Start PROCYSBI immediately after diagnosis of nephropathic cystinosis1

PROCYSBI® (cysteamine bitartrate) delayed-release capsules and delayed-release oral granules should be initiated immediately following diagnosis of nephropathic cystinosis in patients aged ≥1 year.1

Early treatment can delay or limit damage to the patient’s tissues and organs caused by rising cystine levels, but treatment cannot reverse damage that has already occurred.2-4

Determine dose by patient experience with cysteamine bitartrate1

Patients switching from immediate-release (IR) cysteamine bitartrate should start PROCYSBI by taking a total daily dose equal to his or her previous total daily dose.1

For cysteamine-naïve patients, PROCYSBI should be initiated with a dosage equal to one-sixth to one-fourth of the maintenance dose. The maintenance dosage after initial dose escalation is 1.3 g/m2 of body surface area per day divided into 2 doses given every 12 hours.1

Starting and maintenance dosage of PROCYSBI by body weight1,*

Weight in kg Starting PROCYSBI Dosage in mg Every 12 Hours, as a Fraction of the Maintenance Dosage Maintenance PROCYSBI Dosage in mg Every 12 Hours*
⅙ of dosage ¼ of dosage
0-5 25 50 200
6-10 50 75 300
11-15 75 100 400
16-20 100 125 500
21-25 100 150 600
26-30 125 175 700
31-40 125 200 800
41-50 150 225 900
51 and greater 175 250 1000

*Higher dosages may be required to achieve target therapeutic WBC cystine concentration.

Starting low and slowly increasing the dose may reduce the risk of some adverse events1

  • Patients aged 1 year to <6 years: Increase the dosage in 10% increments to the maintenance dosage while monitoring white blood cell (WBC) cystine concentrations. Allow a minimum of 2 weeks between dosage adjustments.
  • Patients aged ≥6 years: Gradually increase the dosage over 4 to 6 weeks until the maintenance dosage is achieved.

Regular WBC cystine level testing is the only way to know your patient has the correct dose of PROCYSBI and controlled cystine levels.1,3,4

Adjust dosage as needed

If patients experience tolerability issues when starting PROCYSBI, the dose should be temporarily adjusted as follows1:

  • Cysteamine-naïve patients: If a patient experiences initial intolerance, temporarily discontinue PROCYSBI, restart at a lower dosage, and gradually increase dosage.
  • Patients switching from IR cysteamine: For patients who may experience temporary intolerance upon starting PROCYSBI, decrease the dosage and then gradually increase to the maintenance dosage.

Ongoing management of cystinosis

Continuous cystine control is critical to limiting the progression of cystinosis. Even brief interruptions in cysteamine dosing allow a rapid return to toxic levels of cystine.5

In a study, patients who delayed their dose of cystine-depleting therapy (CDT) by 3 hours (9 hours vs 6 hours) had WBC cystine levels that were 65% higher and in excess of the target level.5

Comparison of WBC cystine content with 9-hour vs 6-hour dosing of IR cysteamine5

A graph showing significantly higher cystine levels in people who delayed taking their next 6-hour dose by 3 hours (at hour 9)

A graph showing significantly higher cystine levels in people who delayed taking their next 6-hour dose by 3 hours (at hour 9)

Comparison of morning leukocyte content with IR CDT when administered every 6 hours (8 AM, 2 PM, 8 PM, 2 AM) vs 4 times a day with a 9-hour night pause (8 AM, 1 PM, 6 PM, 11 PM) in a cohort of 22 Dutch patients (mean age 14.7 ± 9.7 years) with nephropathic cystinosis.5

WBC cystine levels should be regularly measured to help ensure optimal PROCYSBI dosing1

To reach the correct maintenance dose, WBC cystine levels should be monitored according to the schedules in the table below. Once patients reach their maintenance dose, cystine levels should be measured at least twice a year for both children and adults.1

Monitoring Frequency1
Patients switching from IR cysteamine to PROCYSBI:
  • 2 weeks after PROCYSBI initiation
  • Then quarterly for 6 months
  • Then twice yearly (at minimum)
Cysteamine-naïve patients aged 1 year to <6 years:
  • 2 weeks after PROCYSBI initiation
  • Then monitor until the target WBC cystine concentration is achieved
  • Then monthly for 3 months
  • Then quarterly for 1 year
  • Then twice yearly (at minimum)
Cysteamine-naïve patients ≥6 years:
  • Obtain measurement after reaching the maintenance PROCYSBI dosage
  • Then monthly for 3 months
  • Then quarterly for 1 year
  • Then twice yearly (at minimum)

