Nityr 5mg Tablets
It is used to treat hereditary tyrosinemia type 1 (HT-1).
Drug Class
Agent for inborn errors of metabolism
Pharmacologic Class
4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor
Pregnancy Category
Not available
FDA Approved
Jul 2017
DEA Schedule
Not Controlled
Overview
What is this medicine?
Nitisinone (Nityr) is a medication used to treat a rare genetic disorder called hereditary tyrosinemia type 1 (HT-1). This condition causes harmful substances to build up in the body, which can damage the liver, kidneys, and nervous system. Nitisinone works by blocking an enzyme that helps produce these harmful substances, thereby preventing their accumulation and reducing the risk of serious complications, including liver cancer. It must be used along with a special diet.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, it's essential to take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. You can take this medication with or without food.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you're feeling well. If you have difficulty swallowing the tablets whole, you can dissolve them in room temperature water using an oral syringe. Alternatively, if you can swallow soft foods, you can crush the tablets and mix them with applesauce. However, do not mix the medication with any other liquids or foods. Be sure to follow the mixing instructions provided by your doctor or as outlined in the package insert.
Before preparing your medication, wash your hands thoroughly. If you dissolve the tablets in water, take the mixture within 24 hours of adding the water. If you mix the medication with applesauce, take it within 2 hours of mixing. Do not store the mixture for future use.
Storing and Disposing of Your Medication
To maintain the quality and effectiveness of your medication, 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've mixed the medication with water or applesauce, store it at room temperature, out of direct sunlight.
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 resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To get the most benefit from your medication, it's essential to take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. You can take this medication with or without food.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you're feeling well. If you have difficulty swallowing the tablets whole, you can dissolve them in room temperature water using an oral syringe. Alternatively, if you can swallow soft foods, you can crush the tablets and mix them with applesauce. However, do not mix the medication with any other liquids or foods. Be sure to follow the mixing instructions provided by your doctor or as outlined in the package insert.
Before preparing your medication, wash your hands thoroughly. If you dissolve the tablets in water, take the mixture within 24 hours of adding the water. If you mix the medication with applesauce, take it within 2 hours of mixing. Do not store the mixture for future use.
Storing and Disposing of Your Medication
To maintain the quality and effectiveness of your medication, 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've mixed the medication with water or applesauce, store it at room temperature, out of direct sunlight.
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 resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Strict adherence to a low-tyrosine and low-phenylalanine diet is essential for the effectiveness and safety of nitisinone therapy.
- Regular blood tests (to monitor succinylacetone and tyrosine levels) and follow-up appointments with your doctor are crucial.
- Report any new or worsening symptoms, especially eye problems, skin rashes, or unusual bleeding/bruising, to your healthcare provider immediately.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
0.5 mg/kg once daily
Dose Range:
0.5 - 2 mg
Condition-Specific Dosing:
initialDose:
0.5 mg/kg once daily, adjusted based on plasma succinylacetone and tyrosine levels.
maximumDose:
2 mg/kg once daily
Pediatric Dosing
Neonatal:
Not established (typically diagnosed in infancy/childhood, but can be used)
Infant:
0.5 mg/kg once daily, adjusted based on plasma succinylacetone and tyrosine levels. Max 2 mg/kg/day.
Child:
0.5 mg/kg once daily, adjusted based on plasma succinylacetone and tyrosine levels. Max 2 mg/kg/day.
Adolescent:
0.5 mg/kg once daily, adjusted based on plasma succinylacetone and tyrosine levels. Max 2 mg/kg/day.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, monitor closely.
Moderate:
No specific dose adjustment recommended, monitor closely.
Severe:
No specific dose adjustment recommended, monitor closely.
Dialysis:
Considerations: No specific recommendations, monitor succinylacetone and tyrosine levels closely.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended, monitor closely.
Moderate:
No specific dose adjustment recommended, monitor closely.
Severe:
No specific dose adjustment recommended, monitor closely.
Pharmacology
Mechanism of Action
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme involved in the catabolism of tyrosine. In hereditary tyrosinemia type 1 (HT-1), the enzyme fumarylacetoacetate hydrolase (FAH) is deficient, leading to the accumulation of toxic metabolites (e.g., succinylacetone, maleylacetoacetate, fumarylacetoacetate). By inhibiting HPPD, nitisinone prevents the formation of these toxic metabolites, thereby reducing liver and kidney damage and the risk of hepatocellular carcinoma.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified, but well absorbed orally.
