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Cysteamine
Cysteamine
Cysteamine
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Cysteamine
INN: mercaptamine
Skeletal formula (top)
Ball-and-stick model of the cysteamine
Clinical data
Trade namesCystagon, Procysbi, Cystaran, others
Other names2-Aminoethanethiol, β-Mercaptoethylamine, 2-Mercaptoethylamine, decarboxycysteine, thioethanolamine, mercaptamine bitartrate, cysteamine (USAN US)
AHFS/Drugs.comMicromedex Detailed Consumer Information
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, eye drops
ATC code
Legal status
Legal status
Identifiers
  • 2-Aminoethane-1-thiol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.000.421 Edit this at Wikidata
Chemical and physical data
FormulaC2H7NS
Molar mass77.15 g·mol−1
3D model (JSmol)
Melting point95 to 97 °C (203 to 207 °F)
  • C(CS)N
  • InChI=1S/C2H7NS/c3-1-2-4/h4H,1-3H2 checkY
  • Key:UFULAYFCSOUIOV-UHFFFAOYSA-N

Cysteamine is an organosulfur compound with the formula HSCH2CH2NH2. A white, water-soluble solid, it contains both an amine and a thiol functional group. It is often used as the salt of the ammonium derivative [HSCH2CH2NH3]+,[11] including the hydrochloride, and the bitartrate. Another derivative is phosphocysteamine, H3NCH2CH2SPO3Na.[12][13] The intermediate pantetheine is broken down into cysteamine and pantothenic acid.[12]

It is biosynthesized in mammals, including humans, by the degradation of coenzyme A. It is the biosynthetic precursor to the neurotransmitter hypotaurine.[12][14]

Medical uses

[edit]

As a medication sold under the brand names Procysbi or Cystagon, among others, cysteamine is indicated to treat cystinosis, a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine.[8][9] It removes the excessive cystine that builds up in cells of people with the disease.[8][9] Cysteamine functions by the following chemical reaction converting the disulfide cystine to a more soluble mixed disulfide and cysteine, both of which are more soluble than cystine.

(SCH2CH(NH3)CO−2)2 + HSCH2CH2NH2 → H2NCH2CH2SSCH2CH(NH3)CO−2 + HSCH2CH(NH3)CO−2

It is available by mouth (capsule and extended release capsule) and in eye drops.[6][7][10]

When applied topically, it can lighten skin darkened by post-inflammatory hyperpigmentation, sun exposure or melasma.[15][16][17]

Adverse effects

[edit]

The label for oral formulations of cysteamine carries warnings about symptoms similar to Ehlers-Danlos syndrome, severe skin rashes, ulcers or bleeding in the stomach and intestines, central nervous symptoms including seizures, lethargy, somnolence, depression, and encephalopathy, low white blood cell levels, elevated alkaline phosphatase, and idiopathic intracranial hypertension that can cause headache, tinnitus, dizziness, nausea, double or blurry vision, loss of vision, and pain behind the eye or pain with eye movement.[8][9]

Additional adverse effects of oral cysteamine include bad breath, skin odor, vomiting, nausea, stomach pain, diarrhea, and loss of appetite.[8][9]

For eye drops, the most common adverse effects are sensitivity to light, redness, and eye pain, headache, and visual field defects.[7][9]

Interactions

[edit]

There are no drug interactions for normal capsules or eye drops,[6][7] but the extended release capsules should not be taken with drugs that affect stomach acid like proton pump inhibitors or with alcohol, as they can cause the drug to be released too quickly.[8] It does not inhibit any cytochrome P450 enzymes.[8]

Pharmacology

[edit]

People with cystinosis lack a functioning transporter (cystinosin) which transports cystine from the lysosome to the cytosol. This ultimately leads to the buildup of cystine in lysosomes, where it crystallizes and damages cells.[18] Cysteamine enters lysosomes and converts cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome.[8][9] Cysteamine also promotes the transport of L-cysteine into cells.[8][9]

History

[edit]

