trientine (Rx)

Brand and Other Names:Syprine, Cuvrior

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 250mg (Syprine; hydrochloride salt)

tablet

  • 300mg (Cuvrior; tetrahydrochloride salt)

Wilson Disease

Syprine

  • Indicated for treatment of Wilson disease in patients intolerant of penicillamine
  • 750-1250 mg/day PO divided q6-12hr
  • Increase dose if clinical response not adequate or free serum copper persistently >20 mcg/dL; not to exceed 2 g/day
  • Reassess long-term maintenance dose q6-12Months

Cuvrior

  • Indicated for treatment of adults with stable Wilson disease who are decoppered and tolerant to penicillamine
  • Dose ranges from 300-3,000 mg/day PO divided BID; do not exceed 3,000 mg/day
  • Discontinue penicillamine before starting
  • Adjust total daily dosage according to clinical assessment and laboratory monitoring of copper
  • Recommended Cuvrior starting dose when switching from penicillamine (total daily doses)
    • Penicillamine 125 mg: Cuvrior 300 mg
    • Penicillamine 250 mg: Cuvrior 600 mg
    • Penicillamine 375 mg: Cuvrior 900 mg
    • Penicillamine 500 mg: Cuvrior 900 mg
    • Penicillamine 625 mg: Cuvrior 1,200 mg
    • Penicillamine 750 mg: Cuvrior 1,500 mg
    • Penicillamine 875 mg: Cuvrior 1,800 mg
    • Penicillamine 1,000 mg: Cuvrior 2,100 mg
    • Penicillamine 1,125 mg: Cuvrior 2,400 mg
    • Penicillamine 1,250 mg: Cuvrior 2,400 mg
    • Penicillamine 1,375 mg: Cuvrior 2,700 mg
    • Penicillamine >1,500 mg: Cuvrior 3,000 mg

Dosing Considerations

Evaluate serum non-ceruloplasmin copper (NCC) levels when initiating treatment, after 3 months, and q6months thereafter

May also monitor 24-hr urinary copper excretion periodically (q6-12months)

Manganism (Orphan)

Designated for treatment of manganism

Orphan sponsor

  • Biovail Technologies, Ltd; 700 Route 202/206 North; Bridgewater, NJ 08807

Dosage Forms & Strengths

capsule

  • 250mg (Syprine; hydrochloride salt)

Wilson Disease

Indicated for patients with Wilson disease who are intolerant of penicillamine

Syprine only

<12 years: 500-750 mg/day PO divided q6-12hr; not to exceed 1.5 g/day

≥12 years: 750-1250 mg/day PO divided q6-12hr; not to exceed 2 g/day

Dosing considerations

Syprine: Safety and effectiveness in pediatric patients have not been conducted; pediatric patients ≥6 years treated with Syprine reported no adverse events

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Interactions

Interaction Checker

and trientine

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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (0)

              Serious - Use Alternative (0)

                Monitor Closely (27)

                • acetazolamide

                  acetazolamide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • bendroflumethiazide

                  bendroflumethiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • bumetanide

                  bumetanide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • carbonyl iron

                  trientine, carbonyl iron. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • chlorothiazide

                  chlorothiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • chlorthalidone

                  chlorthalidone decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • cyclopenthiazide

                  cyclopenthiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • ethacrynic acid

                  ethacrynic acid decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • ferric maltol

                  trientine, ferric maltol. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • ferrous fumarate

                  trientine, ferrous fumarate. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • ferrous gluconate

                  trientine, ferrous gluconate. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • ferrous sulfate

                  trientine, ferrous sulfate. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • furosemide

                  furosemide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • hydrochlorothiazide

                  hydrochlorothiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • indapamide

                  indapamide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • iron dextran complex

                  trientine, iron dextran complex. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • iron sucrose

                  trientine, iron sucrose. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • magnesium supplement

                  magnesium supplement will decrease the level or effect of trientine by Other (see comment). Modify Therapy/Monitor Closely. Formation of an insoluble complex reduces absorption of the drug through intestinal tract; administer magnesium 1hr before the trietine or 1hr after the trientine

                • methyclothiazide

                  methyclothiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • metolazone

                  metolazone decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • polysaccharide iron

                  trientine, polysaccharide iron. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • rose hips

                  trientine, rose hips. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hr.

                • selenium

                  selenium will decrease the level or effect of trientine by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer trientine at least 1 hr before or after polyvalent cations (2 hr if oral iron administered).

                • sodium sulfate/?magnesium sulfate/potassium chloride

                  sodium sulfate/?magnesium sulfate/potassium chloride decreases levels of trientine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer trientine at least 1 hr before and after each dose to avoid chelation with magnesium. .

