Syprine

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Syprine uses


DESCRIPTION

Syprine is N,N'-bis (2-aminoethyl)-1,2-ethanediamine dihydrochloride. It is a white to pale yellow crystalline hygroscopic powder. It is freely soluble in water, soluble in methanol, slightly soluble in ethanol, and insoluble in chloroform and ether.

The empirical formula is C6H18N4-2HCl with a molecular weight of 219.2. The structural formula is:

NH2(CH2)2NH(CH2)2NH(CH2)2NH2-2HCI

Syprine is a chelating compound for removal of excess copper from the body. Syprine (trientine hydrochloride) is available as 250 mg capsules for oral administration. Syprine capsules contain gelatin, iron oxides, stearic acid, and titanium dioxide as inactive ingredients.

CLINICAL PHARMACOLOGY

Introduction

Wilson's disease is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper but when their capacity is exceeded copper is released into the blood and is taken up into extrahepatic sites. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body.

Clinical Summary

Forty-one patients (18 male and 23 female) between the ages of 6 and 54 with a diagnosis of Wilson's disease and who were intolerant of d-penicillamine were treated in two separate studies with Syprine. The dosage varied from 450 to 2400 mg per day. The average dosage required to achieve an optimal clinical response varied between 1000 mg and 2000 mg per day. The mean duration of Syprine therapy was 48.7 months (range 2-164 months). Thirty-four of the 41 patients improved, 4 had no change in clinical global response, 2 were lost to follow-up and one showed deterioration in clinical condition. One of the patients who improved while on therapy with Syprine experienced a recurrence of the symptoms of systemic lupus erythematosus which had appeared originally during therapy with penicillamine. Therapy with Syprine was discontinued. No other adverse reactions, except iron deficiency, were noted among any of these 41 patients.

One investigator treated 13 patients with Syprine following their development of intolerance to d-penicillamine. Retrospectively, he compared these patients to an additional group of 12 patients with Wilson's disease who were both tolerant of and controlled with d-penicillamine therapy, but who failed to continue any copper chelation therapy. The mean age at onset of disease of the latter group was 12 years as compared to 21 years for the former group. The Syprine group received d-penicillamine for an average of 4 years as compared to an average of 10 years for the non-treated group.

Various laboratory parameters showed changes in favor of the patients treated with Syprine. Free and total serum copper, SGOT and serum bilirubin all showed mean increases over baseline in the untreated group which were significantly larger than with the patients treated with Syprine. In the 13 patients treated with Syprine, previous symptoms and signs relating to d-penicillamine intolerance disappeared in 8 patients, improved in 4 patients, and remained unchanged in one patient. The neurological status in the Syprine group was unchanged or improved over baseline, whereas in the untreated group, 6 patients remained unchanged and 6 worsened. Kayser-Fleischer rings improved significantly during Syprine treatment.

The clinical outcome of the two groups also differed markedly. Of the 13 patients on therapy with Syprine (mean duration of therapy 4.1 years; range 1 to 13 years), all were alive at the data cutoff date, and in the non-treated group (mean years with no therapy 2.7 years; range 3 months to 9 years), 9 of the 12 died of hepatic disease.

Chelating Properties

Preclinical Studies

Studies in animals have shown that Syprine has cupriuretic activities in both normal and copper-loaded rats. In general, the effects of Syprine on urinary copper excretion are similar to those of equimolar doses of penicillamine, although in one study they were significantly smaller.

Human Studies

Renal clearance studies were carried out with penicillamine and Syprine on separate occasions in selected patients treated with penicillamine for at least one year. Six-hour excretion rates of copper were determined off treatment and after a single dose of 500 mg of penicillamine or 1.2 g of Syprine. The mean urinary excretion rates of copper were as follows:

No. of

Patients

Single Dose Treatment Basal Excretion Rate

Test-dose Excretion Rate

(µg Cu + + /6hr)


6


Trientine, 1.2 g


19


234


4


Penicillamine, 500 mg


17


320


In patients not previously treated with chelating agents, a similar comparison was made:

No. of Patients Single Dose Treatment Basal Excretion Rate

(µg Cu + + /6hr)

Test-dose Excretion Rate

(µg Cu + + /6hr)


8


Trientine, 1.2 g


71


1326


7


Penicillamine, 500 mg


68


1074


These results demonstrate that Syprine is effective as a cupriuretic agent in patients with Wilson's disease although on a molar basis it appears to be less potent or less effective than penicillamine. Evidence from a radio-labelled copper study indicates that the different cupriuretic effect between these two drugs could be due to a difference in selectivity of the drugs for different copper pools within the body.

Pharmacokinetics

Data on the pharmacokinetics of Syprine are not available. Dosage adjustment recommendations are based upon clinical use of the drug.

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INDICATIONS AND USAGE

Syprine is indicated in the treatment of patients with Wilson's disease who are intolerant of penicillamine. Clinical experience with Syprine is limited and alternate dosing regimens have not been well-characterized; all endpoints in determining an individual patient's dose have not been well defined. Syprine and penicillamine cannot be considered interchangeable. Syprine should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects.

Unlike penicillamine, Syprine is not recommended in cystinuria or rheumatoid arthritis. The absence of a sulfhydryl moiety renders it incapable of binding cystine and, therefore, it is of no use in cystinuria. In 15 patients with rheumatoid arthritis, Syprine was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment.

Syprine is not indicated for treatment of biliary cirrhosis.

CONTRAINDICATIONS

Hypersensitivity to this product.

