Nityr 10mg 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
Not available
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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?

Nitisinone 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 and kidneys. It must be used along with a special diet.
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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 prescription 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 difficulty swallowing the tablet whole, you can dissolve it in room temperature water using an oral syringe. Alternatively, if you can swallow soft foods, you can crush the tablet and mix it with applesauce. However, do not mix the medication with any other liquids or foods.
Before mixing your medication, wash your hands thoroughly.
If you dissolve the tablet in water, take it within 24 hours of mixing. If you mix it 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 safety 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 have mixed the medication with water or applesauce, store it at room temperature, away from direct sunlight.

What to Do If You Miss a Dose

If you miss a dose, follow these guidelines:

Take the missed dose as soon as you remember.
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.
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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 preventing high tyrosine levels and associated side effects.
  • 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 increase in toxic metabolites and severe complications.
  • Attend all scheduled appointments for blood tests and eye exams.
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Available Forms & Alternatives

Dosing & Administration

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Adult Dosing

Standard Dose: Initial: 0.5 mg/kg once daily. Adjust based on succinylacetone and plasma nitisinone levels. Max: 2 mg/kg once daily.
Dose Range: 0.5 - 2 mg

Condition-Specific Dosing:

Hereditary Tyrosinemia Type 1 (HT-1): Initial: 0.5 mg/kg once daily. Adjust dose to maintain plasma nitisinone levels between 40-90 micromol/L and normalize succinylacetone levels. Max dose 2 mg/kg once daily.
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Pediatric Dosing

Neonatal: Initial: 0.5 mg/kg once daily. Adjust based on succinylacetone and plasma nitisinone levels. Max: 2 mg/kg once daily.
Infant: Initial: 0.5 mg/kg once daily. Adjust based on succinylacetone and plasma nitisinone levels. Max: 2 mg/kg once daily.
Child: Initial: 0.5 mg/kg once daily. Adjust based on succinylacetone and plasma nitisinone levels. Max: 2 mg/kg once daily.
Adolescent: Initial: 0.5 mg/kg once daily. Adjust based on succinylacetone and plasma nitisinone levels. Max: 2 mg/kg once daily.
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Dose Adjustments

Renal Impairment:

Mild: No specific dose adjustment recommended, but monitor closely.
Moderate: No specific dose adjustment recommended, but monitor closely.
Severe: No specific dose adjustment recommended, but monitor closely.
Dialysis: Not specifically studied; monitor closely and adjust based on clinical response and succinylacetone levels.

Hepatic Impairment:

Mild: No specific dose adjustment recommended, but monitor closely due to underlying disease.
Moderate: No specific dose adjustment recommended, but monitor closely due to underlying disease.
Severe: No specific dose adjustment recommended, but monitor closely due to underlying disease.

Pharmacology

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Mechanism of Action

Nitisinone is a reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme in the tyrosine catabolic pathway. By inhibiting HPPD, nitisinone prevents the formation of maleylacetoacetate and fumarylacetoacetate, which are toxic metabolites that accumulate in patients with hereditary tyrosinemia type 1 (HT-1) due to a deficiency in fumarylacetoacetate hydrolase (FAH). This inhibition reduces the accumulation of these toxic metabolites, thereby preventing liver and kidney damage.
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Pharmacokinetics

Absorption:

Bioavailability: Not available (well absorbed)
Tmax: 3-8 hours
FoodEffect: Can be taken with or without food; food does not significantly affect absorption.

Distribution:

Vd: Approximately 0.11 L/kg
ProteinBinding: >99%
CnssPenetration: Limited

Elimination:

HalfLife: Approximately 54 hours (range 36-96 hours)
Clearance: Not available
ExcretionRoute: Primarily renal (as metabolites)
Unchanged: Less than 1% in urine
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Pharmacodynamics

OnsetOfAction: Within days to weeks (reduction in succinylacetone levels)
PeakEffect: Not precisely defined, but sustained effect with chronic dosing
DurationOfAction: Due to long half-life, once-daily dosing maintains therapeutic levels.

Safety & Warnings

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Side Effects

Serious Side Effects: Seek Medical Help 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 attention 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 (may indicate a low white blood cell count)
Unexplained bruising or bleeding (may indicate a low platelet count)

Other Possible Side Effects

Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience 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:

  • Changes in vision (e.g., sensitivity to light, eye pain, blurry vision, white spots on eyes)
  • Skin changes (e.g., thickening of skin, rash, itching)
  • Unexplained fever, chills, or signs of infection (may indicate low white blood cell count)
  • Unusual bleeding or bruising (may indicate low platelet count)
  • Yellowing of skin or eyes (jaundice)
  • Dark urine or pale stools
  • Swelling in legs or abdomen
  • Increased fatigue or weakness
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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, 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 affect or be affected by other drugs or health problems, so it is crucial to disclose all relevant information.

To ensure safe treatment, provide your doctor and pharmacist with a comprehensive list of:

All prescription and over-the-counter (OTC) medications you are taking
Natural products, such as herbal supplements
Vitamins
Any existing health problems

Carefully review your medications and health conditions to confirm that it is safe to take this medication in conjunction with them. 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 check for any potential issues.

To monitor for any potential eye problems, follow your doctor's instructions for scheduling an eye exam.

