Procysbi

Cysteamine bitartrate · Granule, Delayed Release · Oral

Prescription (Rx) Cystine Depleting Agent

Uses

1 INDICATIONS AND USAGE PROCYSBI is indicated for the treatment of nephropathic cystinosis in adults and pediatric patients 1 year of age and older. PROCYSBI is a cystine-depleting agent indicated for the treatment of nephropathic cystinosis in adults and pediatric patients 1 year of age and older. ( 1 )

Dosage and administration

Recommended Dosage in Cysteamine-Naïve Patients See full prescribing information for weight-based dosing tables for the starting and maintenance dosage. ( 2.2 ) For initial intolerance, temporarily discontinue and then re-start PROCYSBI at a lower dosage and gradually increase to the maintenance dosage. ( 2.2 ) Switching from Immediate-release Cysteamine to PROCYSBI Start with a total daily dose of PROCYSBI equal to the previous total daily dose of immediate-release cysteamine bitartrate. ( 2.3 ) Dose Titration Adjust dose to achieve a therapeutic target white blood cell (WBC) cystine concentration. ( 2.4 , 2.5 ) If a dose adjustment is required, increase the dosage by 10%. The maximum dosage is 1.95 grams/m 2 per day. ( 2.4 ) If adverse reactions occur, decrease the dosage. Some patients may be unable to achieve their therapeutic target. ( 2.4 ) Preparation and Administration ( 2.6 ) Capsules : Swallow whole; do not crush or chew capsules or capsule contents. Take the capsules with fruit juice (except grapefruit juice) or water. Oral Granules: Do not crush or chew the granules. Sprinkle and mix the granules in applesauce, berry jelly or fruit juice (except grapefruit juice). For patients who cannot swallow the capsules or with gastrostomy tubes, see the full prescribing information on how to prepare and administer the capsules and oral granules. 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. Avoid drinking alcohol while taking PROCYSBI. 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/m 2 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/m 2 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. Table 1: Starting and Maintenance Dosage of PROCYSBI by Body Weight in Cysteamine-Naïve Patients 1 Year of Age and Older (Dosage Rounded Using Available Strengths of Capsules or Packets of Oral Granules) Weight in kilograms Starting PROCYSBI Dosage in mg every 12 hours, as a Fraction of the Maintenance Dosage Maintenance PROCYSBI Dosage in mg every 12 hours Higher dosages may be required to achieve target therapeutic WBC cystine concentration [see Dosage and Administration (2.4) ] . ⅙ of dosage ¼ of dosage 5 or less 25 50 200 6 to 10 50 75 300 11 to 15 75 100 400 16 to 20 100 125 500 21 to 25 100 150 600 26 to 30 125 175 700 31 to 40 125 200 800 41 to 50 150 225 900 51 kg and greater 175 250 1000 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/m 2 per day.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS PROCYSBI delayed-release capsules: 25 mg cysteamine: the capsules have a light blue opaque cap imprinted with "PRO" in white ink and a light blue opaque body imprinted with "25 mg" in white ink. 75 mg cysteamine: the capsules have a dark blue opaque cap imprinted with "PRO" in white ink and a light blue opaque body imprinted with "75 mg" in white ink. PROCYSBI delayed-release oral granules: 75 mg cysteamine: white to off-white granules in single-use packets 300 mg cysteamine: white to off-white granules in single-use packets Delayed-release capsules: 25 mg and 75 mg cysteamine ( 3 ) Delayed-release oral granules: 75 mg and 300 mg cysteamine in single-use packets ( 3 )

Contraindications

The use of PROCYSBI is contraindicated in patients with a serious hypersensitivity reaction, including anaphylaxis, to penicillamine or cysteamine. Hypersensitivity to penicillamine or cysteamine ( 4 )

Warnings and precautions

Ehlers-Danlos-like Syndrome: Reduce dosage if skin and bone lesions occur. ( 5.1 ) Skin Rash: Discontinue if severe skin rash such as erythema multiforme bullosa or toxic epidermal necrolysis occurs. ( 5.2 ) Gastrointestinal (GI) Ulcers and Bleeding: Monitor for GI symptoms and consider decreasing the dose if severe symptoms occur. ( 5.3 ) Fibrosing Colonopathy: 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 ( 5.4 ) Central Nervous System (CNS) Symptoms: Monitor for CNS symptoms; interrupt or reduce the dose for severe symptoms or those that persist or progress ( 5.5 ). Leukopenia and/or Elevated Alkaline Phosphatase Levels: Monitor white blood cell count and alkaline phosphatase levels; decrease or discontinue the dose until values revert to normal. ( 5.6 ) Benign Intracranial Hypertension: Monitor for signs and symptoms; interrupt or reduce the dose for signs/symptoms that persist, or discontinue if diagnosis is confirmed. ( 5.7 ) 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.