WARNINGS

Patient experience with Syprine is limited. Patients receiving Syprine should remain under regular medical supervision throughout the period of drug administration. Patients (especially women) should be closely monitored for evidence of iron deficiency anemia.

PRECAUTIONS

General

There are no reports of hypersensitivity in patients who have been administered Syprine for Wilson's disease. However, there have been reports of asthma, bronchitis and dermatitis occurring after prolonged environmental exposure in workers who use Syprine as a hardener of epoxy resins. Patients should be observed closely for signs of possible hypersensitivity.

Information for Patients

Patients should be directed to take Syprine on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed. Because of the potential for contact dermatitis, any site of exposure to the capsule contents should be washed with water promptly. For the first month of treatment, the patient should have his temperature taken nightly, and he should be asked to report any symptom such as fever or skin eruption.

Laboratory Tests

The most reliable index for monitoring treatment is the determination of free copper in the serum, which equals the difference between quantitatively determined total copper and ceruloplasmin-copper. Adequately treated patients will usually have less than 10 mcg free copper/dL of serum.

Therapy may be monitored with a 24-hour urinary copper analysis periodically. Urine must be collected in copper-free glassware. Since a low copper diet should keep copper absorption down to less than one milligram a day, the patient probably will be in the desired state of negative copper balance if 0.5 to 1.0 milligram of copper is present in a 24-hour collection of urine.

Drug Interactions

In general, mineral supplements should not be given since they may block the absorption of Syprine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and Syprine each inhibit absorption of the other, two hours should elapse between administration of Syprine and iron.

It is important that Syprine be taken on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. This permits maximum absorption and reduces the likelihood of inactivation of the drug by metal binding in the gastrointestinal tract.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Data on carcinogenesis, mutagenesis, and impairment of fertility are not available.

Pregnancy

Syprine was teratogenic in rats at doses similar to the human dose. The frequencies of both resorptions and fetal abnormalities, including hemorrhage and edema, increased while fetal copper levels decreased when Syprine was given in the maternal diets of rats. There are no adequate and well-controlled studies in pregnant women. Syprine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Syprine is administered to a nursing mother.

Pediatric Use

Controlled studies of the safety and effectiveness of Syprine in pediatric patients have not been conducted. It has been used clinically in pediatric patients as young as 6 years with no reported adverse experiences.

Geriatric Use

Clinical studies of Syprine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience is insufficient to determine differences in responses between the elderly and younger patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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ADVERSE REACTIONS

Clinical experience with Syprine has been limited. The following adverse reactions have been reported in a clinical study in patients with Wilson's disease who were on therapy with Syprine: iron deficiency, systemic lupus erythematosus. In addition, the following adverse reactions have been reported in marketed use: dystonia, muscular spasm, myasthenia gravis.

Syprine is not indicated for treatment of biliary cirrhosis, but in one study of 4 patients treated with Syprine for primary biliary cirrhosis, the following adverse reactions were reported: heartburn; epigastric pain and tenderness; thickening, fissuring and flaking of the skin; hypochromic microcytic anemia; acute gastritis; aphthoid ulcers; abdominal pain; melena; anorexia; malaise; cramps; muscle pain; weakness; rhabdomyolysis. A causal relationship of these reactions to drug therapy could not be rejected or established.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

There is a report of an adult woman who ingested 30 grams of Syprine without apparent ill effects. No other data on overdosage are available.

DOSAGE AND ADMINISTRATION

Systemic evaluation of dose and/or interval between dose has not been done. However, on limited clinical experience, the recommended initial dose of Syprine is 500-750 mg/day for pediatric patients and 750-1250 mg/day for adults given in divided doses two, three or four times daily. This may be increased to a maximum of 2000 mg/day for adults or 1500 mg/day for pediatric patients age 12 or under.

The daily dose of Syprine should be increased only when the clinical response is not adequate or the concentration of free serum copper is persistently above 20 mcg/dL. Optimal long-term maintenance dosage should be determined at 6-12 month intervals (see PRECAUTIONS, Laboratory Tests ).

It is important that Syprine be given on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed.

HOW SUPPLIED

Syprine capsules, 250 mg, are light brown opaque capsules coded Syprine on one side and ATON 710 on the other. They are supplied as follows:

NDC 0187-2120-10 in bottles of 100.

STORAGE

Keep container tightly closed.

Store at 2°-8°C (36°to 46°F).

Manufactured for:

Valeant Pharmaceuticals North America LLC

Bridgewater, NJ 08807 USA

Manufactured by:

Valeant Pharmaceuticals International, Inc.

Steinbach, MB R5G 1Z7 Canada

Syprine is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.

©Valeant Pharmaceuticals North America LLC

9407801-20001779

Rev. 12/2016

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Syprine pharmaceutical active ingredients containing related brand and generic drugs:

Active 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.


Syprine available forms, composition, doses:

Form 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.


Syprine destination | category:

Destination 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.


Syprine Anatomical Therapeutic Chemical codes:

A 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.


Syprine pharmaceutical companies:

Pharmaceutical 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."SYPRINE (TRIENTINE HYDROCHLORIDE) CAPSULE [VALEANT PHARMACEUTICALS NORTH AMERICA LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Syprine?

Depending on the reaction of the Syprine after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Syprine 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 Syprine 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 Syprine, 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 Syprine 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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One visitor reported doses

What is the dose of Syprine drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 201-500mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
201-500mg1
100.0%

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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