2.1 Important Dosing Instructions

• Initiate cysteamine treatment immediately after diagnosis of nephropathic cystinosis.
• Cysteamine-naïve Patients: Start PROCYSBI at a fraction of the maintenance dosage.
  • Patients 1 year to less than 6 years: Gradually increase the dosage, allowing a minimum of 2 weeks between adjustments [see Dosage and Administration (2.2)].
  • Patients 6 years of age and older: Gradually increase the dosage over 4 to 6 weeks until the maintenance dosage is achieved.
• Patients switching from immediate-release cysteamine: Start the total daily dosage of PROCYSBI at a dosage equal to the previous total daily dosage of immediate-release cysteamine [see Dosage and Administration (2.3)].
• If adverse reactions occur, decrease the PROCYSBI dosage.
• After the maintenance dosage of PROCYSBI is achieved: The dosage may need to be further increased to achieve a therapeutic target WBC cystine concentration. The maximum dosage of PROCYSBI is 1.95 grams/m2 of body surface area per day [see Dosage and Administration (2.4, 2.5)].
• Round dose calculations to the nearest incremental dosage that can be administered using the available strengths of PROCYSBI delayed-release capsules or packets of oral granules. Only use whole capsules or entire contents of the packets.

2.2 Starting and Maintenance Dosing in Cysteamine-Naïve Patients

• Start treatment with a dosage equal to ⅙ to ¼ of the maintenance dosage.
• The maintenance dosage after initial dose escalation is 1.3 g/m2 of body surface area per day divided into two doses given every 12 hours. Table 1 shows the recommended starting and maintenance dosages of PROCYSBI, converted from body-surface area to body weight.
  • Patients 1 year to less than 6 years: Increase the dosage in 10% increments to the maintenance dosage, while monitoring WBC cystine concentrations. Allow a minimum of 2 weeks between dosage adjustments [see Dosage and Administration (2.4, 2.5)]. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation and use the dosage as the patient's maintenance dosage.
  • Patients 6 years of age and older: Gradually increase the dosage over 4 to 6 weeks until the maintenance dosage is achieved.
• If a patient experiences initial intolerance, temporarily discontinue PROCYSBI and then re-start at a lower dosage and gradually increase dosage.

2.3 Switching Patients from Immediate-Release Cysteamine Bitartrate

• When switching patients from immediate-release cysteamine bitartrate to PROCYSBI, the starting total daily dose of PROCYSBI is equal to the previous total daily dose of immediate-release cysteamine bitartrate. Divide the total daily dose by two and administer every 12 hours.
• For patients who may experience temporary intolerance upon starting PROCYSBI, decrease the dosage and then gradually increase to the maintenance dosage.
• Measure the WBC cystine concentration two weeks after initiation of PROCYSBI [see Dosage and Administration (2.5)]. Adjust the PROCYSBI dosage as needed to achieve the therapeutic target WBC cystine concentration [see Dosage and Administration (2.4)]. The maximum dosage of PROCYSBI is 1.95 grams/m2 per day.

2.4 Dosage Titration to Therapeutic Target WBC Cystine Concentration

• Measure WBC cystine concentration and titrate the PROCYSBI dosage as needed to achieve the therapeutic target WBC cysteine concentration [see Dosage and Administration (2.5)].
• If the measured WBC cystine concentration is above the target level for cystine depletion, consider the following before dose adjustment: adherence to medication and dosing interval, the timing between the last dose and the blood draw for the laboratory measurement, and the timing of PROCYSBI administration in relation to food or other administration instructions.
• If a dose adjustment is required, increase the dosage by 10%, rounded to nearest dosage that can be administered using the available strengths of capsules or packets of oral granules. For patients 1 year to less than 6 years of age, allow a minimum of two weeks between dose increments. The maximum dosage of PROCYSBI is 1.95 grams/m2 per day.
• If adverse reactions occur, decrease the PROCYSBI dosage. Some patients may be unable to achieve their therapeutic target due to poor tolerability of PROCYSBI [see Warnings and Precautions (5), Adverse Reactions (6.1)].

