Cysteamine (oral): Difference between revisions
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|useInNursing=It is not known whether cysteamine is excreted in human milk. Because many drugs are excreted in human milk and because of the manifested potential of cysteamine for developmental toxicity in suckling rat pups when it was administered to their lactating mothers at an oral dose of 375 mg/kg/day (2,250 mg/m2/day, 1.7 times the recommended human dose based on body surface area), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. | |useInNursing=It is not known whether cysteamine is excreted in human milk. Because many drugs are excreted in human milk and because of the manifested potential of cysteamine for developmental toxicity in suckling rat pups when it was administered to their lactating mothers at an oral dose of 375 mg/kg/day (2,250 mg/m2/day, 1.7 times the recommended human dose based on body surface area), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. | ||
|useInPed=The safety and effectiveness of CYSTAGON® for cystinotic children have been established. Cysteamine therapy should be initiated as soon as the diagnosis of nephropathic cystinosis has been confirmed. | |useInPed=The safety and effectiveness of CYSTAGON® for cystinotic children have been established. Cysteamine therapy should be initiated as soon as the diagnosis of nephropathic cystinosis has been confirmed. | ||
|overdose=A single oral dose of cysteamine at 660 mg/kg was lethal to rats. Symptoms of acute toxicity were reduction of motor activity and generalized hemorrhage in gastrointestinal tract and kidneys. | |||
Two cases of human overdosage have been reported. In one case, the patient immediately vomited the drug and did not develop any symptoms. The second incident involved an accidental ingestion of a 200 to 250 mg/kg dose by a healthy 13 month old child. Vomiting and dehydration were experienced. The child was hospitalized and fluids were administered. A full recovery was made. Should overdose occur, the respiratory and cardiovascular systems should be supported appropriately. No specific antidote is known. Hemodialysis may be considered since cysteamine is poorly bound to plasma proteins. | |||
|mechAction=Cystinosis is an autosomal recessive inborn error of metabolism in which the transport of cystine out of lysosomes is abnormal; in the nephropathic form, accumulation of cystine and formation of crystals damage various organs, especially the kidney, leading to renal tubular Fanconi Syndrome and progressive glomerular failure, with end stage renal failure by the end of the first decade of life. In four studies of cystinosis patients before cysteamine was available, renal death (need for transplant or dialysis) occurred at median age of less than 10 years. Patients with cystinosis also experience growth failure, rickets, and photophobia due to cystine deposits in the cornea. With time most organs are damaged, including the retina, muscles and central nervous system. | |||
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. | |||
|alcohol=Alcohol-Cysteamine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. | |alcohol=Alcohol-Cysteamine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. | ||
}} | }} | ||
Revision as of 14:14, 16 April 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
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Overview
Cysteamine (oral) is a renal-urologic agent that is FDA approved for the treatment of nephropathic cystinosis in children and adults.. Common adverse reactions include Finding of odor of skin, rash, abdominal pain, breath smells unpleasant, diarrhea, loss of appetite, nausea, vomiting, dizziness, headache, lethargy and fever.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indication
CYSTAGON® is indicated for the management of nephropathic cystinosis in children and adults.
Dosage
New patients should be started on ¼ to 1/6 of the maintenance dose of CYSTAGON®. The dose should then be raised gradually over four to six weeks to avoid intolerance.
The recommended CYSTAGON® maintenance dose for children up to age 12 years is 1.30 grams/m2/day of the free base, given in four divided doses. Intact CYSTAGON® capsules should not be administered to children under the age of approximately six years due to the risk of aspiration. CYSTAGON® capsules may be administered to children under the age of approximately six years by sprinkling the capsule contents over food. Patients over age 12 and over 110 pounds weight should receive 2.0 grams/day, divided four times daily.
If a dose is missed, it should be taken as soon as possible. If it is within two hours of the next dose, skip the missed dose and go back to the regular dosing schedule. Do not double dose.
