Nitisinone Dipharma (Nitisinone) 2 mg Hard Capsules
HPPD inhibitor for hereditary tyrosinemia type 1 (HT-1), used together with a tyrosine- and phenylalanine-restricted diet
Quick Facts About Nitisinone Dipharma
Key Takeaways About Nitisinone Dipharma
- Lifelong, life-saving treatment: Nitisinone is not a cure, but it transforms hereditary tyrosinemia type 1 from an almost universally fatal infant liver disease into a manageable chronic condition.
- Diet is as important as the drug: Nitisinone must always be combined with a tyrosine- and phenylalanine-restricted diet, supervised by a specialist metabolic dietitian.
- Early treatment is best: Starting nitisinone within the first months of life, ideally guided by newborn screening, dramatically reduces the risk of liver cancer and preserves kidney and neurocognitive function.
- Close monitoring is essential: Plasma tyrosine, succinylacetone, liver function, alpha-fetoprotein, and liver imaging must be followed regularly throughout life.
- Most side effects relate to high tyrosine: Eye pain, photophobia, corneal erosions, skin lesions on palms and soles, and potential learning difficulties are almost always linked to dietary non-adherence rather than the medicine itself.
What Is Nitisinone Dipharma and What Is It Used For?
Nitisinone Dipharma is an oral prescription medicine containing nitisinone, used to treat hereditary tyrosinemia type 1 (HT-1). It blocks the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) upstream of the defective enzyme in HT-1, preventing the build-up of toxic metabolites that damage the liver, kidneys, and nerves. It must always be given together with a diet low in the amino acids tyrosine and phenylalanine.
Nitisinone Dipharma is a generic version of nitisinone authorised as a hybrid or generic medicinal product within the European Union. The reference product for nitisinone is the originator medicine that first received a centralised marketing authorisation from the European Medicines Agency (EMA) in 2005. The active substance is chemically identical in Nitisinone Dipharma and in the originator product, which means the same clinical and pharmacological principles apply: the medicine is used to treat a very rare inherited condition that, without therapy, is devastating and often fatal in early childhood.
Hereditary tyrosinemia type 1 is caused by mutations in the gene encoding the enzyme fumarylacetoacetate hydrolase (FAH). This enzyme is responsible for the final step in the breakdown of the amino acid tyrosine. When FAH is defective, metabolic intermediates accumulate – in particular maleylacetoacetate and fumarylacetoacetate, which are converted to succinylacetone. Succinylacetone is highly toxic: it damages liver cells, interferes with kidney tubules, and inhibits an enzyme in haem synthesis, which can trigger porphyria-like neurological crises.
Before nitisinone became available, children with HT-1 typically presented in infancy with progressive liver failure, coagulopathy, rickets, and kidney dysfunction. Many died before the age of two, and the only alternative to early death was liver transplantation. The introduction of nitisinone in the early 1990s, initially as a clinical trial of a herbicide-derived molecule called NTBC, revolutionised the outlook for this disease. Long-term follow-up from registry studies and specialist reference centres shows that early-treated patients can grow into healthy adults with normal school performance, normal liver histology, and a greatly reduced risk of hepatocellular carcinoma.
How Nitisinone Works
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), the second enzyme in the tyrosine catabolic pathway, which sits upstream of the defective FAH. By blocking HPPD, nitisinone prevents the formation of the harmful downstream metabolites maleylacetoacetate, fumarylacetoacetate, and succinylacetone. The protective mechanism relies on shifting the metabolic block from a site where toxic products accumulate to a site where only tyrosine itself accumulates.
Because nitisinone raises blood and tissue tyrosine concentrations, dietary restriction of both tyrosine and its precursor phenylalanine is essential. Without this dietary control, high tyrosine levels can cause painful eye symptoms, skin lesions on the palms and soles, and, over time, may adversely affect neurocognitive development. The therapeutic combination of nitisinone with a specialised diet therefore targets the entire pathway: nitisinone blocks the toxic metabolites, while the diet prevents secondary problems from elevated tyrosine.
