Cysteamine

Cysteamine is a Anticystine Agent belonging to Genetic disorder agent.

Cysteamine is a cystine depleting agent used to treat the effects of cystinosis.

Orally administered cysteamine is absorbed in the gastrointestinal tract and reaches its maximum plasma concentration in about 1.4 hours.Cysteamine is 52% plasma protein boundand is mostly bound to albumin.There is limited information in the literature regarding the metabolism of cysteamine. This drug undergoes significant first-pass metabolism. The half-life of cysteamine is about 3.7 hours. The plasma clearance of cysteamine is about 1.2 - 1.4 L/min.

Cysteamine shows side effects like Drowsiness, feeling tired; stomach pain, nausea, vomiting, loss of appetite, diarrhea; unusual breath odor or skin odor; rash; fever; or headache.

Cysteamine is available in the form of Oral capsule, ophthalmic drops, and oral granules.

Cysteamine is available in India, US, France, Italy, Spain, China , UK, Singapore, Malaysia, Canada, and Australia.

Cysteamine belongs to the Genetic disorder agent acts as a Anticystine Agent.

Cysteamine is an aminothiol that participates within lysosomes in a thiol-disulfide interchange reaction converting cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome in patients with cystinosis.

The Data of Onset and duration of action of Cysteamine is not clinically established.

Cysteamine is available in the form of Oral capsule, ophthalmic drops, and oral granules.

Cysteamine Capsule and granules taken orally, usually in divided dose.

Cysteamine is a cystine depleting agent used to treat the effects of cystinosis.

Cysteamine is a Anticystine Agent belonging to Genetic disorder agent.

Cysteamine is an aminothiol that participates within lysosomes in a thiol-disulfide interchange reaction converting cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome in patients with cystinosis.

Cysteamine is approved for use in the following clinical indications

• Nephropathic cystinosis
• Nutritional deficiency

• Nephropathic cystinosis

Immediate release (Cystagon)

Oral: Initial: ¹/₆ to ¹/₄ of target maintenance dose administered in 4 divided doses; gradually increase dose over 4 to 6 weeks to a target maintenance dose of 500 mg 4 times daily (maximum: 1.95 g/m²/day).

Delayed-release capsules, oral granules (Procysbi)

Oral: Initial: 0.2 to 0.3 g/m²/day in 2 divided doses every 12 hours; increase dose gradually over 4 to 6 weeks to target maintenance dose of 1.3 g/m²/day in 2 divided doses every 12 hours. May further increase in 10% increments if needed up to a maximum daily dose of 1.95 g/m²/day.

• Nutritional deficiency

Intravenous Adult Dose: As part of parenteral nutrition regimen for patients with severe liver disease who may have impaired enzymatic processes and require TPN. Doses are based on the recommended daily protein (amino acid) requirement. As cysteine hydrochloride: 7 mg/g of amino acids (equivalent to 5 mg cysteine/g of amino acids) daily. Correct severe fluid, electrolyte, and acid-base disorders before administration.

Intravenous Child Dose: As additive to crystalline amino acid solution to meet the intravenous nutritional requirements of those receiving TPN: As cysteine hydrochloride: Infants and children ≤11 years 30-40 mg/g of amino acids daily; a lower dose of 20 mg/g of amino acids daily may also be given; ≥12 years Same as adult dose. Dosage recommendations may vary among individual products. Refer to specific product guidelines. Correct severe fluid, electrolyte, and acid-base disorders before administration.

Cysteamine is available in various strengths as 50 mg; 150 mg; 25 mg; 75 mg; 300 mg and 0.37% (5 mL).

Cysteamine is available in the form of Oral capsule, ophthalmic drops, and oral granules.

Cysteamine is contraindicated in patients with

• The use of cysteamine is contraindicated in patients with a serious hypersensitivity reaction, including anaphylaxis, to penicillamine or cysteamine.

• Ehlers-Danlos-like Syndrome

Skin and bone lesions that resemble clinical findings for Ehlers-Danlos-like syndrome have been reported in patients treated with high doses of immediate-release cysteamine bitartrate or other cysteamine salts. These include molluscoid pseudotumors (purplish hemorrhagic lesions), skin striae, bone lesions (including osteopenia, compression fractures, scoliosis and genu valgum), leg pain, and joint hyperextension. One patient on immediate-release cysteamine bitartrate with serious skin lesions subsequently died of acute cerebral ischemia with marked vasculopathy. Monitor patients for development of skin or bone lesions and interrupt cysteamine dosing if patients develop these lesions. cysteamine may be restarted at a lower dose under close supervision, then slowly increase to the appropriate therapeutic dose.

• Skin Rash

Severe skin rashes such as erythema multiforme bullosa or toxic epidermal necrolysis have been reported in patients receiving immediate-release cysteamine bitartrate. If severe skin rashes develop, permanently discontinue use of cysteamine.

• Gastrointestinal Ulcers and Bleeding

Gastrointestinal (GI) ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate. GI tract symptoms including nausea, vomiting, anorexia and abdominal pain, sometimes severe, have been associated with cysteamine. If severe GI tract symptoms develop, consider decreasing the dose of cysteamine.

• Central Nervous System Symptoms

Central Nervous System (CNS) symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with immediate-release cysteamine. Neurological complications have also been described in some patients with cystinosis who have not been treated with cysteamine. Carefully evaluate and monitor patients who develop CNS symptoms. Interrupt medication or adjust the dose as necessary for patients with severe symptoms or with symptoms that persist or progress. Inform patients that cysteamine may impair their ability to perform tasks such as driving or operating machinery.

• Leukopenia and/or Elevated Alkaline Phosphatase Levels

Cysteamine has been associated with reversible leukopenia and elevated alkaline phosphatase levels. Monitor white blood cell counts and alkaline phosphatase levels. If tests values remain elevated, consider decreasing the dose or discontinuing the drug until values revert to normal.

