Nitisinone
Tyrosinemias
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Drug Status
Government Approvals
US(FDA), UK(BNF)
WHO Essential Medicine
NO
Known Teratogen
NO
Pharmaceutical Class
4-Hydroxyphenyl-Pyruvate Dioxygenase Inhibitor
Controlled Drug Substance
NO
Nitisinone
Summary
Nitisinone is primarily used to treat hereditary tyrosinemia type 1 (HT1), a genetic disorder that affects the breakdown of the amino acid tyrosine. It can also be used for alkaptonuria (AKU) in adults.
Nitisinone works by inhibiting an enzyme involved in the breakdown of tyrosine. This prevents the buildup of toxic substances that can cause liver and kidney damage.
The usual starting dose of Nitisinone for both adults and children is 0.5 mg/kg taken orally twice daily. For maintenance, the dose can be adjusted to 1 to 2 mg/kg once daily. The maximum total daily dose should not exceed 2 mg/kg.
The most common side effects of Nitisinone include elevated tyrosine levels, leukopenia, thrombocytopenia, conjunctivitis, corneal opacity, keratitis, and photophobia. Serious adverse effects can include ocular symptoms, developmental delay, and hyperkeratotic plaques due to elevated tyrosine levels.
Nitisinone can cause elevated plasma tyrosine levels leading to ocular symptoms, developmental delays, and hyperkeratotic plaques. Patients should maintain a diet low in tyrosine and phenylalanine. Regular monitoring of blood parameters is necessary. Nitisinone is contraindicated in patients with hypersensitivity to the drug or its components.
Indications and Purpose
How does Nitisinone work?
Nitisinone works by inhibiting the enzyme 4-hydroxyphenyl-pyruvate dioxygenase, which is involved in the catabolism of tyrosine. This inhibition prevents the accumulation of toxic metabolites like maleylacetoacetate and fumarylacetoacetate, which are converted to harmful substances such as succinylacetone. By reducing these toxic metabolites, Nitisinone helps prevent liver and kidney damage in patients with hereditary tyrosinemia type 1 (HT-1).
Is Nitisinone effective?
Nitisinone has been shown to be effective in treating hereditary tyrosinemia type 1 (HT-1) by inhibiting the enzyme responsible for the accumulation of toxic metabolites. Clinical studies have demonstrated that Nitisinone normalizes succinylacetone levels in urine and plasma, reducing the risk of liver and kidney damage. The medication has significantly improved survival rates and reduced the incidence of liver cancer in patients with HT-1.
What is Nitisinone?
Nitisinone is used to treat hereditary tyrosinemia type 1 (HT-1) by inhibiting the enzyme 4-hydroxyphenyl-pyruvate dioxygenase, which prevents the accumulation of toxic metabolites that can cause liver and kidney damage. It is often used in combination with dietary restrictions of tyrosine and phenylalanine. By reducing the levels of harmful substances, Nitisinone helps manage the symptoms and complications associated with HT-1.
Directions for Use
For how long do I take Nitisinone?
Nitisinone is typically used as a long-term treatment for hereditary tyrosinemia type 1 (HT-1). The duration of use is often lifelong, as it helps manage the condition by preventing the accumulation of toxic substances in the body. Regular monitoring and adjustments by a healthcare provider are necessary.
How do I take Nitisinone?
Nitisinone can be taken with or without food. However, it is important to maintain a dietary restriction of tyrosine and phenylalanine while on this medication to prevent elevated plasma tyrosine levels. Patients should follow their healthcare provider's dietary recommendations and report any unexplained symptoms promptly.
How long does it take for Nitisinone to start working?
Nitisinone begins to work by reducing succinylacetone levels in the body. In clinical studies, the median time to normalization of urine succinylacetone was 0.3 months, and for plasma succinylacetone, it was 3.9 months. The exact time may vary depending on individual response and adherence to dietary restrictions.
How should I store Nitisinone?
Nitisinone tablets should be stored at room temperature between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F). The tablets should be kept in the container they are dispensed in, tightly closed, and protected from direct sunlight. If using the oral suspension, it should be stored in the refrigerator before first use and at room temperature after opening, with specific discard dates noted.
What is the usual dose of Nitisinone?
The usual starting dose of Nitisinone for both adults and children is 0.5 mg/kg taken orally twice daily. For maintenance, in patients 5 years and older with undetectable succinylacetone levels, the dose can be adjusted to 1 to 2 mg/kg once daily. The maximum total daily dose should not exceed 2 mg/kg.
Warnings and Precautions
Can I take Nitisinone with other prescription drugs?
Nitisinone is a moderate inhibitor of CYP2C9 and can increase the exposure of drugs metabolized by this enzyme, such as warfarin and phenytoin. It is also a weak inducer of CYP2E1 and an inhibitor of OAT1/OAT3. Patients taking medications metabolized by these pathways should be monitored closely, and dosage adjustments may be necessary to maintain therapeutic drug concentrations.
Can Nitisinone be taken safely while breastfeeding?
There is no data on the presence of Nitisinone in human milk, but it is present in rat milk and has been associated with ocular toxicity and lower body weight in nursing rat pups. The potential benefits of breastfeeding should be weighed against the mother's need for Nitisinone and any potential adverse effects on the breastfed infant. Consultation with a healthcare provider is recommended.
Can Nitisinone be taken safely while pregnant?
There is limited data on the use of Nitisinone during pregnancy, and its effects on fetal development are not well established. Animal studies have shown potential risks, such as incomplete skeletal ossification and decreased pup survival. Nitisinone should only be used during pregnancy if the potential benefits justify the risks. Pregnant women should consult their healthcare provider for personalized advice.
Is it safe to exercise while taking Nitisinone?
Nitisinone does not specifically limit the ability to exercise. However, if you experience any side effects that affect your physical capabilities, such as fatigue or muscle pain, it is advisable to consult your healthcare provider. They can provide guidance on safe exercise practices while on this medication.
Is Nitisinone safe for the elderly?
There is no specific information on the use of Nitisinone in elderly patients. However, as with any medication, dose selection should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population. Regular monitoring and consultation with a healthcare provider are advised.
Who should avoid taking Nitisinone?
Nitisinone can cause elevated plasma tyrosine levels, leading to ocular symptoms, developmental delays, and hyperkeratotic plaques. Patients should maintain a diet low in tyrosine and phenylalanine. Regular monitoring of blood parameters is necessary. Nitisinone is contraindicated in patients with hypersensitivity to the drug or its components. Patients should report any unexplained symptoms to their healthcare provider promptly.