When CYSTAGON® is well tolerated, the goal of therapy is to keep leukocyte cystine levels below 1 nmol/½ cystine/mg protein five to six hours following administration of CYSTAGON®. Patients with poorer tolerability still receive significant benefit if white cell cystine levels are below 2 nmol/½ cystine/mg protein. The CYSTAGON® dose can be increased to a maximum of 1.95 grams/m2/day to achieve this level. The dose of 1.95 grams/m2/day has been associated with an increased rate of withdrawal from treatment due to intolerance and an increased incidence of adverse events.
Cystinotic patients taking cysteamine hydrochloride or phosphocysteamine solutions may be transferred to equimolar doses of CYSTAGON® capsules.
The recommended maintenance dose of 1.30 grams/m2/day can be approximated by administering CYSTAGON® according to the following table, which takes surface area as well as weight into consideration.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cysteamine in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cysteamine in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Indication
CYSTAGON® is indicated for the management of nephropathic cystinosis in children.
Dosage
The recommended CYSTAGON® maintenance dose for children up to age 12 years is 1.30 grams/m2/day of the free base, given in four divided doses. Intact CYSTAGON® capsules should not be administered to children under the age of approximately six years due to the risk of aspiration. CYSTAGON® capsules may be administered to children under the age of approximately six years by sprinkling the capsule contents over food. Patients over age 12 and over 110 pounds weight should receive 2.0 grams/day, divided four times daily.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cysteamine in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cysteamine in pediatric patients.
Contraindications
CYSTAGON® is contraindicated in patients who have developed hypersensitivity to it or to cysteamine or penicillamine.
Warnings
If a skin rash develops, CYSTAGON® should be withheld until the rash clears. CYSTAGON® may be restarted at a lower dose under close supervision, then slowly titrated to the therapeutic dose. If a severe skin rash develops such as erythema multiforme bullosa or toxic epidermal necrolysis, CYSTAGON® should not be readministered.
CNS symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with cysteamine. If CNS symptoms develop, the patient should be carefully evaluated and the dose adjusted as necessary. Neurological complications have been described in some cystinotic patients not on cysteamine treatment. This may be a manifestation of the primary disorder. Patients should not engage in hazardous activities until the effects of CYSTAGON® on mental performance are known.
Gastrointestinal ulceration and bleeding have been reported in patients receiving cysteamine bitartrate. Physicians should remain alert for signs of ulceration and bleeding and should inform patients and/or guardians about the signs and symptoms of serious G.I. toxicity and what steps to take if they occur.
Adverse Reactions
Clinical Trials Experience
In three clinical trials, cysteamine or phosphocysteamine have been administered to 246 children with cystinosis. Causality of side effects is sometimes difficult to determine because adverse effects may result from the underlying disease.
The most frequent adverse reactions seen involve the gastrointestinal and central nervous systems. These are especially prominent at the initiation of cysteamine therapy. Temporarily suspending treatment, then gradual re-introduction may be effective in improving tolerance.
Adverse reactions were not collected systematically in the NCCS, but were often listed by investigators. The following rates may therefore be underestimated. The most common events (> 5%) were vomiting 35%, anorexia 31%, fever 22%, diarrhea 16%, lethargy 11%, and rash 7%.
Less common adverse events are:
Body as a whole: Dehydration.
Cardiovascular: Hypertension.
Digestive: Nausea, bad breath, abdominal pain, dyspepsia, constipation, gastroenteritis, duodenitis, gastrointestinal ulceration and bleeding.
Central Nervous System: Somnolence, encephalopathy, headache, seizures, ataxia, confusion, tremor, hyperkinesia, decreasing hearing, dizziness, jitteriness.
Psychiatric: Nervousness, abnormal thinking, depression, emotional lability, hallucinations, nightmares.
Integumentary: Urticaria.
Urogenital: Interstitial nephritis, renal failure (see WARNINGS).
Clinical Laboratory: Abnormal liver function, anemia, leukopenia.
Adverse reactions or intolerance leading to cessation of treatment occurred in 8% of patients in the U.S. Studies.
Withdrawals due to intolerance, vomiting associated with medication, anorexia, lethargy, and fever appeared dose related, occurring more frequently in those patients receiving 1.95 grams/m2/day as compared to 1.30 grams/m2/day.
Sudden deaths have been reported in this disease state.
