Nitisinone 20mg Capsules
Overview
What is this medicine?
How to Use This Medicine
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Take your medication on an empty stomach, either 1 hour before or 2 hours after meals. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel well.
If you have trouble swallowing the capsules, you can open them and mix the contents with a small amount of water, formula, or applesauce. However, be sure to swallow the mixture immediately and do not store it for later use.
Storing and Disposing of Your Medication
Different brands of this medication may have specific storage instructions. Some brands require refrigeration, while others can be stored at room temperature. If you need to store your medication at room temperature, make sure it is in a cool, dry place and not in the bathroom. Some brands can be stored at room temperature (up to 77°F or 25°C) for up to 45 days. If you do not use your medication within this timeframe, discard it. Check with your pharmacist if you have any questions about storing your specific brand of medication.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is 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 to make up for a missed dose.
Lifestyle & Tips
- Adhere strictly to a low-tyrosine and low-phenylalanine diet as prescribed by your doctor or dietitian. This diet is crucial for managing tyrosine levels and preventing side effects.
- Take nitisinone consistently every day at the same time, with or without food, as directed.
- Do not stop taking nitisinone without consulting your doctor, even if you feel well, as this can lead to severe complications.
- Attend all scheduled doctor appointments and laboratory tests (blood tests, eye exams) to monitor your treatment and detect any potential side effects.
- Report any new or worsening symptoms immediately to your healthcare provider, especially eye problems (light sensitivity, eye pain), skin rashes, or unusual changes in behavior or development.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Condition-Specific Dosing:
Pediatric Dosing
Dose Adjustments
Renal Impairment:
Hepatic Impairment:
Pharmacology
Mechanism of Action
Pharmacokinetics
Absorption:
Distribution:
Elimination:
Pharmacodynamics
Safety & Warnings
Side Effects
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 immediate medical attention:
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. 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. This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, consult your doctor.
Reporting Side Effects
You can report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can also provide guidance on managing side effects and offer medical advice.
Seek Immediate Medical Attention If You Experience:
- Eye pain or redness
- Sensitivity to light (photophobia)
- Blurred vision or changes in vision
- Skin rash or thickening of the skin (hyperkeratosis)
- Unusual changes in behavior or mood
- Numbness, tingling, or weakness in the hands or feet
- Severe headache
- Yellowing of the skin or eyes (jaundice)
- Unexplained bruising or bleeding
- Swelling in the legs or ankles
Before Using This Medicine
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) medications, natural products, and vitamins. This information will help your doctor identify 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 it is safe to take this medication with all your current medications and health conditions. Always consult your doctor before starting, stopping, or changing the dose of any medication, including this one.
Precautions & Cautions
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 require you to have your urine checked periodically. Follow the specific instructions provided by your doctor for urine testing.
An eye exam may also be necessary, as scheduled by your doctor, to assess your eye health.
To ensure optimal management of your condition, adhere to the personalized 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.
Overdose Information
Overdose Symptoms:
- Exaggerated side effects, particularly severe hypertyrosinemia symptoms such as severe eye pain, photophobia, corneal opacities, skin lesions, and neurological symptoms.
What to Do:
Seek immediate medical attention. Contact a poison control center (e.g., 1-800-222-1222) or go to the nearest emergency room. Management is supportive and focuses on reducing tyrosine levels, potentially through dietary adjustments and close monitoring of symptoms.
Drug Interactions
Moderate Interactions
- Drugs metabolized by CYP3A4 or CYP2C9 (potential for altered metabolism of nitisinone or co-administered drug)
- Drugs that affect tyrosine levels (e.g., high protein diet, certain amino acid supplements)
Monitoring
Baseline Monitoring
Rationale: To confirm diagnosis and establish baseline for treatment efficacy.
Timing: Prior to initiation of therapy
Rationale: To establish baseline and guide dietary management, as nitisinone causes hypertyrosinemia.
Timing: Prior to initiation of therapy
Rationale: To assess baseline liver function and monitor for potential hepatotoxicity.
Timing: Prior to initiation of therapy
Rationale: To assess baseline kidney function.
Timing: Prior to initiation of therapy
Rationale: To assess baseline hematologic status.
Timing: Prior to initiation of therapy
Rationale: To establish baseline and monitor for corneal opacities or other ocular effects of hypertyrosinemia.
Timing: Prior to initiation of therapy
Routine Monitoring
Frequency: Weekly for the first month, then monthly or as clinically indicated until stable. Once stable, every 3-6 months.
Target: Undetectable or very low
Action Threshold: Elevated levels indicate inadequate dose or non-adherence; consider dose increase.
Frequency: Weekly for the first month, then monthly or as clinically indicated until stable. Once stable, every 3-6 months.
Target: 200-500 micromol/L (3-8 mg/dL)
Action Threshold: Levels >500-700 micromol/L may require dietary protein restriction or dose adjustment; levels >1000 micromol/L require immediate action due to risk of ocular/skin toxicity.
Frequency: Monthly for the first few months, then every 3-6 months.
Target: Within normal limits
Action Threshold: Significant elevations may indicate liver damage; investigate cause.
Frequency: Every 3-6 months.
Target: Within normal limits
Action Threshold: Significant elevations may indicate kidney damage; investigate cause.
Frequency: Every 3-6 months.
Target: Within normal limits
Action Threshold: Significant abnormalities may indicate bone marrow suppression; investigate cause.
Frequency: Every 6-12 months, or immediately if ocular symptoms develop.
Target: No corneal opacities or other ocular abnormalities
Action Threshold: Development of ocular symptoms or findings (e.g., corneal opacities) may necessitate reduction of tyrosine levels.
Symptom Monitoring
- Ocular symptoms (e.g., photophobia, eye pain, redness, blurred vision)
- Skin lesions (e.g., hyperkeratosis, rash)
- Neurological changes (e.g., developmental delay, peripheral neuropathy, seizures)
- Gastrointestinal symptoms (e.g., abdominal pain, vomiting)
- Signs of liver dysfunction (e.g., jaundice, ascites)
- Signs of renal dysfunction (e.g., edema, changes in urine output)
Special Patient Groups
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. Untreated HT-1 in pregnant women can lead to severe maternal and fetal complications.
Trimester-Specific Risks:
Lactation
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.
Pediatric Use
Nitisinone is indicated for the treatment of hereditary tyrosinemia type 1 (HT-1) in pediatric patients. Dosing is weight-based and adjusted according to plasma succinylacetone and tyrosine levels. It is the cornerstone of treatment for HT-1 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. 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
Clinical Pearls
- Nitisinone must always be used in conjunction with a strict low-tyrosine and low-phenylalanine diet to prevent severe hypertyrosinemia and associated side effects (ocular, dermatologic, neurological).
- Regular monitoring of plasma succinylacetone and tyrosine levels is critical for dose adjustment and dietary management.
- Patients should be educated on the importance of adherence to both medication and diet, as non-adherence can lead to severe complications of HT-1.
- Ophthalmologic examinations are essential due to the risk of corneal opacities and other ocular symptoms from elevated tyrosine levels.
- Nitisinone has a long half-life, allowing for once-daily dosing, but also means that steady-state levels take time to achieve and changes in dose take time to manifest effects.
Alternative Therapies
- Liver transplantation (considered for patients who fail to respond to nitisinone therapy or present with advanced liver disease at diagnosis)