2.5 Laboratory Monitoring

• WBC cystine concentration may be measured using the mixed leukocyte assay or by using assays for specific WBC subsets (e.g., granulocyte method). The methods used for measuring cystine and total protein content may also vary among individual laboratories [see Clinical Pharmacology (12.2)].
• Normal WBC cystine ranges and therapeutic target levels for cystine depletion depend upon the assay method used by the individual laboratory. WBC cystine values obtained from using different assay methods may not be comparable. Refer to the assay-specific therapeutic target for cystine depletion. When using the mixed leukocyte assay, the recommended target WBC cystine concentration is less than 1 nmol ½ cystine/mg protein.
• The recommended frequency of monitoring WBC cystine concentration is as follows:
  • Cysteamine-naïve patients 1 year to less than 6 years: Obtain measurement two weeks after initiation of PROCYSBI treatment and continue monitoring during dosage titration period until the therapeutic target WBC cystine concentration is achieved. Once the therapeutic target is achieved, continue monitoring monthly for 3 months, then quarterly for 1 year, and then twice-yearly, at a minimum.
  • Cysteamine-naïve patients greater than 6 years: Obtain measurement after reaching the maintenance PROCYSBI dosage, then monthly for 3 months, quarterly for 1 year, and then twice-yearly, at a minimum.
  • Patients switching from immediate-release cysteamine to PROCYSBI: Obtain measurement two weeks after initiation of PROCYSBI treatment and continue monitoring if further dosage titration is required to achieve therapeutic target WBC cystine concentration. Once the therapeutic target is achieved, continue monitoring quarterly for 6 months, then twice yearly, at a minimum.
• Obtain blood samples for WBC cystine concentration measurement 12 hours after the patient's last PROCYSBI dose, prior to administration of the next dose (i.e., trough concentration). In addition, it is important to accurately record the time of the last dose, the actual dose, and the time the blood sample was taken.

2.6 Preparation and Administration

• PROCYSBI delayed-release capsules:
  • Swallow capsules whole. Do not crush or chew capsules or capsule contents.
  • Take capsules with fruit juice (except grapefruit juice) or water.
  • For patients who cannot swallow the capsules, the capsules can be opened and the capsule contents sprinkled on and mixed in applesauce, berry jelly or fruit juice (except grapefruit juice) and administered orally, as described below.
  • For patients with a gastrostomy tube, the capsules can be opened and the capsule contents mixed in applesauce and administered via the gastrostomy tube, as described below.
• PROCYSBI delayed-release oral granules:
  • Do not crush or chew oral granules.
  • Sprinkle and mix the intact granules in applesauce, berry jelly or fruit juice (except grapefruit juice) and administered orally, as described below.
  • For patients with a gastrostomy tube, the oral granules can be mixed in applesauce and administered via a gastrostomy tube, as described below.
• Administer PROCYSBI at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate [see Drug Interactions (7.1)].
• Do not eat for at least 2 hours before taking PROCYSBI and for at least 30 minutes after to maximize absorption. If patients are unable to take PROCYSBI without eating, take with food and limit the amount of food to approximately 4 ounces (½ cup) within 1 hour before taking PROCYSBI through 1 hour after taking PROCYSBI. Take PROCYSBI in a consistent manner in regard to food. Avoid high fat food close to dosing of PROCYSBI.
• Avoid drinking alcohol while taking PROCYSBI [see Drug Interactions (7.2)].

5.1 Ehlers-Danlos-like Syndrome

Skin and bone lesions that resemble clinical findings for Ehlers-Danlos-like syndrome have been reported in patients treated with high doses of immediate-release cysteamine bitartrate or other cysteamine salts. These include molluscoid pseudotumors (purplish hemorrhagic lesions), skin striae, bone lesions (including osteopenia, compression fractures, scoliosis and genu valgum), leg pain, and joint hyperextension. One patient on immediate-release cysteamine bitartrate with serious skin lesions subsequently died of acute cerebral ischemia with marked vasculopathy. Monitor patients for development of skin or bone lesions and interrupt PROCYSBI dosing if patients develop these lesions. PROCYSBI may be restarted at a lower dose under close supervision, then slowly increase to the appropriate therapeutic dose [see Dosage and Administration (2.1, 2.4)].

5.2 Skin Rash

Severe skin rashes such as erythema multiforme bullosa or toxic epidermal necrolysis have been reported in patients receiving immediate-release cysteamine bitartrate. If severe skin rashes develop, permanently discontinue use of PROCYSBI [see Contraindications (4)].