• Benign Intracranial Hypertension

Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema have been reported in patients receiving immediate-release cysteamine bitartrate treatment. Monitor patients for signs and symptoms of PTC, including headache, tinnitus, dizziness, nausea, diplopia, blurry vision, loss of vision, pain behind the eye or pain with eye movement. If signs/symptoms persist, interrupt dosing or decrease the dose and refer the patient to an ophthalmologist. If the diagnosis is confirmed, permanently discontinue use of cysteamine.

Consumption of alcohol with cysteamine may increase the rate of cysteamine release and/or adversely alter the pharmacokinetic properties, as well as the effectiveness and safety of cysteamine.

There is no information on the presence of cysteamine in human milk, the effects on the breast-fed infant, or the effects on milk production. Cysteamine is present in the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants from cysteamine, breastfeeding is not recommended.

Pregnancy Category C

There are no available data on cysteamine use in pregnant women to inform any drug-associated risks for birth defects or miscarriage. Cysteamine (administered as cysteamine bitartrate) was teratogenic and fetotoxic in rats at doses less than the recommended human maintenance dose. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Advise pregnant women of the potential risk to a fetus.

Common

• Abdominal distress, abdominal pain, anorexia, diarrhea, nausea, vomiting, Lethargy, Fever, Headache, blurred vision, deposits on or around the surface of the eye, eye discomfort (instillation site), eye irritation, eye pain, eye pruritus, eye redness, increased lacrimation, ocular hyperemia, photophobia, visual field defect.

• Drugs that Increase Gastric pH

Drugs that increase the gastric pH (e.g., proton pump inhibitors, medications containing bicarbonate or carbonate) may alter the pharmacokinetics of cysteamine due to the premature release of cysteamine from cysteamine and increase WBC cystine concentration. Concomitant administration of 20 mg omeprazole did not significantly affect the pharmacokinetics of cysteamine when cysteamine was administered with 240 mL of orange juice. The effect of omeprazole on the pharmacokinetics of cysteamine was not studied after cysteamine administration with water. Monitor WBC cystine concentration when drugs that increase the gastric pH are concomitantly used.

• Use with Alcohol

Consumption of alcohol with cysteamine may increase the rate of cysteamine release and/or adversely alter the pharmacokinetic properties, as well as the effectiveness and safety of cysteamine. Therefore, do not consume alcoholic beverages during treatment with cysteamine.

• Other Medications Used for the Management of Fanconi syndrome

cysteamine can be administered with other electrolyte and mineral replacements necessary for management of Fanconi syndrome, as well as vitamin D and thyroid hormone.

The common side effects of cysteamine include the following

Common side effects

• Drowsiness, feeling tired; stomach pain, nausea, vomiting, loss of appetite, diarrhea; unusual breath odor or skin odor; rash; fever; or headache.

Rare side effects

• Depressed mood, extreme drowsiness; a seizure; unusual bruising or streaks on the skin; bone pain, abnormal joint movement; an electrolyte imbalance--increased thirst or urination, confusion, constipation, leg cramps, irregular heartbeats, tingly feeling; increased pressure inside the skull--severe headaches, ringing in your ears, dizziness, vision problems, pain behind your eyes; or stomach problems--pain, nausea, vomiting, loss of appetite, coughing up blood or vomit that looks like coffee grounds.

• Pregnancy

Pregnancy Category C

There are no available data on cysteamine use in pregnant women to inform any drug-associated risks for birth defects or miscarriage. Cysteamine (administered as cysteamine bitartrate) was teratogenic and fetotoxic in rats at doses less than the recommended human maintenance dose. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Advise pregnant women of the potential risk to a fetus.

• Nursing Mothers

There is no information on the presence of cysteamine in human milk, the effects on the breast-fed infant, or the effects on milk production. Cysteamine is present in the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants from cysteamine, breastfeeding is not recommended.

• Pediatric Use

The safety and effectiveness of cysteamine have been established in pediatric patients aged 2 years and older for the treatment of nephropathic cystinosis. Use of cysteamine is supported by evidence from an open-label, randomized, cross-over trial in adult and pediatric patients aged 6 years and older, and an openlabel extension trial which included patients aged 2 years and older. The safety and effectiveness of cysteamine in pediatric patients under 2 years of age have not been established.

• Geriatric Use

No studies with cysteamine have been conducted in geriatric patients.

Pharmacodynamic

Cystine accumulation is the cause of organ damage in cystinosis. Cysteamine prevents the accumulation of cystine crystals in the body and is specifically prescribed to prevent kidney and eye damage. Cysteamine converts cystine into a form that may easily exit cells, preventing harmful accumulation.

Pharmacokinetics

• Absorption

Orally administered cysteamine is absorbed in the gastrointestinal tract and reaches its maximum plasma concentration in about 1.4 hours.

• Distribution

Cysteamine is 52% plasma protein bound and is mostly bound to albumin.

• Metabolism and Excretion

There is limited information in the literature regarding the metabolism of cysteamine. This drug undergoes significant first-pass metabolism. The half-life of cysteamine is about 3.7 hours. The plasma clearance of cysteamine is about 1.2 - 1.4 L/min.

• https://www.drugs.com/mtm/cysteamine.html
• https://go.drugbank.com/drugs/DB00847
• https://www.mims.com/malaysia/drug/info/cysteine?mtype=generic
• https://www.uptodate.com/contents/cysteamine-ophthalmic-drug-information#F15404040
• https://www.uptodate.com/contents/cysteamine-systemic-drug-information#F15510944
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203389s010lbl.pdf
• https://www.everydayhealth.com/drugs/cysteamine#drug-side-effects