Side effects

The following adverse reactions are also discussed in other sections of the labeling: Ehlers-Danlos-like Syndrome [see Warnings and Precautions (5.1) ] Skin Rash [see Warnings and Precautions (5.2) ] Gastrointestinal (GI) Ulcers and Bleeding [see Warnings and Precautions (5.3) ] Fibrosing Colonopathy [see Warnings and Precautions (5.4) ] Central Nervous System Symptoms [see Warnings and Precautions (5.5) ] Leukopenia and/or Elevated Phosphatase Levels [see Warnings and Precautions (5.6) ] Benign Intracranial Hypertension [see Warnings and Precautions (5.7) ] Most common adverse reactions in: Patients 6 years of age and older previously treated with cysteamine (≥5%) are: vomiting, nausea, abdominal pain, breath odor, diarrhea, skin odor, fatigue, rash, and headache. ( 6.1 ) Patients 1 year to less than 6 years naïve to cysteamine treatment (>10%) are: vomiting, gastroenteritis/viral gastroenteritis, diarrhea, breath odor, nausea, electrolyte imbalance and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1 800 77 AMGEN (1 800 772 6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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. Clinical Trials Experience with PROCYSBI in Patients Switched from Immediate-Release Cysteamine Bitartrate Sixty-two patients with nephropathic cystinosis (38 males and 24 females) received PROCYSBI in two clinical trials at doses ranging from 0.29 grams/m 2 per day to 2.19 grams/m 2 per day [see Clinical Studies (14.2) ]. All patients were switched from immediate-release cysteamine to PROCYSBI. Forty-three patients, ages 6 to 26 years old, received PROCYSBI in an 8-week, open-label, randomized, cross-over trial comparing PROCYSBI to immediate-release cysteamine bitartrate. Forty of 43 patients continued PROCYSBI treatment in an open-label extension trial (36 patients were treated with PROCYSBI for longer than 2 years, and 20 patients were treated for longer than 5 years). An additional 19 patients (6 renal transplanted patients and 13 patients aged 2 to 6 years) were enrolled directly into this trial (12 patients were treated with PROCYSBI for longer than 2 years, and 9 patients were treated for longer than 5 years). In the open-label, randomized, cross-over trial, a higher incidence of adverse reactions was reported in patients during the PROCYSBI treatment period compared with the immediate-release cysteamine bitartrate treatment period (see Table 2 ). Other significant adverse reactions reported during clinical trials included hypersensitivity reactions, including anaphylaxis. Table 2: Adverse Reactions in ≥5% of Patients with Nephropathic Cystinosis in a Randomized, Cross-Over Trial Adverse Reaction Immediate-Release Cysteamine PROCYSBI (n = 41) % (n = 43) % Vomiting/emesis 12 19 Nausea 7 16 Abdominal pain/discomfort 0 14 Headache 0 9 Dizziness 0 5 Anorexia/loss of appetite 5 2 In the open-label extension trial (N=59), the most commonly reported adverse reactions (>15%) were vomiting, headache, diarrhea, nausea, conjunctivitis, influenza, gastroenteritis, nasopharyngitis, abdominal pain, dehydration, ear infection, upper respiratory tract infection, fatigue, arthralgia, cough, and pain in extremity. Clinical Trials Experience with PROCYSBI in Cysteamine-Naïve Patients Seventeen cysteamine-naïve patients (fifteen patients between the ages of 1 and 5 years, one 9-year old and one 22-year old) received PROCYSBI in an open-label clinical trial [see Clinical Studies (14.2) ] . Serious adverse reactions occurring in at least 2 patients (>10%) were: gastroenteritis/viral gastroenteritis (n=6), vomiting (n=4), and electrolyte imbalance (n=2). Three patients with serious adverse reactions of gastroenteritis also had dehydration. Common adverse reactions reported at a frequency of >10% (occurring in at least 2 patients) are shown in Table 3. Table 3: Adverse Reactions in >10% of Patients with Nephropathic Cystinosis Naïve to Cysteamine Treatment in an Open-Label Trial Adverse Reaction PROCYSBI N = 17 n (%) Vomiting 13 (77) Gastroenteritis/viral gastroenteritis 9 (53) Diarrhea 6 (35) Breath odor 4 (24) Nausea 3 (18) Electrolyte imbalance 2 (12) Headache 2 (12) Clinical Trials Experience with Immediate-Release Cysteamine The most frequent adverse reactions involved the gastrointestinal and central nervous systems and were especially prominent at the initiation of cysteamine therapy. Most patients were able to resume therapy at lower doses. The most common reactions (>5%) were vomiting, anorexia, fever, diarrhea, lethargy, and rash. Other adverse reactions included nausea, bad breath, abdominal pain, headache, dizziness, and urticaria. Withdrawals due to intolerance, vomiting, anorexia, lethargy, and fever occurred more frequently in those patients receiving 1.95 grams/m 2 per day as compared with 1.3 grams/m 2 per day of immediate-release cysteamine bitartrate. 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) ] .