Tmax:
3-4 hours
FoodEffect:
Food does not significantly affect absorption; can be taken with or without food.
Distribution:
Vd:
Approximately 0.12 L/kg
ProteinBinding:
>97% (primarily to albumin)
CnssPenetration:
Limited, but reduces succinylacetone levels in CSF.
Elimination:
HalfLife:
Approximately 54 hours (range 36-90 hours)
Clearance:
Approximately 0.0015 L/hr/kg
ExcretionRoute:
Primarily renal (as metabolites), with minimal unchanged drug.
Unchanged:
<1% in urine
Pharmacodynamics
OnsetOfAction:
Reduction in succinylacetone levels typically observed within days to weeks of initiation.
PeakEffect:
Sustained reduction in toxic metabolites with chronic dosing.
DurationOfAction:
Long half-life supports once-daily dosing.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while 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 infection, such as:
+ Fever
+ Chills
+ Sore throat (due to low white blood cell counts, which may increase the risk of infection)
Unexplained bruising or bleeding (due to low platelet counts, which may increase the risk of bleeding)
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or 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. This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor.
Reporting Side Effects
To report side effects, you can:
Call your doctor for medical advice
Contact the FDA at 1-800-332-1088
* Visit the FDA's MedWatch website at https://www.fda.gov/medwatch
Although rare, some people may experience severe and potentially life-threatening side effects while 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 infection, such as:
+ Fever
+ Chills
+ Sore throat (due to low white blood cell counts, which may increase the risk of infection)
Unexplained bruising or bleeding (due to low platelet counts, which may increase the risk of bleeding)
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or 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. This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor.
Reporting Side Effects
To report side effects, you can:
Call your doctor for medical advice
Contact the FDA at 1-800-332-1088
* Visit the FDA's MedWatch website at https://www.fda.gov/medwatch
Seek Immediate Medical Attention If You Experience:
- Eye pain, redness, sensitivity to light (photophobia), or blurred vision
- Skin rash, hyperkeratotic lesions (thickened skin), or changes in skin color
- Unusual bleeding or bruising
- Frequent infections or fevers
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Severe or persistent fatigue
- Numbness or tingling in hands or feet
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, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced as a result of the allergy.
Potential interactions with other medications or health conditions. This medication may interact with other drugs or worsen certain health problems.
To ensure your safety, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Existing health problems
Carefully review your medications and health conditions with your doctor to confirm that it is safe to take this medication. Do not initiate, discontinue, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced as a result of the allergy.
Potential interactions with other medications or health conditions. This medication may interact with other drugs or worsen certain health problems.
To ensure your safety, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Existing health problems
Carefully review your medications and health conditions with your doctor to confirm that it is safe to take this medication. Do not initiate, discontinue, or adjust the dosage of any medication without first consulting your doctor.
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 check for any potential issues.
To monitor your eye health, follow your doctor's recommendations for scheduling an eye exam.
Adhere to the personalized diet plan that your doctor has outlined for you.
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.
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 check for any potential issues.
To monitor your eye health, follow your doctor's recommendations for scheduling an eye exam.
Adhere to the personalized diet plan that your doctor has outlined for you.
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.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are primarily related to excessive tyrosine levels, which may include severe ocular symptoms (e.g., corneal opacities, photophobia) and dermatologic symptoms (e.g., hyperkeratotic lesions, rash).
What to Do:
In case of suspected overdose, contact a poison control center (1-800-222-1222) or seek emergency medical attention immediately. Management is supportive, focusing on dietary adjustments to reduce tyrosine intake and close monitoring of tyrosine levels and clinical symptoms.
Drug Interactions
Moderate Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital): May decrease nitisinone exposure. Monitor succinylacetone levels and consider dose adjustment.
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): May increase nitisinone exposure. Monitor tyrosine levels and consider dose adjustment.
Monitoring
Baseline Monitoring
Plasma succinylacetone levels
Rationale: To confirm diagnosis and establish baseline for treatment efficacy.
Timing: Prior to initiation of therapy
Plasma tyrosine levels
Rationale: To establish baseline and guide dietary management.
Timing: Prior to initiation of therapy
Liver function tests (ALT, AST, bilirubin, albumin, INR)
Rationale: To assess baseline liver damage and monitor for hepatotoxicity.