                • sodium sulfate/potassium sulfate/magnesium sulfate

                  sodium sulfate/potassium sulfate/magnesium sulfate decreases levels of trientine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer trientine at least 1 hr before and after each dose to avoid chelation with magnesium. .

                • torsemide

                  torsemide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

                • zinc

                  zinc will decrease the level or effect of trientine by cation binding in GI tract. Modify Therapy/Monitor Closely. Separate administration of trientine and oral polyvalent cation containing products by at least 1 hr.

                Minor (1)

                • copper

                  trientine decreases levels of copper by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Indicated action (for Wilson's disease).

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                Adverse Effects

                >10%

                Tetrahydrochloride salt

                • Abdominal pain (19%)
                • Change of bowel habits (15%)
                • Rash (12%)

                1-10%

                Tetrahydrochloride salt

                • Alopecia (8%)
                • Mood swings (8%)
                • Anemia (4%)

                Frequency Not Defined

                Hydrochloride salt

                • Metabolism and nutrition disorders: Iron deficiency
                • Musculoskeletal and connective tissue disorders: Systemic lupus erythematosus

                Postmarketing Reports

                Hydrochloride salt

                • Gastrointestinal disorders: Colitis
                • Musculoskeletal and connective tissue disorders: Muscle spasms, rhabdomyolysis
                • Nervous system disorders: Dystonia, myasthenia gravis
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                Warnings

                Contraindications

                Hypersensitivity to product or components

                Cautions

                Not indicated for cystinuria, RA (cf penicillamine) or biliary cirrhosis

                May cause iron deficiency anemia

                Hepatic iron oveload may result from copper deficiency induced by therapy

                Monitor urinary copper and for signs of hypersensitivity (eg, elevated body temperature)

                Worsening of clinical symptoms, including neurological deterioration, may occur when beginning therapy owing to mobilization of excess stores of copper; adjust dose or discontinue trientine if patient’s clinical condition worsens

                Drug interaction overview

                • Mineral supplements
                  • Avoid coadministration with mineral supplements (eg, iron, zinc, calcium, magnesium)
                  • If unavoidable, administer trientine at least 2 hr before or after iron supplements OR at least 1 hr before or 2 hr after other mineral supplements
                  • Trientine has potential to chelate non-copper cations in mineral supplements and other oral drugs, and thereby decreasing systemic absorption and efficacy
                • Other oral drugs
                  • Separate doses by at least 1 hr
                  • Trientine may potentially bind other drugs in GI tract and decrease their systemic absorption
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                Pregnancy & Lactation

                Pregnancy

                Available data on use of trientine for treatment of Wilson disease have not identified any drug-associated risks for major birth defects, miscarriages, or other adverse maternal or fetal outcomes

                Monitor copper levels throughout pregnancy and use the minimum effective dose

                Clinical considerations

                • Untreated Wilson disease or discontinuation of treatment during pregnancy may result in worsening neurological and hepatic symptoms, including rare reports of hepatic decompensation and liver failure
                • Untreated Wilson disease may also increase risk of miscarriage in some symptomatic patients
                • Increased copper deposition in placenta and fetal liver may adversely impact fetus
                • Maternal adverse effects
                  • Trientine may chelate non-copper cations (eg, iron, calcium); maintain appropriate levels during pregnancy
                • Fetal/neonatal adverse effects
                  • Chelator-induced copper deficiency may have adverse effects on fetus

                Animal studies

                • Oral administration in rats during organogenesis resulted in increased embryo-fetal loss at a dose lower than the maximum recommended dose (MDR) and produced fetal abnormalities at 2.7 x the MRD
                • Copper supplementation in pregnant rats produced a marked reduction in trientine-induced fetal abnormalities
                • Oral administration of trientine dihydrochloride to pregnant mice during organogenesis increased the percentage of mice with total embryofetal loss at ~4.3 x MDR and produced fetal abnormalities at ~1.1 x the MDR

                Lactation

                Published data are inconsistent regarding detection of trientine in breastmilk

                Available published literature have not reported drug-associated adverse effects in infants exposed to trientine through breastmilk

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Oral chelating agent; eliminates absorbed copper from body by forming stable complex that is then eliminated through urinary excretion

                Also chelates copper in intestinal tract, reducing copper absorption

                Absorption

                Tetrahydrochloride salt

                • Peak plasma time: 1.25-2 hr (single dose, fasting)
                • Peak plasma concentration: 2,030 ng/mL; 3,430 ng/mL (900 mg; 1,500 mg respectively)
                • AUC: 9,750 ng⋅hr/mL; 17,200 ng⋅hr/mL (900 mg; 1,500 mg respectively)
                • Administration of 1,500 mg of tetrahydrochloride salt, the mean AUC was comparable to 1,250 mg of trientine hydrochloride