Drug interactions

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.

Use in specific populations

Lactation: Breastfeeding is not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no available data on PROCYSBI use in pregnant women to inform any drug-associated risks for birth defects or miscarriage [see Data ] . Cysteamine (administered as cysteamine bitartrate) was teratogenic and fetotoxic in rats at doses less than the recommended human maintenance dose. The background risk of major birth defects and miscarriage for the indicated population is 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. Advise pregnant women of the potential risk to a fetus. Data Animal Data Embryo-fetal development studies were conducted in rats using oral administration of cysteamine bitartrate, with a dose range of 37.5 to 150 mg/kg per day of cysteamine equivalent (about 0.2 to 0.7 times the recommended human maintenance dose based on body surface area). Cysteamine bitartrate was fetotoxic and produced adverse developmental effects. Observed teratogenic findings were cleft palate, kyphosis, heart ventricular septal defects, microcephaly and exencephaly. 8.2 Lactation Risk Summary There is no information on the presence of cysteamine in human milk, the effects on the breast-fed infant, or the effects on milk production. Cysteamine is present in the milk of lactating rats [see Data ]. Because of the potential for serious adverse reactions in breastfed infants from cysteamine, breastfeeding is not recommended. Data A decrease in survival occurred in neonatal rats nursed by mothers receiving cysteamine [see Nonclinical Toxicology (13) ] . 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.

Pregnancy

8.1 Pregnancy Risk Summary There are no available data on PROCYSBI use in pregnant women to inform any drug-associated risks for birth defects or miscarriage [see Data ] . Cysteamine (administered as cysteamine bitartrate) was teratogenic and fetotoxic in rats at doses less than the recommended human maintenance dose. The background risk of major birth defects and miscarriage for the indicated population is 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. Advise pregnant women of the potential risk to a fetus. Data Animal Data Embryo-fetal development studies were conducted in rats using oral administration of cysteamine bitartrate, with a dose range of 37.5 to 150 mg/kg per day of cysteamine equivalent (about 0.2 to 0.7 times the recommended human maintenance dose based on body surface area). Cysteamine bitartrate was fetotoxic and produced adverse developmental effects. Observed teratogenic findings were cleft palate, kyphosis, heart ventricular septal defects, microcephaly and exencephaly.

Pediatric use

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.

Geriatric use

8.5 Geriatric Use No studies with PROCYSBI have been conducted in geriatric patients.

Overdosage

One case of overdosing with PROCYSBI has been reported. A 16-year-old male patient suffered nausea and vomiting after he mistakenly took a second dose of PROCYSBI 30 minutes after his usual dose. Two cases of overdosing with immediate-release cysteamine bitartrate have been reported in two patients. In the first case, the patient immediately vomited after ingesting an unknown dose and did not develop any symptoms. The second case involved an accidental ingestion of a 200 to 250 mg/kg dose by a healthy 13-month-old child. Vomiting and dehydration were experienced. The child was hospitalized and fluids were administered. The patient fully recovered from the overdosing. Should overdosing occur, the respiratory and cardiovascular systems should be supported appropriately. No specific antidote is known. Hemodialysis may be considered since cysteamine is poorly bound to plasma proteins.

