nitisinone (Rx)

Brand and Other Names:Orfadin, Nityr
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule (Orfadin)

  • 2mg
  • 5mg
  • 10mg
  • 20mg

oral suspension (Orfadin)

  • 4mg/mL

tablet (Nityr)

  • 2mg
  • 5mg
  • 10mg

Hereditary Tyrosinemia Type 1

Indicated for hereditary tyrosinemia type 1 (HT-1) as an adjunct to dietary restriction of tyrosine and phenylalanine

Starting dose: 0.5 mg/kg PO q12hr (morning and evening); titrate dose based on biochemical and/or clinical response, as described in the full prescribing information  

Succinylacetone detectable in blood or urine 4 weeks after initiating: May increase to 0.75 mg/kg q12hr; maximum total daily dose (TDD) of 2 mg/kg may be needed based on evaluation of all biochemical parameters

Undetectable serum and urine succinylacetone concentrations after at least 4 weeks on stable dose: TDD may be given once daily (eg, 1-2 mg/kg qDay)

If satisfactory biochemical response (undetectable blood and/or urine succinylacetone), adjust dose according to body weight gain and not according to plasma tyrosine levels

Dosing Considerations

Monitoring parameters

  • Monitor plasma and/or urine succinylacetone concentrations, liver function parameters, and alpha-fetoprotein levels
  • During initiation, when switching from q12hr to qDay dosing, or if condition is deteriorating, consider closely monitoring all available biochemical parameters (ie, plasma and/or urine succinylacetone, urine 5-aminolevulinate [ALA], erythrocyte porphobilinogen [PBG]-synthase activity)
  • Maintain plasma tyrosine levels <500 mmol/L by dietary restriction of tyrosine and phenylalanine intake
  • Plasma tyrosine levels >500 micromol/L: Assess dietary tyrosine and phenylalanine intake; do not adjust dosage in order to lower plasma tyrosine concentration

Alkaptonuria (Orphan)

Treatment of alkaptonuria

Orphan indication sponsor

  • Swedish Orphan AB; Kungsgatan 37, 7th Floor; SE-111 56, Sweden

Dosage Forms & Strengths

capsule (Orfadin)

  • 2mg
  • 5mg
  • 10mg
  • 20mg

oral suspension (Orfadin)

  • 4mg/mL

tablet (Nityr)

  • 2mg
  • 5mg
  • 10mg

Hereditary Tyrosinemia Type 1

Indicated for hereditary tyrosinemia type 1 (HT-1) in adult and pediatric patients as an adjunct to dietary restriction of tyrosine and phenylalanine

Starting dose: 0.5 mg/kg PO q12hr; titrate dose based on biochemical and/or clinical response  

Succinylacetone detectable in blood or urine 4 weeks after initiating: May increase to 0.75 mg/kg q12hr; maximum total daily dose (TDD) of 2 mg/kg may be needed based on evaluation of all biochemical parameters

Patients aged 5 years or older with undetectable serum and urine succinylacetone concentrations after at least 4 weeks on a stable dosage of nitisinone: TDD may be given once daily (eg, 1-2 mg/kg qDay)

If satisfactory biochemical response (undetectable blood and/or urine succinylacetone), adjust dose according to body weight gain and not according to plasma tyrosine levels

Dosing Considerations

Monitoring parameters

  • Monitor plasma and/or urine succinylacetone concentrations, liver function parameters, and alpha-fetoprotein levels
  • During initiation, when switching from q12hr to qDay dosing, or if condition is deteriorating, consider closely monitoring all available biochemical parameters (ie, plasma and/or urine succinylacetone, urine 5-aminolevulinate [ALA], erythrocyte porphobilinogen [PBG]-synthase activity)
  • Maintain plasma tyrosine levels <500 mmol/L by dietary restriction of tyrosine and phenylalanine intake
  • Plasma tyrosine levels >500 micromol/L: Assess dietary tyrosine and phenylalanine intake; do not adjust dosage in order to lower plasma tyrosine concentration
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Interactions