5.3 Gastrointestinal Ulcers and Bleeding

Gastrointestinal (GI) ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate. GI tract symptoms including nausea, vomiting, anorexia and abdominal pain, sometimes severe, have been associated with cysteamine. If severe GI tract symptoms develop, consider decreasing the dose of PROCYSBI [see Dosage and Administration (2.1, 2.4)].

5.4 Fibrosing Colonopathy

Fibrosing colonopathy, including colonic stricture formation, has been reported with postmarketing use of PROCYSBI in pediatric and young adult patients with nephropathic cystinosis. Some of these patients had been treated with PROCYSBI for prolonged periods of time. Reported symptoms include: abdominal pain, vomiting, bloody or persistent diarrhea, and fecal incontinence. Evaluate patients with severe, persistent, and/or worsening abdominal symptoms for fibrosing colonopathy. If the diagnosis is confirmed, permanently discontinue PROCYSBI and switch to immediate-release cysteamine bitartrate capsules. An association between methacrylic acid-ethyl acrylate copolymer (an inactive ingredient in PROCYSBI) and fibrosing colonopathy cannot be ruled out.

5.5 Central Nervous System Symptoms

Central Nervous System (CNS) symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with immediate-release cysteamine. Neurological complications have also been described in some patients with cystinosis who have not been treated with cysteamine. Carefully evaluate and monitor patients who develop CNS symptoms. Interrupt medication or adjust the dose as necessary for patients with severe symptoms or with symptoms that persist or progress. Inform patients that PROCYSBI may impair their ability to perform tasks such as driving or operating machinery.

5.6 Leukopenia and/or Elevated Alkaline Phosphatase Levels

Cysteamine has been associated with reversible leukopenia and elevated alkaline phosphatase levels. Monitor white blood cell counts and alkaline phosphatase levels. If tests values remain elevated, consider decreasing the dose or discontinuing the drug until values revert to normal.

5.7 Benign Intracranial Hypertension

Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema have been reported in patients receiving immediate-release cysteamine bitartrate treatment. Monitor patients for signs and symptoms of PTC, including headache, tinnitus, dizziness, nausea, diplopia, blurry vision, loss of vision, pain behind the eye or pain with eye movement. If signs/symptoms persist, interrupt dosing or decrease the dose and refer the patient to an ophthalmologist. If the diagnosis is confirmed, permanently discontinue use of PROCYSBI.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described below reflect exposure to cysteamine in 345 patients with nephropathic cystinosis (246 patients receiving immediate-release cysteamine as cysteamine hydrochloride or phosphocysteamine, and 80 patients receiving PROCYSBI) in open-label clinical trials.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of cysteamine bitartrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Musculoskeletal: Joint hyperextension, leg pain, osteopenia, compression fracture, scoliosis, genu valgum [see Warnings and Precautions (5.1)].
• Skin: Erythema multiforme bullosa, toxic epidermal necrolysis, Ehlers-Danlos-like syndrome, molluscoid pseudotumors, skin striae, skin fragility [see Warnings and Precautions (5.1, 5.2)].
• Gastrointestinal: Fibrosing colonopathy reported with PROCYSBI [see Warnings and Precautions (5.4)].
• Central Nervous System: seizures, lethargy, somnolence, depression and encephalopathy [see Warnings and Precautions (5.5)], benign intracranial hypertension (or PTC) and/or papilledema [see Warnings and Precautions (5.7)].

7.1 Drugs that Increase Gastric pH

Drugs that increase the gastric pH (e.g., medications containing bicarbonate or carbonate) may alter the pharmacokinetics of cysteamine due to the premature release of cysteamine from PROCYSBI and increase WBC cystine concentration. Concomitant administration of 20 mg omeprazole did not affect the pharmacokinetics of cysteamine when PROCYSBI was administered with 240 mL of orange juice or with 240 mL of water [see Clinical Pharmacology (12.3)]. Monitor WBC cystine concentration when drugs that increase the gastric pH are concomitantly used [see Dosage and Administration (2.5)].

7.2 Use with Alcohol

Consumption of alcohol with PROCYSBI may increase the rate of cysteamine release and/or adversely alter the pharmacokinetic properties, as well as the effectiveness and safety of PROCYSBI. Therefore, do not consume alcoholic beverages during treatment with PROCYSBI [see Dosage and Administration (2.6)].