The therapeutic effect of cysteamine on cystinosis was reported in the 1950s. Cysteamine was approved as a drug for cystinosis in the US in 1994.[8] An extended release form was approved in 2013.[19]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Cysteamine

View on Grokipedia
from Grokipedia
Cysteamine is a simple organosulfur compound with the HSCH₂CH₂NH₂, also known as 2-aminoethanethiol or mercaptamine, featuring both an and a that enable its role as a and cystine depleter. It appears as a white, water-soluble solid with a molecular weight of 77.15 g/mol, a of 95–97°C, and in and alcohols, while it oxidizes in air to form . As a pharmaceutical agent, cysteamine is primarily FDA-approved for the treatment of nephropathic cystinosis, a rare autosomal recessive lysosomal storage disorder characterized by cystine accumulation in organs, where it works by converting cystine into and cysteine-cysteamine mixed disulfides through thiol-disulfide exchange, thereby reducing toxic lysosomal cystine levels. Oral formulations, such as cysteamine bitartrate (e.g., Procysbi), are indicated for patients aged 1 year and older to manage systemic effects, while ophthalmic solutions like Cystadrops (0.37% cysteamine hydrochloride, approved in 2020) treat corneal cystine crystal accumulation with four daily instillations, minimizing systemic exposure. Beyond cystinosis, cysteamine exhibits radioprotective properties by scavenging free radicals and has been investigated for applications in neurodegenerative diseases like Huntington's and Parkinson's, where it mitigates , upregulates (BDNF), and inhibits 2 in preclinical models, though clinical trials (e.g., CYTE-I-HD for Huntington's) have shown tolerability with gastrointestinal side effects like and . It is also explored for neuropsychiatric conditions such as and autism spectrum disorders, as well as peripheral uses including anti-malarial activity and protection against acetaminophen-induced liver damage, highlighting its broader therapeutic potential as an and modulator. Common adverse effects include (up to 35%), anorexia, and diarrhea, with monitoring required for and elevated liver enzymes.

Chemistry

Chemical properties

Cysteamine is an organosulfur compound with the molecular formula C₂H₇NS and a of 77.15 g/mol. It features the structure of 2-aminoethanethiol, consisting of an chain substituted with an amino group (-NH₂) at the C-2 position and a group (-SH) at the C-1 position, represented as HSCH₂CH₂NH₂. The of cysteamine appears as a white crystalline powder or colorless crystals. It has a of 95–97 °C and a of approximately 130 °C, though it decomposes at higher temperatures. Cysteamine is freely soluble in water (miscible) and soluble in organic solvents such as and , with enhanced in alkaline media. Due to the presence of the thiol functional group, cysteamine exhibits significant chemical reactivity, including oxidation in air to form (the dimer) or other compounds. It readily participates in thiol- exchange reactions, which contribute to its role in processes. The compound is unstable upon exposure to air, oxidizing on standing, but demonstrates sufficient stability under physiological conditions when properly formulated to prevent degradation. Common pharmaceutically relevant salt forms of cysteamine include the salt, which presents as a white crystalline powder, and the bitartrate salt, also a white solid. These salts improve handling and stability compared to the free base.

