Deferiprone Lipomed
Iron chelating agent for the treatment of iron overload in thalassemia major
Quick facts about Deferiprone Lipomed
Key takeaways about Deferiprone Lipomed
- Mandatory weekly blood tests: Agranulocytosis is a rare but potentially fatal side effect, making weekly complete blood count monitoring essential throughout treatment
- Second-line therapy: Deferiprone Lipomed is used when deferoxamine (the standard first-line iron chelator) is inadequate or not tolerated by the patient
- Effective cardiac iron removal: Deferiprone has demonstrated particular efficacy in reducing iron deposits in the heart, which is the leading cause of death in thalassemia patients
- Strictly contraindicated in pregnancy: Animal studies have shown teratogenic effects; reliable contraception is mandatory for women of childbearing potential
- Urine discoloration is normal: Reddish-brown urine (chromaturia) is a common, harmless effect caused by the iron-deferiprone complex being excreted
What Is Deferiprone Lipomed and What Is It Used For?
Deferiprone Lipomed is an oral iron chelating medicine containing the active substance deferiprone. It is used to treat iron overload (hemosiderosis) in patients with thalassemia major who receive regular blood transfusions, when first-line chelation therapy with deferoxamine is inadequate or cannot be tolerated.
Thalassemia major is a hereditary blood disorder in which the body cannot produce enough functional hemoglobin. Patients with this condition require regular blood transfusions to survive, often every two to four weeks throughout their lives. While these transfusions are life-saving, each unit of transfused blood delivers approximately 200 to 250 milligrams of iron into the body. The human body has no natural mechanism for actively excreting large amounts of iron, so this iron accumulates progressively in vital organs.
Without treatment, this iron overload (also known as transfusional hemosiderosis) leads to severe and potentially fatal damage to the heart, liver, and endocrine glands. Cardiac iron overload remains the leading cause of death in patients with thalassemia major. Iron chelation therapy is therefore an essential component of thalassemia management, as critical as the transfusions themselves.
Deferiprone belongs to the chemical class of 3-hydroxypyridin-4-ones. It works by binding to ferric iron (Fe3+) in a 3:1 molar ratio, meaning three molecules of deferiprone bind to one iron atom. This creates a stable, water-soluble complex that is then excreted primarily through the kidneys in the urine. One of the distinctive clinical advantages of deferiprone is its particular efficacy in removing iron from the heart. Multiple clinical studies, including the landmark randomized controlled trial by Pennell et al. (2006), have demonstrated that deferiprone is more effective than deferoxamine at reducing cardiac iron concentration as measured by cardiac T2* magnetic resonance imaging (MRI).
Deferiprone Lipomed is available as 500 mg film-coated tablets and is typically prescribed by hematologists experienced in the management of thalassemia. It is classified as a second-line iron chelator, meaning it is used when the first-line agent deferoxamine (administered as subcutaneous or intravenous infusions) is either insufficiently effective at controlling iron levels or when patients cannot tolerate the demanding infusion regimen that deferoxamine requires.
How deferiprone compares to other iron chelators
Three iron chelating agents are currently available for the treatment of transfusional iron overload: deferoxamine (Desferal), deferiprone, and deferasirox (Exjade/Jadenu). Each has distinct properties regarding route of administration, efficacy profile, and side effect spectrum. Deferoxamine requires prolonged subcutaneous or intravenous infusions (typically 8–12 hours per day, 5–7 days per week), which significantly impacts quality of life. Both deferiprone and deferasirox are oral medications, offering greater convenience and improved treatment adherence.
Deferiprone's unique advantage lies in its superior ability to remove iron from the myocardium (heart muscle). The Thalassemia International Federation (TIF) and international clinical guidelines recognize this property, often recommending deferiprone (alone or in combination with deferoxamine) for patients with evidence of cardiac iron loading. Deferasirox, while also effective and convenient as a once-daily oral preparation, has a different side effect profile and may be preferred in certain clinical situations.
What Should You Know Before Taking Deferiprone Lipomed?
Before starting Deferiprone Lipomed, your doctor must check your blood count, liver function, and zinc levels. The medicine is contraindicated in pregnancy, during breastfeeding, and in patients with a history of agranulocytosis or recurrent neutropenia. Weekly blood monitoring is mandatory throughout treatment.
