Orfadin 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. 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 the medication is not used within 45 days, it should be discarded. Other brands can be stored at room temperature in a dry place, but should not be kept in the bathroom. Make sure you understand the storage instructions for your specific brand, and ask your pharmacist if you have any questions.
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 continue with your regular 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 is critical to prevent side effects from high tyrosine levels.
- Take the medication consistently at the same time each day.
- Do not stop taking nitisinone without consulting your doctor, even if you feel well.
- Attend all scheduled doctor appointments and laboratory tests (blood tests, eye exams) to monitor your condition and medication effectiveness/safety.
- Report any new or worsening symptoms, especially eye problems (light sensitivity, eye pain), skin changes, or unusual bleeding/bruising.
Available Forms & 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 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. 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.
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
Seek Immediate Medical Attention If You Experience:
- Increased sensitivity to light (photophobia)
- Eye pain or redness
- Blurred vision or vision changes
- Skin thickening or discoloration (hyperpigmentation, hyperkeratosis)
- Unexplained fever or signs of infection
- Unusual bleeding or bruising
- Yellowing of skin or eyes (jaundice)
- Swelling in legs or abdomen
- Changes in behavior or neurological symptoms (e.g., numbness, tingling, weakness)
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 symptoms you experienced as a result of the allergy.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial to avoid potential interactions between this medication and other substances.
* Any existing health problems, as they may affect the safety and efficacy of this medication.
To ensure your safety, it is vital to verify that this medication can be taken in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor. By sharing this information with your doctor and pharmacist, you can help prevent potential interactions and ensure the safe use of this medication.
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 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, it is crucial to discuss this with your doctor. You and your doctor will need to weigh the benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Exaggerated side effects, particularly very high tyrosine levels leading to severe ocular or dermatological symptoms.
- Potential for increased myelosuppression (low white blood cells, low platelets).
What to Do:
Seek immediate medical attention. Contact a poison control center (Call 1-800-222-1222 in the US). Treatment is supportive and may involve reducing or temporarily stopping nitisinone, and strict dietary management to lower tyrosine levels.
Drug Interactions
Moderate Interactions
- Drugs that significantly induce or inhibit CYP3A4 (potential to alter nitisinone levels)
- Drugs that cause leukopenia or thrombocytopenia (additive risk)
Monitoring
Baseline Monitoring
Rationale: To confirm diagnosis and establish baseline for therapeutic monitoring.
Timing: Prior to initiation of therapy.
Rationale: To establish baseline and guide dietary management.
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 and monitor for myelosuppression.
Timing: Prior to initiation of therapy.
Rationale: Tumor marker for hepatocellular carcinoma, common complication of HT-1.
Timing: Prior to initiation of therapy.
Rationale: To assess for corneal opacities or other ocular abnormalities related to elevated tyrosine.
Timing: Prior to initiation of therapy.
Routine Monitoring
Frequency: Weekly for the first month, then monthly for 2-3 months, then every 3-6 months once stable.
Target: Undetectable or very low.
Action Threshold: If detectable, consider dose increase or adherence issues.
Frequency: Weekly for the first month, then monthly for 2-3 months, then every 3-6 months once stable.
Target: 200-500 µmol/L (3.6-9 mg/dL).
Action Threshold: If >500-600 µmol/L, consider dietary adjustment; if persistently high (>1000 µmol/L), consider dose reduction or re-evaluation of diet.
Frequency: Monthly for the first 2-3 months, then every 3-6 months.
Target: Within normal limits.
Action Threshold: Significant elevations may require dose adjustment or investigation.
Frequency: Monthly for the first 2-3 months, then every 3-6 months.
Target: Within normal limits.
Action Threshold: Leukopenia or thrombocytopenia may require dose adjustment or discontinuation.
Frequency: Every 3-6 months.
Target: Decreasing or stable low levels.
Action Threshold: Persistent elevation or increase may indicate hepatocellular carcinoma and require further imaging.
Frequency: Every 6-12 months, or if visual symptoms occur.
Target: No corneal opacities or photophobia.
Action Threshold: Presence of ocular symptoms or opacities may require tyrosine level reduction.
Symptom Monitoring
- Changes in vision (photophobia, eye pain, blurred vision)
- Skin changes (hyperpigmentation, hyperkeratosis)
- Neurological symptoms (neuropathy, developmental delay, seizures)
- Signs of liver dysfunction (jaundice, ascites, easy bruising)
- Signs of infection (fever, chills) due to potential leukopenia
- Unusual bleeding or bruising due to potential thrombocytopenia
Special Patient Groups
Pregnancy
Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nitisinone has been shown to be teratogenic and embryotoxic in animal studies. The underlying disease (HT-1) itself poses significant risks to both mother and fetus if not adequately controlled.
Trimester-Specific Risks:
Lactation
Nitisinone is excreted into breast milk in animal studies. Due to the potential for serious adverse reactions in the 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.
Pediatric Use
Nitisinone is approved for use in pediatric patients of all ages with HT-1. Dosing is weight-based and adjusted according to succinylacetone and tyrosine levels. Close monitoring of growth and development is essential.
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 therapy for HT-1 MUST be accompanied by a strict low-tyrosine and low-phenylalanine diet. Failure to adhere to the diet can lead to severe complications from elevated tyrosine, including ocular (corneal opacities, photophobia) and dermatological (hyperpigmentation, hyperkeratosis) issues, and potentially neurological problems.
- Regular monitoring of plasma succinylacetone levels is crucial to ensure therapeutic efficacy (target: undetectable).
- Regular monitoring of plasma tyrosine levels is crucial to prevent complications from hypertyrosinemia (target: 200-500 µmol/L).
- Patients should be educated on the importance of reporting any visual changes or skin abnormalities immediately.
- Nitisinone is a lifelong therapy for HT-1. Adherence is paramount for long-term outcomes.
- Alpha-fetoprotein (AFP) levels should be monitored regularly as patients with HT-1 are at increased risk for hepatocellular carcinoma, even with treatment.
Alternative Therapies
- Liver transplantation (curative, but associated with significant risks and lifelong immunosuppression; often considered for patients who fail nitisinone therapy or present with advanced liver disease).
- Dietary management alone (historically used, but less effective and associated with higher morbidity/mortality compared to nitisinone + diet).