Orfadin 4mg/ml Suspension
Overview
What is this medicine?
How to Use This Medicine
To use this medication correctly, follow your doctor's instructions and read all the information provided. If the adapter is not already attached to the bottle, prepare it according to the instructions you received or as described in the package insert. You can take this medication with or without food.
Before each use, shake the bottle well for at least 5 seconds to ensure the particles are fully dissolved. To measure the correct dose, use the measuring device that comes with the medication. If one is not provided, ask your pharmacist for a suitable measuring device.
Continue taking this medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
If the adapter is not attached to the bottle when you receive it, store the bottle in the refrigerator until you are ready to prepare it. Do not freeze the medication.
Once the adapter is attached, store the bottle at room temperature (up to 77°F or 25°C).
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 resume your regular dosing 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 of nitisinone and to prevent complications like hypertyrosinemia. Dietary management should be supervised by a metabolic dietitian.
- Regular follow-up appointments and blood tests are essential to monitor drug levels, tyrosine levels, and overall health.
- Report any new or worsening symptoms, especially eye problems (like sensitivity to light, eye pain, or blurred vision), skin rashes, or signs of infection/bleeding.
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 medical help right away:
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
Most people taking this medication will not experience side effects, or they will be mild. However, if you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help:
Headache
Upset stomach
* Diarrhea
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult 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:
- Eye pain, redness, or sensitivity to light (photophobia)
- Blurred vision or changes in vision
- Skin rash or lesions (especially on palms and soles)
- Unexplained bruising or bleeding
- Unusual tiredness or weakness
- Signs of infection (fever, sore throat)
- Yellowing of skin or eyes (jaundice)
- Swelling in the abdomen or legs
- 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 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 is crucial to ensure safe use and avoid potential interactions.
* Any existing health problems, as this medication may interact with other medical conditions.
To guarantee your safety, carefully review all your medications and health issues with your doctor and pharmacist. Never start, stop, or adjust the dosage of any medication without first consulting your doctor to confirm it is safe to do so.
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:
- Exaggerated adverse effects, particularly severe hypertyrosinemia with associated ocular symptoms (corneal opacities, photophobia, keratitis), skin lesions, and neurological symptoms.
- Increased risk of myelosuppression (leukopenia, thrombocytopenia).
What to Do:
There is no specific antidote for nitisinone overdose. Management should be supportive and symptomatic. Discontinue nitisinone and monitor plasma tyrosine and succinylacetone levels, CBC, liver and renal function. Consult a poison control center (Call 1-800-222-1222 in the US) or emergency medical services immediately.
Drug Interactions
Moderate Interactions
- Drugs that significantly induce or inhibit CYP3A4 or CYP2C9 (monitor nitisinone levels and adjust dose if necessary).
- Drugs that cause myelosuppression (e.g., chemotherapy, immunosuppressants) - increased risk of leukopenia/thrombocytopenia.
- Drugs that can cause ocular toxicity (e.g., amiodarone, chloroquine) - potential additive risk of ocular adverse effects, especially with elevated tyrosine levels.
Monitoring
Baseline Monitoring
Rationale: To establish baseline and guide initial dose titration.
Timing: Prior to initiation of therapy.
Rationale: To establish baseline and guide initial dose titration, and to monitor for 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 renal function.
Timing: Prior to initiation of therapy.
Rationale: To assess baseline hematologic status and monitor for myelosuppression.
Timing: Prior to initiation of therapy.
Rationale: To establish baseline ocular health and monitor for tyrosine-induced ocular toxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Frequency: Weekly during initial dose titration, then monthly or as clinically indicated once stable.
Target: Undetectable
Action Threshold: If detectable, consider dose increase or adherence issues.
Frequency: Weekly during initial dose titration, then monthly or as clinically indicated once stable.
Target: < 500 micromol/L
Action Threshold: If > 500 micromol/L, consider dose reduction, dietary adherence, or other causes.
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 investigation.
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., leukopenia, thrombocytopenia) may require dose adjustment or investigation.
Frequency: Every 6-12 months, or more frequently if ocular symptoms develop or tyrosine levels are persistently high.
Target: Normal ocular findings
Action Threshold: Development of corneal opacities, photophobia, or other ocular symptoms requires immediate evaluation and potential dose adjustment/dietary review.
Symptom Monitoring
- Changes in vision (e.g., photophobia, eye pain, blurred vision)
- Skin rash or lesions
- Unexplained bleeding or bruising (signs of thrombocytopenia)
- Frequent infections (signs of leukopenia)
- Neurological symptoms (e.g., peripheral neuropathy, developmental regression)
- Signs of liver dysfunction (e.g., jaundice, ascites, easy bruising)
Special Patient Groups
Pregnancy
Nitisinone is classified as Pregnancy Category C. Animal studies have shown adverse effects on fetal development (e.g., skeletal abnormalities, reduced fetal weight) at doses higher than human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. Nitisinone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Untreated HT-1 in the mother can also pose significant risks to both mother and fetus.
Trimester-Specific Risks:
Lactation
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 and the potential risks to the infant. The long half-life of nitisinone suggests potential for accumulation in breast milk.
Pediatric Use
Nitisinone is indicated for pediatric patients with HT-1. Dosing is weight-based and adjusted based on biochemical markers. Early initiation of therapy is crucial to prevent irreversible organ damage. Long-term safety and efficacy have been established 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. However, HT-1 is typically diagnosed and managed from infancy, so geriatric patients are rare.
Clinical Information
Clinical Pearls
- Nitisinone therapy must always be accompanied by a strict low-tyrosine and low-phenylalanine diet to prevent hypertyrosinemia and its associated complications (e.g., ocular toxicity, neurological symptoms).
- Regular monitoring of plasma succinylacetone (target undetectable) and tyrosine (target < 500 micromol/L) levels is critical for effective dose titration and management.
- Ophthalmologic examinations are essential due to the risk of tyrosine-induced ocular toxicity (corneal opacities, photophobia, keratitis).
- Patients should be educated on the importance of adherence to both medication and diet, and to report any new or worsening symptoms promptly.
- Nitisinone is an orphan drug, and patient assistance programs are often available to help with the high cost.
Alternative Therapies
- Dietary management (low-tyrosine, low-phenylalanine diet) is a cornerstone of HT-1 treatment, always used in conjunction with nitisinone.
- Liver transplantation: Considered for patients who fail to respond to nitisinone therapy, develop hepatocellular carcinoma, or have severe liver disease despite treatment. It is a curative option for the liver disease but does not address renal or neurological complications as effectively as nitisinone.