Synthesis and preparation

Cysteamine is primarily synthesized industrially through the reaction of with or related sulfur sources, often involving intermediate formation of thiazoline derivatives followed by . One established route entails treating with to produce 2-mercaptothiazoline, which is then subjected to high-pressure acidolysis with under optimized conditions of 0.3 MPa pressure and 7 hours reaction time, yielding at 95.6%. Alternative industrial methods include the ethanolamine-sulfuric acid-cyclohexylamine process or direct reaction with , though these may generate more byproducts. An additional route involves the reduction of cystine, typically using sodium in liquid or electrochemical methods, but this is less common due to the higher cost of cystine as a starting material. In laboratory settings, cysteamine preparation mirrors industrial approaches but on smaller scales with precise control for purity. For instance, is reacted with or in aqueous or alcoholic media at elevated temperatures (around 100–150°C) under , followed by acidification to form the salt, achieving yields of 80–95% depending on conditions. Purification typically involves under reduced to remove volatiles, followed by recrystallization from or water- mixtures to isolate the product as colorless crystals, with melting points around 95–97°C for the . These steps minimize impurities like , which forms via oxidation, ensuring high-purity cysteamine for research applications. Pharmaceutical formulations of cysteamine commonly employ the bitartrate salt for improved stability and solubility. Cysteamine bitartrate is prepared by liberating the free base from cysteamine hydrochloride through basification with sodium hydroxide in aqueous solution, followed by addition of L-(+)-tartaric acid at controlled pH (around 4–5) and temperature (20–60°C), then cooling to induce crystallization with yields exceeding 90%. For Cystagon, immediate-release capsules contain cysteamine bitartrate equivalent to 50 or 150 mg of cysteamine free base, formulated by blending the salt with excipients like cellulose and encapsulating directly. Procysbi's delayed-release granules involve extrusion-spheronization of cysteamine bitartrate pellets, coating them with an enteric polymer (e.g., hypromellose phthalate) via fluidized bed technology to enable twice-daily dosing, with sachets providing 75 mg or 300 mg cysteamine free base equivalents. Cystadrops eye drops are formulated as a 0.55% cysteamine hydrochloride solution (3.8 mg/mL cysteamine base, equivalent to 5.6 mg/mL hydrochloride), stabilized with carmellose sodium for viscosity and benzalkonium chloride as preservative, manufactured under sterile conditions to a pH of 4.5–5.5. Due to cysteamine's group, oxidation to during manufacturing poses a key stability challenge, accelerated by oxygen, light, and elevated temperatures. Protection strategies include conducting reactions and formulations under atmosphere, incorporating chelators like 0.01% EDTA to bind trace metals that catalyze oxidation, and storing intermediates at low temperatures (e.g., 4°C or below) to maintain >95% purity for weeks. In production, degassing solutions and using opaque packaging further minimize degradation, ensuring less than 10% formation over the .

Pharmacology

Mechanism of action

is an autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene, which encodes the lysosomal cystine transporter cystinosin, resulting in the intralysosomal accumulation of cystine and subsequent crystal formation in affected organs such as the kidneys and corneas. , a thiol-containing aminothiol, addresses this defect by penetrating cells and accumulating in s, where it participates in a thiol-disulfide exchange reaction with accumulated cystine to deplete its levels. This reaction converts cystine into more soluble and permeable products that can exit the via alternative transporters, thereby preventing toxic cystine buildup without relying on the defective cystinosin. The primary biochemical pathway involves the following net reaction: cystine+2 cysteamine→2 cysteine+cystamine\text{cystine} + 2 \text{ cysteamine} \rightarrow 2 \text{ cysteine} + \text{cystamine} In this disulfide interchange, cysteamine's free group (-SH) reduces the disulfide bond in cystine (-), forming and the cysteine-cysteamine mixed intermediate, which can further react to yield (the oxidized dimer of cysteamine). These breakdown products are more readily exported from the compared to cystine, facilitating their removal from cells and mitigating the crystalline deposits that drive organ damage in . Beyond its cystine-depleting action, cysteamine exhibits secondary effects through its moiety, which can scavenge and elevate intracellular levels in cystinotic cells, potentially alleviating . In non- applications, these properties may contribute to reducing and oxidative , as explored in contexts like neurodegenerative disorders, though the primary therapeutic specificity remains tied to lysosomal cystine modulation in cystinosis.