Maintenance doses may require adjustment to achieve the target WBC cystine levels.1

If the WBC cystine concentration is greater than the target level, consider the following before dose adjustment1:

  • Adherence to medication and dosing interval
  • The timing between the last dose and the blood draw for the laboratory measurement
  • The timing of PROCYSBI administration in relation to food or other administration instructions

Regular WBC cystine level testing is an important element in the effective treatment of cystinosis1,4,7

There are 2 WBC cystine level tests available and they are not interchangeable. It’s recommended to use the same test type each time in order to compare results over time. Be sure to recommend that your patients obtain their blood draw just before they take their next dose of PROCYSBI.1,6,7

Type of Test Testing Institution Test-Specific Target Cystine Level6
Granulocytes University of California San Diego Less than 1.9 nmol ½ cystine/mg protein
Mixed leukocytes Baylor Genetics Less than 1.0 nmol ½ cystine/mg protein
Monitoring Timing1
Obtain WBC sample 12 hours after dosing with PROCYSBI. It is important to accurately record the time of the last dose, the actual dose, and the time the blood sample was taken.

Administration options

PROCYSBI offers flexibility in administration, with 3 different ways your patients can take it.1

  • Two sizes of PROCYSBI® (cysteamine bitartrate) delayed-release capsules

    1 - Swallowed whole

    PROCYSBI capsules can be swallowed whole with fruit juice (except grapefruit juice) or water. Do not crush or chew the capsules.1

  • PROCYSBI® (cysteamine bitartrate) delayed-release capsules and delayed-release oral granules microbeads mixed with food or liquid

    2 - Opened and mixed with select foods or liquids

    For patients who cannot tolerate PROCYSBI on an empty stomach or have difficulty swallowing, capsules or packets should be opened and the microbeads mixed with select foods or liquids.1

  • A gastrostomy tube icon

    3 - Through a G-tube

    For individuals with a G-tube that is size 14 French or larger, PROCYSBI capsules or packets should be opened and the microbeads mixed with strained applesauce with no chunks.1

Stomach icon

Stomach acidity affects PROCYSBI’s release and absorption

To maintain the right stomach acid levels for continuous cystine control, patients should1:

Take PROCYSBI at least 1 hour before or after they take medicines that contain bicarbonate or carbonate

And

not eat for at least 2 hours before and 30 minutes after taking PROCYSBI.

Or

Take PROCYSBI with no more than ½ cup (4 oz) of food up to 1 hour before or after they take it, if they cannot tolerate PROCYSBI on an empty stomach.

Patients should be directed to take PROCYSBI correctly for best results. They should1:

  • Take PROCYSBI the same way each time
  • Not eat for at least 2 hours before and at least 30 minutes after taking PROCYSBI
    • Take PROCYSBI with no more than ½ cup (4 oz) of food up to 1 hour before or after they take it, if they cannot tolerate PROCYSBI on an empty stomach
  • Take PROCYSBI at least 1 hour before or after they take medicines that contain bicarbonate or carbonate

References: 1. PROCYSBI (cysteamine bitartrate) delayed-release capsules and delayed-release oral granules [prescribing information] Horizon. 2. Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol. 2013;28(1):51-59. 3. Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med. 2007;147(4):242-250. 4. Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. Cystinosis: a review. Orphanet J Rare Dis. 2016;11(47):1-17. 5. Levtchenko EN, van Dael CM, de Graaf-Hess AC, et al. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006;21(1):110-113. 6. Gertsman I, Johnson WS, Nishikawa C, Gangoiti JA, Holmes B, Barshop BA. Diagnosis and monitoring of cystinosis using immunomagnetically purified granulocytes. Clin Chem. 2016;62(5):766-772. 7. Langman CB, Barshop BA, Deschênes G, et al. Controversies and research agenda in nephropathic cystinosis: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2016;89(6):1192-1203.

INDICATION

PROCYSBI (cysteamine bitartrate) delayed-release capsules and delayed-release oral granules is a cystine-depleting agent indicated for the treatment of nephropathic cystinosis in adults and pediatric patients 1 year of age and older.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
  • Patients with serious hypersensitivity reaction, including anaphylaxis to penicillamine or cysteamine.
WARNINGS AND PRECAUTIONS
  • 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. Monitor patients for development of skin or bone lesions and reduce PROCYSBI dosing if patients develop these lesions.
  • Skin Rash: Severe skin rashes such as erythema multiforme bullosa or toxic epidermal necrolysis have been reported in patients receiving immediate-release cysteamine bitartrate. Discontinue use if severe skin rash occurs.
  • Gastrointestinal (GI) Ulcers and Bleeding: GI ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate. Monitor for GI symptoms and consider decreasing the dose if severe symptoms occur.
  • Central Nervous System (CNS) Symptoms: CNS symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with immediate-release cysteamine. Monitor for CNS symptoms; interrupt or reduce the dose for severe symptoms or those that persist or progress.
  • 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; decrease or discontinue the dose until values revert to normal.
  • Benign lntracranial Hypertension: Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema has been reported in patients receiving immediate-release cysteamine bitartrate treatment. Monitor for signs and symptoms of PTC; interrupt or reduce the dose for signs/symptoms that persist, or discontinue if diagnosis is confirmed.
ADVERSE REACTIONS

