Nityr 2mg Tablets

Manufacturer CYCLE Active Ingredient Nitisinone Tablets(ni TIS i known) Pronunciation ni TIS i known
It is used to treat hereditary tyrosinemia type 1 (HT-1).
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Drug Class
Enzyme inhibitor
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Pharmacologic Class
4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor
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Pregnancy Category
Category C
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FDA Approved
Jul 2017
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DEA Schedule
Not Controlled

Overview

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What is this medicine?

Nityr is a medication used to treat a rare genetic disorder called hereditary tyrosinemia type 1 (HT-1). It works by blocking a specific enzyme in the body, which helps prevent the buildup of harmful substances that can damage the liver, kidneys, and nervous system. It must be used along with a special diet that is low in tyrosine and phenylalanine.
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How to Use This Medicine

Taking Your Medication Correctly

To ensure you get the most benefit from your medication, follow these steps:

Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
You can take your medication with or without food.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start feeling well.

If you have trouble swallowing the medication whole, you have two options:

Dissolve the tablet in room temperature water using an oral syringe. If you choose this method, take the dose within 24 hours of mixing.
Crush the tablet and mix it with applesauce, but do not mix it with any other liquids or foods. Take the dose within 2 hours of mixing. Be sure to follow the instructions provided by your doctor or the package insert for mixing.

Before mixing your medication, wash your hands thoroughly.

Storing and Disposing of Your Medication

To keep your medication effective and safe:

Store the tablets in their original container at room temperature, keeping the cap tightly closed.
Keep the container in a dry place, away from the bathroom.
* If you have mixed your medication with water or applesauce, store it at room temperature, out of direct sunlight, and use it within the recommended time frame (24 hours for water or 2 hours for applesauce). Do not store the mixture for future use.

What to Do If You Miss a Dose

If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take two doses at the same time or take extra doses.
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Lifestyle & Tips

  • Adhere strictly to a low-tyrosine and low-phenylalanine diet as prescribed by your doctor or dietitian. This diet is crucial for the effectiveness and safety of nitisinone.
  • Take the medication consistently at the same time each day.
  • Do not stop taking nitisinone without consulting your doctor, as this can lead to a rapid worsening of HT-1 symptoms.
  • Attend all scheduled medical appointments and laboratory tests to monitor your treatment and health.
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Available Forms & Alternatives

Dosing & Administration

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Adult Dosing

Standard Dose: Initial: 0.5 mg/kg/day orally, adjusted based on succinylacetone levels and plasma tyrosine levels. Max: 2 mg/kg/day.
Dose Range: 0.5 - 2 mg

Condition-Specific Dosing:

hereditaryTyrosinemiaType1: Initial: 0.5 mg/kg/day, given once daily. Dose adjustments based on plasma succinylacetone and tyrosine levels. Target succinylacetone undetectable, tyrosine < 500 micromol/L. Max dose 2 mg/kg/day.
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Pediatric Dosing

Neonatal: Initial: 0.5 mg/kg/day orally, adjusted based on succinylacetone levels and plasma tyrosine levels. Max: 2 mg/kg/day.
Infant: Initial: 0.5 mg/kg/day orally, adjusted based on succinylacetone levels and plasma tyrosine levels. Max: 2 mg/kg/day.
Child: Initial: 0.5 mg/kg/day orally, adjusted based on succinylacetone levels and plasma tyrosine levels. Max: 2 mg/kg/day.
Adolescent: Initial: 0.5 mg/kg/day orally, adjusted based on succinylacetone levels and plasma tyrosine levels. Max: 2 mg/kg/day.
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Dose Adjustments

Renal Impairment:

Mild: No specific dose adjustment recommended.
Moderate: No specific dose adjustment recommended.
Severe: No specific dose adjustment recommended.
Dialysis: Not established. Nitisinone is highly protein bound and unlikely to be significantly removed by dialysis.

Hepatic Impairment:

Mild: No specific dose adjustment recommended.
Moderate: No specific dose adjustment recommended.
Severe: Use with caution. No specific dose adjustment recommended, but close monitoring for adverse effects is advised due to potential for increased exposure.
Confidence: Medium

Pharmacology

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Mechanism of Action

Nitisinone is a reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme upstream of fumarylacetoacetate hydrolase (FAH) in the tyrosine catabolic pathway. By inhibiting HPPD, nitisinone prevents the accumulation of toxic metabolites such as maleylacetoacetate, fumarylacetoacetate, and succinylacetone, which are responsible for the hepatorenal damage and neurological dysfunction seen in hereditary tyrosinemia type 1 (HT-1).
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Pharmacokinetics

Absorption:

Bioavailability: Not available (oral absorption is good)
Tmax: 3-8 hours
FoodEffect: Food does not significantly affect absorption. Can be taken with or without food.