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              Serious - Use Alternative (2)

              • erdafitinib

                nitisinone will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

              • siponimod

                nitisinone will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              Monitor Closely (32)

              • bosentan

                nitisinone will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • carvedilol

                nitisinone will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • chlorpropamide

                nitisinone will increase the level or effect of chlorpropamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • dapsone

                nitisinone will increase the level or effect of dapsone by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • diclofenac

                nitisinone will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • etravirine

                nitisinone will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • fluoxetine

                nitisinone will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • fluvastatin

                nitisinone will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • fosphenytoin

                nitisinone will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • glimepiride

                nitisinone will increase the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • glipizide

                nitisinone will increase the level or effect of glipizide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • glyburide

                nitisinone will increase the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • imatinib

                nitisinone will increase the level or effect of imatinib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • ketamine

                nitisinone will increase the level or effect of ketamine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • lacosamide

                nitisinone will increase the level or effect of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • lesinurad

                nitisinone will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • losartan

                nitisinone will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • mestranol

                nitisinone will increase the level or effect of mestranol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • montelukast

                nitisinone will increase the level or effect of montelukast by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • nateglinide

                nitisinone will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • ospemifene

                nitisinone will increase the level or effect of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • phenytoin

                nitisinone will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • propofol

                nitisinone will increase the level or effect of propofol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • sulfadiazine

                nitisinone will increase the level or effect of sulfadiazine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • sulfisoxazole

                nitisinone will increase the level or effect of sulfisoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • tamoxifen

                nitisinone will increase the level or effect of tamoxifen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • tolbutamide

                nitisinone will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • torsemide

                nitisinone will increase the level or effect of torsemide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • trimethoprim

                nitisinone will increase the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • voriconazole

                nitisinone will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • warfarin

                nitisinone will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • zafirlukast

                nitisinone will increase the level or effect of zafirlukast by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              Minor (0)

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                Adverse Effects

                >10%

                Liver transplantation (13%)

                Elevated tyrosine levels (>10%)

                1-10%

                Liver failure (7%)

                Malignant hepatic neoplasm (5%)

                Leukopenia (3%)

                Thrombocytopenia (3%)

                Conjunctivitis (2%)

                Corneal opacity (2%)

                Keratitis (2%)

                Photophobia (2%)

                Alopecia (1%)

                Blepharitis (1%)

                Cataracts (1%)

                Dry skin (1%)

                Epistaxis (1%)

                Exfoliative dermatitis (1%)

                Eye pain (1%)

                Granulocytopenia (1%)

                Maculopapular rash (1%)

                Porphyria (1%)

                Pruritus (1%)

                <1%

                Seizure

                Brain tumor

                Encephalopathy

                Hyperkinesia

                Cyanosis

                Abdominal pain

                Diarrhea

                Enanthema

                Gastrointestinal hemorrhage

                Melena

                Elevated hepatic enzymes

                Liver enlargement hypoglycemia

                Septicemia

                Bronchitis

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                Warnings

                Contraindications

                None

                Cautions

                May develop transient leukopenia, thrombocytopenia, or both; monitor CBC during therapy

                Increase tyrosine levels

                • May cause increase in plasma tyrosine levels in patient with HT-1
                • Maintain concomitant reduction in dietary tyrosine and phenylalanine during treatment
                • Inadequate restriction of tyrosine and phenylalanine may lead to elevated plasma levels of tyrosine
                • Do not adjust dosage in order to lower plasma tyrosine concentration; maintain plasma tyrosine levels below 500 micromol/L
                • In patients with HT-1 treated with dietary restrictions and receive therapy who develop elevated plasma tyrosine levels, assess dietary tyrosine and phenylalanine intake
                • Tyrosine levels >500 mmol/L may lead to
                  • Variable degrees of intellectual disability and developmental delay; perform a clinical assessment if abrupt changes in neurologic status occur OR
                  • Painful hyperkeratotic plaques on the soles and palms OR
                  • Ocular signs and symptoms (eg, corneal ulcers, corneal opacities, keratitis, conjunctivitis, eye pain, photophobia); rerform a baseline ophthalmologic examination including slit-lamp examination prior to initiating treatment and regularly thereafter; if photophobia, eye pain, or signs of inflammation develops or tyrosine levels are > 500 micromol/L during treatment, undergo slit-lamp reexamination and immediately measure plasma tyrosine concentration

