Nitisinone
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From MedlinePlus, U.S. National Library of Medicine
4-Hydroxyphenyl-Pyruvate Dioxygenase Inhibitor
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
Preparation and Administration Instructions Preparation of the Oral Suspension The oral suspension will be dispensed with an oral syringe of appropriate size and a bottle adaptor provided by a pharmacist or other healthcare provider. Preparing a Bottle Without the Adapter Already Inserted: Store the bottle in the refrigerator prior to first use.
Remove the bottle from the refrigerator. Calculate 60 days from when the bottle is removed from the refrigerator. Write this date as the “Discard after” date on the bottle label. Allow the bottle to warm to room temperature (30 to 60 minutes). Shake the bottle vigorously for at least 20 seconds until the solid cake at the bottom of the bottle is completely dispersed.
Check that there are no particles left at the bottom of the bottle. Foam will form in the bottle. Insert the bottle adapter. Preparing a Bottle With the Adapter Inserted: Shake the 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. Measuring and Administering the Dose Once the bottle is prepared with the adapter: Use the oral syringe to measure the dose.
Keep the bottle upright and insert the oral syringe into the adapter. Carefully turn the bottle upside down with the oral syringe in place. Wait for the foam to rise to the top of the bottle. Pull back on the syringe plunger to withdraw the dose. Leave the syringe in the adapter and turn the bottle upright. Remove the syringe from the adapter by gently twisting it out of the bottle.
Dispense the dose into the patient's mouth. Do not remove the bottle adapter. Store the bottle at room temperature (not above 25°C). Administration of ORFADIN Capsules and Oral Suspension Maintain dietary restriction of tyrosine and phenylalanine when taking ORFADIN. Capsules: Take at least one hour before, or two hours after a meal [see Clinical Pharmacology] .
For patients who have difficulty swallowing the capsules and who are intolerant to the oral suspension [see Warnings and Precautions] , the capsules may be opened and the contents suspended in a small amount of water, formula or apple sauce immediately before use. Oral suspension: Take without regard to meals [see Clinical Pharmacology] .
Drug interactions
Check nitisinone against a medication listLabel text (3 paragraphs)
Nitisinone is a moderate CYP2C9 inhibitor, a weak CYP2E1 inducer and an inhibitor of OAT1/OAT3. Table 2 includes drugs with clinically important drug interactions when administered concomitantly with ORFADIN and instructions for preventing or managing them. Table 2: Clinically Relevant Interactions Affecting Co-Administered Drugs Sensitive CYP2C9 Substrates (e.g., celecoxib, tolbutamide) or CYP2C9 Substrates with a Narrow Therapeutic Index (e.g., phenytoin, warfarin) Clinical Impact Increased exposure of the co-administered drugs metabolized by CYP2C9. [see Clinical Pharmacology ( 12.3 )] Intervention Reduce the dosage of the co-administered drugs metabolized by CYP2C9 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 (e.g., adefovir, ganciclovir, methotrexate) Clinical Impact Increased exposure of the interacting drug [see Clinical Pharmacology ( 12.3 )] Intervention Monitor for potential adverse reactions related to the co-administered drug. CYP2C9 Substrates : Increased systemic exposure of these co-administered drugs; reduce the dosage. Additional dosage adjustments may be needed to maintain therapeutic drug concentrations for narrow therapeutic index drugs.
( 7 ) OAT1/OAT3 Substrates : Increased systemic exposure of these co-administered drugs; monitor for potential adverse reactions. ( 7 )
Contraindications
None. None ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have been conducted for nitisinone. In these studies, nitisinone was administered to mice and rabbits during organogenesis with oral doses of nitisinone up to 20 and 8 times respectively, the recommended initial dose of 1 mg/kg/day. In mice, nitisinone caused incomplete skeletal ossification of fetal bones and decreased pup survival at doses 0.4 times the recommended initial dose, and increased gestational length at doses 4 times the recommended initial dose.
In rabbits, nitisinone caused maternal toxicity and incomplete skeletal ossification of fetal bones at doses 1.6 times the recommended initial dose [see Data ] . The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data Reproduction studies have been performed in mice at oral doses of about 0.4, 4 and 20 times the recommended initial dose (1 mg/kg/day) and in rabbits at oral doses of about 1.6, 4 and 8 times the recommended initial dose based on the body surface area. In mice, nitisinone has been shown to cause incomplete skeletal ossification of fetal bones at 0.4, 4 and 20 times the recommended initial dose, increased gestational length at 4 and 20 times the recommended initial dose, and decreased pup survival at 0.4 times the recommended initial dose based on the body surface area.
In rabbits, nitisinone caused incomplete skeletal ossification of fetal bones at 1.6, 4 and 8 times the recommended initial dose based on the body surface area.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.