Dosing and uses of Cystagon, Procysbi (cysteamine)
Adult dosage forms and strengths
capsule, immediate-release (Cystagon)
- 50mg
- 150mg
capsule, delayed-release (Procysbi)
- 25mg
- 75mg
Nephropathic Cystinosis
Immediate-release capsule (Cystagon)
- Starting dose: one-sixth to one-fourth of target maintenance dose
- Maintenance: 2 g/day PO divided q6hr; dose should be reached after 4-6 weeks of incremental dosage increases; not to exceed 1.95 g/m²/day or 90 mg/kg/day
Delayed-release capsule (Procysbi)
- Cysteamine-naïve patients
- Starting dose: one-sixth to one-fourth of target maintenance dose
- Gradually increase dose over 4-6 weeks until maintenance dosage is achieved to help reduce the risk of adverse reactions
- Maintenance dose: 1.3 g/m²/day PO divided q12hr; may increase to 1.95 g/m⊃2/day if WBC cystine level remains higher than the target, or cysteamine concentration has not been achieved
- Switching from immediate-release capsules to Procysbi
- Starting total daily dose of Procysbi should be equal to previous total daily dose of immediate-release cysteamine bitartrate
- Measure WBC cystine concentration 2 weeks after initiation
- Titrate dose as needed to achieve target WBC cystine concentrations
- Do not exceed 1.95 g/m²/day
Dosage modifications
Raise dose if leukocyte cystine level remains >2 nmol / ½ cystine/mg of protein
Dosing Considerations
Monitor leukocyte cystine levels
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
Procysbi: Obtain blood samples for WBC cystine concentration measurement 12 hr after dose
Cysteamine-naive patients: Obtain measurement after reaching the maintenance 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 2 weeks of Procysbi treatment while titrating the dose, then quarterly for 6 months, then twice yearly, at a minimum
Cystic Fibrosis (Orphan)
Lynovex: Orphan designation for cystic fibrosis
Sponsor
- NovaBiotics Ltd.; Cruickshank Building, Craibstone; Aberdeen AB21 9TR; United Kingdom
Huntington Disease (Orphan)
Orphan indication sponsor
- Bennu Pharmaceuticals, Inc (dual EMEA); 9 Commercial Blvd; Novato, CA 94949
Batten Disease (Orphan)
Treatment of neuronal ceroid lipofuscinoses (Batten disease)
Orphan indication sponsor
- Bennu Pharmaceuticals, Inc. (dual EMEA); 9 Commercial Blvd; Novato, CA 94949
Pancreatic Cancer (Orphan)
Orphan designation for treatment of pancreatic cancer
Orphan sponsor
- Raptor Pharmaceuticals, Inc.; 5 Hamilton Landing, Suite 160, Novato, CA 94949
Pediatric dosage forms and strengths
capsule, immediate-release (Cystagon)
- 50mg
- 150mg
capsule, delayed-release (Procysbi)
- 25mg
- 75mg
Nephropathic Cystinosis
Immediate-release capsule (Cystagon)
- Initial: give one-sixth to one-fourth of maintenace dose
- Maintenance (<12 years): 1.3 g/m²/day or 60 mg/kg/day of free base PO divided q6hr; not to exceed 1.95 g/m²/day or 90 mg/kg/day
- Maintenance (≥12 years or >110 lbs): 2 g/day PO divided q6hr; dose should be reached after 4-6 weeks of incremental dosage increases; not to exceed 1.95 g/m²/day or 90 mg/kg/day
Delayed-release capsule (Procysbi)
- <2 years: Safety and efficacy not established
- Cysteamine-naïve patients
- Starting dose: 0.2-0.3 g/m²/day divided q12hr
- Gradually increase dose over 4-6 weeks until maintenance dosage is achieved to help reduce the risk of adverse reactions
- Maintenance dose: 1.3 g/m²/day PO divided q12hr; may increase to 1.95 g/m²/day if WBC cystine level remains higher than the target, or cysteamine concentration has not been achieved
- Switching from immediate-release capsules to Procysbi
- Starting total daily dose of Procysbi should be equal to previous total daily dose of immediate-release cysteamine bitartrate
- Measure WBC cystine concentration 2 weeks after initiation
- Titrate dose as needed to achieve target WBC cystine concentrations
- Do not exceed 1.95 g/m²/day
Fanconi Syndrome (Off-label)
Delayed-release capsule (Procysbi)