Distribution:

Vd: 0.11-0.13 L/kg
ProteinBinding: Greater than 99% (primarily to albumin)
CnssPenetration: Limited

Elimination:

HalfLife: 54 hours (range 36-90 hours) in pediatric patients; up to 200 hours in adults
Clearance: 0.015-0.02 L/hr/kg
ExcretionRoute: Primarily renal (as metabolites and unchanged drug), some fecal excretion.
Unchanged: Approximately 60% of the dose is excreted in urine as unchanged drug and metabolites over 10 days.
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Pharmacodynamics

OnsetOfAction: Within days to weeks (reduction in succinylacetone levels)
PeakEffect: Weeks to months (stabilization of succinylacetone and tyrosine levels)
DurationOfAction: Prolonged due to long half-life; effects persist as long as treatment continues.
Confidence: Medium

Safety & Warnings

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Side Effects

Urgent Side Effects: Seek Medical Attention Immediately

While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Changes in eyesight, eye pain, or severe eye irritation
Sensitivity to bright light
Confusion, difficulty focusing, or changes in behavior
Redness, irritation, pain, or thick skin on the palms of the hands or soles of the feet
Signs of low white blood cell count, such as:
+ Fever
+ Chills
+ Sore throat
Signs of low platelet count, such as:
+ Unexplained bruising or bleeding

Other Possible Side Effects

Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild ones. If you have any side effects that bother you or do not go away, contact your doctor or seek medical help.

Reporting Side Effects

If you have questions about side effects or want to report any, you can:

Call your doctor for medical advice
Contact the FDA at 1-800-332-1088
* Report side effects online at https://www.fda.gov/medwatch
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Seek Immediate Medical Attention If You Experience:

  • Eye problems: sensitivity to light (photophobia), eye pain, blurred vision, or changes in vision.
  • Skin problems: rash, itching, or skin lesions.
  • Signs of infection: fever, chills, sore throat, or unusual tiredness (may indicate low white blood cell count).
  • Unusual bleeding or bruising (may indicate low platelet count).
  • Signs of liver problems: yellowing of skin or eyes (jaundice), dark urine, pale stools, severe stomach pain, nausea, or vomiting.
  • Numbness, tingling, or weakness in hands or feet (signs of peripheral neuropathy).
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Before Using This Medicine

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced as a result of the allergy.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This information will help your doctor and pharmacist assess potential interactions between this medication and other substances.
* Any existing health problems, as this medication may interact with certain conditions.

To ensure your safety, it is crucial to verify that this medication can be taken with all your current medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
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Precautions & Cautions

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.

Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to discuss any concerns or questions you have with your doctor.

Additionally, your doctor may recommend regular urine tests to assess your health. It is crucial to follow your doctor's instructions for these tests.

An eye exam may also be necessary, as prescribed by your doctor, to monitor your vision and overall eye health.

To ensure optimal results, adhere to the diet plan recommended by your doctor.

If you are pregnant, planning to become pregnant, or are breastfeeding, notify your doctor immediately. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby.
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Overdose Information

Overdose Symptoms:

  • Exaggerated adverse effects such as severe eye irritation (photophobia, corneal opacities), skin lesions, or hematologic abnormalities (leukopenia, thrombocytopenia).
  • Increased plasma tyrosine levels.

What to Do:

There is no specific antidote for nitisinone overdose. Treatment should be symptomatic and supportive. Contact a poison control center immediately (Call 1-800-222-1222 in the US). Monitor vital signs, blood counts, liver function, and plasma tyrosine levels. Consider activated charcoal if ingestion is recent and significant. Due to high protein binding, dialysis is unlikely to be effective.

Drug Interactions

Monitoring

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Baseline Monitoring

Plasma succinylacetone levels

Rationale: To establish baseline and guide initial dosing.

Timing: Prior to initiation of therapy.

Plasma tyrosine levels

Rationale: To establish baseline and guide initial dosing, as high tyrosine levels can lead to ocular and dermatologic adverse effects.

Timing: Prior to initiation of therapy.

Liver function tests (ALT, AST, bilirubin)

Rationale: To assess baseline liver function and monitor for potential hepatotoxicity.

Timing: Prior to initiation of therapy.

Complete Blood Count (CBC) with differential

Rationale: To assess baseline hematologic status and monitor for leukopenia or thrombocytopenia.

