Nitisinone 5mg 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 45 days, 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
- Strict adherence to a low-tyrosine, low-phenylalanine diet is crucial for the effectiveness of nitisinone and to prevent complications from high tyrosine levels.
- Regular follow-up appointments and blood tests are essential to monitor the disease and medication levels.
- Do not stop taking nitisinone without consulting your doctor, as this can lead to a rapid worsening of the condition.
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
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 attention immediately:
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 experience no side effects or only mild ones. If you have any side effects that bother you or do not go away, contact your doctor or seek medical attention. This is not an exhaustive list of possible side effects. If you have questions or concerns, discuss them with 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, or sensitivity to light (photophobia)
- Blurred vision or changes in vision
- Skin rash, especially on palms and soles
- Unusual tiredness or weakness
- Yellowing of the skin or eyes (jaundice)
- Easy bruising or bleeding
- Changes in behavior or neurological symptoms (e.g., confusion, seizures, numbness/tingling)
Before Using This Medicine
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 allergic reaction you experienced, including any symptoms that occurred.
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 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, do not start, stop, or change the dose of any medication without first consulting your doctor. It is crucial to verify that it is safe to take this medication with all your other medications and health conditions. Your doctor and pharmacist will work together to determine the best course of treatment for you.
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 regarding these tests.
Additionally, your doctor may require you to have your urine checked periodically. It is crucial to follow your doctor's instructions for urine testing.
An eye exam may also be necessary, as scheduled by your doctor, to assess any potential effects of the medication on your vision.
To maximize the benefits of this medication, it is vital to adhere to the diet plan recommended by your doctor.
If you are pregnant, planning to become pregnant, or are breastfeeding, you must notify your doctor. Your doctor will discuss the potential benefits and risks of taking this medication during pregnancy or breastfeeding, allowing you to make an informed decision about your care and the well-being of your baby.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are primarily related to excessive plasma tyrosine levels, which can lead to ocular symptoms (corneal opacities, photophobia), skin lesions (hyperkeratotic papules), and neurological symptoms (developmental delay, intellectual disability, peripheral neuropathy).
What to Do:
In case of suspected overdose, contact a poison control center (e.g., 1-800-222-1222) or seek emergency medical attention immediately. Management is supportive and focuses on reducing plasma tyrosine levels, primarily through strict dietary restriction of tyrosine and phenylalanine. Nitisinone is highly protein-bound, so dialysis is unlikely to be effective.
Drug Interactions
Major Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital): May decrease nitisinone plasma concentrations, potentially reducing efficacy. Avoid co-administration or monitor closely.
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir): May increase nitisinone plasma concentrations, potentially increasing risk of adverse effects. Monitor closely.
Moderate Interactions
- Moderate CYP3A4 inducers/inhibitors: Monitor for altered nitisinone levels and adjust dose as needed.
Monitoring
Baseline Monitoring
Rationale: To assess baseline hepatic function and monitor for potential liver damage due to HT-1 or drug effects.
Timing: Prior to initiation of therapy.
Rationale: To assess baseline renal function and monitor for potential kidney damage due to HT-1.
Timing: Prior to initiation of therapy.
Rationale: To assess baseline hematologic status.
Timing: Prior to initiation of therapy.
Rationale: Primary biomarker for HT-1 disease activity and response to nitisinone.
Timing: Prior to initiation of therapy.
Rationale: To monitor for hypertyrosinemia, a common side effect of nitisinone, and ensure dietary compliance.
Timing: Prior to initiation of therapy.
Rationale: To assess for baseline ocular abnormalities, particularly corneal opacities, which can be associated with hypertyrosinemia.
Timing: Prior to initiation of therapy.
Routine Monitoring
Frequency: Weekly for the first month, then monthly, or as clinically indicated.
Target: Undetectable or as low as possible.
Action Threshold: If detectable, consider dose increase or dietary review. If persistently high, re-evaluate diagnosis or compliance.
Frequency: Weekly for the first month, then monthly, or as clinically indicated.
Target: 200-500 µmol/L (3.6-9.0 mg/dL).
Action Threshold: If >500 µmol/L, review dietary protein intake and consider dietary adjustments. If persistently high, consider nitisinone dose reduction.
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 indicate disease progression or drug-induced liver injury; investigate cause.
Frequency: Every 3-6 months, or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant changes may indicate disease progression; investigate cause.
Frequency: Every 6-12 months, or if ocular symptoms develop.
Target: No corneal opacities or other ocular abnormalities.
Action Threshold: Development of corneal opacities or other ocular symptoms may indicate excessive tyrosine levels; review diet and tyrosine levels.
Symptom Monitoring
- Ocular symptoms (e.g., eye pain, photophobia, redness, blurred vision)
- Skin lesions (e.g., hyperkeratotic lesions on palms and soles)
- Neurological changes (e.g., developmental delay, peripheral neuropathy, seizures)
- Gastrointestinal symptoms (e.g., abdominal pain, vomiting)
- Signs of liver dysfunction (e.g., jaundice, ascites, easy bruising)
Special Patient Groups
Pregnancy
Nitisinone is classified as 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
Nitisinone is excreted into breast milk. Due to the potential for serious adverse reactions in the breastfed infant, 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 approved for use in pediatric patients of all ages, including neonates, for the treatment of HT-1. Dosing is weight-based and adjusted according to biochemical parameters (succinylacetone and tyrosine levels).
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. However, HT-1 is typically diagnosed and managed in pediatric populations.
Clinical Information
Clinical Pearls
- Nitisinone is a life-saving medication for patients with hereditary tyrosinemia type 1 (HT-1) and has significantly improved outcomes compared to liver transplantation alone.
- Strict adherence to a low-tyrosine, low-phenylalanine diet is paramount for treatment success and to prevent complications from hypertyrosinemia.
- Regular monitoring of plasma succinylacetone (to assess disease control) and plasma tyrosine (to monitor for hypertyrosinemia) is critical.
- Patients should be educated on the signs and symptoms of hypertyrosinemia, particularly ocular and dermatological manifestations.
- Nitisinone is an orphan drug, and patient assistance programs are often available to help with the high cost.
Alternative Therapies
- Liver transplantation (historically the primary treatment for HT-1 before nitisinone, now often reserved for cases unresponsive to nitisinone or with advanced liver disease at diagnosis).