Used to reduce cystine levels, potentially delaying kidney and other damage
Initial: Use one-sixth to one-fourth the maintenance dose
Maintenance: 1.3 g/m²/day PO divided q12hr; may increase to 1.95 g/m²/day if WBC cystine level remains higher than the target, or cysteamine concentration has not been achieved
Dosage modifications
Raise dose if leukocyte cystine level remains >2 nmol / ½ cystine/mg of protein
Dosing Considerations
Monitor leukocyte cystine levels
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
Procysbi: Obtain blood samples for WBC cystine concentration measurement 12 hr after dose
Cysteamine-naive patients: Obtain measurement after reaching the maintenance 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 2 weeks of Procysbi treatment while titrating the dose, then quarterly for 6 months, then twice yearly, at a minimum
Cystagon, Procysbi (cysteamine) adverse (side) effects
>10%
Vomiting (35%)
Anorexia (31%)
Diarrhea (16%)
Fever (11%)
Lethargy (11%)
1-10%
Rash (7%)
Frequency not defined
Seizures
Ataxia
Encephalophathy
Somnolence
Depression
Nightmare
Impaired cognition
Hypertension
Urticaria
Bad breath
Warnings
Contraindications
Hypersensitivity to cysteamine or penicillamine
Cautions
Blood disorders, hepatic impairment, seizures
Withhold if mild/moderate rash develops and restart at lower dose with subsequent titration to therapeutic dose; do not rechallenge if severe skin rash (eg, erythema multiforme bullosa, toxic epidermal necrolysis) develops
Scoliosis, osteopenia, compression fractures accompanied by leg pain and joint hyperextension may occur
Do NOT give whole capsules to <6 years due to risk of aspiration, open capsule & sprinkle on food
Temporarily suspend if serious GI or CNS symptoms
Monitor: Leukocyte cystine levels
May cause abnormal liver function tests
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cystagon, Procysbi (cysteamine)
Mechanism of action
Converts lysosomal cystine to cysteine & to cysteine-cysteamine mixed disulfide which then can exit lysosome in patients with cystinosis (inherited defect of lysosomal transport)
Pharmacokinetics
Onset: 1-1.8 hr
Duration: 6-12 hr
Peak plasma time: 1.4 hr
Vd: 156 L
Bioavailability: Rapidly absorbed
Protein Bound: 52% (mainly albumin)
Excretion: Small amount excreted in urine
Dialyzable: PD: yes, HD: no data
Administration
Cystagon
May open capsules and sprinkle on food
Missed dose
- If a dose is missed, take the dose as soon as possible; if it is within 2 hr of the next dose, skip the missed dose and go back to the regular dosing schedule
- Do not double the dose
Procysbi
Do not eat for at least 2 hr before taking Procysbi and for at least 30 minutes after to maximize absorption
If patients are unable to take Procysbi without eating, give with food and limit the amount of food to approximately 4 ounces within 1 hr before taking Procysbi through 1 hr after taking Procysbi; take Procysbi in a consistent manner in regard to food
Avoid high fat food close to dosing
Swallow whole with fruit juice (except grapefruit juice), do not crush or chew capsule or capsule contents
Unable to swallow capsule
- If unable to swallow, may open capsule and sprinkle intact granules on ~4 oz applesauce or berry jelly; eat mixture within 30 minutes, OR
- May disperse intact granules into small volume of either orange juice or apple juice (~4 oz), shake gently for 5 minutes, then administer by spoon or cup within 30 minutes
- ≥12 French G-tube: Mix intact granules with 4 oz applesauce and administer via feeding tube within 30 minutes; flush with ~8 oz or orange juice or apple juice to clear the tube
Missed dose
- If a dose is missed, take the dose as soon as possible up to 8 hr after the scheduled time
- However, if a dose is missed and the next scheduled dose is due in <4 hr, do not take the missed dose and take the next dose at the usual scheduled time
- Do not take 2 doses at the same time to make up for a missed dose
