DRUGS & SUPPLEMENTS

Citrate de Betaine Conseil

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Citrate de Betaine Conseil uses


1 INDICATIONS AND USAGE

Cystadane® (betaine anhydrous for oral solution) is indicated for the treatment of homocystinuria to decrease elevated homocysteine blood levels. Included within the category of homocystinuria are:

  • Cystathionine beta-synthase (CBS) deficiency
  • 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency
  • Cobalamin cofactor metabolism (cbl) defect


  • Usual dose in adult and pediatric patients is 6 grams per day, administered orally in divided doses of 3 grams two times a day.(2)
  • In children less than 3 years of age, may initiate dosing at 100 mg/kg/day, divided in twice daily doses, and then increased weekly by 50 mg/kg increments.(2)
  • Dose can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts.(2)
  • Monitor patient response by plasma homocysteine levels.(2)
  • Prescribed amount of Cystadane should be measured with the measuring scoop provided and then dissolved in 4 to 6 ounces of water, juice, milk, or formula, or mixed with food for immediate ingestion.(2)

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

The usual dosage in adult and pediatric patients is 6 grams per day administered orally in divided doses of 3 grams twice daily. In pediatric patients less than 3 years of age, dosage may be started at 100 mg/kg/day divided in twice daily doses, and then increased weekly by 50 mg/kg increments.

Therapy with Cystadane should be directed by physicians knowledgeable in the management of patients with homocystinuria. Patient response to Cystadane can be monitored by homocysteine plasma levels. Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts. Response usually occurs within several days and steady state within a month. Plasma methionine concentrations should be monitored in patients with CBS deficiency .

Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients. However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Cystadane.

2.2 Administration

The prescribed amount of Cystadane should be measured with the measuring scoop provided (one level 1.7 mL scoop is equal to 1 gram of Citrate de Betaine Conseil anhydrous powder) and then dissolved in 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula, or mixed with food for immediate ingestion.

  • Powder for oral solution available in bottles containing 180 grams of Citrate de Betaine Conseil anhydrous.(3)

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3 DOSAGE FORMS AND STRENGTHS

Cystadane is a white, granular, hygroscopic powder for oral solution available in bottles containing 180 grams of Citrate de Betaine Conseil anhydrous.

  • None (4)

4 CONTRAINDICATIONS

None.

  • Hypermethioninemia: Cystadane may worsen elevated plasma methionine concentrations in patients with CBS deficiency. Cerebral edema has been reported in patients receiving Cystadane.( 5.1)
  • Monitoring: Monitor plasma methionine concentrations in patients with CBS deficiency. Keep plasma methionine concentrations below 1,000 µmol/L through dietary medication and, if necessary, a reduction of Cystadane dose. ( 5.1)

5 WARNINGS AND PRECAUTIONS

5.1 Hypermethioninemia

Risk of Hypermethioninemia in Patients with CBS Deficiency

Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations. Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine. Cerebral edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.

  • Most common adverse reactions (incidence > 2%) were nausea and gastrointestinal distress, based on physician survey.

    To report SUSPECTED ADVERSE REACTIONS, contact 877-828-8874, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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6 ADVERSE REACTIONS

6.1 Adverse Reactions in Clinical Studies

The most serious adverse reaction reported with Cystadane treatment is the development of hypermethioninemia and cerebral edema in patients with CBS Deficiency .

