Orfadin

About Orfadin

• The active substance present in Orfadin is Nitisinone which is used in the treatment of hereditary tyrosinemia type 1 (HT‑1) in all age group patients who also follow diet restrictions and alkaptonuria (AKU) in adults. 
• It occurs when the body is unable to break down certain amino acids. As a result, toxic substances are produced which can cause liver problems and liver cancer in patients with HT-1 and joint problems in patients with AKU.
• Patients with HT-1 and AKU are short of enzymes that break amino tyrosine and as a result, it is converted to toxin. The active substance Nitisinone blocks the enzymes that convert tyrosine into toxins. 
• Orfadin is a prescription medicine and treatment should be started under the supervision of an experienced doctor. 

Strength: 

• Capsules: 2 mg, 5 mg, 10 mg, 20 mg
• Oral suspension: 4 mg/mL 

Recommended Dosage:

• The dosage of Orfadin initially is 0.5 mg/kg orally twice daily. 
• Dose is titrated based on biochemical and/or clinical response. 
• Dose of Nitisinone should be adjusted individually and the plasma and/or urine succinylacetone concentrations, liver function parameters and alpha-fetoprotein is monitored.
• If succinylacetone is detected one month after the start of nitisinone treatment, the dose should be increased to 0.75 mg/kg twice daily. 
• A maximum dosage of 1 mg/kg orally twice daily may be needed based on biochemical parameters and body weight gain.
• For patients with HT-1, the recommended starting dose of Orfadin is 1 mg/kg of body weight daily. The dose is then adjusted according to the patient’s response and weight.
• For adults with AKU, the recommended dose is 10 mg daily.
• Maintain dietary restriction of tyrosine and phenylalanine while taking Orfadin.
• For Capsules, taken one hour before or two hours after a meal and for those who have difficulty swallowing and are intolerant to the oral suspension, the capsules may be opened and the contents mixed in a small amount of water, formula, or apple sauce immediately before use.
• For oral suspension it should be taken without regard to meals.

Warnings & Precautions

• In case of leukopenia and severe thrombocytopenia the platelets and white blood cells should be monitored.
• Plasma tyrosine levels should be monitored in patients with an abrupt change in neurologic status.
• Observe for adverse reactions due to the presence of glycerol in Orfadin composition 
• In patients with elevated plasma tyrosine levels, ocular symptoms, developmental delay, and hyperkeratotic plaques, Inadequate restriction of tyrosine and phenylalanine can lead to elevations in plasma tyrosine, which at levels above 500 micromol/L which can result in intellectual disability and developmental delay or painful hyperkeratotic plaques on the soles and palms; 
• Do not adjust the Orfadin dose to lower the plasma tyrosine concentration. 

Common Orfadin Side Effects

• Elevated tyrosine levels
• Thrombocytopenia
• Leukopenia
• Conjunctivitis
• Corneal opacity
• Keratitis
• Photophobia
• Eye pain
• Blepharitis
• Cataracts
• Granulocytopenia
• Epistaxis
• Pruritus
• Exfoliative dermatitis
• Dry skin
• Maculopapular rash
• Alopecia

Use in Specific Population

Pregnancy: Limited data on Nitisinone is available in pregnant women and is not sufficient to inform any drug-associated risk.

Pediatric use: Plasma and urine succinylacetone levels should be monitored are recommended in pediatric patients to ensure adequate control. A skilled nutritionist to manage inborn errors of metabolism should be hired to create a tyrosine and phenylalanine deficient low protein diet.

Storage and Handling

Orfadin white capsules: 

• The capsules are packed in a high-density polyethylene container with a tamper-resistant low-density polyethylene cap.
• Store refrigerated at 2° to 8°C (36° to 46°F). 
• Orfadin capsules at room temperature up to 25°C (77°F) for up to 45 days. And if not used within 45 days, capsules should be discarded.

Orfadin oral suspension: White, slightly viscous opaque suspension.

• The suspension is provided in a 100 mL brown bottle (type III glass) with a white child-resistant screw cap with sealing and tamper. 
• Each bottle contains 90 mL oral suspension.
• Store upright, refrigerated at 2°C to 8°C (36°F to 46°F) prior to first use. Do not freeze. 

• After first opening, if stored at room temperature (up to 25°C (77°F) for up to 60 days. If not used within 60 days, discard the remaining portion.