Nitisinone is absorbed well from the gastrointestinal tract after oral administration. It binds extensively to plasma proteins and is eliminated slowly, with a long plasma half-life that allows once- or twice-daily dosing. The medicine is metabolised primarily in the liver and excreted in urine and faeces. Its long half-life and predictable pharmacokinetics explain why stable patients can often be maintained on a single daily dose once control is established.
Who Can Benefit from Nitisinone Dipharma?
Nitisinone Dipharma is indicated for the treatment of confirmed hereditary tyrosinemia type 1 in both adults and children of any age, from newborn onwards. The diagnosis is based on elevated plasma tyrosine, detection of succinylacetone in blood and urine, and genetic confirmation of biallelic pathogenic variants in the FAH gene. In countries with newborn screening for HT-1 using succinylacetone as the primary marker, the disease can be detected before symptoms appear, allowing nitisinone to be started within the first days or weeks of life for optimal outcomes.
Internationally, HT-1 is included in expanded newborn screening panels in many European countries, parts of North America, and Australia. Programmes such as those coordinated by the Society for the Study of Inborn Errors of Metabolism (SSIEM) and Orphanet Reference Networks recommend presymptomatic treatment, because survival and long-term liver health correlate closely with the age at which therapy is started.
Although Nitisinone Dipharma is authorised specifically for HT-1, nitisinone as an active substance is also used in some countries for other metabolic conditions such as alkaptonuria. Prescribing for indications other than HT-1 should only occur under specialist supervision and may require a different authorised product or off-label use, depending on local regulations.
Nitisinone Dipharma treats only one specific inherited metabolic disorder. It has no role in other liver diseases, general liver support, or non-hereditary causes of elevated tyrosine. Treatment should always be initiated and supervised by a physician experienced in inherited metabolic disorders, ideally at a specialist metabolic or paediatric liver centre.
What Should You Know Before Taking Nitisinone Dipharma?
Before starting Nitisinone Dipharma, your doctor will confirm the diagnosis of HT-1, check liver and kidney function, measure baseline plasma tyrosine, phenylalanine and succinylacetone, and ensure a specialist dietitian is available. You must not take nitisinone if you are allergic to the active substance or any excipient. Special caution is needed during pregnancy, breastfeeding, in case of eye symptoms, and when combining with certain other medicines.
Nitisinone Dipharma is a highly specialised medicine that requires careful patient selection and ongoing supervision. Your metabolic team will perform a comprehensive assessment before starting treatment and will continue to monitor you throughout your life. Understanding the precautions and contraindications helps you participate actively in your own care and recognise early warning signs of complications.
Contraindications
You must not take Nitisinone Dipharma if:
- You are allergic (hypersensitive) to nitisinone or to any of the other ingredients of the capsules.
- You have known intolerance to any of the excipients listed in the composition section of the package leaflet.
If you think you may be allergic to any ingredient, discuss this with your doctor before starting or continuing treatment. In the rare case of a hypersensitivity reaction, contact a healthcare professional immediately.
Warnings and Precautions
Talk to your doctor before taking Nitisinone Dipharma, and continue to discuss with them during treatment, if any of the following apply:
- Eye symptoms: Pain, redness, sensitivity to light, burning sensation, excessive tearing, or clouded vision may indicate elevated plasma tyrosine levels or tyrosine crystal deposits on the cornea. Report these symptoms immediately, as they usually respond rapidly to stricter diet and dose adjustment.
- Skin changes: Painful skin lesions on the palms of the hands and soles of the feet (hyperkeratosis) can occur when tyrosine is too high and should prompt review of dietary adherence.
- Liver problems: Your doctor will arrange regular liver blood tests, alpha-fetoprotein measurements, and liver imaging (ultrasound, and in some cases MRI) to monitor for possible hepatocellular carcinoma, which can still occur even on treatment, especially if started late.
