WHAT IS TYROSINEMIA?

Tyrosinemia is a serious inherited rare disease caused by the inability to metabolise the amino acid Tyrosine.

The most severe form of the disorder is type 1, commonly referred to as HT-1.

The disease is inherited in an autosomal recessive manner, meaning that in order to have the disease, a child must inherit two defective genes, one from each parent. In families where both parents are carriers of the gene for the disease, there is a one in four risk that a child will develop tyrosinemia.

In the so-called acute form of the disease, abnormalities appear in the first month of life.  Left untreated, HT-1 can cause severe liver and kidney damage.

Tyrosine

Phenylalanine

Proteins are made of simple organic compounds called amino acids.

Tyrosine and Phenylalanine are two of 20 amino acids, which are found in most animal and plant proteins. The metabolism of both amino acids in humans takes place primarily in the liver.

NITISINONE TABLETS are used to treat hereditary tyrosinemia type-1 (HT-1), a lifelong and rare genetic disease.

In combination with a controlled diet, NITISINONE TABLETS block the breakdown of the amino acid tyrosine, preventing the formation of toxic substances.

HOW DOES HT-1 AFFECT PATIENTS?

LIVER

KIDNEY

NEURONS

The defective gene results in a disruption of the final step of metabolism of tyrosine (absence of fumarylacetoacetate hydrolase (FAH) enzyme).

As a result, high levels of tyrosine build up in the blood, forming a toxic substance called succinylacetone.

Left untreated, HT-1 can cause hepatic, renal and peripheral nerve damage. The disease is characterized by progressive liver disease with increased risk of hepatocellular carcinoma (the liver), renal tubular dysfunction with hypophosphatemic rickets (kidneys) and a porphyria-like syndrome (nervous system).

In conjunction with a controlled diet, treatment with NITISINONE TABLETS can prevent the formation of succinylacetone further preventing liver and kidney damage. Regular blood and urine tests are used to monitor succinylacetone levels in the body to ensure nitisinone levels are appropriate for treatment.

HOW IS HT-1 DIAGNOSED?

 

The diagnosis of tyrosinemia is based on blood and urine tests to measure levels of succinylacetone.

In both the acute and chronic forms of the disease, liver function tests are often abnormal. Low serum albumin and clotting factors are also frequently found. Transaminase levels in the blood may be mildly to moderately elevated, and the bilirubin level is increased to a variable extent.

Because of the biochemical defect, abnormal products may be measured in the urine which confirm the diagnosis.

Prenatal diagnosis is possible and can be performed by measuring succinylacetone or FAH levels in the amniotic fluid.

NITISINONE TABLETS INDICATIONS

NITISINONE TABLETS, also known as NTBC tablets, are indicated for the treatment of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.

Treatment with NITISINONE TABLETS should be initiated and supervised by a physician experienced in the treatment of HT-1.

IMPORTANT SAFETY INFORMATION ABOUT NITISINONE TABLETS

Contraindications:

  • Do not prescribe NITISINONE TABLETS to a patient that is hypersensitive to nitisinone or to any ingredient in the formulation.
  • Do not prescribe NITISINONE TABLETS if the patient is breast-feeding. Patients should not breast feed while taking NITISINONE TABLETS.

Warning and Precautions:

Endocrine and Metabolism: Elevated plasma tyrosine levels. Hematologic: Leukopenia and thrombocytopenia. Hepatic/Biliary/Pancreatic: Liver status should be assessed regularly through liver function tests. Neurologic: Variable degrees of intellectual disability and developmental delay have been observed in HT-1 patients treated with nitisinone. In patients treated with nitisinone who exhibit a change in neurologic status, a clinical laboratory assessment including plasma tyrosine should be performed. Ophthalmologic: Ocular signs and symptoms including corneal ulcers, corneal opacities, keratitis, conjunctivitis, eye pain, and photophobia have been reported in patients treated with nitisinone. Patients who develop photophobia, eye pain, or signs of inflammation such as redness, swelling, or burning of the eyes during treatment with NITISINONE TABLETS should undergo slit-lamp re-examination and immediate measurement of plasma tyrosine concentration.

Special Populations:

  • Pregnant women: NITISINONE TABLETS should be used in pregnancy only when the benefits of continued treatment are judged to outweigh the risks.
  • Nursing women: Because of the potential serious adverse reactions to nitisinone in nursing infants, mothers taking NITISINONE TABLETS should not breast-feed.
  • Pediatrics (< 18 years of age): Patients under 18 years should be monitored to ensure adequate control. It is recommended that a dietitian experienced in managing children with inborn errors of metabolism is consulted to design a low-protein diet restricted in tyrosine and phenylalanine.
  • Geriatrics (>65 years of age): Clinical studies of nitisinone did not include subjects over the age of 65 years, and no pharmacokinetic studies have been conducted in geriatric subjects.

Common Adverse Reactions:

The most common adverse reactions (≥1%) reported in patients treated with nitisinone (NTBC) are: Eye Disorders: conjunctivitis, corneal opacity, keratitis, photophobia, blepharitis and eye pain. Blood and lymphatic System Disorders: thrombocytopenia, leukopenia and granulocytopenia. Skin and subcutaneous tissue disorders: pruritis, exfoliative dermatitis and maculopapular rash. Investigations: elevated tyrosine levels.

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