The assessment of clinical adverse reactions is based on a survey study of 41 physicians, who treated a total of 111 homocystinuria patients with Cystadane. Adverse reactions were retrospectively recalled and were not collected systematically in this open-label, uncontrolled, physician survey. Thus, this list may not encompass all types of potential adverse reactions, reliably estimate their frequency, or establish a causal relationship to drug exposure. The following adverse reactions were reported (Table 1):

Table 1: Number of Patients with Adverse Reactions to Cystadane by Physician Survey

Adverse Reactions Number of Patients
Nausea 2
Gastrointestinal distress 2
Diarrhea 1
"Bad Taste" 1
"Caused Odor" 1
Questionable psychological changes 1
“Aspirated the powder” 1

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Cystadane. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In postmarketing experience with Cystadane, severe cerebral edema and hypermethioninemia have been reported within 2 weeks to 6 months of starting Citrate de Betaine Conseil therapy, with complete recovery after discontinuation of Cystadane. All patients who developed cerebral edema had homocystinuria due to CBS deficiency and had severe elevation in plasma methionine levels (range 1,000 to 3,000 µM). As cerebral edema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to Citrate de Betaine Conseil therapy has been postulated as a possible mechanism of action.

The following adverse reactions have been reported in patients during postmarketing use of Cystadane: anorexia, agitation, depression, irritability, personality disorder, sleep disturbed, dental disorders, diarrhea, glossitis, nausea, stomach discomfort, vomiting, hair loss, hives, skin odor abnormalities, and urinary incontinence.

  • Pregnancy: Animal reproduction studies have not been conducted with Cystadane. Use only if clearly needed.(8.1)
  • Nursing women: It is not known whether Cystadane is excreted in human milk. Use only if clearly needed.(8.3)
  • Pediatrics: Pediatric patients ranging in age from 24 days to 17 years have been treated with Cystadane. Children younger than 3 years of age may benefit from dose titration.
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8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Cystadane. It is also not known whether Cystadane can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cystadane should be given to a pregnant woman only if clearly needed.

8.3 Nursing Mothers

It is not known whether Cystadane is excreted in human milk. Use only if clearly needed.

8.4 Pediatric Use

The majority of case studies of homocystinuria patients treated with Cystadane have been pediatric patients, including patients ranging in age from 24 days to 17 years . Children younger than 3 years of age may benefit from dose titration .

10 OVERDOSAGE

In an acute toxicology study in rats, death occurred frequently at doses equal to or greater than 10 g/kg.

11 DESCRIPTION

Cystadane (betaine anhydrous for oral solution) is an agent for the treatment of homocystinuria. It contains no ingredients other than anhydrous Citrate de Betaine Conseil. Cystadane is a white, granular, hygroscopic powder, which is diluted in water and administered orally. The chemical name of Citrate de Betaine Conseil anhydrous powder is trimethylglycine. It has a molecular weight of 117.15. The structural formula is:

Chemical Structure for Citrate de Betaine Conseil

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Cystadane acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. Cystadane occurs naturally in the body. It is a metabolite of choline and is present in small amounts in foods such as beets, spinach, cereals, and seafood.

12.2 Pharmacodynamics

Cystadane was observed to lower plasma homocysteine levels in three types of homocystinuria, including CBS deficiency; MTHFR deficiency; and cbl defect. Patients have taken Cystadane for many years without evidence of tolerance. There has been no demonstrated correlation between Cystadane levels and homocysteine levels.

In CBS-deficient patients, large increases in methionine levels over baseline have been observed. Cystadane has also been demonstrated to increase low plasma methionine and S-adenosylmethionine levels in patients with MTHFR deficiency and cbl defect.

12.3 Pharmacokinetics

Pharmacokinetic studies of Cystadane are not available. Plasma levels of Cystadane have not been measured in patients and have not been correlated to homocysteine levels.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term carcinogenicity and fertility studies have not been conducted with Cystadane. No evidence of genotoxicity was demonstrated in the following tests: metaphase analysis of human lymphocytes; bacterial reverse mutation assay; and mouse micronucleus test.

14 CLINICAL STUDIES

Cystadane was studied in a double-blind, placebo-controlled, crossover study in 6 patients with CBS deficiency, ages 7 to 32 years at enrollment. Cystadane was administered at a dosage of 3 grams twice daily, for 12 months. Plasma homocystine levels were significantly reduced (p<0.01) compared to placebo. Plasma methionine levels were variable and not significantly different compared to placebo. No adverse events were reported in any patient.