Pharmacokinetics

Cysteamine exhibits rapid absorption following of the immediate-release , with a time to maximum plasma concentration (T_max) of about 1.4 hours. The delayed-release , such as Procysbi, shows a prolonged T_max of around 3.1 hours due to , allowing for twice-daily dosing while maintaining comparable systemic exposure. Topical application as (e.g., 0.37% solution) achieves high local concentrations in the for cystine crystal depletion with negligible systemic absorption, as the daily ocular dose represents less than 4% of the oral dose. The volume of distribution for cysteamine is approximately 2 L/kg, indicating moderate tissue distribution, with about 52% primarily to . It crosses the blood-brain barrier to a limited extent, resulting in low exposure. Cysteamine accumulates in lysosomes where it interacts with cystine via exchange. Metabolism occurs primarily in the liver through oxidation by cysteamine dioxygenase to hypotaurine, which is further converted to . The elimination is 1-2 hours for oral formulations, supporting frequent dosing to maintain therapeutic levels. Excretion is predominantly renal, with cysteamine and its mixed disulfides cleared via the kidneys; apparent clearance is about 20-30 mL/min/kg. Dose adjustments are recommended in renal impairment due to reduced clearance in patients with progressive kidney dysfunction. Formulation-specific pharmacokinetics differ notably: immediate-release cysteamine (e.g., Cystagon) achieves peak plasma levels rapidly but requires every-6-hour dosing to sustain cystine depletion, whereas the delayed-release form (e.g., Procysbi) provides a flatter concentration profile with lower peak-to-trough ratios, enabling every-12-hour administration and improved patient adherence.

Medical uses

Indications

Cysteamine is primarily indicated for the treatment of nephropathic cystinosis, a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene, leading to excessive cystine accumulation in lysosomes and subsequent damage to organs such as the kidneys, eyes, , and . By reacting with cystine to form a mixed that can be transported out of lysosomes, cysteamine reduces intracellular cystine levels and mitigates crystal formation. Long-term clinical trials, including open-label studies and randomized controlled trials, have shown that cysteamine therapy, when initiated early, significantly delays the onset of renal failure, with patients experiencing improved glomerular filtration rates and prolonged time to end-stage compared to untreated historical controls. For the ocular manifestations of nephropathic , cysteamine ophthalmic solution (Cystadrops, 0.37%) is approved to treat corneal cystine deposition, which causes , pain, and blurred vision. This topical formulation penetrates the to deplete cystine crystals directly in the affected tissue. Phase 3 clinical trials have demonstrated its efficacy, with significant reductions in corneal cystine crystal scores after 90 days of treatment and sustained improvements in symptoms like and ocular discomfort over 5 years of follow-up. Off-label, topical cysteamine cream (5%) is used for dermatological conditions involving , such as , post-inflammatory , and solar lentigines. Its depigmenting action primarily involves inhibition of , the rate-limiting enzyme in melanogenesis, as well as scavenging of reactive intermediates like dopaquinone and of metal ions essential for production. Randomized controlled trials and meta-analyses have established its efficacy, showing comparable or superior reduction in modified Melasma Area and Severity Index (mMASI) scores to hydroquinone-based treatments after 8-16 weeks, with minimal irritation. Investigational applications of cysteamine extend to other conditions, including neurodegenerative diseases like Huntington's disease, where a phase 2/3 trial of delayed-release cysteamine (RP103) reported slower progression of motor symptoms as measured by the Total Motor Score over 18 months compared to placebo. Preclinical and early-phase studies also suggest potential neuroprotective effects through upregulation of brain-derived neurotrophic factor (BDNF) and reduction of mutant huntingtin aggregates, though no new trials were active as of 2025. For radiation protection, cysteamine's antioxidant properties have been explored in animal models, demonstrating mitigation of radiation-induced DNA damage and tissue injury, but human clinical trials remain limited to historical data without recent advancements. Potential utility in non-cystic fibrosis bronchiectasis stems from its mucolytic and anti-inflammatory actions in preclinical models, but efficacy has not been confirmed in ongoing or completed trials as of 2025. Cysteamine is contraindicated in patients with a history of reactions, including , to cysteamine, , or any formulation components. It is not indicated for non-nephropathic (ocular or intermediate) , as these forms lack systemic organ involvement requiring oral cystine depletion, and therapy is limited to topical ocular treatment for corneal symptoms.

