Drug Guide
Nitisinone
Classification
Therapeutic: Tyrosine metabolism disorder agent
Pharmacological: Inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD)
FDA Approved Indications
- Hereditary tyrosinemia type 1 (HT-1), including in pediatric patients
Mechanism of Action
Nitisinone inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), which reduces the formation of downstream toxic metabolites in tyrosine catabolism, thereby decreasing the buildup of harmful substances in hereditary tyrosinemia type 1.
Dosage and Administration
Adult: Typically 2 mg/kg/day, divided into one or two doses, orally. Adjust based on clinical response and tyrosine levels.
Pediatric: Starting dose usually 1 mg/kg/day, titrated up to 2 mg/kg/day based on response and tolerability.
Geriatric: No specific dose adjustment; consider renal and hepatic function.
Renal Impairment: Use caution; no specific dosage adjustment established, monitor renal function.
Hepatic Impairment: Use with caution; no specific dosage adjustment, monitor liver function.
Pharmacokinetics
Absorption: Excellent oral absorption.
Distribution: Wide distribution, crosses the blood-brain barrier.
Metabolism: Metabolized minimally; primarily excreted unchanged.
Excretion: Excreted mainly in urine.
Half Life: Approximately 54 hours (varies among individuals).
Contraindications
- Known hypersensitivity to nitisinone or any component of the formulation.
Precautions
- Monitor plasma tyrosine levels; risk of keratopathy and neurological symptoms with elevated tyrosine.
- Use caution in patients with hepatic or renal impairment.
- Pregnancy category C; potential risk to fetus. Use only if clearly needed.
- Lactation: unclear; caution advised.
Adverse Reactions - Common
- Diarrhea (Common)
- Abdominal pain (Common)
- Elevated tyrosine levels (Common)
Adverse Reactions - Serious
- Keratopathy (corneal plaques) (Less common)
- Neurological symptoms (e.g., irritability, tremors) (Uncommon)
- Hepatic dysfunction (Uncommon)
Drug-Drug Interactions
- None well-documented; monitor closely with other hepatotoxic or neurotoxic agents.
Drug-Food Interactions
- High-protein diet may affect amino acid levels.
Drug-Herb Interactions
- Limited data; assess for herbal interactions influencing hepatic enzymes.
Nursing Implications
Assessment: Monitor plasma tyrosine, liver and renal function, ocular health, and neurological status.
Diagnoses:
- Risk for visual disturbances due to keratopathy.
- Risk for hepatic or renal dysfunction.
Implementation: Administer orally as prescribed; educate patient on dietary management; monitor laboratory parameters regularly.
Evaluation: Evaluate efficacy by reduction in toxic metabolites and clinical symptoms; monitor for adverse effects.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Attend regular follow-up appointments for lab tests.
- Maintain low-tyrosine diet as advised.
- Report any visual changes, neurological symptoms, or allergic reactions immediately.
Special Considerations
Black Box Warnings:
- Use during pregnancy only if clearly necessary; potential fetal risk.
Genetic Factors: Genetic testing may be indicated for underlying hereditary tyrosinemia.
Lab Test Interference: May alter levels of certain amino acids; monitor accordingly.
Overdose Management
Signs/Symptoms: No specific overdose data; symptoms may include increased adverse effects such as hepatic or neurological symptoms.
Treatment: Supportive care; gastrointestinal decontamination if ingestion was recent; notify poison control.
Storage and Handling
Storage: Store at room temperature, away from moisture and light.
Stability: Stable under recommended storage conditions for duration of shelf life.