Contraindications
Deferiprone Lipomed must not be used in the following situations:
- Hypersensitivity to deferiprone or any of the excipients in the tablet formulation
- History of recurrent episodes of neutropenia (low neutrophil count, defined as absolute neutrophil count below 1.5 × 109/L)
- History of agranulocytosis (absolute neutrophil count below 0.5 × 109/L)
- Pregnancy – due to demonstrated teratogenic and embryotoxic effects in animal studies
- Breastfeeding – it is unknown whether deferiprone passes into breast milk
In addition, deferiprone should not be used in combination with other medicinal products known to cause neutropenia or agranulocytosis, such as clozapine, unless the benefits clearly outweigh the risks and no alternative therapy is available. Your prescribing physician will carefully evaluate these risks before initiating treatment.
Warnings and Precautions
Deferiprone can cause agranulocytosis, a severe and potentially fatal reduction in white blood cells (neutrophils). This condition occurs in approximately 1–2% of patients and can lead to life-threatening infections. A complete blood count including differential white cell count must be performed every week during treatment. If you develop fever, sore throat, mouth ulcers, or any signs of infection, contact your doctor immediately and have your blood count checked the same day.
Your doctor should discuss the following important precautions before you begin treatment:
- Blood monitoring: Weekly complete blood count (CBC) with differential is mandatory. If the neutrophil count falls below 1.5 × 109/L, treatment should be interrupted. If it falls below 0.5 × 109/L (agranulocytosis), treatment must be permanently discontinued.
- Infections: If you develop an infection during treatment, more frequent blood monitoring (daily) may be necessary. Treatment should be interrupted during active infections with neutropenia.
- Liver function: Regular monitoring of liver enzymes (ALT) is recommended, as elevated liver enzymes have been reported. Treatment should be discontinued if persistent increases in serum ALT occur.
- Zinc deficiency: Deferiprone may chelate zinc as well as iron. Serum zinc levels should be monitored, and zinc supplementation may be required.
- Renal function: Although deferiprone is primarily excreted through the kidneys, dose adjustment is generally not required in mild to moderate renal impairment. However, renal function should be monitored.
- HIV-positive patients: There is limited experience with deferiprone in HIV-positive patients, and additional caution is warranted.
Pregnancy and Breastfeeding
Deferiprone Lipomed is strictly contraindicated during pregnancy. Preclinical studies in animals (rats and rabbits) have demonstrated teratogenic effects (birth defects) and embryotoxic effects (harm to the developing embryo). There are no adequate data on the use of deferiprone in pregnant women, but given the animal findings, the risk to the unborn child is considered significant.
Women of childbearing potential must use effective contraception during treatment with Deferiprone Lipomed. A pregnancy test should be performed before starting treatment, and contraception must be used consistently throughout the treatment period. If a patient becomes pregnant while taking deferiprone, treatment must be discontinued immediately and the patient counseled regarding the potential risk to the fetus.
It is not known whether deferiprone or its metabolites are excreted in human breast milk. Because of the potential for serious adverse reactions in nursing infants, breastfeeding must be discontinued before initiating treatment with Deferiprone Lipomed. Women should not breastfeed while taking this medication.
Animal studies have not shown significant effects on male or female fertility at therapeutic doses. However, as with all iron chelators, maintaining appropriate iron balance is important for reproductive health. Patients planning to conceive should discuss timing of treatment with their hematologist.
How Does Deferiprone Lipomed Interact with Other Drugs?
Deferiprone Lipomed can interact with aluminum-containing antacids, vitamin C supplements, and other medications that may cause neutropenia. It should be taken at least 4 hours apart from antacids or mineral supplements to prevent reduced absorption.
Drug interactions are an important consideration when taking deferiprone. Because deferiprone works by binding to metal ions, any medication or supplement containing metals can potentially interfere with its absorption or efficacy. Additionally, because deferiprone carries a risk of neutropenia and agranulocytosis, combination with other drugs that suppress bone marrow function requires extreme caution.
