Raptor Therapeutics Inc.

Raptor Therapeutics Inc. Drugs

• Procysbi Delayed-releas...
  

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  Procysbi Delayed-release

  

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  2.1 Dosage

  Starting Dosage in Cysteamine-Naïve Patients

  Treatment with cysteamine should be started immediately after diagnosis. The recommended starting dosage of PROCYSBI for cysteamine-naïve patients is 0.2 to 0.3 grams/m2 per day divided into two doses given every 12 hours. Table 1 shows the recommended weight-based starting dosage and the number of capsules needed to achieve each dose. Increase the dosage gradually over 4 to 6 weeks until the maintenance dosage is achieved to help reduce the risk of adverse reactions [see Dosage and Administration (2.2)].

  Table 1: Recommended Weight-Based Starting Dosage (⅙ to ¼ of maintenance dosage) Target Maintenance Dosage Starting Dosage as a Fraction of the Maintenance Dosage Weight PROCYSBI dosage in mg Number of capsules every 12 hours in kilograms every 12 hours ⅙ of target ¼ of target 75mg 25mg 75mg 25mg 0-5 200 0 1 0 2 6-10 300 0 2 1 0 11-15 400 1 0 1 1 16-20 500 1 1 1 2 21-25 600 1 1 2 0 26-30 700 1 2 2 1 31-40 800 1 2 2 2 41-50 900 2 0 3 0 51 and greater 1000 2 1 3 1

  Maintenance Dosage in Cysteamine-Naïve Patients

  The recommended maintenance dosage of PROCYSBI for cysteamine-naive patients is 1.3 gram/m2 per day, divided into two equal doses given every 12 hours. Table 2 shows the recommended weight-based maintenance dosage of PROCYSBI and the number of capsules needed to achieve each dose. After maintenance dose has been achieved, measure the white blood cell (WBC) cystine concentration [See Dosage and Administration (2.3)]. Titrate the PROCYSBI dosage as needed to achieve target WBC cystine concentrations [see Dosage and Administration (2.2)]. Do not exceed 1.95 grams/m2 per day.

  Table 2: Target Weight-Based Maintenance Dosage Weight PROCYSBI MaintenanceDosage in mg Number of capsules every 12 hours in kilograms every 12 hours 75 mg 25 mg 0-5 200 2 2 6-10 300 4 0 11-15 400 5 1 16-20 500 6 2 21-25 600 8 0 26-30 700 9 1 31-40 800 10 2 41-50 900 12 0 51 kg and greater 1000 13 1

  Switching Patients from Immediate-release Cysteamine Bitartrate Capsules

  When switching patient from immediate-release cysteamine bitartrate to PROCYSBI, starting total daily dose of PROCYSBI is equal to his/her previous total daily dose of immediate-release cysteamine bitartrate. Measure WBC cystine concentration two weeks after initiation of PROCYSBI [see Dosage and Administration (2.3)].Titrate the PROCYSBI dose as needed to achieve target WBC cystine concentrations [see Dosage and Administration (2.2)]. Do not exceed 1.95 grams/m2 per day.

  2.2 Dose Titration

  The target WBC cystine concentration is less than 1.0 nmol ½ cystine/mg protein[see Dosage and Administration (2.3)]. If the WBC cystine concentration is greater than the target level of less than 1.0 nmol ½ cystine/mg protein, 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 dose by 10%. Do not exceed a maximum dose of 1.95 grams/m2 per day due to an increased risk of adverse reactions If adverse reactions occur, decrease the PROCYSBI dose. For patients who have initial intolerance, temporarily discontinue PROCYSBI and then re-start at a lower dose and gradually increase to the target dose. 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)].

  2.3 Laboratory Monitoring

  Because the measured WBC cystine concentration depends on the assays used for cystine and total protein content, individual patient sample concentration values from different assays may not be interchangeable. Consideration of assay results must be made with knowledge of the specific assays used. Therefore, communication should be maintained with the laboratory performing the assay [see Clinical Pharmacology (12.2)]. The recommended frequency of monitoring WBC cystine concentration is as follows: For cysteamine-naive patients: Obtain measurement after reaching the maintenance PROCYSBI dose, then monthly for 3 months, quarterly for 1 year, and then twice-yearly, at a minimum. For patients switching from immediate-release cysteamine to PROCYSBI: Obtain measurement after two weeks of PROCYSBI treatment while titrating the dose, then quarterly for 6 months, then twice yearly, at a minimum. Obtain blood samples for WBC cystine concentration measurement 12 hours after dosing with PROCYSBI. 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.

  2.4 Administration

  Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents. Take PROCYSBI capsules with fruit juice (except grapefruit juice). 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 (1/2 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)]. Administer PROCYSBI at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate [see Drug Interactions (7.1)].

  For patients who have difficulty swallowing capsules, follow the instructions below for administration with food or liquid. Administration of PROCYSBI with foods and liquids not included below has not been studied clinically and is not recommended.

  Administration with Applesauce or Berry Jelly:

  Place approximately 4 ounces (1/2 cup) of either applesauce or berry jelly into a clean container Open the capsule(s) Sprinkle the intact granules on applesauce or berry jelly Mix the granules with the applesauce Consume the entire contents within 30 minutes of mixing. Do not chew the granules. Do not save the applesauce or berry jelly and granules for later use.

  Administration with Fruit Juice (except grapefruit juice):

  Pour approximately 4 ounces (1/2 cup) of fruit juice into a clean cup Open the capsule(s) Sprinkle the intact granules into the juice Gently stir until mixed Drink the entire contents within 30 minutes of mixing. Do not chew the granules. Do not save the fruit juice and granules for later use.

  Administration with Applesauce via a Gastrostomy (G) Tube (14 French or larger)

  A bolus (straight) feeding tube is recommended.

  Flush the gastrostomy tube button first with 5 mL of water to clear the button Open the capsule and empty the granules into a clean container with approximately 4 ounces (1/2 cup) of applesauce. Use only strained applesauce with no chunks. A minimum of 1 ounce (1/8 cup) of applesauce may be used for children ≤ 25 kg starting PROCYSBI at a dose of 1 or 2 capsules. Mix the intact granules into the applesauce Draw up the mixture into a syringe. Keep the feeding tube horizontal during administration and apply rapid and steady pressure (10 mL/10 seconds) to dispense the syringe contents into the tube within 30 minutes of preparation. Repeat step 3 until all of the mixture is administered. Do not save the applesauce and granule mixture for later use. Draw up a minimum of 10 mL of fruit juice into another syringe, swirly gently, and flush the tube.

  Missed 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 take the next dose at the usual scheduled time. Do not take 2 doses at one time to make up for a missed dose.

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