Orfadin 2mg 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 to you 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. If you mix the medication with one of these substances, be sure to swallow it right away. Do not store the mixture for later use.
Storing and Disposing of Your Medication
Different brands of this medication may have specific storage instructions. Some brands should be stored in the refrigerator, but do not freeze. If you need to store the medication at room temperature, it can be kept at a temperature up to 77°F (25°C) for up to 45 days. If you store the medication at room temperature and do not use it within 45 days, discard it. Other brands can be stored at room temperature in a dry place, but not in the bathroom. Make sure you understand how to store your specific brand of medication. If you have any questions, ask your pharmacist.
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 dose, skip the missed dose and return to your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Strict adherence to a low-tyrosine and low-phenylalanine diet is crucial for the effectiveness and safety of nitisinone. This diet must be maintained for life.
- Regular follow-up appointments and blood tests are essential to monitor tyrosine levels, succinylacetone levels, and overall health.
- Report any new or worsening symptoms, especially eye problems (like sensitivity to light or blurred vision), skin changes, or unusual bleeding/bruising, to your doctor immediately.
- Wear sunglasses if you experience increased sensitivity to light (photophobia).
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
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 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. 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 persist, contact your doctor or seek medical attention.
Remember, this is not an exhaustive list of possible side effects. If you have questions or concerns, don't hesitate to reach out to your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe eye pain, redness, or blurred vision
- Increased sensitivity to light (photophobia)
- Skin rash or thickening of the skin (hyperkeratosis)
- Unexplained bleeding or bruising
- Frequent infections, fever, or sore throat (signs of low white blood cell count)
- Numbness, tingling, or weakness in hands or feet (signs of peripheral neuropathy)
- Significant changes in behavior or development (in children)
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.
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 and vitamins you are using
* Any health problems you have
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.
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 recommend regular urine tests to assess your health. It is crucial to follow the testing schedule as advised by your doctor.
An eye exam may also be necessary, as prescribed by your doctor, to monitor any potential effects of the medication on your vision.
To maximize the benefits of this medication, it is essential to follow the diet plan recommended by your doctor.
If you are pregnant, planning to become pregnant, or are breastfeeding, inform 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 to make an informed decision.
Overdose Information
Overdose Symptoms:
- Exaggerated adverse effects, particularly severe ocular symptoms (e.g., photophobia, corneal opacities), skin lesions, or hematologic abnormalities (thrombocytopenia, leukopenia) due to very high tyrosine levels.
What to Do:
There is no specific antidote. Management is supportive. Discontinue nitisinone, manage symptoms, and closely monitor tyrosine levels, ocular status, and hematologic parameters. Contact a poison control center (Call 1-800-222-1222) or seek emergency medical attention immediately.
Drug Interactions
Moderate Interactions
- Drugs that are highly protein-bound (e.g., warfarin, phenytoin): Nitisinone is highly protein-bound and could displace other highly protein-bound drugs, potentially increasing their free concentrations and toxicity. Monitor for increased effects of co-administered drugs.
- Drugs metabolized by CYP3A4 (minor interaction): Nitisinone is a weak inhibitor of CYP3A4. Clinical significance is generally low, but monitor for altered effects of sensitive CYP3A4 substrates.
Monitoring
Baseline Monitoring
Rationale: To assess baseline hepatic status and monitor for potential hepatotoxicity.
Timing: Prior to initiation
Rationale: To assess baseline renal status.
Timing: Prior to initiation
Rationale: To assess baseline hematologic status and monitor for potential myelosuppression (thrombocytopenia, leukopenia).
Timing: Prior to initiation
Rationale: To establish baseline levels and guide dietary management.
Timing: Prior to initiation
Rationale: To confirm diagnosis and establish baseline for monitoring treatment efficacy.
Timing: Prior to initiation
Rationale: To establish baseline ocular health and monitor for potential ocular adverse effects (e.g., corneal opacities, photophobia).
Timing: Prior to initiation
Routine Monitoring
Frequency: Weekly for the first month, then monthly or as clinically indicated
Target: 200-500 micromol/L (to minimize ocular toxicity)
Action Threshold: If > 500 micromol/L, reassess diet and consider dose adjustment. If > 1000 micromol/L, urgent action needed.
Frequency: Monthly or as clinically indicated
Target: Undetectable or very low
Action Threshold: If detectable, consider dose increase or adherence issues.
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.
Frequency: Monthly for the first few months, then every 3-6 months or as clinically indicated
Target: Within normal limits
Action Threshold: Significant decreases (e.g., thrombocytopenia, leukopenia) may require dose adjustment or discontinuation.
Frequency: Every 6-12 months or if ocular symptoms develop
Target: Normal findings
Action Threshold: Development of corneal opacities, photophobia, or other ocular symptoms may require dose adjustment or discontinuation.
Frequency: Regularly at clinic visits
Target: Normal for age
Action Threshold: Growth faltering may indicate inadequate dietary management or other issues.
Symptom Monitoring
- Changes in vision (e.g., photophobia, eye pain, blurred vision)
- Skin changes (e.g., hyperkeratosis, rash)
- Neurological symptoms (e.g., peripheral neuropathy, developmental delay)
- Signs of infection (fever, sore throat)
- Unexplained bleeding or bruising
- Gastrointestinal symptoms (nausea, vomiting, abdominal pain)
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 the mother can lead to severe complications for both mother and fetus.
Trimester-Specific Risks:
Lactation
Nitisinone is excreted into breast milk in animal studies. It is not known whether nitisinone is excreted in human 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. The benefits of breastfeeding should be weighed against the potential risks.
Pediatric Use
Nitisinone is indicated for pediatric patients of all ages with HT-1. Dosing is weight-based. Close monitoring of tyrosine levels, succinylacetone levels, growth, and development is essential. Adherence to the low-tyrosine/low-phenylalanine diet is critical.
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 is a life-saving medication for HT-1, but its efficacy is highly dependent on strict adherence to a concomitant low-tyrosine and low-phenylalanine diet.
- Regular monitoring of plasma tyrosine levels is critical to prevent ocular toxicity (corneal opacities, photophobia). Target tyrosine levels are typically 200-500 micromol/L.
- If tyrosine levels are consistently high, first assess dietary adherence before considering dose adjustments.
- Patients should be educated on the importance of reporting any visual changes or increased light sensitivity immediately.
- Orfadin capsules can be opened and the contents mixed with a small amount of water or food for patients who have difficulty swallowing capsules.
Alternative Therapies
- Liver transplantation (historically the primary treatment for HT-1, now often reserved for patients who fail nitisinone therapy or present with advanced liver disease)
- Dietary management alone (prior to nitisinone, but less effective and associated with higher morbidity/mortality)