                Metabolism

                Trientine is acetylated into 2 major active metabolites, N(1)-acetyltriethylenetetramine (MAT) and N(1),N(10)-diacetyltriethylenetetramine (DAT)

                Elimination

                Half-life: 13.8-16.5 hr

                Excretion: Urine (trientine and its metabolites)

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                Administration

                Oral Administration

                Take on empty stomach 1 hr before or 2 hr after meals

                Take at least 1 hr apart from any drug, food, or milk

                Mineral supplements

                • Avoid coadministration
                • If unavoidable, administer trientine at least 2 hr before or after iron supplements OR at least 1 hr before or 2 hr after other mineral supplements
                • For other oral drugs, separate doses by at least 1 hr

                Products not interchangeable

                • Not substitutable on a mg-per-mg basis
                • Trientine tetrahydrochloride (Cuvrior) 300 mg tablet contains 150 mg trientine base
                • Trientine hydrochloride (Syprine) 250 mg capsule contains 167 mg of trientine base

                Syprine

                • Swallow capsule whole with water; do not open or chew
                • Any skin exposed to capsule contents should be promptly washed

                Cuvrior

                • Discontinue penicillamine before starting
                • Swallow tablets without crushing, chewing, or dissolving
                • Unable to swallow tablets whole
                  • Scored tablet can be divided into 2 equal halves for patient who have difficulty swallowing tablet whole
                  • Do not store tablet for future use after blister packaging opened
                  • Avoid in patients who are unable to swallow tablets

                Storage

                Syprine

                • Refrigerate at 2-8ºC (36-46ºF)
                • Keep container tightly closed

                Cuvrior

                • Do not remove tablets from blister pack until time of dosing
                • Store at 20-25ºC (68-77ºF); excursions between 15-30ºC (59-86ºF)

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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Syprine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule
                trientine oral
                -
                250 mg capsule

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                Patient Education
                trientine oral

                TRIENTINE - ORAL

                (TRYE-en-teen)

                COMMON BRAND NAME(S): Cuvrior, Syprine

                USES: This medication is used to treat a certain inherited disorder (Wilson's disease). This disorder causes too much copper to build up in the liver, brain, and other parts of the body. Trientine works by binding to copper, which helps your body get rid of extra copper. This can decrease symptoms such as problems with speech/swallowing/coordination, tiredness, lack of appetite, abdominal pain, yellowing eyes/skin, fluid buildup in the legs/abdomen, uncontrolled movements, or muscle stiffness.

                HOW TO USE: Take this medication by mouth on an empty stomach, at least 1 hour before meals or 2 hours after meals as directed by your doctor, usually 2 to 4 times daily. Take this medication at least 1 hour apart from any other drug, food, or milk.If you are taking the capsule form of this medication, swallow the capsules whole with water. Do not open or chew the capsules. If you accidentally come in contact with the capsule contents, wash the area promptly with water to avoid an allergic reaction.If you are taking the tablet form of this medication, do not crush, chew or dissolve the tablets. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing. Do not remove the tablet from the blister pack until right before using.If you are taking a certain medication called penicillamine, your doctor will direct you to stop the medication before starting trientine. Consult your doctor or pharmacist for more details.The dosage is based on your medical condition and response to treatment. Do not change dosage forms of this medication without checking with your doctor or pharmacist.If your doctor directs you to also take an iron supplement, take it at least 2 hours before or after trientine.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.You may notice worsening in certain symptoms of Wilson's disease (such as problems with speech/swallowing/coordination, uncontrolled movements) when you start taking trientine as the medication begins to work to reduce the copper levels in your body. Always tell your doctor right away about these symptoms.Tell your doctor if you do not get better or if you get worse.

                SIDE EFFECTS: Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication and a low-copper diet may increase the risk for iron deficiency. Tell your doctor right away if you have symptoms such as feeling very tired, weakness, pale skin, chest pain, fast heartbeat, shortness of breath, cold hands/feet. Your doctor may direct you to take an iron supplement for a short time (see also How to Use section).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Before taking trientine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Children and pregnant or menstruating women may be at greater risk for developing iron deficiency while taking this drug.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

                OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: Do not share this medication with others.Lab and/or medical tests (such as blood/urine copper levels) should be done while you are taking this medication. Keep all medical and lab appointments.For the best effect, follow a low-copper diet as directed by your doctor.

                MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

                STORAGE: Different brands of this medication have different storage needs. Check the product package for instructions on how to store your brand, or ask your pharmacist. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

                Information last revised April 2023. Copyright(c) 2023 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

                FormularyPatient Discounts

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                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.