	2.00 (1.03, 4.00)	2.03 (1.23, 2.08)	1.26 (1.00, 2.53)	3.02 (2.00, 4.03)
t1/2 (hours) mean  SD	1.63 ± 0.70	1.65  0.59	2.29 ± 1.65	8.15 ± 6.77
AUC(0-8) (μM∙hr) mean  SD	237.98  163.22	311.18  153.26	278.67  148.49	465.60  95.27

Data shown are from patients previously treated with oral uridine
The dose of XURIDEN was increased on Day 116 to 120 mg/kg per day. Serial plasma samples were taken on Day 160 (44 days after the dose increase) for plasma uridine levels.
Tmax range is expressed as the minimum and maximum values obtained
Food Effect on Uridine PK: A study in healthy adult subjects receiving a slightly different formulation of uridine triacetate granules (6 gram dose) under fed and fasted conditions showed no difference in the overall rate and extent of uridine exposure.
Distribution
Circulating uridine is taken up into mammalian cells via specific nucleoside transporters, and also crosses the blood brain barrier.
Excretion
Uridine can be excreted via the kidneys, but is also metabolized by normal pyrimidine catabolic pathways present in most tissues.
Drug Interaction Studies
In vitro enzyme inhibition data did not reveal meaningful inhibitory effects of uridine triacetate or uridine on CYP3A4, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. In vitro e nzyme induction data did not reveal an inducing effect of XURIDEN or uridine on CYP1A2, CYP2B6, or CYP3A4.
In vitro data showed that uridine triacetate was a weak substrate for P-glycoprotein. Uridine triacetate inhibited the transport of a known P-glycoprotein substrate, digoxin with an IC50 of 344 μM. Due to potential for high local (gut) concentrations of the drug after dosing, interaction of Xuriden with orally administered P-gp substrate drugs cannot be ruled out.
In vivo data in humans are not available.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of uridine triacetate.
Uridine triacetate was not genotoxic in the Ames test, the mouse lymphoma assay and the mouse micronucleus test.
Orally administered uridine triacetate did not affect fertility or general reproductive performance in male and female rats at doses up to 2000 mg/kg per day (about 1.3 times the maximum recommend human dose (MRHD) of 240 mg/kg per day on a body surface area basis).
14 CLINICAL STUDIES
The efficacy of XURIDEN was evaluated in an open-label study in 4 patients with hereditary orotic aciduria (3 male, 1 female; age range from 3 to 19 years). Three patients were previously treated with uridine and were switched at study entry to XURIDEN. All patients were administered XURIDEN orally at a daily dosage of 60 mg/kg once daily. The study duration was 6 weeks.
The study assessed changes in the patients' pre-specified hematologic parameter during the 6-week trial period. The pre-specified hematologic parameters were: percent neutrophils (Patient 1), white blood cell count (Patient 2), and mean corpuscular volume (Patients 3 and 4).
For patients switched from oral uridine to oral XURIDEN (Patients 1, 2, and 3), the primary endpoint was stability of the hematologic parameter; for the treatment-naïve patient (Patient 4), the primary endpoint was improvement of the hematologic parameter. Secondary endpoints were urine orotic acid and orotidine levels, and growth (height and weight).
After six weeks of treatment, hematologic values remained stable for all 4 patients. Table 6 summarizes the primary efficacy results.
Table 6: Primary Efficacy Results for Study 1 

Patient	Pre-specified hematologic parameter (Age-specific reference range)	Primary Endpoint	Baseline (Day 0)	Week 6 (Day 42)	% Change from Baseline
Patient #1	Neutrophil % (26-48%)	Stable hematologic value	21	23	10%
Patient #2	WBC Count (3.8-10.6 ×109/L)	Stable hematologic value	7.8	7.4	-5%
Patient #3	MCV (75-91 fL)	Stable hematologic value	109.9	108.5	-1%
Patient #4	MCV (72-90 fL)	Improved hematologic value	114.6	113.4	-2%