7.3 Other Medications Used for the Management of Fanconi Syndrome

PROCYSBI can be administered with other electrolyte and mineral replacements necessary for management of Fanconi syndrome, as well as vitamin D and thyroid hormone.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of PROCYSBI have been established in pediatric patients 1 year of age and older for the treatment of nephropathic cystinosis. Use of PROCYSBI is supported by evidence from patients switched to PROCYSBI from immediate-release cysteamine bitartrate in two trials: an open-label, randomized, cross-over trial in adults and pediatric patients aged 6 years and older (n=43) and an open-label extension trial in pediatric patients aged 2 years and older (n=59). Another open-label trial was conducted in cysteamine naïve pediatric patients 1 year to less than 6 years of age (n=15) [see Clinical Trials (14.2)]. The safety profile in pediatric patients was similar to adults. In patients less than 6 years of age, vomiting occurred in 12/15 cysteamine treatment naïve patients compared to 11/13 patients switched from immediate-release cysteamine to PROCYSBI.

The safety and effectiveness of PROCYSBI have not been established in patients less than 1 year of age.

8.5 Geriatric Use

No studies with PROCYSBI have been conducted in geriatric patients.

12.1 Mechanism of Action

Cysteamine is an aminothiol that participates within lysosomes in a thiol-disulfide interchange reaction converting cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome in patients with cystinosis.

12.2 Pharmacodynamics

Normal individuals and persons heterozygous for cystinosis have WBC cystine concentrations of less than 0.2 and usually below 1 nmol ½ cystine/mg protein, respectively, when measured using the mixed leukocyte assay. Untreated patients with nephropathic cystinosis have elevations of WBC cystine concentration above 2 nmol ½ cystine/mg protein.

After the administration of a single dose of PROCYSBI, peak concentrations of cysteamine were observed at 3 hours post-dose. The nadir of WBC cystine closely followed the peak concentrations at 3.5 hours post-dose, and returned to baseline WBC concentrations at 12 hours-post dose. The cystine concentration in WBC lysate was measured with LC/MS/MS and total protein content in human WBC lysate was measured using the bicinchoninic acid (BCA) assay. A correction factor was applied to the total protein content for the difference in results from the Lowry method. The cystine concentration in nmol ½ cystine/mg protein was calculated by multiplying nmol cystine/mg protein by 2 [see Dosage and Administration (2.5)].

12.3 Pharmacokinetics

The pharmacokinetics of cysteamine with administration of PROCYSBI were evaluated in 43 patients age ranged from 6 to 26 years (mean age 12 years) with cystinosis and with an estimated glomerular filtration rate of greater than 30 mL/minutes/1.73 m2. Table 4 shows the mean pharmacokinetic parameters for PROCYSBI and immediate-release cysteamine bitartrate at steady state. The mean (± SD) dose for PROCYSBI was 656 ± 144 mg/m2 (given every 12 hours) and for immediate-release cysteamine bitartrate was 404 ± 88 mg/m2 (given every 6 hours).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Cysteamine has not been tested for its carcinogenic potential in long-term animal studies.

PROCYSBI was not mutagenic in the Ames test. It produced a negative response in an in-vitro sister chromatid exchange assay in human lymphocytes, but a positive response in a similar assay in hamster ovarian cells.

Repeat breeding reproduction studies were conducted in male and female rats. Cysteamine was found to have no effect on fertility and reproductive performance at an oral dose of 75 mg/kg per day (450 mg/m2 per day, 0.4 times the recommended human dose based on body surface area). At an oral dose of 375 mg/kg per day (2250 mg/m2 per day, 1.7 times the recommended human maintenance dose based on body surface area), it reduced the fertility of the adult rats and the survival of their offspring.

14.1 Clinical Trials with Immediate-Release Cysteamine

Efficacy of immediate-release cysteamine bitartrate was demonstrated in open-label clinical trials of cysteamine hydrochloride and phosphocysteamine.

