Procysbi

PROCYSBI is indicated for the treatment of nephropathic cystinosis in adults and pediatric patients 1 year of age and older.

• See full prescribing information for weight-based dosing tables for the starting and maintenance dosage. (
  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/m²of 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 hoursHigher 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
  )
• For initial intolerance, temporarily discontinue and then re-start PROCYSBI at a lower dosage and gradually increase to the maintenance dosage. (
  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/m²of 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 hoursHigher 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
  )

• Start with a total daily dose of PROCYSBI equal to the previous total daily dose of immediate-release cysteamine bitartrate. (
  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/m²per day.
  )

• Adjust dose to achieve a therapeutic target white blood cell (WBC) cystine concentration. (
  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/m²per 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.
  )
• If a dose adjustment is required, increase the dosage by 10%. The maximum dosage 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/m²per 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)].
  )
• If adverse reactions occur, decrease the dosage. Some patients may be unable to achieve their therapeutic target. (
  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/m²per 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)].
  )

• 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.

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