cysteamine

Derm: ERYTHEMA MULTIFORME, rash, striae, TOXIC EPIDERMAL NECROLYSIS, urticaria

EENT: hearing loss, papilledema

GI: ↓appetite, diarrhea, vomiting, GI bleeding, GI ulcers, abdominal pain, bad breath, constipation, dyspepsia, fibrosing colonopathy, nausea

Hemat: anemia, leukopenia

MS: fractures, leg pain, osteopenia, tremor

Neuro: lethargy, ataxia, confusion, depression, dizziness, encephalopathy, hallucinations, headache, intracranial hypertension, nightmares, SEIZURES, somnolence

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Medications that ↑ gastric pH including proton pump inhibitors, H2 receptor antagonists, antacids (including those that contain carbonate and bicarbonate), may cause premature release of cysteamine and ↑ WBC cystine concentrations; need to closely monitor WBC cystine concentrations during concomitant use; administer cysteamine ≥1 hr before or after medications containing bicarbonate or carbonate

Route/Dosage ⬆ ⬇

Cystagon

PO (Adults and Children >12 yr and >110 lb): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ gradually over 4–6 wk to maintenance dose. Maintenance dose: 500 mg 4 times daily.
PO (Children <12 yr): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ gradually over 4–6 wk to maintenance dose. Maintenance dose: 1.3 g/m²/day or 60 mg/kg/day in 4 divided doses.

Procysbi

PO (Adults and Children ≥1 yr and ≥51 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 1000 mg every 12 hr.
PO (Adults and Children ≥1 yr and 41–50 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 900 mg every 12 hr.
PO (Adults and Children ≥1 yr and 31–40 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 800 mg every 12 hr.
PO (Adults and Children ≥1 yr and 26–30 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 700 mg every 12 hr.
PO (Adults and Children ≥1 yr and 21–25 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 600 mg every 12 hr.
PO (Adults and Children ≥1 yr and 16–20 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 500 mg every 12 hr.
PO (Adults and Children ≥1 yr and 11–15 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 400 mg every 12 hr.
PO (Adults and Children ≥1 yr and 6–10 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 300 mg every 12 hr.
PO (Adults and Children ≥1 yr and 0–5 kg): Initial dose: 1/4–1/6 of the maintenance dose in divided doses; ↑ dose in 10% increments to the maintenance dose with ≥2 wk between dose adjustments for those 1–5 yr; ↑ dose gradually over 4–6 wk to maintenance dose for those ≥6 yr. Maintenance dose: 200 mg every 12 hr.

Availability ⬆ ⬇

Delayed-release capsules (Procysbi): 25 mg; 75 mg
Delayed-release granules (Procysbi): 75 mg/pkt; 300 mg/pkt
Immediate-release capsules (Cystagon): 50 mg; 150 mg

Assessment ⬆ ⬇

Assess patient for rash during therapy. If rash occurs, withhold cysteamine until rash clears; then resume at a lower dose and monitor closely for recurrence. Titrate slowly to maintenance dose. If severe rash (erythema multiforme bullosa, toxic epidermal necrolysis) occurs, do not readminister cysteamine.
Monitor neurologic status during therapy. If CNS symptoms develop (seizures, lethargy, somnolence, depression, encephalopathy), hold dose until symptoms resolve. Resume at a lower dose and titrate slowly to maintenance dose.
Assess patient for anorexia, nausea, vomiting, and abdominal pain. If symptoms are severe, hold dose until symptoms resolve, then resume at a lower dose. Titrate slowly to maintenance dose.

Lab Test Considerations:

Monitor WBC cystine levels monthly for 3 mo once maintenance dose is achieved, then quarterly for 1 yr, then twice yearly. Patients transferred from immediate-release cysteamine or to delayed-release cysteamine should have WBC cystine levels measured in 2 wk, then quarterly for 6 mo, then twice yearly. Obtain WBC cystine measurements 12 hr after cysteamine administration. WBC cystine levels of <1 nmol/ 1/2 cystine/mg protein are the goal of therapy. WBC cystine concentration depends on assays used for cystine and total protein content; individual patient sample concentration values from different assays may not be interchangeable. Maintain communication with lab performing assay to know what assay is used when interpreting results.
- Monitor CBC and liver function tests periodically during therapy. May occasionally cause reversible leukopenia and abnormal liver function studies.

Implementation ⬆ ⬇

Therapy should be started as soon as the diagnosis of nephropathic cystinosis is confirmed. Increase dose gradually over 4–6 wk to avoid intolerance.
When switching from immediate-release (Cystagon) to delayed-release (Procysbi), total daily dose should be equal for both products. After 2 wks on delayed-release, measure WBC cystine concentration and titrate dose as needed to achieve target WBC cystine concentrations; do not exceed 1.95 grams/m² per day.
PO: Administer Procysbion empty stomach at least 30 min before or 2 hrs after meals. If unable to take without eating, take with food and limit amount of food to approximately 4 ounces (1∕2 cup) within 1 hr before through 1 hr after administration. Take in a consistent manner in regard to food. Avoid high fat food close to dose. DNC: Swallow capsule whole; do not crush or chew. If unable to swallow capsule, may sprinkle capsule contents over 1/2 cup of applesauce or berry jelly or mix in 1/2 cup of fruit juice (not grapefruit) and stir until mixed. Administer within 30 min of mixing. May also mix with 1/2 cup of applesauce and administer via feeding tube within 30 min. Flush with 10 mL of fruit juice (not grapefruit). If unable to take without mixing with food, take only 1/2 cup of food mixture between 1 hr before and 1 hr after administration. Must be taken consistently with relation to food. Avoid high-fat food close to dose.
- Sprinkle and mix intact delayed-release granules in applesauce, berry jelly or fruit juice (except grapefruit juice) and administered orally. Do not crush or chew delayed-release granules. For patients with a gastrostomy tube, oral granules can be mixed in applesauce and administered via a gastrostomy tube. Administer at least 1 hr before or 1 hr after medications containing bicarbonate or carbonate.

Patient/Family Teaching ⬆ ⬇

Instruct patient or parents to take cysteamine exactly as directed. If a dose is missed, take as soon as possible unless within 2 hrs of next dose (Cystagon) or <4 hrs before next dose (Procysbi). Do not double doses.
Instruct patient to remain well-hydrated (2–3 L/day).
May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional immediately if signs and symptoms of benign intracranial hypertension (headache, tinnitus, dizziness, nausea, double vision, blurry vision, loss of vision, eye pain), drowsiness, fever, increased thirst, nausea or vomiting, rash, sore throat, trembling, or seizures occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications and avoid alcohol during therapy.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy.
Emphasize the importance of routine lab tests to monitor progress and side effects.

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1.4 hr‡	5–6 hr

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