An open-label clinical trial of cysteamine hydrochloride was conducted in 94 pediatric patients (mainly from the United States) with nephropathic cystinosis. Patients were treated with increasing doses of cysteamine hydrochloride (mean dose 54 mg/kg per day) to attain WBC cystine concentrations of less than 2 nmol ½ cystine/mg protein 5 to 6 hours post-dose. The clinical outcomes were compared with a historical control group of 17 pediatric patients who had been in the placebo group of a randomized placebo-controlled trial of ascorbic acid. Cysteamine-treated patients had been diagnosed at a mean age of 22 months and had a mean age of 46 months old at study entry; placebo patients had been diagnosed at about 29 months and had a mean age of about 52 months old at trial entry. The principal measures of effectiveness were serum creatinine and calculated creatinine clearance and growth (height).

The average median WBC cystine concentration during treatment was 1.7 ± 0.2 nmol ½ cystine/mg protein. There were 70 cysteamine-treated patients with a baseline serum creatinine of less than 2 mg/dL who were followed for at least 1 year, and 17 placebo patients. Twelve of the 94 cysteamine-treated patients required early dialysis or renal transplant. Median follow-up of cysteamine patients was over 32 months, and 20% were followed more than 5 years. Median follow-up of the placebo group was 20 months; only 1 patient was followed more than 24 months. Glomerular function among cysteamine-treated patients was maintained over time. Placebo-treated patients experienced a gradual rise in serum creatinine. Renal tubular function was not affected by treatment.

Calculated creatinine clearances were evaluated for two groups of pediatric patients, one with poor WBC cystine depletion (defined as median WBC cystine concentrations greater than 3 nmol ½ cystine/mg protein or WBC cystine concentrations not measured at least 2 times per year) and one with good WBC cystine depletion. The final mean creatinine clearance of the good depletion group was 20.8 mL/min/1.73 m2 greater than the mean for the poor-depletion group.

Height-for-age measurements of treated patients were compared with height-for-age measurements of 143 patients initially screened for inclusion in the trial. Patients on treatment maintained growth (i.e., did not show increasing growth failure compared with normal scales) although growth velocity did not increase enough to allow patients to catch up to age norms for height.

In another open-label clinical trial, 46 patients who had completed the clinical trial of cysteamine hydrochloride (averaging 6.5 years of treatment) and 93 treatment naïve patients were treated with either cysteamine hydrochloride or phosphocysteamine (patient's choice). Patients had cystinosis diagnosed by elevated WBC cystine (mean 3.63 nmol ½ cystine/mg). Newly enrolled patients and the 46 continuing patients were required to have serum creatinine less than 3 mg/dL and 4 mg/dL, respectively. Patients were randomized to doses of 1.3 or 1.95 grams/m2 per day and stratified according to whether the serum creatinine was above 1.2 mg/dL or not. Doses could be raised if WBC cystine concentrations were approximately 2 nmol ½ cystine/mg protein and lowered due to intolerance. The mean age of the newly enrolled patients was about 49 months for the cysteamine group and about 34 months for the phosphocysteamine group. The mean age of the patients in the long-term follow-up group was about 9 years.

Mean doses were 1.27 grams/m2 per day and 1.87 grams/m2 per day in the two groups and WBC cystine concentrations averaged 1.72 ± 1.65 nmol ½ cystine/mg protein and 1.86 ± 0.92 nmol ½ cystine/mg protein in the 1.3 grams/m2 per day and 1.95 grams/m2 per day in the two groups, respectively. In new patients, serum creatinine was essentially unchanged over the period of follow-up (about half of the patients were followed for 24 months) and phosphocysteamine and cysteamine hydrochloride had similar effects. The long-term follow-up group also had essentially no change in renal function (almost 80% were followed at least 2 years). In four studies of patients with untreated cystinosis, renal death (need for transplant or dialysis) occurred at median age of less than 10 years. Both new patients and patients in the long-term follow-up group maintained height (although they did not catch up from baseline). There was no apparent difference in height maintenance between the two doses.

14.2 Clinical Trials with PROCYSBI

How Supplied

Storage and Handling

• Prior to dispensing, store PROCYSBI delayed-release capsules and PROCYSBI delayed-release oral granules in a refrigerator, 2°C to 8°C (36°F to 46°F).
• Dispense PROCYSBI delayed-release capules and PROCYSBI delayed-release oral granules with a 4 month discard date.
• Dispense in original packaging. Do not subdivide or repackage.
• Do not remove desiccant or oxygen absorber(s) from the bottle of PROCYSBI delayed-release capsules. Keep bottles tightly closed in a dry place.
• Protect from light and moisture.