- Kidney problems: Nitisinone can reduce but not always fully reverse tubular dysfunction caused by HT-1. Regular blood and urine tests are needed.
- Neurological or behavioural symptoms: Although nitisinone itself is not typically associated with neuropsychiatric problems, very high tyrosine levels over long periods have been linked to learning difficulties in some children, particularly if dietary control is poor.
- White blood cell and platelet counts: Transient leukopenia, thrombocytopenia, and mild granulocytopenia have been reported. Your doctor will check these with routine blood counts.
- Vaccinations: Nitisinone does not interfere with routine vaccination. However, if you are pregnant or immunocompromised for other reasons, vaccination advice should be coordinated with your specialist.
Even with optimal nitisinone treatment, a small risk of liver cancer (hepatocellular carcinoma) remains, particularly in patients who started therapy late, have persistently elevated alpha-fetoprotein, or have pre-existing liver damage. Lifelong surveillance with liver imaging and alpha-fetoprotein measurement is essential. Starting nitisinone as early as possible, ideally after detection by newborn screening, is the best-known way to reduce this risk.
Regular Tests and Monitoring
Before and during treatment with Nitisinone Dipharma, you or your child will have regular medical assessments typically including:
- Plasma succinylacetone measurement (on treatment this should become undetectable, confirming adequate dosing).
- Plasma tyrosine and phenylalanine levels to guide both medication dose and dietary adjustments.
- Liver blood tests (ALT, AST, bilirubin, alkaline phosphatase, INR) and alpha-fetoprotein (AFP) as a liver cancer marker.
- Kidney function tests including creatinine and urinary markers of tubular function (glucose, phosphate, amino acids).
- Complete blood count to detect thrombocytopenia or leukopenia.
- Liver ultrasound and, when indicated, MRI of the liver to screen for nodules or tumours.
- Regular eye examinations, especially if tyrosine levels are difficult to control.
- Neuropsychological assessments in children, coordinated with the metabolic team.
Parents and carers of young children should keep a clear record of doses, clinic visits, and laboratory results. In many centres, a shared care plan is agreed between the family, the specialist metabolic team, the local paediatrician, and, for adults, the general practitioner.
Pregnancy, Breastfeeding, and Fertility
Nitisinone crosses the placenta and has been associated with ocular and developmental effects in animal studies. Human data on pregnancy are limited. At the same time, uncontrolled hereditary tyrosinemia type 1 during pregnancy carries significant risks for both mother and fetus. For these reasons:
- Nitisinone Dipharma should only be used during pregnancy when the potential benefit justifies the potential risk to the fetus, and after careful discussion with a specialist metabolic team and obstetrician.
- Dietary control becomes even more important during pregnancy, and plasma tyrosine and phenylalanine levels may need more frequent monitoring.
- Because it is not known whether nitisinone passes into breast milk, breastfeeding during treatment should be discussed with your healthcare team; in many centres, breastfeeding while on nitisinone is avoided.
- There is no evidence that nitisinone impairs fertility in either sex, but untreated HT-1 can cause reproductive and endocrine complications.
Driving and Operating Machinery
Nitisinone Dipharma has a minor influence on the ability to drive and use machines. Eye problems caused by elevated tyrosine may temporarily impair vision. If you experience visual disturbances, do not drive or operate machinery until your vision has fully recovered and your metabolic team has assessed the cause.
Children and Adolescents
Nitisinone Dipharma is specifically used in children and is, in many patients, started in infancy. Paediatric use is supported by the original clinical development programme of nitisinone, subsequent registry data, and professional consensus guidelines. Dose is calculated by body weight, and children should be seen frequently during periods of rapid growth to ensure the dose remains adequate.
Adolescents are at particular risk of non-adherence, both to the medicine and to the diet. Multidisciplinary support including psychologists and social workers can help young people maintain treatment and prepare for transition from paediatric to adult metabolic services.