Your prescribing physician and pharmacist should be aware of all medications you are taking, including over-the-counter products, vitamins, and herbal supplements. The following table summarizes the most clinically significant interactions:
| Interacting Drug | Type | Effect | Recommendation |
|---|---|---|---|
| Aluminum-containing antacids | Pharmacokinetic | Reduced deferiprone absorption due to chelation with aluminum ions in the gastrointestinal tract | Separate administration by at least 4 hours |
| Vitamin C (ascorbic acid) | Pharmacodynamic | May increase iron availability and potentially worsen iron toxicity; vitamin C mobilizes iron from tissue stores | Avoid high-dose vitamin C; if needed, limit to 100–200 mg/day under medical supervision |
| Deferoxamine | Pharmacodynamic | Additive iron chelation effect; combination may enhance iron removal, particularly from the heart | Combination use only under specialist supervision with enhanced monitoring |
| Clozapine and other drugs causing neutropenia | Pharmacodynamic | Additive risk of neutropenia and agranulocytosis; potentially life-threatening | Avoid combination; if unavoidable, intensified blood monitoring required |
| Iron and mineral supplements | Pharmacokinetic | Chelation in the gut reduces absorption of both deferiprone and the mineral supplement | Separate administration by at least 4 hours |
| UGT1A6 inhibitors (e.g., probenecid) | Pharmacokinetic | May reduce metabolism of deferiprone via glucuronidation, potentially increasing plasma levels | Monitor for increased side effects; dose adjustment may be needed |
Major Interactions
The most clinically significant interaction is with drugs that cause neutropenia or agranulocytosis. These include certain antipsychotics (particularly clozapine), some antirheumatic agents (such as methotrexate and gold salts), certain antibiotics (chloramphenicol, co-trimoxazole), antithyroid drugs (carbimazole, propylthiouracil), and some anticonvulsants. The concurrent use of these medications with deferiprone substantially increases the risk of a dangerous drop in white blood cells. Your doctor should carefully review all your medications before starting deferiprone and throughout treatment.
Minor Interactions
Some interactions are less clinically significant but should still be managed. Food can moderately reduce the absorption of deferiprone, but taking the medication with meals is often recommended to minimize gastrointestinal side effects such as nausea and abdominal discomfort. The slight reduction in absorption when taken with food is generally not clinically important. Dairy products and calcium-containing foods may slightly reduce absorption but do not typically require specific timing adjustments beyond general awareness.
What Is the Correct Dosage of Deferiprone Lipomed?
The standard dose of Deferiprone Lipomed is 25 mg/kg body weight, taken three times daily (total daily dose: 75 mg/kg). The maximum recommended daily dose is 100 mg/kg. Dosage should be individualized based on serum ferritin levels and response to treatment.
Dosing of Deferiprone Lipomed must be individualized by a hematologist experienced in the management of thalassemia and iron overload. The dose is calculated based on body weight and adjusted according to the patient's response, as measured by serum ferritin levels and, where available, liver and cardiac iron concentrations assessed by MRI.
| Patient Group | Recommended Dose | Maximum Dose | Notes |
|---|---|---|---|
| Adults (18+ years) | 25 mg/kg three times daily (75 mg/kg/day) | 33 mg/kg three times daily (100 mg/kg/day) | Individualize based on ferritin levels and clinical response |
| Adolescents (10–17 years) | 25 mg/kg three times daily (75 mg/kg/day) | 33 mg/kg three times daily (100 mg/kg/day) | Same as adult dosing; close monitoring of growth and zinc levels |
| Children (6–10 years) | 25 mg/kg three times daily (75 mg/kg/day) | 33 mg/kg three times daily (100 mg/kg/day) | Limited clinical experience; specialist supervision essential |
| Elderly (>65 years) | As per adult dosing | As per adult dosing | Limited data; monitor renal function and adjust if impaired |
| Renal impairment | No specific adjustment for mild–moderate | Use with caution | No data in severe renal impairment; not recommended |
Adults
The standard recommended dose for adults is 25 mg/kg body weight, taken three times daily, giving a total daily dose of 75 mg/kg. The tablets should be taken at approximately evenly spaced intervals throughout the day, ideally in the morning, at midday, and in the evening. For example, a patient weighing 70 kg would take approximately 1,750 mg three times daily, equating to 3–4 tablets of 500 mg per dose.