Administration and dosage

Cysteamine is primarily administered orally for the treatment of nephropathic cystinosis, with two main formulations available: immediate-release capsules (Cystagon) and delayed-release capsules or granules (Procysbi). For Cystagon, the recommended maintenance dosage is 1.3 g/m²/day, divided into four doses every 6 hours, while for patients over 12 years and weighing more than 110 pounds (50 kg), it is 2 g/day divided similarly. For Procysbi, the maintenance dosage is also 1.3 g/m²/day, but divided into two doses every 12 hours, with a maximum of 1.95 g/m²/day if tolerated. Therapy is initiated at one-fourth to one-sixth of the maintenance dose in cysteamine-naïve patients, with gradual titration over 4 to 6 weeks to minimize gastrointestinal intolerance. Dosage adjustments are based on for pediatric patients, who start at lower doses due to age-related tolerability concerns, and leukocyte cystine levels are monitored to guide , targeting less than 1 nmol half-cystine per mg protein. No specific renal function-based adjustments are required, as cysteamine dosing aims to maintain therapeutic cystine depletion regardless of status, though monitoring is intensified in patients with renal impairment. Initial monitoring of leukocyte cystine levels occurs biweekly during , followed by monthly assessments for the first three months, then quarterly. For ophthalmic use in corneal cystine crystal accumulation associated with , cysteamine is formulated as a 0.37% ophthalmic solution (Cystadrops), administered as one drop in each eye every 6 hours (four times daily during waking hours). The solution is viscous to prolong contact time, and the bottle should be discarded 7 days after opening to prevent contamination. Unopened bottles are stored refrigerated at 2°C to 8°C, while opened bottles are kept at (20°C to 25°C) in the original carton to protect from light and oxidation. Topical cysteamine is used off-label for conditions such as , typically as a 5% cream applied once daily at night to affected areas on clean, dry . The cream is left on for 15 to 30 minutes before rinsing with a gentle and applying , with application time gradually increased after 6 weeks if tolerated to enhance efficacy while minimizing irritation. Patient instructions emphasize adherence to timing for optimal efficacy; for oral formulations, Cystagon is preferably taken with or to reduce gastrointestinal upset, while Procysbi is ideally administered on an empty but may be taken with a small amount (up to 4 ounces) of low-fat if necessary. Procysbi capsules or granules can be mixed with or fruit juice (excluding grapefruit) for patients unable to swallow whole, or administered via tube. Missed doses should be taken if more than 2 hours remain before the next scheduled dose, without doubling.

Safety and tolerability

Adverse effects

Cysteamine therapy, particularly the oral form used in nephropathic , is associated with a high incidence of gastrointestinal adverse effects, affecting up to 90% of patients in some clinical cohorts. Common manifestations include , , , and , with reported in 65% of patients on immediate-release formulations. These effects can lead to , imbalances, and reduced compliance; severe cases may result in gastrointestinal ulcers or , necessitating symptomatic monitoring and dose adjustments. Systemic side effects are also frequent, occurring in over 70% of treated patients in long-term studies. These encompass , which requires regular (CBC) monitoring to detect and manage potential . Neurological symptoms such as seizures, drowsiness, lethargy, and have been observed, often resolving with dose reduction. An Ehlers-Danlos-like syndrome, characterized by skin laxity, joint hypermobility, vascular lesions, and bone abnormalities like or fractures, emerges in some patients on high doses, prompting recommendations to lower the dose if symptoms appear. Ophthalmic administration of cysteamine eye drops for corneal cystine crystal deposition commonly causes local irritation, with adverse effects including , eye , redness (ocular hyperemia), , and reported in more than 10% of users during clinical trials. These symptoms typically occur upon instillation and may decrease with continued use, but persistent discomfort warrants evaluation for corneal abrasions or alternative dosing. Topical cysteamine creams, employed for disorders like , generally produce mild dermatological reactions such as transient , burning sensation, pruritus, and dryness, affecting approximately 42% of patients in meta-analyses. Severe skin reactions are rare, but users should avoid contact with fabrics, as cysteamine can cause bleaching or discoloration due to its reducing properties. Long-term use of oral cysteamine is linked to growth retardation in pediatric patients if not adequately managed, alongside potential dysfunction, though early initiation reduces incidence to about 56% compared to 87% in poorly treated patients, per long-term studies. reduction remains a concern; however, DEXA scans are not recommended in pediatric patients due to limitations in accuracy and reliability for predicting risk, as noted in recent reviews. As of 2025, systematic reviews emphasize the need for improved adherence strategies to mitigate side effects, with emerging therapies under investigation that may offer alternative safety profiles. The incidence of serious adverse events with delayed-release formulations is similar to or potentially slightly higher than with immediate-release, based on low-certainty evidence from recent reviews. Lifelong surveillance for these effects is essential.