Elderly
Hereditary tyrosinemia type 1 is almost always diagnosed in infancy or childhood, so treatment-naive elderly patients are extremely rare. Adults who have been treated successfully since childhood may continue nitisinone lifelong. There is no specific dose adjustment recommendation for elderly patients, but liver and kidney function should be reviewed as part of routine care, as for any long-term medication.
How Does Nitisinone Dipharma Interact with Other Drugs?
Nitisinone mildly induces CYP3A4 and moderately inhibits CYP2C9, and it inhibits the renal transporters OAT1 and OAT3. Clinically relevant interactions can occur with warfarin, phenytoin, and some non-steroidal anti-inflammatory drugs. Always tell your doctor about every medicine, herbal product, or supplement you take, including over-the-counter treatments.
Because nitisinone is taken over decades and often from infancy, interactions with other medicines, vaccines, and dietary supplements must be considered carefully at every stage of life. Many patients with HT-1 take a stable set of medicines with few changes, but new prescriptions, hospital admissions, and over-the-counter purchases all introduce possibilities for interactions.
Major Interactions
| Interacting Drug/Class | Effect | Recommendation |
|---|---|---|
| Warfarin and coumarin anticoagulants | Increased exposure via CYP2C9 inhibition; higher risk of bleeding with elevated INR. | Monitor INR closely when starting, stopping, or changing dose of nitisinone; expect possible warfarin dose reduction. |
| Phenytoin | Higher plasma levels via CYP2C9 inhibition; increased risk of toxicity. | Monitor phenytoin plasma concentrations and adjust dose accordingly. |
| Certain NSAIDs (e.g., ibuprofen, diclofenac) | Metabolised by CYP2C9; plasma levels may rise. | Use the lowest effective dose and monitor for gastrointestinal or renal adverse effects. |
| CYP3A4 substrates (e.g., some statins, hormonal contraceptives, ciclosporin) | Mild CYP3A4 induction by nitisinone may slightly reduce exposure of co-administered drugs. | Assess clinical response; consider therapeutic drug monitoring for narrow-therapeutic-index drugs. |
| OAT1/OAT3 substrates (e.g., methotrexate, furosemide, benzylpenicillin) | Nitisinone inhibits organic anion transporters in the kidney, potentially raising plasma levels. | Monitor for enhanced pharmacological and toxic effects; adjust doses as needed. |
| High-protein nutritional products not intended for HT-1 | Sudden increases in tyrosine and phenylalanine intake can cause ocular and dermatological symptoms. | Use only metabolic formulas recommended by your metabolic dietitian. |
Minor Interactions and Practical Considerations
Beyond the most important interactions listed above, a number of additional points are worth being aware of in daily practice:
- Paracetamol (acetaminophen): May be used safely for pain or fever at standard doses; however, hepatic tolerance should be respected in patients with chronic liver disease.
- Antibiotics: Most common antibiotics can be prescribed, but pharmacist review of interactions via CYP2C9/CYP3A4 is prudent.
- Herbal remedies: Products such as St John's wort (Hypericum perforatum) can alter CYP3A4 activity and should be avoided or discussed before starting.
- Alcohol: Regular alcohol use is discouraged because of the underlying hepatic vulnerability in HT-1.
- Grapefruit juice: Though specific data with nitisinone are limited, patients taking CYP3A4 substrates alongside nitisinone may be advised to avoid large quantities.
Always inform any doctor, dentist, pharmacist, or other prescriber that you are taking nitisinone for hereditary tyrosinemia type 1. Consider carrying a medicine list or a medical alert card, and update family members about the name of the diagnosis and the treatment plan in case of emergencies.
What Is the Correct Dosage of Nitisinone Dipharma?