If the therapeutic response is inadequate (i.e., serum ferritin levels do not decrease sufficiently), the dose may be increased to a maximum of 33 mg/kg three times daily (100 mg/kg/day). Doses exceeding 100 mg/kg/day are not recommended due to insufficient safety data. The goal of therapy is to achieve and maintain serum ferritin concentrations between 500 and 1,000 micrograms per liter, though the specific target should be determined by the treating hematologist based on overall clinical assessment.
Children
The safety and efficacy of deferiprone in children below the age of 6 years have not been established, and its use in this age group is not recommended. For children aged 6 years and above, the same weight-based dosing as adults applies (25 mg/kg three times daily). However, particular attention should be paid to growth monitoring and zinc supplementation, as growing children may be more susceptible to the effects of zinc depletion.
Elderly
There is limited clinical experience with deferiprone in patients over 65 years of age. No specific dose adjustment is required based on age alone, but elderly patients may be more likely to have decreased renal function. Therefore, renal function should be assessed before starting treatment and monitored periodically. If renal impairment is detected, dose adjustment may be warranted.
Missed Dose
If you forget to take a dose of Deferiprone Lipomed, take it as soon as you remember, unless it is almost time for your next scheduled dose. In that case, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you frequently forget doses, discuss this with your healthcare provider, as inconsistent chelation therapy reduces its effectiveness and allows iron to continue accumulating in vital organs.
Overdose
Experience with acute overdose of deferiprone is limited. Symptoms of overdose may include nausea, vomiting, diarrhea, and abdominal pain. In severe cases, over-chelation may lead to zinc deficiency or other electrolyte disturbances. There is no specific antidote for deferiprone overdose. Treatment is supportive: gastric lavage may be considered if the ingestion is recent, and electrolytes (including zinc) should be monitored. If you suspect an overdose, contact a poison control center or seek immediate medical attention.
What Are the Side Effects of Deferiprone Lipomed?
The most common side effects of Deferiprone Lipomed include reddish-brown urine discoloration (chromaturia), nausea, abdominal pain, vomiting, and joint pain (arthralgia). The most serious side effect is agranulocytosis, occurring in approximately 1–2% of patients, which requires immediate medical attention.
Like all medicines, Deferiprone Lipomed can cause side effects, although not everybody gets them. It is important to be aware of both the common and serious side effects so you can recognize them early and seek medical attention when necessary. The following frequency categories are used to describe how often side effects occur:
Very Common (affects more than 1 in 10 patients)
- Chromaturia – reddish-brown discoloration of urine. This is harmless and results from excretion of the iron-deferiprone complex. It is not blood in the urine.
- Nausea – often mild and may improve with time or when taken with food
Common (affects 1 in 10 to 1 in 100 patients)
- Abdominal pain and discomfort – typically mild to moderate; may improve when tablets are taken with meals
- Vomiting – particularly during the first weeks of treatment
- Arthralgia – joint pain, especially in the knees and other large joints; may resolve spontaneously or require dose adjustment
- Elevated ALT (liver enzymes) – usually transient; requires monitoring
- Fatigue – tiredness and general malaise
- Increased appetite
- Headache
Uncommon (affects 1 in 100 to 1 in 1,000 patients)
- Neutropenia – low neutrophil count (1.0–1.5 × 109/L); treatment must be interrupted and blood counts monitored daily until recovery
- Zinc deficiency – due to chelation of zinc as well as iron; monitor zinc levels and supplement as needed
- Diarrhea
Rare (affects fewer than 1 in 1,000 patients)
- Agranulocytosis – absolute neutrophil count below 0.5 × 109/L; potentially life-threatening. Treatment must be permanently discontinued. Reported in approximately 1–2% in some studies, but classified as uncommon to rare in post-marketing surveillance.