Timing: Prior to initiation of therapy.

Ophthalmologic examination (slit lamp, visual acuity)

Rationale: To establish baseline ocular health and monitor for corneal opacities or other eye abnormalities.

Timing: Prior to initiation of therapy.

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Routine Monitoring

Plasma succinylacetone levels

Frequency: Weekly for the first month, then monthly, or as clinically indicated.

Target: Undetectable

Action Threshold: If detectable, consider dose increase or adherence issues. If persistently high, re-evaluate diagnosis or treatment.

Plasma tyrosine levels

Frequency: Weekly for the first month, then monthly, or as clinically indicated.

Target: < 500 micromol/L (ideally 200-500 micromol/L)

Action Threshold: If > 500 micromol/L, consider dietary protein restriction or nitisinone dose reduction. If persistently high, re-evaluate diet or treatment.

Liver function tests (ALT, AST, bilirubin)

Frequency: Monthly for the first few months, then every 3-6 months, or as clinically indicated.

Target: Within normal limits

Action Threshold: Significant elevations may require dose adjustment or discontinuation, and investigation for other causes.

Complete Blood Count (CBC) with differential

Frequency: Monthly for the first few months, then every 3-6 months, or as clinically indicated.

Target: Within normal limits

Action Threshold: Significant decreases in WBC or platelet count may require dose adjustment or discontinuation.

Ophthalmologic examination (slit lamp, visual acuity)

Frequency: Every 6-12 months, or if new ocular symptoms develop.

Target: No new corneal opacities or other abnormalities.

Action Threshold: Development of corneal opacities, photophobia, or other ocular symptoms may require dose adjustment or discontinuation.

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Symptom Monitoring

  • Changes in vision (e.g., photophobia, blurred vision, eye pain)
  • Skin rash or lesions
  • Unexplained fever, sore throat, or signs of infection (due to potential leukopenia)
  • Unusual bleeding or bruising (due to potential thrombocytopenia)
  • Signs of liver dysfunction (e.g., jaundice, dark urine, pale stools, abdominal pain)
  • Neurological changes (e.g., peripheral neuropathy, developmental regression)

Special Patient Groups

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Pregnancy

Nitisinone is Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. HT-1 is a severe disease, and untreated maternal HT-1 can pose significant risks to both mother and fetus.

Trimester-Specific Risks:

First Trimester: Animal studies have shown developmental toxicity (e.g., skeletal malformations, reduced fetal weight) at doses higher than clinical exposure. Human data are limited.
Second Trimester: Continued monitoring of maternal tyrosine levels is crucial to prevent potential fetal harm from high tyrosine.
Third Trimester: Continued monitoring of maternal tyrosine levels is crucial. Neonates exposed in utero should be monitored for adverse effects.
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Lactation

Nitisinone is excreted into breast milk in animals. It is not known whether nitisinone is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Infant Risk: Risk is unknown but potential for serious adverse effects exists. Monitor breastfed infants for adverse effects such as eye problems, skin reactions, or blood count abnormalities.
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Pediatric Use

Nitisinone is indicated for pediatric patients of all ages with HT-1. Dosing is weight-based and adjusted according to plasma succinylacetone and tyrosine levels. Close monitoring of growth and development, as well as the specific monitoring parameters, is essential.

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Geriatric Use

Clinical studies of nitisinone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient 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.

Clinical Information

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Clinical Pearls

  • Nitisinone therapy must always be accompanied by a strict low-tyrosine and low-phenylalanine diet. Dietary adherence is critical for efficacy and to prevent tyrosine-related adverse effects.
  • Regular monitoring of plasma succinylacetone and tyrosine levels is essential for dose adjustment and to ensure therapeutic efficacy and safety.
  • Ophthalmologic examinations are crucial due to the risk of corneal opacities and photophobia, which are often related to high plasma tyrosine levels.
  • Patients should be educated on the importance of reporting any new visual symptoms, skin changes, or signs of infection/bleeding promptly.
  • Nitisinone has a very long half-life, meaning it takes a long time to reach steady state and for drug levels to decline after discontinuation.
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Alternative Therapies

  • Liver transplantation (curative for HT-1, but associated with significant risks and complications)
  • Dietary management alone (historically used, but less effective and associated with higher morbidity/mortality compared to nitisinone therapy)
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Cost & Coverage

Average Cost: Highly variable, typically several thousand USD per 30 tablets
Generic Available: Yes
Insurance Coverage: Specialty Tier (requires prior authorization and often medical necessity documentation)
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General Drug Facts

If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.