The usual starting dose is 1 mg per kilogram of body weight per day, typically divided into two doses, and adjusted individually based on succinylacetone and plasma tyrosine levels. The total daily dose rarely exceeds 2 mg per kg. Capsules should be swallowed whole, or opened and mixed with a small amount of water or food immediately before administration, particularly in infants.
Nitisinone Dipharma doses are calculated by body weight and adjusted based on laboratory monitoring. Treatment should be initiated and supervised by a physician experienced in inherited metabolic diseases, in close collaboration with a specialist metabolic dietitian. The 2 mg hard capsule strength supports flexible dosing in infants and small children; higher strengths of nitisinone are typically available in other authorised products and are not part of Nitisinone Dipharma 2 mg.
| Patient Group | Starting Dose | Typical Range | Dosing Schedule |
|---|---|---|---|
| Newborns & infants with HT-1 | 1 mg/kg/day | 1–2 mg/kg/day | Two divided doses |
| Children & adolescents | 1 mg/kg/day | 1–2 mg/kg/day | Once or twice daily |
| Adults | 1 mg/kg/day | 1–2 mg/kg/day | Once daily often adequate |
| Patients with renal impairment | Standard weight-based dose | Individualised | Closer monitoring recommended |
| Patients with hepatic impairment | Standard weight-based dose | Individualised | Closer monitoring recommended |
Adults
Adult Dosing
The recommended starting dose for adults with confirmed HT-1 is 1 mg per kilogram of body weight per day. Once treatment stabilises and plasma succinylacetone becomes undetectable, many adults can be maintained on a once-daily schedule. The total daily dose may be adjusted upward to a maximum of approximately 2 mg/kg/day based on laboratory response and clinical findings. Capsules are swallowed whole with water. Doses should be taken at the same time each day to support adherence.
Children
Paediatric Dosing
In infants and young children, the starting dose is also 1 mg/kg/day, typically divided into two equal doses given approximately 12 hours apart. Because children grow rapidly, the absolute dose should be recalculated regularly based on updated body weight, with more frequent re-evaluation in the first two years of life. In infants who cannot yet swallow whole capsules, the capsules may be opened and the contents dispersed in a small volume of water, infant formula, apple juice, or pureed food immediately before administration.
Elderly
Older Adults
There are no specific dose recommendations for elderly patients. As with other medicines used lifelong, routine review of liver and kidney function is recommended, and other concurrent medications should be checked for potential interactions whenever new prescriptions are added.
Missed Dose
What to Do If You Forget a Dose
If you forget to take a dose, take it as soon as you remember the same day. Do not take a double dose to make up for the one you missed; simply continue with the next scheduled dose. If more than one dose is missed, contact your metabolic team for advice, because even short gaps in therapy can allow succinylacetone to rise, with risk of acute symptoms such as abdominal pain or porphyria-like neurological crises.
Overdose
If Too Much Nitisinone Is Taken
Accidental ingestion of excess nitisinone causes a rapid and large increase in plasma tyrosine levels, which may be accompanied by ocular symptoms, skin lesions, and transient blood count abnormalities. If an overdose is suspected, contact your doctor, a poisons information service, or emergency services immediately. Treatment is supportive and consists of stricter tyrosine- and phenylalanine-restricted diet while plasma tyrosine is monitored until levels normalise.
How to Take the Capsules
Nitisinone Dipharma hard capsules should be swallowed whole with a glass of water. They can be taken with or without food, but the chosen routine – for example, with breakfast and the evening meal – should be consistent from day to day. For infants and small children, the capsule can be opened just before dosing and its contents dispersed in 5–10 mL of water or a small amount of formula, juice, or soft food. The mixture should be used immediately and not stored for later use.
The medicine should always be taken together with the prescribed low-tyrosine, low-phenylalanine diet. Stopping or altering the diet while continuing nitisinone, or vice versa, can lead to rapid clinical deterioration and should not be done without explicit advice from the metabolic team.
What Are the Side Effects of Nitisinone Dipharma?