Description

11 DESCRIPTION PROCYSBI, for oral administration, is a cystine-depleting agent that lowers the cystine content of cells in patients with nephropathic cystinosis, an inherited defect of lysosomal transport. PROCYSBI contains the bitartrate salt of cysteamine. The chemical name for cysteamine bitartrate is ethanethiol, 2-amino, (2 R ,3 R )-2,3-dihydroxybutanedioate (1:1) (salt). Cysteamine bitartrate is a highly water soluble white powder with a molecular weight of 227.24 and the molecular formula C 2 H 7 NS ∙ C 4 H 6 O 6 . It has the following chemical structure: Each PROCYSBI delayed-release capsule contains either 25 mg cysteamine (equivalent to 74 mg cysteamine bitartrate) or 75 mg cysteamine (equivalent to 221 mg cysteamine bitartrate). Each packet of PROCYSBI delayed-release oral granules contains either 75 mg cysteamine (equivalent to 221 mg cysteamine bitartrate) or 300 mg cysteamine (equivalent to 884 mg cysteamine bitartrate). PROCYSBI delayed release granules contain the following inactive ingredients: Eudragit ® L 30 D-55 (methacrylic acid-ethyl acrylate copolymer), hypromellose, microcrystalline cellulose, purified water, sodium lauryl sulfate, talc, and triethyl citrate. Additionally the capsule shell contains the following inactive ingredients: gelatin, ink (blue and white), and titanium dioxide. Chemical Structure

Mechanism of action

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.

How supplied

How Supplied PROCYSBI (cysteamine bitartrate) delayed-release capsules 25 mg cysteamine : A hard gelatin capsule with light blue opaque cap imprinted with "PRO" in white ink and light blue opaque body imprinted with "25 mg" in white ink, supplied as bottle of 60 capsules (NDC 75987-100-04). Each bottle contains one desiccant canister and one oxygen absorber canister. 75 mg cysteamine : A hard gelatin capsule with dark blue opaque cap imprinted with "PRO" in white ink and light blue opaque body imprinted with "75 mg" in white ink, supplied as bottle of 250 capsules (NDC 75987-101-08). Each bottle contains one desiccant canister and two oxygen absorber canisters. PROCYSBI (cysteamine bitartrate) delayed-release oral granules 75 mg cysteamine: Single-use packets containing white to off-white granules, supplied as 60 packets in a carton (NDC 75987-140-13). 75 mg cysteamine: Single-use packets containing white to off-white granules, supplied as 120 packets in a carton (NDC 75987-140-14). 300 mg cysteamine: Single-use packets containing white to off-white granules, supplied as 60 packets in a carton (NDC 75987-145-13). 300 mg cysteamine: Single-use packets containing white to off-white granules, supplied as 120 packets in a carton (NDC 75987-145-14). 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.

Storage

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.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use) 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) ] .

Label text from the FDA structured product label by Horizon Therapeutics USA, Inc. (revised Jun 25, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Cysteamine Bitartrate in 4 products

Procysbi NDC products (4)

NDC	Strength & form	Labeler	Type
75987-100	Cysteamine Bitartrate 25 mg/1 Capsule, Delayed Release Pellets	Horizon Therapeutics USA, Inc.	NDA
75987-101	Cysteamine Bitartrate 75 mg/1 Capsule, Delayed Release Pellets	Horizon Therapeutics USA, Inc.	NDA
75987-140	Cysteamine Bitartrate 75 mg/1 Granule, Delayed Release	Horizon Therapeutics USA, Inc.	NDA
75987-145	Cysteamine Bitartrate 300 mg/1 Granule, Delayed Release	Horizon Therapeutics USA, Inc.	NDA

Frequently asked questions

What is Procysbi used for?

What are the side effects of Procysbi?

Who makes Procysbi?

Procysbi is listed by 1 labeler in the FDA NDC directory, including Horizon Therapeutics USA, Inc..