The most common adverse reactions reported in PROCYSBI clinical trials (≥ 5%) were:

  • Patients 2 years of age and older previously treated with cysteamine: vomiting, nausea, abdominal pain, headache, conjunctivitis, influenza, gastroenteritis, nasopharyngitis, dehydration, ear infection, upper respiratory tract infection, fatigue, arthralgia, cough, and pain in extremity.
  • Patients 1 year of age and older naïve to cysteamine treatment: vomiting, gastroenteritis/viral gastroenteritis, diarrhea, breath odor, nausea, electrolyte imbalance, headache.
DRUG INTERACTIONS
  • Drugs that increase gastric pH may alter the pharmacokinetics of cysteamine due to the premature release of cysteamine from PROCYSBI and increase WBC cystine concentration. Monitor WBC cystine concentration with concomitant use.
  • 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.
  • PROCYSBI can be administered with electrolyte (except bicarbonate) and mineral replacements necessary for management of Fanconi Syndrome as well as vitamin D and thyroid hormone.
USE IN SPECIFIC POPULATIONS
  • Lactation: Because of the potential risk for serious adverse reactions in breastfed children from cysteamine, breastfeeding is not recommended during treatment with PROCYSBI.

Please see Full Prescribing Information.

INDICATION

PROCYSBI (cysteamine bitartrate) delayed-release capsules and delayed-release oral granules is a cystine-depleting agent indicated for the treatment of nephropathic cystinosis in adults and pediatric patients 1 year of age and older.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
  • Patients with serious hypersensitivity reaction, including anaphylaxis to penicillamine or cysteamine.
WARNINGS AND PRECAUTIONS
  • 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. Monitor patients for development of skin or bone lesions and reduce PROCYSBI dosing if patients develop these lesions.
  • Skin Rash: Severe skin rashes such as erythema multiforme bullosa or toxic epidermal necrolysis have been reported in patients receiving immediate-release cysteamine bitartrate. Discontinue use if severe skin rash occurs.
  • Gastrointestinal (GI) Ulcers and Bleeding: GI ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate. Monitor for GI symptoms and consider decreasing the dose if severe symptoms occur.
  • Central Nervous System (CNS) Symptoms: CNS symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with immediate-release cysteamine. Monitor for CNS symptoms; interrupt or reduce the dose for severe symptoms or those that persist or progress.
  • 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; decrease or discontinue the dose until values revert to normal.
  • Benign lntracranial Hypertension: Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema has been reported in patients receiving immediate-release cysteamine bitartrate treatment. Monitor for signs and symptoms of PTC; interrupt or reduce the dose for signs/symptoms that persist, or discontinue if diagnosis is confirmed.
ADVERSE REACTIONS

The most common adverse reactions reported in PROCYSBI clinical trials (≥ 5%) were:

  • Patients 2 years of age and older previously treated with cysteamine: vomiting, nausea, abdominal pain, headache, conjunctivitis, influenza, gastroenteritis, nasopharyngitis, dehydration, ear infection, upper respiratory tract infection, fatigue, arthralgia, cough, and pain in extremity.
  • Patients 1 year of age and older naïve to cysteamine treatment: vomiting, gastroenteritis/viral gastroenteritis, diarrhea, breath odor, nausea, electrolyte imbalance, headache.
DRUG INTERACTIONS
  • Drugs that increase gastric pH may alter the pharmacokinetics of cysteamine due to the premature release of cysteamine from PROCYSBI and increase WBC cystine concentration. Monitor WBC cystine concentration with concomitant use.
  • 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.
  • PROCYSBI can be administered with electrolyte (except bicarbonate) and mineral replacements necessary for management of Fanconi Syndrome as well as vitamin D and thyroid hormone.
USE IN SPECIFIC POPULATIONS
  • Lactation: Because of the potential risk for serious adverse reactions in breastfed children from cysteamine, breastfeeding is not recommended during treatment with PROCYSBI.

Please see Full Prescribing Information.