Drug interactions

Cysteamine, particularly in its delayed-release oral formulations such as Procysbi, may interact with agents that increase gastric pH, including inhibitors (e.g., omeprazole) and medications containing or carbonate, potentially leading to premature release of the drug and altered that could affect white blood cell cystine concentrations. Although a clinical study showed no significant pharmacokinetic changes when Procysbi was co-administered with 20 mg omeprazole, monitoring of cystine levels is recommended during concomitant use to ensure . Alcohol consumption should be avoided during cysteamine , as it can accelerate the release rate of the drug from delayed-release formulations, potentially increasing gastrointestinal side effects such as , , and ulceration risk while altering overall effectiveness and safety profile. Oral solutions of cysteamine often contain as an , which can contribute to osmotic , particularly in patients sensitive to alcohols or at higher doses; alternative sorbitol-free formulations or dosage adjustments may be considered to mitigate this risk. Coadministration with other cystine-depleting agents, such as penicillamine, may result in additive effects on cystine reduction, but such combinations are not typically recommended due to overlapping mechanisms and the established preference for cysteamine monotherapy in conditions like nephropathic cystinosis; hypersensitivity to penicillamine is also a contraindication for cysteamine use. Cysteamine exhibits no significant inhibition of cytochrome P450 enzymes (including CYP1A2, CYP2C9, CYP2D6, and CYP3A4), indicating a low potential for pharmacokinetic interactions via this pathway with other medications metabolized by these enzymes. For the ophthalmic formulation (Cystaran), systemic absorption is minimal, resulting in negligible drug interaction risks compared to oral forms. Given cysteamine's renal clearance and the underlying involvement in , co-administration with drugs that impair renal function or alter clearance (e.g., certain nephrotoxic agents) necessitates close monitoring of cystine levels and potential dose adjustments to maintain therapeutic efficacy and avoid accumulation.

History and society

Development and discovery

Cysteamine, originally known as β-mercaptoethylamine, was first investigated in the for its radioprotective properties following reports of its ability to mitigate damage from in animal models. Early clinical trials in 1955 explored its use in treating radiation sickness in humans. During this period, derivatives like WR-638 (cysteamine ) were developed as latent radioprotectors to enhance stability and targeted release in biological systems, shifting initial focus from direct cysteamine administration. In the late 1960s, research pivoted toward cystinosis after investigators at the US National Institutes of Health identified defective lysosomal cystine efflux as the underlying cause of cystine accumulation in patient cells. Key contributions came from A.D. Patrick and B.D. Lake, who in 1968 used electron microscopy to confirm the presence of cystine crystals within lysosomes of cystinotic tissues, establishing the lysosomal basis of the disease and prompting exploration of thiol compounds for cystine depletion. Animal models in the early 1970s further validated these lysosomal effects, showing cysteamine's capacity to reduce cystine levels in rodent tissues affected by similar storage disorders. Pre-clinical studies in the demonstrated cysteamine's mechanism through thiol- exchange, where it reacts with lysosomal to form a mixed that can exit the , effectively depleting intracellular in cultured cystinotic fibroblasts and leukocytes. This work, led by Jess G. Thoene, Robert G. Oshima, John C. Crawhall, and Jerry A. Schneider, marked a shift from radioprotection to , with rat models confirming sustained reduction without toxicity at therapeutic doses. Building on these findings, the first human trials began in , administering oral and intravenous cysteamine to patients and achieving over 80% reduction in leukocyte levels, as reported by Thoene and colleagues. A major milestone in the 1980s was the identification of the salt form of cysteamine, which improved and reduced hygroscopicity compared to the salt, facilitating reliable oral formulations for long-term use in clinical settings. This development, pursued by Schneider's team at the , addressed early challenges with the compound's odor and instability, paving the way for broader therapeutic application.