The most common side effects of Nitisinone Dipharma are elevated tyrosine levels, eye symptoms (pain, photophobia, conjunctivitis, corneal opacity), reduced platelet and white blood cell counts, and skin changes on palms and soles. Most of these side effects are dose-dependent, reversible, and closely linked to dietary adherence. Severe allergic reactions are very rare.
Like all medicines, Nitisinone Dipharma can cause side effects, although not everybody experiences them. In clinical experience and long-term registry data, the majority of adverse effects are mild to moderate and relate directly to elevated plasma tyrosine concentrations rather than to direct toxicity of nitisinone itself. A careful balance between dose, diet, and monitoring can prevent most problems.
Contact your doctor or emergency services immediately if you or your child experiences: severe eye pain or sudden loss of vision; unexplained severe bruising or bleeding; a widespread rash with fever or difficulty breathing; severe abdominal pain with confusion or weakness (possible porphyria-like crisis); or jaundice (yellowing of the skin or eyes). These symptoms may require rapid adjustment of treatment and hospital evaluation.
Frequency of Side Effects
The following frequencies reflect reports from the originator nitisinone clinical development programme and long-term pharmacovigilance, which are applicable to Nitisinone Dipharma as a hybrid or generic product containing the same active substance:
Very Common (affects more than 1 in 10 patients)
- Elevated tyrosine levels in blood, particularly if dietary control is suboptimal.
- Thrombocytopenia: low platelet count, which may cause increased bruising or minor bleeding.
- Leukopenia: reduced white blood cell count increasing susceptibility to infection.
- Conjunctivitis and other eye irritation.
Common (affects up to 1 in 10 patients)
- Corneal opacity, keratitis, photophobia, and eye pain.
- Granulocytopenia: reduced granulocyte count, a subset of white blood cells.
- Blepharitis (inflammation of the eyelids).
- Skin changes: exfoliative dermatitis, rash, itching, and painful hyperkeratosis on palms and soles.
Uncommon (affects up to 1 in 100 patients)
- Porphyria-like attacks with abdominal pain, muscle weakness, and neurological symptoms, especially with missed doses.
- Increased liver enzymes and, rarely, hepatic nodular changes requiring evaluation.
- Behavioural or learning difficulties in children with poor tyrosine control.
Rare or Very Rare (affects up to 1 in 1,000 or fewer)
- Severe allergic reactions including angioedema or anaphylaxis (very rare).
- Hepatocellular carcinoma, more often in late-treated patients and despite adequate biochemical control.
- Severe cytopenias requiring dose review or supportive treatment.
Why Most Side Effects Relate to Tyrosine, Not Nitisinone
Many of the ocular, dermatological, and cognitive effects listed above are direct consequences of elevated plasma tyrosine. When plasma tyrosine exceeds approximately 500 micromol per litre, tyrosine crystals can deposit in the cornea and skin, causing pain, photophobia, and hyperkeratotic lesions. Returning tyrosine into the recommended range through stricter dietary protein restriction and specialised metabolic formulas usually resolves these symptoms within days to weeks.
Because of this relationship, it is rarely necessary to stop nitisinone in response to side effects; instead, the first step is almost always a review of the diet, the dose, and recent laboratory values. Treatment decisions should be made jointly with the specialist metabolic centre, not by the patient alone.
Reporting Side Effects
Every patient, parent, or carer can help improve the safety of medicines by reporting suspected side effects to their healthcare professional or to the national pharmacovigilance system. In the European Union, this is typically the national competent authority that feeds into the EMA's EudraVigilance database. In the United States, reports can be made to the FDA MedWatch programme. Reporting side effects helps provide more information on the safety of Nitisinone Dipharma and all nitisinone-containing products.
How Should You Store Nitisinone Dipharma?
Store Nitisinone Dipharma capsules below 25°C in the original container, tightly closed to protect them from moisture. Keep the medicine out of the sight and reach of children. Do not use after the expiry date printed on the packaging, and return any unused capsules to a pharmacy for safe disposal.