                Glycerol content in oral suspension

                • Doses of 20 mL of oral suspension (10 g glycerol) may cause headache, upset stomach and diarrhea due to glycerol content
                • Oral suspension contains 500 mg/mL of glycerol
                • Consider switching patients who are unable to tolerate the oral suspension to the oral capsules (see Administration)

                Drug interaction overview

                Nitisinone is a moderate CYP2C9 inhibitor, a weak CYP2E1 inducer, and an OAT1/OAT3 inhibitor

                • Sensitive CYP2C9 substrates or CYP2C9 substrates with a narrow therapeutic index
                  • Nitisinone increases exposure of CYP2C9 substrates
                  • Reduce dose of coadministered CYP2C9 substrates drug by half
                  • Additional dosage adjustments may be needed to maintain therapeutic drug concentrations for narrow therapeutic index drugs; see prescribing information for those drugs
                • OAT1/OAT3 substrates
                  • Nitisinone increases exposure of OAT1/OAT3 substrate Monitor for potential adverse reactions related to coadministered drug
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                Pregnancy & Lactation

                Pregnancy

                Limited data on use in pregnant women insufficiently informs a drug-associated risk of major birth defects and miscarriage

                Animal data

                • Reproduction studies were performed in mice at PO doses ~0.4, 4 and 20x the recommended human dose (1 mg/kg/day), nitisinone reported to cause incomplete skeletal ossification of fetal bones, increased gestational length at 4 and 20x the recommended human dose, and decreased pup survival at 0.4x the recommended human dose based on the body surface area
                • Studies in rabbits at PO doses ~1.6, 4, and 8x the recommended human dose based on body surface area; nitisinone caused incomplete skeletal ossification of fetal bones

                Lactation

                No data on the presence of enasidenib or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production

                Data suggest that nitisinone may be present in rat milk due ocular toxicity and lower body weight seen in drug naïve pups; consult women of the risk versus benefits for nitisinone and any potential adverse effects on breastfed infant from nitisinone

                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

                4-Hydroxyphenylpyruvate dioxygenase inhibitor; inhibits catabolism of tyrosine in patients with HT-1, preventing accumulation of maleylacetoacetate & fumarylacetoacetate which are converted to toxic succinylacetone & succinylacetoacetate; succinylacetone can inhibit the porphyrin synthesis pathway, which may lead to the accumulation of the neurotoxin 5-aminolevulinate, causing the porphyric crises typical of hereditary tyrosinemia type 1

                Absorption

                Fasting

                • Peak plasma time: 3.5 hr (Orfadin capsule); 0.38 hr (Orfadin suspension); 3.5 hr (Nityr)
                • Peak plasma concentration: 10.2 micromol/L (Orfadin capsule); 9.74 micromol/L (Orfadin suspension); 1278 ng/mL (Nityr)
                • AUC: 403 micromol·hr/L (Orfadin capsule); 346 micromol·hr/L (Orfadin suspension); 77874 ng·h/mL (Nityr) (Nityr)

                Distribution

                Protein bound: >95%

                Vd: 8.2 L (Nityr)

                Metabolism

                Relatively stable in human liver microsomes with minor metabolism possibly mediated by CYP3A4 enzyme

                Elimination

                Half-life: 54 hr; 59.3 hr (Nityr)

                Excretion: Unknown

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                Administration

                Oral Suspension Preparation (Orfadin)

                Bottle without oral syringe adapter already inserted

                • Allow bottle to warm to room temperature (30-60 minutes)
                • Shake bottle vigorously for at least 20 seconds until solid cake is completely dispersed; ensure no particles left at the bottom of the bottle; foam will form in the bottle
                • Insert bottle adapter