Cystadane has also been evaluated in observational studies without concurrent controls in patients with homocystinuria due to CBS deficiency, MTHFR deficiency, or cbl defect. A review of 16 case studies and the randomized controlled trial previously described was also conducted, and the data available for each study were summarized; however, no formal statistical analyses were performed. The studies included a total of 78 male and female patients with homocystinuria who were treated with Cystadane. This included 48 patients with CBS deficiency, 13 with MTHFR deficiency, and 11 with cbl defect, ranging in age from 24 days to 53 years. The majority of patients (n=48) received 6 gm/day, 3 patients received less than 6 gm/day, 12 patients received doses from 6 to 15 gm/day, and 5 patients received doses over 15 gm/day. Most patients were treated for more than 3 months (n=57) and 30 patients were treated for 1 year or longer (range 1 month to 11 years). Homocystine is formed nonenzymatically from two molecules of homocysteine, and both have be used to evaluate the effect of Cystadane in patients with homocystinuria. Plasma homocystine or homocysteine levels were reported numerically for 62 patients, and 61 of these patients showed decreases with Cystadane treatment. Homocystine decreased by 83-88% regardless of pre-treatment level, and homocysteine decreased by 71-83%, regardless of the pre-treatment level. Clinical improvement, such as improvement in seizures, or behavioral and cognitive functioning, was reported by the treating physicians in about three-fourths of patients. Many of these patients were also taking other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), and folate with variable biochemical responses. In most cases, adding Cystadane resulted in a further reduction of either homocystine or homocysteine.

16 HOW SUPPLIED/STORAGE AND HANDLING

Cystadane is available in plastic bottles containing 180 grams of Citrate de Betaine Conseil anhydrous. Each bottle is equipped with a plastic child-resistant cap and is supplied with a polystyrene measuring scoop. One level scoop is equal to 1 gram of Citrate de Betaine Conseil anhydrous powder.

NDC 66621-4000-1 180 g/bottle

Cystadane can be ordered by calling AnovoRx Group, LLC, Customer service at 1-888-487-4703

16.1 Storage

Store at room temperature, 15 – 30 ˚C (59 – 86 ˚F). Protect from moisture.

17 PATIENT COUNSELING INFORMATION

Patients should be advised of the following information before beginning treatment with Cystadane:

17.1 Dosing and Administration

  • Instruct patients and caregivers that Cystadane should only be taken as directed by their healthcare professional.
  • Instruct patients and caregivers to administer Cystadane as follows:
  • Shake bottle lightly before removing cap.

- Measure with the scoop provided.

- Measure the number of scoops as prescribed by their healthcare professional. One level scoop (1.7 mL) is equivalent to 1 gram of Citrate de Betaine Conseil anhydrous powder.

- Mix powder with 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula until completely dissolved, or mix with food, then ingest mixture immediately.

- Always replace the cap tightly after using, and protect powder from moisture.

Manufactured For:

Rare Disease Therapeutics, Inc.

Franklin, TN 37067

Under License From:

Orphan Europe, s.a.r.l. Puteaux France

Distributed By:

AnovoRx Distribution, LLC

Memphis, TN 38134

Part No.: RDT C PI007

Part No.: Orphan Europe OEP 829

Cystadane (betaine anhydrous) for oral solution

Citrate de Betaine Conseil pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Citrate de Betaine Conseil available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Citrate de Betaine Conseil destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Citrate de Betaine Conseil Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Citrate de Betaine Conseil pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."BETAINE HYDROCHLORIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "betaine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "betaine". http://www.drugbank.ca/drugs/DB0675... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Citrate de Betaine Conseil?

Depending on the reaction of the Citrate de Betaine Conseil after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Citrate de Betaine Conseil not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Citrate de Betaine Conseil addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Citrate de Betaine Conseil, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Citrate de Betaine Conseil consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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