Safe storage helps maintain the stability and effectiveness of Nitisinone Dipharma over time and reduces the risk of accidental ingestion or exposure, particularly in households with young children or vulnerable adults.
Recommended Storage Conditions
- Store below 25°C. Do not refrigerate or freeze unless specifically instructed on the packaging.
- Keep the container tightly closed to protect against moisture.
- Do not transfer the capsules to a different container, such as a daily pill organiser, unless your pharmacist confirms that this is appropriate.
- Use within the period specified on the pack after first opening.
- Keep out of direct sunlight and away from heat sources such as radiators and car dashboards.
Expiry and Disposal
Do not use Nitisinone Dipharma after the expiry date (month and year) shown on the blister and the outer carton. The expiry date refers to the last day of that month. Never dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer required. These measures will help to protect the environment and prevent misuse.
When travelling, carry Nitisinone Dipharma in your hand luggage together with a copy of the prescription and a brief medical summary. If travelling through different time zones, agree a clear dosing schedule with your metabolic team before departure so that doses are not accidentally missed or doubled.
What Does Nitisinone Dipharma Contain?
Each hard capsule of Nitisinone Dipharma contains 2 mg of nitisinone as the active substance. The capsule also contains excipients such as pregelatinised maize starch inside the capsule and gelatin with titanium dioxide and iron oxide colourants in the capsule shell. Patients with specific hypersensitivities to any excipient should discuss this with their doctor or pharmacist.
The exact qualitative and quantitative composition of the excipients is listed in the official package leaflet that accompanies each pack of Nitisinone Dipharma. Always read this leaflet before starting treatment and whenever you receive a new batch, as excipient information may be updated.
Active Substance
- Nitisinone: 2 mg per hard capsule.
Typical Excipients
The capsules generally contain the following excipients, although the exact formulation should be confirmed via the package leaflet:
- Capsule content: pregelatinised maize starch.
- Capsule shell: gelatin, titanium dioxide (E171), and iron oxide colourants (for example yellow or red iron oxides, depending on the strength).
- Printing ink on the capsule shell, based on shellac and suitable black or coloured inks.
Appearance and Pack Sizes
Nitisinone Dipharma 2 mg hard capsules are typically small capsules with a distinctive colour. They are supplied in high-density polyethylene (HDPE) bottles with child-resistant closures, containing the number of capsules specified on the outer packaging. Not all pack sizes may be marketed in every country.
Marketing Authorisation and Manufacturer
Nitisinone Dipharma is manufactured and distributed by Dipharma B.V., based in the European Union. Specific details of the marketing authorisation number, country-specific pack sizes, and full list of excipients can be found in the package leaflet and in the Summary of Product Characteristics (SmPC) published by the relevant regulatory authority.
Frequently Asked Questions About Nitisinone Dipharma
Nitisinone Dipharma is used to treat a rare genetic disorder called hereditary tyrosinemia type 1 (HT-1). It must be taken together with a special diet low in the amino acids tyrosine and phenylalanine. By blocking an enzyme in the tyrosine breakdown pathway, nitisinone prevents the accumulation of toxic metabolites that damage the liver, kidneys, and nervous system. Early diagnosis through newborn screening and prompt initiation of treatment are associated with the best long-term outcomes.
Nitisinone prevents tyrosine from being broken down, so tyrosine levels in the blood rise during treatment. High tyrosine levels can damage the eyes and skin and may impair neurocognitive development. A diet restricted in both tyrosine and phenylalanine, usually supported by a specialist metabolic dietitian with protein substitute formulas, is essential to keep plasma tyrosine levels safe, typically below 500 micromol per litre. Dietary management is as important as the medicine itself.
The most common side effects are elevated blood tyrosine levels, eye symptoms such as pain, redness and sensitivity to light, low platelet and white blood cell counts, skin rashes, and itching. These side effects are often related to poor dietary compliance or require monitoring adjustments. Most patients tolerate the medicine well when treatment is combined with careful dietary management and regular follow-up at a specialist centre.