                Bottle with oral syringe adapter

                • Shake bottle vigorously for at least 5 seconds
                • Check that there are no particles left at the bottom of the bottle
                • Foam will form in the bottle

                Oral Suspension Preparation (Nityr)

                Prepare only 1-2 tablets per PO syringe at one time; use 5-mL PO syringe with a cap

                Remove plunger from oral syringe and insert tablet(s)

                Replace plunger and draw up 2.6 mL (1 tablet) or 5 mL (2 tablets) of room temperature water

                Cap oral syringe and leave for ≥60 minutes

                Turn syringe up and down for at least 30 seconds to suspend contents

                Administer immediately; do not administer unless tablet(s) has fully disintegrated

                If tablet(s) not fully disintegrated, leave for an additional 10 minutes and again turn syringe up and down to suspend contents; do not administer unless tablet has fully disintegrated

                Administer immediately or store suspension at room temperature in the capped oral syringe, protected from direct sunlight for up to 24 hr after adding water to the tablets; discard after 24 hr

                Uncap oral syringe and administer suspension into patient’s mouth; avoid depressing plunger to end of oral syringe (ie, leave a gap between the plunger and the oral syringe)

                Rinse oral syringe by drawing up 2 mL of water; cap syringe and shake well for 10 seconds; uncap syringe and administer remaining suspension; if particle remain in syringe, repeat this process

                Oral Administration

                Adjunct to dietary reduction of tyrosine/phenylalanine

                Orfadin

                • Suspension: May take without regard to meals
                • Capsules
                  • Take at least 1 hr before or 2 hr after a meals
                  • For patients who have difficulty swallowing the capsules, open contents suspend in a small amount of water, formula, or apple sauce immediately before use

                Nityr

                • Maintain dietary restriction of tyrosine and phenylalanine
                • Take with or without food
                • Patients who have difficulty swallowing intact tablets: Disintegrate tablets in water
                • Patients can swallow semi-solid foods: Crush and mix with applesauce
                • Administration with other liquids or foods not studied and not recommended

                Storage

                Orfadin

                • Capsules
                  • Refrigerate between 2-8°C (36-46°F)
                • Suspension
                  • Refrigerate at 2-8°C (36-46°F) prior to first use
                  • Do not freeze
                  • After first opening, store at room temperature (up to 25°C [77°F]) for up to 60 days; if not used within 60 days, discard unused portion

                Nityr

                • Tablets: Store at controlled room temperature of 20-25°C (68-77°F)
                • Tablets mixed in water: Store at room temperature up to 24 hr; protect from light
                • Tablets mixed in applesauce: Store at room temperature, out of direct sunlight, for up to 2 hr after adding crushed tablets to applesauce
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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                nitisinone oral
                -
                2 mg capsule
                nitisinone oral
                -
                5 mg capsule
                nitisinone oral
                -
                10 mg capsule
                Orfadin oral
                -
                10 mg capsule
                Orfadin oral
                -
                5 mg capsule
                Orfadin oral
                -
                2 mg capsule

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                Patient Education
                nitisinone oral

                NITISINONE - ORAL

                (nye-TIS-i-none)

                COMMON BRAND NAME(S): Orfadin

                USES: Nitisinone is used to treat a certain inherited disorder (hereditary tyrosinemia type 1, also known as HT-1). HT-1 is usually discovered in infants and needs lifelong treatment. This condition is caused by a shortage of a certain natural substance that is needed to break down a nutrient (tyrosine) found in food. This effect causes a build-up of too much tyrosine and related substances in the liver. Nitisinone works by helping to prevent the formation and build-up of several toxic substances that cause damage to the liver, kidneys, and nervous system. This drug must be used along with a diet low in protein, tyrosine, and phenylalanine.