Timing: Prior to initiation of therapy
Complete Blood Count (CBC) with differential and platelet count
Rationale: To assess baseline hematologic status and monitor for myelosuppression.
Timing: Prior to initiation of therapy
Ophthalmologic examination
Rationale: To establish baseline for potential ocular adverse effects (e.g., corneal opacities, photophobia) due to elevated tyrosine.
Timing: Prior to initiation of therapy
Routine Monitoring
Plasma succinylacetone levels
Frequency: Monthly until stable, then every 3 months
Target: Undetectable
Action Threshold: If detectable, consider dose increase or re-evaluation of adherence.
Plasma tyrosine levels
Frequency: Weekly for the first month, then monthly until stable, then every 3 months
Target: 200-500 micromol/L
Action Threshold: If >500 micromol/L, re-evaluate dietary adherence; if persistently high, consider dose reduction. If <200 micromol/L, consider dose reduction.
Liver function tests (ALT, AST, bilirubin, albumin, INR)
Frequency: Every 3-6 months
Target: Within normal limits
Action Threshold: Abnormalities may indicate disease progression or drug-related toxicity; investigate further.
Complete Blood Count (CBC) with differential and platelet count
Frequency: Every 3-6 months
Target: Within normal limits
Action Threshold: Significant decreases may indicate myelosuppression; investigate further.
Ophthalmologic examination
Frequency: Annually, or more frequently if ocular symptoms occur
Target: Normal findings
Action Threshold: Development of corneal opacities, photophobia, or other ocular symptoms may require dose adjustment or discontinuation.
Symptom Monitoring
- Ocular symptoms (photophobia, eye pain, redness, blurred vision, corneal opacities)
- Dermatologic symptoms (hyperkeratotic lesions, rash, skin discoloration)
- Neurological symptoms (peripheral neuropathy, developmental delay)
- Signs of liver dysfunction (jaundice, ascites, easy bruising, fatigue)
- Signs of bone marrow suppression (unusual bleeding, bruising, frequent infections, persistent fatigue)
Special Patient Groups
Pregnancy
Based on animal studies, nitisinone may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Nitisinone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. A pregnancy registry is available.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity observed in animal studies (e.g., skeletal malformations, visceral anomalies).
Second Trimester:
Potential for adverse developmental effects based on animal data.
Third Trimester:
Potential for adverse developmental effects based on animal data.
Lactation
No human data are available on the presence of nitisinone in human milk, the effects on the breastfed infant, or the effects on milk production. Due to the potential for serious adverse reactions in a breastfed infant (e.g., transient tyrosinemia), breastfeeding is not recommended during nitisinone therapy.
Infant Risk:
High risk (L5 - Contraindicated/Hazardous)
Pediatric Use
Nitisinone is indicated for pediatric patients with hereditary tyrosinemia type 1 (HT-1). Dosing is weight-based and adjusted according to plasma succinylacetone and tyrosine levels. Efficacy and safety have been established in this population.
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. HT-1 is typically diagnosed in infancy or childhood. Use with caution in elderly patients, generally starting at the lower 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
Clinical Pearls
- Nitisinone therapy is lifelong and must always be combined with a strict low-tyrosine and low-phenylalanine diet.
- Regular and meticulous monitoring of plasma succinylacetone and tyrosine levels is paramount for optimizing dose and ensuring treatment efficacy and safety.
- Patients and caregivers must be educated on the importance of dietary adherence, as non-adherence can lead to elevated tyrosine levels and associated adverse effects (e.g., ocular and dermatologic issues).
- Annual ophthalmologic examinations are crucial due to the risk of ocular complications (e.g., corneal opacities, photophobia) from elevated tyrosine levels.
- While nitisinone is highly effective, liver transplantation remains a therapeutic option for patients with HT-1 who do not respond adequately to nitisinone or develop complications despite therapy.
Alternative Therapies
- Liver transplantation: The primary alternative treatment for hereditary tyrosinemia type 1, especially for patients who do not respond to nitisinone or present with advanced liver disease.
Cost & Coverage
Average Cost:
Highly variable, typically several thousand dollars per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Specialty tier, often requires prior authorization and may be subject to step therapy.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. 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. If you have any questions or concerns about this medication, don't hesitate to discuss them with 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 information about the medication taken, the amount, and the time it happened.