Orfadin 10mg 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 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 the storage instructions for your specific brand. 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
- Adhere strictly to a low-tyrosine, low-phenylalanine diet as prescribed by your doctor or dietitian. This is crucial to prevent high tyrosine levels, which can cause eye problems and skin lesions.
- 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 doctor appointments and laboratory tests (blood tests, eye exams) to monitor treatment effectiveness and side effects.
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 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. 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 help.
Reporting Side Effects
If you have questions or concerns about side effects, you can:
Contact your doctor for medical advice
Report side effects to the FDA at 1-800-332-1088
* Submit a report online 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 rashes or thickening of the skin (hyperkeratosis), especially on palms and soles
- Unexplained fever, chills, or signs of infection
- Unusual bleeding or bruising
- Yellowing of the skin or eyes (jaundice)
- Swelling in the abdomen or legs
- Changes in urination (amount or frequency)
- New or worsening neurological symptoms (e.g., weakness, numbness, pain, developmental regression 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, 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 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 this medication can be taken with all your current medications and health conditions. 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 require you to have your urine checked periodically. It is crucial to follow your doctor's instructions regarding urine tests.
An eye exam may also be necessary, as scheduled by your doctor. This will help monitor any potential effects of the medication on your vision.
To ensure optimal results and minimize potential side effects, it is crucial to follow the diet plan recommended by your doctor.
If you are pregnant, planning to become pregnant, or are breast-feeding, you must notify your doctor. 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:
- Severe hypertyrosinemia (very high tyrosine levels)
- Corneal opacities
- Skin lesions (hyperkeratosis)
- Neurological symptoms (e.g., peripheral neuropathy, developmental regression)
What to Do:
In case of suspected overdose, contact a poison control center immediately (e.g., 1-800-222-1222 in the US) or seek emergency medical attention. Management typically involves supportive care and close monitoring of plasma tyrosine levels. Dietary adjustments may be necessary.
Drug Interactions
Moderate Interactions
- Drugs that induce or inhibit CYP3A4 (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice) - may alter nitisinone levels.
- Drugs that are highly protein-bound (e.g., warfarin, phenytoin) - potential for displacement, though clinical significance is low due to low therapeutic index of nitisinone.
Monitoring
Baseline Monitoring
Rationale: Confirm diagnosis before initiating treatment.
Timing: Prior to initiation
Rationale: To establish baseline and guide initial dosing.
Timing: Prior to initiation
Rationale: To establish baseline and guide dietary management.
Timing: Prior to initiation
Rationale: To establish baseline and monitor treatment efficacy.
Timing: Prior to initiation
Rationale: Assess baseline liver status, as HT-1 affects the liver.
Timing: Prior to initiation
Rationale: Assess baseline kidney status, as HT-1 affects the kidneys.
Timing: Prior to initiation
Rationale: To establish baseline for potential corneal opacities/keratopathy due to hypertyrosinemia.
Timing: Prior to initiation
Routine Monitoring
Frequency: Weekly for the first month, then monthly for 2-3 months, then every 3-6 months once stable.
Target: 40-90 µmol/L
Action Threshold: Below target: consider dose increase. Above target: consider dose decrease. Adjust dose to maintain target.
Frequency: Weekly for the first month, then monthly for 2-3 months, then every 3-6 months once stable.
Target: <500 µmol/L
Action Threshold: Above target: reinforce dietary adherence, consider nitisinone dose adjustment if succinylacetone is also high. Below target: ensure adequate protein intake.
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: Detectable/elevated: indicates inadequate treatment, consider nitisinone dose increase or re-evaluate dietary adherence.
Frequency: Monthly for the first 3 months, then every 3-6 months.
Target: Within normal limits or stable for patient's condition
Action Threshold: Significant worsening: investigate underlying cause, consider dose adjustment if drug-related.
Frequency: Every 3-6 months.
Target: Within normal limits
Action Threshold: Significant worsening: investigate underlying cause.
Frequency: Every 6-12 months, or if visual symptoms occur.
Target: No corneal opacities/keratopathy
Action Threshold: Development of corneal opacities: indicates hypertyrosinemia, reinforce dietary adherence, consider nitisinone dose adjustment if tyrosine levels are high.
Symptom Monitoring
- Changes in vision (e.g., photophobia, eye pain, blurred vision)
- Skin lesions (e.g., hyperkeratosis)
- Neurological symptoms (e.g., peripheral neuropathy, developmental regression, pain crises)
- Signs of liver dysfunction (e.g., jaundice, ascites, easy bruising)
- Signs of kidney dysfunction (e.g., edema, changes in urine output)
- Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, abdominal pain)
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of nitisinone in pregnant women. Animal studies have shown developmental toxicity (e.g., skeletal malformations, reduced fetal weight) at doses higher than clinical exposure. Nitisinone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Untreated HT-1 is a severe, life-threatening condition for both mother and fetus.
Trimester-Specific Risks:
Lactation
Nitisinone is present in the milk of lactating rats. It is not known whether 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.
Pediatric Use
Nitisinone is indicated for the treatment of HT-1 in pediatric patients. Dosing is weight-based and adjusted according to plasma nitisinone, tyrosine, and succinylacetone levels. Long-term safety and efficacy have been established in this population. Strict dietary management 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. However, HT-1 is primarily a pediatric disease, and geriatric patients with HT-1 are rare.
Clinical Information
Clinical Pearls
- Nitisinone treatment must always be accompanied by a strict low-tyrosine, low-phenylalanine diet to prevent severe hypertyrosinemia and its associated complications (e.g., corneal opacities, skin lesions).
- Regular monitoring of plasma nitisinone, tyrosine, and succinylacetone levels is crucial for optimizing dosing and ensuring treatment efficacy and safety.
- Patients and caregivers should be educated on the importance of dietary adherence and the signs/symptoms of hypertyrosinemia.
- Early diagnosis and initiation of nitisinone therapy significantly improve outcomes in HT-1, reducing the risk of liver failure, hepatocellular carcinoma, and neurological crises.
- Consider genetic counseling for families affected by HT-1.
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/hepatocellular carcinoma)