Adhere to the personalized diet plan that your doctor has recommended 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.
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Overdose Information

Overdose Symptoms:

  • Exaggerated side effects, particularly severe hypertyrosinemia symptoms (e.g., severe ocular symptoms, neurological changes, skin lesions)
  • Increased risk of liver or kidney dysfunction

What to Do:

Seek immediate medical attention. Contact a poison control center (Call 1-800-222-1222). Management is supportive, focusing on managing symptoms and monitoring blood levels.

Drug Interactions

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Moderate Interactions

  • Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir): May increase nitisinone levels. Monitor for increased adverse effects.
  • Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): May decrease nitisinone levels. Monitor for decreased efficacy.

Monitoring

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Baseline Monitoring

Plasma succinylacetone levels

Rationale: To confirm diagnosis and establish baseline for therapeutic efficacy.

Timing: Prior to initiation of therapy

Plasma nitisinone levels

Rationale: To establish baseline and guide initial dosing.

Timing: Prior to initiation of therapy

Plasma tyrosine levels

Rationale: To establish baseline and monitor for hypertyrosinemia, a common side effect.

Timing: Prior to initiation of therapy

Liver function tests (ALT, AST, bilirubin, albumin, INR)

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

Timing: Prior to initiation of therapy

Renal function tests (BUN, creatinine)

Rationale: To assess baseline renal function.

Timing: Prior to initiation of therapy

Complete Blood Count (CBC) with differential

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

Timing: Prior to initiation of therapy

Ophthalmologic examination (slit lamp, fundoscopy)

Rationale: To establish baseline and monitor for ocular symptoms associated with hypertyrosinemia.

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 until stable, then every 3-6 months.

Target: Undetectable or normalized

Action Threshold: If elevated, consider dose adjustment or adherence issues.

Plasma nitisinone levels

Frequency: Weekly for the first month, then monthly or as clinically indicated until stable, then every 3-6 months.

Target: 40-90 micromol/L

Action Threshold: If outside range, adjust dose. If too low, consider increasing dose or adherence. If too high, consider decreasing dose.

Plasma tyrosine levels

Frequency: Weekly for the first month, then monthly or as clinically indicated until stable, then every 3-6 months.

Target: <500 micromol/L (or as per dietary guidelines)

Action Threshold: If persistently >500-700 micromol/L, consider dietary adjustments (tyrosine/phenylalanine restriction) or nitisinone dose adjustment.

Liver function tests (ALT, AST, bilirubin, albumin, INR)

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

Target: Within normal limits

Action Threshold: Significant elevations may indicate liver dysfunction; investigate cause, consider dose adjustment.

Renal function tests (BUN, creatinine)

Frequency: Every 3-6 months or as clinically indicated.

Target: Within normal limits

Action Threshold: Significant elevations may indicate renal dysfunction; investigate cause.

Complete Blood Count (CBC) with differential

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

Target: Within normal limits

Action Threshold: Significant decreases in WBC or platelets may indicate myelosuppression; investigate cause, consider dose adjustment.

Ophthalmologic examination

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

Target: Normal findings

Action Threshold: Presence of corneal opacities, photophobia, or other ocular symptoms may indicate hypertyrosinemia; adjust diet/nitisinone dose.

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Symptom Monitoring

  • Visual disturbances (e.g., photophobia, eye pain, corneal opacities)
  • Skin changes (e.g., hyperkeratosis, rash)
  • Neurological symptoms (e.g., developmental delay, peripheral neuropathy)
  • Signs of liver dysfunction (e.g., jaundice, ascites, easy bruising)
  • Signs of renal dysfunction (e.g., edema, changes in urine output)
  • Signs of infection (e.g., fever, sore throat) due to potential leukopenia
  • Unusual bleeding or bruising due to potential thrombocytopenia

Special Patient Groups

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Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited human data are available. Animal studies have shown developmental toxicity (e.g., skeletal malformations, reduced fetal weight) at doses similar to or higher than clinical exposure.

Trimester-Specific Risks:

First Trimester: Potential for teratogenicity based on animal data; human data limited.
Second Trimester: Potential for developmental effects; human data limited.
Third Trimester: Potential for developmental effects; human data limited.
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Lactation

It is unknown if nitisinone is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother.

Infant Risk: Unknown; potential for serious adverse effects.
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Pediatric Use

Nitisinone is indicated for pediatric patients of all ages with HT-1. Dosing is weight-based (0.5 mg/kg/day initially) and adjusted based on succinylacetone and nitisinone levels. Close monitoring of growth, development, and tyrosine levels 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 to prevent hypertyrosinemia and its associated complications (e.g., ocular symptoms, skin lesions, neurological issues).
  • Regular monitoring of plasma succinylacetone, nitisinone, and tyrosine levels is critical for guiding dose adjustments and ensuring therapeutic efficacy and safety.
  • Patients should be educated on the importance of adherence to both medication and diet, as non-adherence can lead to severe and rapid clinical deterioration.
  • Ophthalmologic examinations are essential to monitor for corneal opacities and other ocular symptoms related to elevated tyrosine levels.
  • Nitisinone is an orphan drug and is very expensive; patient assistance programs are often available through the manufacturer.
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Alternative Therapies

  • Liver transplantation (curative, but associated with significant risks and lifelong immunosuppression; typically reserved for patients who fail medical management or develop hepatocellular carcinoma).
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Cost & Coverage

Average Cost: Extremely high (e.g., $10,000 - $30,000+) per 30 tablets (variable by strength)
Insurance Coverage: Specialty Tier (requires prior authorization, often covered by Medicaid/private insurance for approved indications)
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General Drug Facts

If your symptoms or health issues persist or worsen, it's 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 be sure 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 medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.