At baseline, three patients had normal urine orotic acid levels and all four patients had normal urine orotidine levels. After 6 weeks of treatment, orotic acid and orotidine levels remained stable.
During an extension phase of the trial, patients continued to receive uridine triacetate. Dosing during the extension phase ranged from 60 mg/kg to 120 mg/kg once daily. After 6 months of treatment, Patient #1's neutrophil percent value normalized; hematologic parameters for the other three patients remained stable. Orotic acid and orotidine levels also remained stable for all four patients.
The treatment effect of XURIDEN on growth was assessed in the three pediatric patients (Patients 1, 3, and 4). At baseline, weight and height measurements were at or below the lower limit of normal for age (<5th percentile for age) for Patients 1 and 4; height and weight measurements were within the normal range for age for Patient 3. After 6 months of treatment, Patients 1 and 3 experienced improved weight growth, as reflected in increases in their weight-for-age percentiles and weight velocity percentiles; Patient 4's weight growth remained stable (i.e., weight percentile for age and weight velocity percentile for age was unchanged). Height growth remained stable in all three patients (i.e., height percentiles for age and height velocity percentiles for age were unchanged).
INSERT 12 MONTH GROWTH RESULTS
Case reports
Nineteen (19) case reports of patients with HOA have been documented in published literature. Eighteen (18) were diagnosed as infants or children between the ages of 2 months and 12 years, and one was diagnosed at age 28.
All 19 patients presented with significantly elevated levels of urinary orotic acid. Fifteen of 19 had abnormal hematologic parameters at presentation, including 15 with megaloblastic anemia, 8 with leukopenia and at least 2 with neutropenia. Oral administration of exogenous sources of uridine was reported to significantly improve hematologic abnormalities (megaloblastic anemia, leukopenia and neutropenia) within 2 to 3 weeks in almost all documented cases when administered in sufficient amounts. Concentrations of urinary orotic acid were significantly reduced within 1 to 2 weeks of initiating uridine replacement therapy. Some fluctuation in levels of urinary orotic acid were observed, but always at much lower levels than those reported prior to treatment. Improvements in body weight and other developmental parameters were also documented over time with continued uridine replacement therapy.
The effects of exogenous uridine were maintained over months and years, as long as treatment continued at sufficient doses (with appropriate dose increases based on body weight increases). Within days up to 2 or 3 weeks, most hematologic abnormalities and orotic aciduria reappeared when administration of uridine was stopped or doses reduced. If treatment was interrupted for longer periods, body weight and other gains receded. If absolute dosages were not adjusted adequately to compensate for body weight gains, signs and symptoms of HOA recurred.
16 HOW SUPPLIED/STORAGE AND HANDLING
XURIDEN orange-flavored oral granules (95% w/w) are available in single-use packets (NDC 69468-152-02) containing 2 grams of uridine triacetate in cartons of 30 packets each (NDC 69468-152-30) of uridine triacetate in cartons of 30 packets each.
Store at controlled room temperature, 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
17 PATIENT COUNSELING INFORMATION
Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information)
Advise the patient or caregiver to measure the prescribed dose using either a balance accurate to at least 0.1 gram, or a pharmacy-provided graduated teaspoon, accurate to the fraction of the dose to be administered. For some doses 1 or more entire 2 gram packets can be used without weighing out the granules. [see Dosage and Administration (2.1)].
Advise the patient or caregiver that XURIDEN can be taken without regard to meals.
Advise the patient or caregiver to discard the unused portion of granules in a packet after measuring out the dose. Advise the patient or caregiver to not use any granules left in the open packet.
Advise the patient or caregiver that XURDEN can be taken mixed in applesauce, pudding or yogurt, or mixed in milk or water. The dose should be taken immediately after mixing and should not be saved for later use. Advise the patient or caregiver not to chew the granules and to drink a glass of water after swallowing the mixture. [see Preparation and Administration (2.2)].
Advise the caregiver of an infant patient that XURIDEN can be mixed with milk or infant formula and given using a pharmacy-provided 10 mL syringe. If desired, administration can be followed by a bottle of milk or infant formula.