- Severe hepatotoxicity – significant liver injury with persistently elevated liver enzymes
- Cerebellar syndrome – neurological effects including ataxia (loss of coordination) and gait disturbance; reported very rarely
- Skin rash and allergic reactions
Contact your doctor or go to the nearest emergency department immediately if you experience any of the following symptoms, as they may indicate agranulocytosis or a serious infection:
- Fever (temperature above 38°C / 100.4°F)
- Sore throat or mouth ulcers
- Flu-like symptoms that worsen rapidly
- Signs of any infection (painful urination, persistent cough, skin infections)
- Unusual bruising or bleeding
- Severe abdominal pain with jaundice (yellowing of skin or eyes)
Many of the gastrointestinal side effects (nausea, vomiting, abdominal pain) tend to be most pronounced during the initial weeks of treatment and often diminish as the body adjusts to the medication. Taking the tablets with meals can help reduce these effects. Joint pain (arthralgia) may occur at any time during treatment and can range from mild discomfort to more significant pain that may require dose reduction or temporary interruption.
If you experience any side effects, including those not listed here, inform your doctor or pharmacist. You can also report side effects directly to your national adverse drug reaction reporting system (such as the Yellow Card Scheme in the UK, MedWatch in the US, or EudraVigilance in the EU), which helps to provide more information on the safety of this medicine.
How Should You Store Deferiprone Lipomed?
Store Deferiprone Lipomed at room temperature below 25°C (77°F). Keep the tablets in their original packaging to protect from moisture. Do not use after the expiry date printed on the packaging.
Proper storage of Deferiprone Lipomed is essential to ensure the medication remains effective and safe throughout its shelf life. Follow these storage guidelines carefully:
- Temperature: Store below 25°C (77°F). Do not freeze. Do not store in direct sunlight or near sources of heat.
- Packaging: Keep the tablets in the original blister packaging until you are ready to take them. This protects the tablets from moisture and light.
- Moisture: Do not store in the bathroom or other humid environments. Do not transfer tablets to a damp pill organizer for extended periods.
- Expiry date: Do not use Deferiprone Lipomed after the expiry date stated on the carton and blister pack. The expiry date refers to the last day of that month.
- Children: Keep out of the sight and reach of children. Store in a secure location.
- Disposal: Do not dispose of unused or expired medicines in household waste or down the drain. Return them to your pharmacy for safe disposal according to local regulations.
If you notice any changes in the appearance of the tablets, such as discoloration, crumbling, or an unusual odor, do not take them. Contact your pharmacist for advice on whether the medication is still suitable for use.
What Does Deferiprone Lipomed Contain?
Each film-coated tablet of Deferiprone Lipomed contains 500 mg of the active substance deferiprone. The tablets also contain inactive ingredients (excipients) used in manufacturing the tablet formulation.
Understanding what your medication contains can help you identify potential allergens or substances you may be sensitive to. The composition of Deferiprone Lipomed 500 mg film-coated tablets is as follows:
Active substance
Each film-coated tablet contains 500 mg deferiprone (also known by its chemical name 3-hydroxy-1,2-dimethylpyridin-4(1H)-one). Deferiprone has a molecular weight of 139.15 g/mol and appears as a white to slightly yellowish crystalline powder. It is freely soluble in water, which contributes to its excellent oral bioavailability of approximately 75%.
Inactive ingredients (excipients)
The tablet core and film coating contain the following excipients, which serve various functions in the formulation:
- Microcrystalline cellulose – used as a filler and binder to give the tablet its structure
- Croscarmellose sodium – a disintegrant that helps the tablet break apart in the gastrointestinal tract for proper absorption
- Magnesium stearate – a lubricant used in the tableting process to prevent sticking to the manufacturing equipment
- Colloidal anhydrous silica – a flow agent that ensures uniform tablet weight during production
- Hypromellose (HPMC) – used in the film coating to provide a smooth, protective outer layer
- Titanium dioxide (E171) – a white pigment used in the film coating
- Macrogol (polyethylene glycol) – a plasticizer used in the film coating to ensure flexibility and smooth appearance
Patients with known allergies or intolerances to any of these excipients should inform their healthcare provider before starting treatment. The tablets do not contain lactose, gluten, or sucrose.
Deferiprone Lipomed 500 mg film-coated tablets are white to off-white, capsule-shaped tablets. They are scored on one side, allowing the tablet to be divided into two equal halves if a lower dose is required.
