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nitisinone (Rx)Brand and Other Names:Orfadin

 
 
 

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 2mg
  • 5mg
  • 10mg
  • 20mg

oral suspension

  • 4mg/mL
more...

Hereditary Tyrosinemia Type 1

0.5 mg/kg PO q12hr (morning and evening); after 1 month, may increase dose to 0.75 mg/kg q12hr if necessary 

If needed, may further increase to 1 mg/kg q12hr

Alkaptonuria (Orphan)

Treatment of alkaptonuria

Orphan indication sponsor

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

Dosage Forms & Strengths

capsule

  • 2mg
  • 5mg
  • 10mg
  • 20mg

oral suspension

  • 4mg/mL
more...

Hereditary Tyrosinemia Type 1

0.5 mg/kg PO q12hr (morning and evening); after 1 month, may increase to 0.75 mg/kg q12hr if necessary 

If needed, may further increase (especially infants) to 1 mg/kg q12hr

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Interactions

Interaction Checker

nitisinone and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            1-10%

            Alopecia

            Blepharitis

            Cataracts

            Conjunctivitis

            Corneal opacity

            Dry skin

            Epistaxis

            Exfoliative dermatitis

            Eye pain

            Hepatic neoplasm

            Keratitis

            Leukopenia

            Liver failure

            Maculopapular rash

            Photophobia

            Porphyria

            Pruritus

            Thrombocytopenia

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            Warnings

            Contraindications

            None known

            Cautions

            Monitor urine succinylacetone, LFTs, alpha fetoprotein, serum tyrosine, and phenylalanine

            Serious adverse effects include thrombocytopenia, leukopenia, porphyria, and ocular/visual complaints associated with elevated tyrosine levels

            Preexisting myelosuppression

            Restrict dietary intake of tyrosine and phenylalanine

            Keep plasma level of tyrosine <500 umol/L to avoid toxicity

            Perform slit lamp ophthalmologic exam of eyes before initiating treatment

            May take >3 months for plasma succinylacetone to normalize

            Glycerol content in oral suspension

            • Oral doses of glycerol ≥10 g have been reported to cause headache, upset stomach and diarrhea
            • The oral suspension contains 500 mg/mL of glycerol
            • Patients who receive >20 mL of the oral suspension (ie, 10 g glycerol) as a single dose are at increased risk of these adverse reactions
            • Consider switching patients who are unable to tolerate the oral suspension to the oral capsules (see Administration)
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            Pregnancy & Lactation

            Pregnancy Category: C

            Lactation: Not known if distributed into breast milk, use caution

            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.

            more...
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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

            Peak plasma time: 3.5 hr (capsule); 0.38 hr (suspension)

            Peak plasma concentration: 10.2 micromol/L (capsule); 9.74 micromol/L (suspension)

            AUC: 403 micromol·h/L (capsule); 346 micromol·h/L (suspension)

            Distribution

            Protein bound: >95%

            Metabolism

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

            Elimination

            Half-life: 54 hr

            Excretion: Unknown

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            Administration

            Oral Capsules

            Take at least 1 hr before or 2 hr after a meals

            Adjunct to dietary reduction of tyrosine/phenylalanine

            For patients who have difficulty swallowing the capsules and who are intolerant to the oral suspension, the capsules may be opened and the contents suspended in a small amount of water, formula, or apple sauce immediately before use

            Oral Suspension

            May take without regard to meals

            Preparation

            • Oral suspension is dispensed with an oral syringe of appropriate size and a bottle adaptor provided by the pharmacist
            • Bottle without oral syringe 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 and write this date as the “Discard after” date on the bottle label
              • Allow the bottle to warm to room temperature (30-60 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
            • Bottle with oral syringe adapter
              • 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

            Storage

            Oral capsules: Store refrigerated, 2-8°C (36-46°F)

            Oral suspension

            • Refrigerate at 2-8°C (36-46°F) prior to first use
            • Do not freeze
            • Store bottle upright
            • After first opening, store the product at room temperature (up to 25°C [77°F]) for up to 60 days; if not used within 60 days, discard unused portion
            • The discard after date should be noted on the bottle
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            Images

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            Formulary

            FormularyPatient Discounts

            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.
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