Postmarketing Experience
Benign intracranial hypertension (or pseudotumor cerebri; PTC) with papilledema; skin lesions, molluscoid pseudotumors, skin striae, skin fragility; joint hyperextension, leg pain, genu valgum, osteopenia, compression fracture and scoliosis have been reported.
Post marketing reports include one report of interstitial nephritis with early renal failure. A causal relationship between this event and cysteamine bitartrate therapy has not been established.
Drug Interactions
None have been described. CYSTAGON® can be administered with electrolyte and mineral replacements necessary for management of the Fanconi Syndrome as well as vitamin D and thyroid hormone.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C
Teratology studies have been performed in rats at oral doses in a range of 37.5 to 150 mg/kg/day (about 0.2 to 0.7 times the recommended human maintenance dose on a body surface basis) and have revealed cysteamine bitartrate to be teratogenic and fetotoxic. Observed teratogenic findings were cleft palate, Kyphosis, heart ventricular septal defects, microcephaly and exencephaly. There are no adequate and well-controlled studies in pregnant women. CYSTAGON® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cysteamine (oral) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Cysteamine (oral) during labor and delivery.
Nursing Mothers
It is not known whether cysteamine is excreted in human milk. Because many drugs are excreted in human milk and because of the manifested potential of cysteamine for developmental toxicity in suckling rat pups when it was administered to their lactating mothers at an oral dose of 375 mg/kg/day (2,250 mg/m2/day, 1.7 times the recommended human dose based on body surface area), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
The safety and effectiveness of CYSTAGON® for cystinotic children have been established. Cysteamine therapy should be initiated as soon as the diagnosis of nephropathic cystinosis has been confirmed.
Geriatic Use
There is no FDA guidance on the use of Cysteamine (oral) in geriatric settings.
Gender
There is no FDA guidance on the use of Cysteamine (oral) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Cysteamine (oral) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Cysteamine (oral) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Cysteamine (oral) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Cysteamine (oral) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Cysteamine (oral) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Cysteamine (oral) Administration in the drug label.
Monitoring
There is limited information regarding Cysteamine (oral) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Cysteamine (oral) and IV administrations.
Overdosage
A single oral dose of cysteamine at 660 mg/kg was lethal to rats. Symptoms of acute toxicity were reduction of motor activity and generalized hemorrhage in gastrointestinal tract and kidneys.
Two cases of human overdosage have been reported. In one case, the patient immediately vomited the drug and did not develop any symptoms. The second incident involved an accidental ingestion of a 200 to 250 mg/kg dose by a healthy 13 month old child. Vomiting and dehydration were experienced. The child was hospitalized and fluids were administered. A full recovery was made. Should overdose occur, the respiratory and cardiovascular systems should be supported appropriately. No specific antidote is known. Hemodialysis may be considered since cysteamine is poorly bound to plasma proteins.
Pharmacology
There is limited information regarding Cysteamine (oral) Pharmacology in the drug label.
Mechanism of Action
Cystinosis is an autosomal recessive inborn error of metabolism in which the transport of cystine out of lysosomes is abnormal; in the nephropathic form, accumulation of cystine and formation of crystals damage various organs, especially the kidney, leading to renal tubular Fanconi Syndrome and progressive glomerular failure, with end stage renal failure by the end of the first decade of life. In four studies of cystinosis patients before cysteamine was available, renal death (need for transplant or dialysis) occurred at median age of less than 10 years. Patients with cystinosis also experience growth failure, rickets, and photophobia due to cystine deposits in the cornea. With time most organs are damaged, including the retina, muscles and central nervous system.
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.
Structure
There is limited information regarding Cysteamine (oral) Structure in the drug label.
Pharmacodynamics
There is limited information regarding Cysteamine (oral) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Cysteamine (oral) Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Cysteamine (oral) Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Cysteamine (oral) Clinical Studies in the drug label.
How Supplied
There is limited information regarding Cysteamine (oral) How Supplied in the drug label.
Storage
There is limited information regarding Cysteamine (oral) Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Cysteamine (oral) Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Cysteamine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Cysteamine (oral) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Cysteamine (oral) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.