Medication Summary
Cysteamine, introduced in the 1980s, blunts the decline in renal function and improves the linear growth of these children, despite the fact that it does not ameliorate the defect in renal tubule transport. Oral therapy should be initiated as soon as the diagnosis is made. The delayed-release capsule (Procysbi) allows twice daily dosing (ie, q12h), whereas the immediate-release capsule (Cystagon) has to be administered every 6 hours, including throughout the night, to prevent nocturnal accumulation of cystine.
Some cystinosis patients treated with high-dose cysteamine are reported to develop skin, vascular, neurologic, muscular, and bone lesions. These lesions improved after dose reduction. [7]
Cysteamine ophthalmic solution 0.44% (Cystaran) must be administered to each eye every hour while awake.
Cystine-depleting agents
Class Summary
Cysteamine is an aminothiol compound used to treat cystinosis. Various cysteamine salts are used. Cysteamine HCl has an unpleasant taste and odor, and, therefore, other forms have been developed. Cysteamine bitartrate (Cystagon, Procysbi) are available in the United States. Another form, phosphocysteamine, is the phosphorothioester of cysteamine and is rapidly converted to cysteamine in the gut. Phosphocysteamine is designated as an orphan drug in the United States. Much of the clinical data refers to cysteamine HCl or phosphocysteamine.
In addition to the oral products that are available, an ophthalmic product was approved by the FDA in October 2012 to decrease corneal cystine crystals, which develop with nephropathic cystinosis. [6]
Cysteamine (Cystagon, Procysbi)
Used as a cystine-depleting agent in cystinosis. It is a weak base that enters the cystinotic lysosome and reacts with cystine, forming a mixed disulfide of half-cystine and cysteamine. This mixed disulfide rapidly exits the lysosome via the transport system for cationic amino acids, which is normal in cystinosis. Cysteamine and its prodrug analog, phosphocysteamine, are very beneficial to patients with cystinosis, especially when started early in life. Therapy does not prevent or affect Fanconi syndrome. Diagnosis of cystinosis as early as possible is important because efficacy of cysteamine or phosphocysteamine treatment clearly relates to age at which the drugs are started.
Goal of therapy is to keep leukocyte cystine levels < 1 nmol/half-cystine/mg protein measured 5-6 h following administration of cysteamine. Check cystine levels after maintenance dose is achieved; then check every 3 mo; if cysteamine is poorly tolerated initially because of GI tract symptoms or transient rashes, temporarily stop therapy; restart at lower dose and gradually increase to proper dose. Dose is expressed as free base of drug. Cystagon (immediate-release) was approved by the FDA in August 1994. The sole distributor of this drug in the United States is CVS Procare (888-700-0024). Procysbi (delayed-release) was approved in April 2013 and will also be distributed by a specialty pharmacy service (Raptor Cares).
Cysteamine ophthalmic (Cystaran)
Cysteamine ophthalmic is a cystine-depleting agent indicated for corneal cystine crystal accumulation in patients with cystinosis. It converts cystine to cysteine-cysteamine mixed disulfides and reduces corneal cystine crystal accumulation.
-
An 8-month-old male infant at the time his cystinosis is diagnosed.
-
The same child as in the previous image, at age 20 months, fed via gastric tube.
-
The same child as in the previous images, at age 3 years, fed via jejunal tube.
-
The same child as in the previous images, at age 4 years, on total parenteral nutrition via central line.
-
The same child as in the previous images, at age 9 years, off total parenteral nutrition for 1 year and tolerating oral intake.