Frequently Asked Questions About Deferiprone Lipomed
Deferiprone Lipomed is used to treat iron overload (transfusional hemosiderosis) in patients with thalassemia major who receive regular blood transfusions. It is specifically indicated when first-line chelation therapy with deferoxamine is either inadequate at controlling iron levels or when patients cannot tolerate deferoxamine's demanding infusion regimen. It works by binding to excess iron in the body and helping to remove it through the urine.
You must have a complete blood count (including white blood cell count and neutrophil differential) performed every week during treatment with Deferiprone Lipomed. This weekly monitoring is non-negotiable because of the risk of agranulocytosis, a potentially life-threatening reduction in white blood cells. If you develop any signs of infection such as fever or sore throat, your blood should be checked on the same day. More frequent monitoring (daily) may be required during episodes of neutropenia or infection.
Reddish-brown discoloration of urine (called chromaturia) is a very common and completely harmless side effect. It occurs because the iron-deferiprone complex formed when the drug chelates iron is excreted through the kidneys, and this complex has a characteristic reddish-brown color. This is not blood in the urine and does not indicate any kidney damage or other problem. It simply shows that the medication is successfully removing iron from your body.
No. Deferiprone Lipomed is strictly contraindicated during pregnancy because animal studies have shown it causes birth defects (teratogenic effects) and harm to the developing embryo (embryotoxic effects). Women of childbearing potential must use effective contraception during treatment. A pregnancy test should be performed before starting treatment, and if pregnancy occurs during treatment, the medication must be stopped immediately and the patient should consult their doctor about potential risks to the fetus.
Yes, in certain clinical situations. Deferiprone is sometimes used in combination with deferoxamine (Desferal) under specialist supervision, particularly for patients with severe cardiac iron overload. Clinical studies have shown that this combination can be more effective at reducing cardiac iron than either agent alone. However, combination therapy requires careful monitoring as it may increase the risk of side effects, including excessive iron depletion. Your hematologist will determine whether combination therapy is appropriate based on your individual iron burden, cardiac function, and response to monotherapy.
If you forget to take a dose, take it as soon as you remember unless it is nearly time for your next dose. In that case, skip the missed dose and take the next dose at the usual time. Never take a double dose to make up for one you missed. Consistent dosing is important for effective iron chelation, so if you frequently forget doses, speak with your doctor about strategies to improve adherence, such as setting alarms or linking doses to daily routines like mealtimes.
References and Sources
This article is based on the following peer-reviewed sources and international guidelines. All medical claims are supported by Level 1A evidence (systematic reviews and meta-analyses of randomized controlled trials) or established clinical guidelines from major medical organizations.
- European Medicines Agency (EMA). Ferriprox (deferiprone) – Summary of Product Characteristics. EMA/CHMP Assessment Report. Last updated 2024.
- Pennell DJ, Berdoukas V, Karagiorga M, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. The Lancet. 2006;368(9546):1463–1471. DOI: 10.1016/S0140-6736(06)69481-6
- Tanner MA, Galanello R, Dessi C, et al. A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation. 2007;115(14):1876–1884.
- World Health Organization. WHO Model List of Essential Medicines. 23rd list, 2023. Geneva: WHO.
- Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, eds. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 4th ed. Thalassemia International Federation; 2021.
- British National Formulary (BNF). Deferiprone. National Institute for Health and Care Excellence (NICE). Accessed 2025.
- Kontoghiorghes GJ, Neocleous K, Kolnagou A. Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine. Drug Safety. 2003;26(8):553–584.
- Fisher SA, Brunskill SJ, Doree C, et al. Oral deferiprone for iron chelation in people with thalassaemia. Cochrane Database of Systematic Reviews. 2013;(8):CD004839. DOI: 10.1002/14651858.CD004839.pub2
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, consisting of licensed physicians with expertise in hematology and clinical pharmacology. Our team follows the GRADE evidence framework and adheres to international guidelines from the WHO, EMA, and Thalassemia International Federation.
Medical Writing
Content created by specialists in hematology, following peer-reviewed literature and international clinical guidelines. All medical claims are verified against primary sources.
Medical Review
Independently reviewed by the iMedic Medical Review Board. Fact-checked against EMA assessment reports, WHO essential medicines list, and current BNF guidelines.
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