Regulatory approvals and availability

Cysteamine bitartrate immediate-release capsules, marketed as Cystagon, received approval from the U.S. (FDA) on August 15, 1994, for the treatment of nephropathic in patients aged 12 months and older. The delayed-release , Procysbi, was approved by the FDA on April 30, 2013, offering twice-daily dosing for the same indication in patients aged 1 year and older. In 2020, the FDA approved Cystadrops, a 0.37% cysteamine ophthalmic solution, on August 19 for the treatment of corneal cystine crystal accumulation in patients aged 1 year and older, providing a more stable alternative to compounded . In the European Union, the (EMA) granted orphan drug designation to cysteamine bitartrate for nephropathic in 2010, recognizing its potential to address an unmet need in a rare condition affecting fewer than 5 in 10,000 people. Procysbi received centralized marketing authorization from the on September 6, 2013, for the treatment of proven nephropathic , with availability extended across member states shortly thereafter. Approvals in other regions, such as via in 2013 for Procysbi, have followed similar pathways to facilitate access for patients. Key brand names for cysteamine formulations include Cystagon (manufactured by Pharmaceuticals), Procysbi (developed by and now under following acquisition in October 2023), and Cystadrops (by Recordati Rare Diseases). As of November 2025, no generic versions of Procysbi or Cystagon are available due to ongoing patent protections and exclusivity periods, though generic cysteamine bitartrate capsules have entered markets in select regions post-patent expiry for earlier formulations. Access to cysteamine remains challenged by its high cost, estimated at approximately $300,000 annually for oral formulations like Procysbi in the U.S., driven by the small population and extensive development requirements for . assistance programs, such as those offered by and Recordati, provide financial support, copay assistance, and free medication to eligible uninsured or underinsured individuals with , helping mitigate barriers in high-income countries. Cysteamine's development has benefited from U.S. Act incentives, including seven years of market exclusivity, tax credits for clinical testing, and expedited review processes, which have encouraged investment in treatments for rare diseases like . However, these policies have sparked controversies over pricing, with critics arguing that status enables excessive costs—often exceeding $100,000 per annually—disproportionately burdening healthcare systems and families despite the drugs' life-extending benefits. Global disparities persist, as lower-income regions face limited availability due to import challenges and lack of local , underscoring ongoing debates about equitable access to therapies.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Cysteamine
  2. https://go.drugbank.com/drugs/DB00847
  3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/203389s027,213491s002lbl.pdf
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC6920251/
  5. https://www.chemspider.com/Chemical-Structure.5834.html
  6. https://www.chembk.com/en/chem/cysteamine
  7. https://amp.chemicalbook.com/ProductChemicalPropertiesCB2223766_EN.htm
  8. https://www.sciencedirect.com/science/article/pii/S2095177919309025
  9. https://pubchem.ncbi.nlm.nih.gov/compound/Cysteamine-Hydrochloride
  10. https://asianpubs.org/index.php/ajchem/article/download/11535/11517
  11. https://pubs.acs.org/doi/10.1021/jm00161a015
  12. https://www.chemicalbook.com/synthesis/cysteamine-hydrochloride.htm
  13. https://patents.google.com/patent/JPH05140087A/en
  14. https://www.tdcommons.org/cgi/viewcontent.cgi?article=5036&context=dpubs_series
  15. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213491Orig1s000ChemR.pdf
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC7992283/
  17. https://anovorx.com/wp-content/uploads/2023/08/Cystadrops-PI-August-2020.pdf