Instructions for the Patient

• Store PROCYSBI delayed-release capsules and PROCYSBI delayed-relase oral granules at room temperature, 20°C to 25°C (68°F to 77°F) in the original packaging. Do not subdivide or repackage.
• Protect from light and moisture.
• Do not store PROCYSBI delayed-release oral granules in opened packets.

Ehlers-Danlos-like Syndrome

Advise patients and caregivers that PROCYSBI may cause abnormalities of the skin, bones, and joints. Advise patients to report any skin changes or problems with their bones or joints to their physician [see Warnings and Precautions (5.1)].

Skin Rash

Advise patients and caregivers to contact their physician immediately if they experience a skin rash [see Warnings and Precautions (5.2)].

Gastrointestinal Ulcers and Bleeding

Advise patients and caregivers that PROCYSBI may cause ulcers and bleeding. Advise patients to contact their physician immediately if they experience stomach pain, nausea, vomiting, loss of appetite, or are vomiting blood [see Warnings and Precautions (5.3)].

Fibrosing Colonopathy

Advise patients and caregivers that fibrosing colonopathy has been reported with PROCYSBI. Advise patients to contact their physician immediately if they experience severe, persistent and/or worsening stomach pain, vomiting, bloody or persistent diarrhea, or inability to control bowel movements [see Warnings and Precautions (5.4)].

Central Nervous System Symptoms

Advise patients and caregivers that PROCYSBI may impair their ability to perform tasks such as driving or operating machinery. Advise patients to contact their physician immediately if they experience seizures, lethargy, somnolence, depression, and encephalopathy [see Warnings and Precautions (5.5)].

Benign Intracranial Hypertension

Advise patients and caregivers that PROCYSBI may cause benign intracranial hypertension. Advise patients to contact their physician immediately if they experience headache, tinnitus, dizziness, nausea, double vision, blurry vision, loss of vision, or eye pain [see Warnings and Precautions (5.7)].

Use by Pregnant Women

Advise patients and to contact their physician immediately if they suspect they may be pregnant. Discuss with the patient the individual risks and benefits of continuing PROCYSBI during pregnancy [see Use in Specific Populations (8.1)].

Breastfeeding

Advise patients that breastfeeding is not recommended while taking PROCYSBI [see Use in Specific Populations (8.2)].

Laboratory Monitoring

Discuss with the patient and caregivers the importance of required laboratory testing to determine the correct dose of PROCYSBI [see Dosage and Administration (2.5)].

Administration

• Advise patients and caregivers to follow the instruction below for taking PROCYSBI.
  Capsules:
  • Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents.
  • Take PROCYSBI capsules with fruit juice (except grapefruit juice) or water.
  • For patients who cannot swallow the capsules, the capsules can be opened and the capsule contents sprinkled on and mixed in applesauce, berry jelly or fruit juice (except grapefruit juice) and administered orally.
  • For patients with a gastrostomy tube, follow the instructions in the Instructions for Use.
  Oral Granules:
  • Do not crush or chew the granules.
  • Sprinkle and mix intact granules from on applesauce, berry jelly or fruit juice (except grapefruit juice) and administer orally.
  • For patients with a gastrostomy tube, follow the instruction in the Instructions for Use
• Administer PROCYSBI at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate.
• Do not eat for at least 2 hours before and for at least 30 minutes after taking PROCYSBI. If unable to take PROCYSBI without eating, take with food but limit the amount of food to approximately 4 ounces (½ cup) 1 hour before through 1 hour after administration. Avoid high fat food close to dosing of PROCYSBI.
• Avoid drinking alcohol while taking PROCYSBI.
• Take PROCYSBI consistently and to not miss doses. If a dose is missed, take the dose as soon as possible up to 8 hours after the scheduled time. However, if a dose is missed and the next scheduled dose is due in less than 4 hours, do not take the missed dose, and to take the next dose at the usual scheduled time. Do not take 2 doses at one time to make up for a missed dose [see Dosage and Administration (2.6)].

Storage

Advise patients and caregivers to keep PROCYSBI in a dry place. Protect from moisture. For bottles, keep PROCYSBI delayed-release capsules in the original bottle. Do not remove the dessicant or oxygen absorber from the bottle. Do not store PROCYSBI delayed-release oral granules in opened packets [see How Supplied/Storage and Handling (16)].