Usual Adult Dose for Nephropathic Cystinosis

Immediate-release capsule:
Less than 110 lbs: Data not available
110 lbs or more:

• Initial dose: 0.3 to 0.5 g/day orally divided in 4 doses. Increase dose gradually over 4 to 6 weeks if the WBC cystine level remains above 2 nmol half-cystine/mg protein.
• Maintenance dose: 2 g/day orally divided in 4 doses

• Initial dose: 0.2 to 0.3 g/m2/day orally divided in 2 doses, every 12 hours. Increase dose gradually over 4 to 6 weeks if the WBC cystine level remains above 1 nmol half-cystine/mg protein.
• Maintenance dose: 1.3 g/m2/day orally divided in 2 doses, every 12 hours
• Maximum dose: 1.95 g/m2/day

• Measurements of WBC cystine level and/or cysteamine concentration taken one half hour after dose administration are recommended for new patients after the maintenance dose is achieved.
• The goal is to keep WBC cystine levels below 1 nmol half-cystine/mg protein or 2 nmol half-cystine/mg protein (in patients with poorer tolerability), five to six hours following drug administration.

Usual Pediatric Dose for Nephropathic Cystinosis

Immediate-release capsule:
Less than 12 years old:

• Initial dose: 0.2 to 0.3 g/m2/day orally divided in 4 doses. Increase dose gradually over 4 to 6 weeks.
• Maintenance dose: 1.3 g/m2/day orally divided in 4 doses
• Maximum dose: 1.95 g/m2/day

• Initial dose: 0.3 to 0.5 g/day orally divided in 4 doses. Increase dose gradually over 4 to 6 weeks if the WBC cystine level remains above 2 nmol half-cystine/mg protein.
• Maintenance dose: 2 g/day orally divided in 4 doses

• Initial dose: 0.2 to 0.3 g/m2/day orally divided in 2 doses, every 12 hours. Increase dose gradually over 4 to 6 weeks if the WBC cystine level remains above 1 nmol half-cystine/mg protein.
• Maintenance dose: 1.3 g/m2/day orally divided in 2 doses, every 12 hours
• Maximum dose: 1.95 g/m2/day

• Measurements of WBC cystine level and/or cysteamine concentration taken one half hour after dose administration are recommended for new patients after the maintenance dose is achieved.
• The goal is to keep WBC cystine levels below 1 nmol half-cystine/mg protein or 2 nmol half-cystine/mg protein (in patients with poorer tolerability), five to six hours following drug administration.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Transferring patients from immediate-release to delayed-release capsules:

• Total daily dose of delayed-release capsules should be equal to the total daily dose of immediate-release.
• Measure WBC cystine levels and/or plasma cysteamine concentration 2 weeks after transfer and quarterly for 6 months; then, minimum twice a year.

• May be transferred to equimolar doses of immediate release capsules
• Patients should have their WBC cystine levels measured in 2 weeks, and thereafter every 3 months to assess optimal dosage.

• Adjust dosage to reach the target WBC cystine level of less than 1 nmol half-cystine/mg protein.

• If WBC cystine measurements are not available, plasma cysteamine measurement may be used for dose titration.
• Titrate dose to maintain a cysteamine concentration greater than 0.1 mg/L, 30 minutes after dosing.

• Monthly for 3 months, then quarterly for one year, then minimum twice a year for patients never treated with immediate release cysteamine before.
• Measurement timing: 12.5 hours after the evening dose the day before, and 30 minutes after the following morning dose is given.
• If the plasma cysteamine is greater than 0.1 mg/L, and the WBC cystine is greater than 1 nmol half-cystine/mg protein, investigate the following parameters: Adherence to dosing interval, adherence to medication, or the relationship between administration of this drug and fasted/fed state.

Precautions

Safety and efficacy for the delayed-release capsules have not been established in patients younger than 6 years.

Consult WARNINGS section for additional precautions.

Dialysis

Cysteamine is dialyzable; however, no dose adjustment guidelines have been reported.

Other Comments

Administration advice:

• Swallow capsule whole, do not crush or chew capsule or its contents.
• Intact capsules should not be administered to children under the age of 6 due to the risk of aspiration.
• The immediate-release capsule can be administered to children under the age of 6 by sprinkling its contents over food.
• Take 2 hours after and at least 30 minutes before eating.
• Avoid high fat food close to administration.
• Patients needing to eat prior to treatment should only eat a small amount (half cup) of food between 1 hour before and after taking cysteamine. Cysteamine should be taken in a consistent manner with regards to food.

• If a dose is missed, take it as soon as possible.
• Skip the missed dose and go back to the regular dosing schedule, if it is within two hours(immediate-release) or 4 hours (delayed-release) of the next dose. The dose should not be doubled.

• For patients with difficulty swallowing capsules: Open the capsule and sprinkle or mix contents over 4 ounces (half a cup) of applesauce or berry jelly, or empty contents into 4 ounces of orange or apple juice and shake gently for 5 minutes. Administer mixture within 30 minutes of preparation.
• For patients with a 12 french or larger gastrostomy (G)-tube: Open capsule and mix contents into 4 ounces of applesauce, administer mixture through the feeding tube within 30 minutes, flush with 8 ounces of orange or apple juice.

• The therapy with this drug should be initiated promptly after confirmation of the diagnosis of nephropathic cystinosis to achieve maximum benefit.
• Laboratory testing is required to determine the correct dose of the drug.
• If plasma cysteamine is greater than 0.1 mg/L, and the WBC cystine is also greater than 1.0 nmol half-cystine/mg protein, investigate the dosing interval adherence, medication adherence, and the fasted/fed administration state.

• WBC and elevated alkaline phosphatase
• Plasma cysteamine should be greater than 0.1 mg/L, 30 minutes after dosing
• WBC cystine should be less than 1 nmol half-cystine/mg protein

• Use caution when driving or engaging in hazardous activities.
• Patients should contact their physician if they experience stomach pain, nausea, vomiting, loss of appetite, vomiting blood, skin rash, headache, tinnitus, dizziness, double or blurred vision, loss of vision, eye pain, or any skin changes.