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC7775854/
  19. https://www.mdpi.com/1424-8247/15/1/2
  20. https://www.ncbi.nlm.nih.gov/books/NBK608010/
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC1145021/
  22. https://www.ncbi.nlm.nih.gov/books/NBK548701/
  23. https://www.sciencedirect.com/science/article/pii/S0014480025000450
  24. https://pmc.ncbi.nlm.nih.gov/articles/PMC1884393/
  25. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203389s010lbl.pdf
  26. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211302Orig1s000MedR.pdf
  27. https://pubmed.ncbi.nlm.nih.gov/23113697/
  28. https://pmc.ncbi.nlm.nih.gov/articles/PMC3257201/
  29. https://pubmed.ncbi.nlm.nih.gov/17153586/
  30. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020392s010lbl.pdf
  31. https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02724-3
  32. https://clinicaltrials.gov/study/NCT00359684
  33. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211302Orig1s000SumR.pdf
  34. https://pubmed.ncbi.nlm.nih.gov/40886257/
  35. https://bjo.bmj.com/content/105/5/608
  36. https://pubmed.ncbi.nlm.nih.gov/34898155/
  37. https://onlinelibrary.wiley.com/doi/10.1111/jocd.14494
  38. https://www.mdpi.com/2077-0383/13/23/7483
  39. https://clinicaltrials.gov/study/NCT02101957
  40. https://pubmed.ncbi.nlm.nih.gov/30856117/
  41. https://www.mdpi.com/1422-0067/25/19/10490
  42. https://my.clevelandclinic.org/health/diseases/24657-cystinosis
  43. https://link.springer.com/article/10.1007/s00467-010-1680-1
  44. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211302s000lbl.pdf
  45. https://pmc.ncbi.nlm.nih.gov/articles/PMC11022844/
  46. https://pmc.ncbi.nlm.nih.gov/articles/PMC11642093/
  47. https://dermnetnz.org/topics/cysteamine-cream
  48. https://pmc.ncbi.nlm.nih.gov/articles/PMC6394685/
  49. https://cystinosis.org/wp-content/uploads/2019/01/Besouw_et_al._2011.pdf
  50. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/200740s000lbl.pdf
  51. https://www.cystadrops.com/hcp/clinical-data-safety/
  52. https://www.nejm.org/doi/full/10.1056/NEJMoa052263
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC12507550/
  54. https://ojrd.biomedcentral.com/articles/10.1186/s13023-025-03974-z
  55. https://reference.medscape.com/drug/cystagon-cysteamine-procysbi-342843
  56. https://medicinesauthority.gov.mt/file.ashx?f=629DD1DD9663034F2746F2183239F992F8CDC67C9DFDD15C
  57. https://www.rxlist.com/cystaran-drug.htm
  58. https://pmc.ncbi.nlm.nih.gov/articles/PMC10508993/
  59. https://pubmed.ncbi.nlm.nih.gov/14378547/
  60. https://pubmed.ncbi.nlm.nih.gov/187547/
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC3195959/
  62. https://pubmed.ncbi.nlm.nih.gov/5697361/
  63. https://pubmed.ncbi.nlm.nih.gov/932205/
  64. https://pmc.ncbi.nlm.nih.gov/articles/PMC8945924/
  65. https://www.mdpi.com/2073-4409/11/6/945
  66. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf
  67. https://www.pharmacytimes.com/view/fda-approves-procysbi-for-nephropathic-cystinosis
  68. https://www.drugs.com/history/cystadrops.html
  69. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-10-778
  70. https://www.ema.europa.eu/en/medicines/human/EPAR/procysbi
  71. https://www.ncbi.nlm.nih.gov/books/NBK534498/
  72. https://www.webmd.com/drugs/2/drug-10707/cystagon-oral/details
  73. https://www.cystadrops.com/
  74. https://www.prnewswire.com/news-releases/amgen-completes-acquisition-of-horizon-therapeutics-plc-301949517.html
  75. https://www.drugs.com/availability/generic-procysbi.html
  76. https://www.drugs.com/availability/generic-cystagon.html
  77. https://www.cbc.ca/news/health/procysbi-kidney-disease-drug-price-1.6601422
  78. https://www.drugs.com/price-guide/procysbi
  79. https://pmc.ncbi.nlm.nih.gov/articles/PMC6664588/
  80. https://link.springer.com/article/10.1007/s00467-016-3520-4
  81. https://pmc.ncbi.nlm.nih.gov/articles/PMC10899370/
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