The usual starting dose is 1 mg per kilogram of body weight per day, divided into two daily doses or given once daily after stabilisation. Swallow the capsules whole with water. If your child cannot swallow capsules, the capsule contents can be opened and mixed with a small amount of water, formula, or apple juice immediately before use. Always follow the exact dose prescribed by your metabolic specialist, and do not change the dose or stop the medicine without medical advice.
No. Nitisinone is a lifelong treatment, not a cure. When started early in infancy and combined with strict dietary management, it prevents most of the severe liver, kidney, and neurological complications of hereditary tyrosinemia type 1 and dramatically reduces the need for liver transplantation. However, patients still require lifelong therapy, dietary control, and regular surveillance, including screening for hepatocellular carcinoma.
Nitisinone should only be used during pregnancy if the potential benefit to the mother clearly outweighs potential risks to the fetus, since human pregnancy data are limited. At the same time, untreated tyrosinemia type 1 itself carries significant risks for both mother and baby. A woman planning pregnancy or who becomes pregnant while on nitisinone should be managed jointly by an obstetrician and a metabolic specialist with close monitoring of plasma tyrosine and phenylalanine levels.
Store Nitisinone Dipharma capsules below 25°C in the original container to protect them from moisture. Keep the bottle tightly closed. After first opening, use within the period specified on the packaging. Keep out of the sight and reach of children. Do not use the capsules after the expiry date printed on the bottle, and dispose of any unused medicine through a pharmacy rather than household waste.
References
- European Medicines Agency (EMA). Nitisinone Dipharma — Summary of Product Characteristics. Available at: ema.europa.eu/en/medicines/human/EPAR/nitisinone-dipharma. Accessed February 2026.
- European Medicines Agency (EMA). Orfadin (nitisinone) — European Public Assessment Report (reference product). Updated annual safety reports.
- U.S. Food and Drug Administration (FDA). Nitisinone — Prescribing Information. Updated 2025.
- Lindstedt S, Holme E, Lock EA, Hjalmarson O, Strandvik B. Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet. 1992;340(8823):813-817. doi:10.1016/0140-6736(92)92685-9
- Chinsky JM, Singh R, Ficicioglu C, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017;19(12):1380-1395. doi:10.1038/gim.2017.101
- de Laet C, Dionisi-Vici C, Leonard JV, et al. Recommendations for the management of tyrosinaemia type 1. Orphanet J Rare Dis. 2013;8:8. doi:10.1186/1750-1172-8-8
- Mayorandan S, Meyer U, Gokcay G, et al. Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice. Orphanet J Rare Dis. 2014;9:107. doi:10.1186/s13023-014-0107-7
- van Ginkel WG, Rodenburg IL, Harding CO, Hollak CEM, Heiner-Fokkema MR, van Spronsen FJ. Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1. Paediatr Drugs. 2019;21(6):413-426.
- World Health Organization (WHO). International Classification of Diseases, 11th Revision (ICD-11). Tyrosinemia type 1 classification and coding.
- British National Formulary (BNF). Nitisinone monograph. London: BMJ Group and Royal Pharmaceutical Society. Updated 2025.
About the Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialists in inherited metabolic disorders, paediatric hepatology, clinical genetics, and pharmacology. Our content follows the GRADE evidence framework and is based on peer-reviewed research, international clinical guidelines (EMA, FDA, SSIEM, Orphanet), and established medical standards.
Every article undergoes a rigorous multi-step review: initial research by medical writers, clinical accuracy verification by specialist physicians, editorial review for clarity and accessibility, and final approval by the Medical Review Board.
We prioritise Level 1A evidence from systematic reviews, registry studies, and international consensus guidelines for rare diseases. All medical claims are referenced to peer-reviewed sources. No commercial funding influences our content.
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