                HOW TO USE: Take this medication by mouth as directed by your doctor, usually twice daily.If you are taking the capsules, take them on an empty stomach at least 1 hour before or 2 hours after a meal. If you are unable to swallow the capsules and/or have side effects with the suspension, you may open up the capsules and mix the contents in a small amount of water, formula, or apple sauce immediately before use.If you are taking the suspension, read the Patient Information Leaflet provided by your pharmacist before you start taking it and each time you get a refill. If you have any questions, ask your doctor or pharmacist. Shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose. You may take the suspension with or without food. When using an unopened bottle of suspension for the first time, remove it from the refrigerator and let it warm to room temperature for 30 to 60 minutes before use.If you are taking the tablets, read the Patient Information Leaflet if available from your pharmacist before you start taking nitisinone and each time you get a refill. You may take the tablets with or without food. If you are unable to swallow the tablets, you may crush the tablets and mix them in a small amount of water or applesauce. Take the mixture right away. If you are using a special measuring device/syringe to prepare and give the tablets mixed with water, carefully follow the directions from the manufacturer. Ask your doctor or pharmacist if you have any questions.The dosage is based on your medical condition, weight, and response to treatment. Your doctor may adjust your dose and schedule based on your response to treatment. Carefully follow your doctor's directions for taking this medication.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.It is very important that patients taking this medication follow a special diet low in protein, tyrosine, and phenylalanine. Consult your doctor, pharmacist, or dietician for more details. (See also Drug Interactions and Precautions sections.)

                SIDE EFFECTS: The suspension may cause headache, upset stomach, or diarrhea. If any of these effects occur, tell your doctor or pharmacist promptly and discuss switching to other forms of nitisinone.Remember that this medication has been prescribed because the doctor has judged that the benefit is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may rarely cause a low number of blood cells such as white cells and platelets. This effect can decrease your body's ability to fight an infection or cause easy bruising/bleeding. Tell your doctor right away if you develop any of the following unlikely symptoms: signs of infection (such as fever, chills, persistent sore throat), easy bruising/bleeding.Your condition and this medication can cause liver problems. Tell the doctor right away if any of these symptoms of liver problems occur: severe stomach/abdominal pain, persistent nausea or vomiting, yellowing eyes/skin, dark urine.Your condition and this medication can cause high levels of tyrosine in the blood. It is very important to follow the low protein/low tyrosine diet recommended by your doctor. See also Precautions section. Too much tyrosine may cause skin, eye, or brain problems. Tell the doctor right away if any of these symptoms occur: eye redness/itching/discharge, vision changes, eye pain, eye sensitivity (especially to light), dry/itchy skin, sores on palms of hands/soles of feet, developmental delays (such as holding head up, rolling over, crawling).A very serious allergic reaction to this drug is rare. However, seek immediate medical attention 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 the 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 giving nitisinone, tell the doctor or pharmacist if your child is allergic to it; or if your child has 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 the doctor or pharmacist your child's medical history, especially of: eye problems (such as cataracts, corneal ulcers).Patients taking this medication are at risk for developing high levels of tyrosine in the blood, possibly leading to eye, skin, and nervous system problems. (See Side effects section.) To decrease the risk of high tyrosine levels, patients should follow a diet low in tyrosine and phenylalanine. Avoid foods and beverages that contain aspartame or are high in tyrosine or phenylalanine. Foods high in tyrosine include soy products, turkey, fish, avocados, bananas, yogurt, and lima beans. Foods high in phenylalanine include milk, chicken, eggs, cheese, peanut butter. (See also Drug Interactions section.)During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: 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.Many foods, drugs, or supplements may contain aspartame, tyrosine, or phenylalanine, which must be limited in patients taking this drug. Check the labels on all products (especially artificially sweetened products) for aspartame, tyrosine and phenylalanine content. Consult your doctor, pharmacist, or dietician for more details.

                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.Laboratory and/or medical tests (such as eye exams, compete blood count, liver function tests, blood and urine tests for tyrosine and related substances) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

                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: Store the tablets at room temperature. Store the capsules in the refrigerator. Store the suspension in the refrigerator before the first use. Do not freeze. After the first use, store the bottle of suspension at room temperature. Discard any unused liquid 60 days after the date the bottle was removed from the refrigerator. 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 July 2021. Copyright(c) 2021 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

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                Additional Offers
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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.