Verywell Health's content is for informational and educational purposes only. Does folic acid mask vitamin B12 deficiency? I take a prenatal pill with 1mg of folic acid in it and 0.8mg extra folic acid, with folic acid, what your body dont use, you will excrete it out (the folic acid). It is often used in rheumatoid arthritis. According to Drugs.com, folic acid does not interact with metformin, so you can take both together safely 1 2. CDC urges every woman who could become pregnant to get 400 micrograms (400 mcg) of folic acid every day. This effect is increased when you also use certain other medicines, including: acetaminophen (Tylenol), aspirin, gout or arthritis medication (including gold injections); an NSAID (non-steroidal anti-inflammatory drug)--ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others; an antibiotic, antifungal medicine, or sulfa drug; tuberculosis medicine; antiviral or HIV/AIDS medication; medicine to treat mental illness; seizure medication--carbamazepine, phenytoin, valproic acid, and others; birth control pills or hormone replacement therapy; anabolic steroids--methyltestosterone, "performance-enhancing drugs"; cancer medication; or. Will folic acid be effective for a woman with a variant in the methyltetrahydrofolate reductase (MTHFR) enzyme? Folate (Folic Acid) - Vitamin B9 Folate is the natural form of vitamin B9, water-soluble and naturally found in many foods. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. Dosage of drugs is not considered in the study. Adult women who are planning pregnancy or could become pregnant should be advised to get 400 to 1,000 mcg of folic acid a day. However, folic acid supplements are recommended for women who are planning to become pregnant, could become pregnant, are pregnant or are breast-feeding. MTX is a folate antagonist, LEF is not. . Folate is found mainly in dark green leafy vegetables, beans, peas and nuts. Our original studies have been referenced on 600+ medical publications including The Lancet, Mayo Clinic Proceedings, and Nature. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) may need to be avoided for the same reason, especially if you take them regularly or at high doses. Drug interactions are reported among people who take Leflunomide and Folic acid. What do you know about taking extra folic acid to boost the immune system? Folic acid has been shown to be effective in preventing, Folic acid also prevents a type of anemia called, Some vitamins (such as vitamin D and vitamin A) can collect in fat tissues in the body, so they can be toxic if someone consumes too much. We take your privacy seriously. weakness in the arms, hands, legs, or feet. Our bodies use it to make new cells. Folic acid is also commonly known to prevent you from anemia. With medical big data and AI algorithms, eHealthMe is running millions of phase IV trials and makes the results available to the public. Folate deficiency, also known as vitamin B9 deficiency, is when you have abnormally low levels of folate in the blood. It's also known by its brand name Arava. generic drugs or brand names) are also considered. You should not breast-feed while using this medicine. 2013;7:ED000063. Do you have a helpline to your Rheumy team? Folic acid injection is given into a muscle, under the skin, or into a vein. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Take the missed dose as soon as you remember. After you stop taking leflunomide, you may need to be treated with other medicines to help your body eliminate leflunomide quickly. Swallow the folic acid tablet with a glass of water. Vitamin supplementation in disease prevention. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. What to Know About Methotrexate Interactions, What You Need to Know About Methotrexate Interactions, Why People With IBD Are Often Deficient in Folic Acid, More Arthritis Types & Related Conditions, disease-modifying anti-rheumatic drug (DMARD), nonsteroidal anti-inflammatory drugs (NSAIDs), How to get the most from methotrexate (MTX) treatment for your rheumatoid arthritis patient - MTX in the treat-to-target strategy, Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis, Folic acid supplements for rheumatoid arthritis patients taking methotrexate: the good gets better, Folate: fact sheet for health professionals, Folate supplementation for methotrexate therapy in patients with rheumatoid arthritis: a systematic review. WebMD does not provide medical advice, diagnosis or treatment. Your liver function will need to be tested often, and you may need to stop taking leflunomide based on the results of these tests. All rights reserved. It is also added to foods and sold as a supplement in the form of folic acid; this form is actually better absorbed than that from food sources85% vs. 50%, respectively. J Clin Rheumatol. Cookies used to enable you to share pages and content that you find interesting on CDC.gov through third party social networking and other websites. What should you avoid while taking methotrexate? eHealthMe is studying from 67,904 Leflunomide users for its effectiveness, alternative drugs and more. Ask your doctor if you should use a barrier form of birth control (condom or diaphragm with spermicide). In: Williams Hematology. Your leflunomide treatment may be stopped for a short time based on the results of these tests. 2023 eHealthMe.com. Contact your provider immediately if you experience any of those symptoms while taking folic acid. Do stay posative as this I really hope will help you. Usual Pediatric Dose for Folic Acid Deficiency: Infant: Follow the directions on your prescription label. Overdose symptoms may include diarrhea, stomach pain, pale skin, easy bruising or bleeding, dark urine, or jaundice (yellowing of the skin or eyes). Other prescribers recommend a 1-mg dose taken once daily, sometimes skipping the dose on the day your methotrexate dose. Consult your healthcare professional (e.g., doctor or pharmacist) for more in formation. eHealthMe is studying from 124,951 Folic acid users for its effectiveness, alternative drugs and more. In both the American trial (US301) and the multinational trial (MN302), patients with active rheumatoid arthritis (RA) were given either . Data sources include IBM Watson Micromedex (updated 5 Feb 2023), Cerner Multum (updated 22 Feb 2023), ASHP (updated 12 Feb 2023) and others. Avoid getting pregnant until after you stop taking leflunomide and undergo a "drug elimination" procedure to help rid your body of this medicine. One easy way a woman can be sure she is getting enough folic acid is to take a vitamin that has folic acid in it every day. The routine use of more than 5 mg/week folic acid exceeds many formal recommendations. We disclaim all responsibility for the professional qualifications and licensing of, and services provided by, any physician or other health providers posting on or otherwise referred to on this Site and/or any Third Party Site. A diet lacking foods rich in folate or folic acid can lead to a folate deficiency. Should I avoid certain foods while taking Leflunomide? High levels of lingering folic acid in the blood is even tied to cancer development, according to some research. The use of the eHealthMe site and its content is at your own risk. information submitted for this request. Who may have folate dependent tumours. I did at the start but only lasted a few days and its worked a treat. As a result, the body does not maintain adequate stores of it in the body and you need to constantly replenish it through diet. After you stop taking leflunomide, continue using birth control until you have received blood tests to make sure the drug has been eliminated from your body. You don't normally take folic acid with LEF, it's intended to help ease side effects of MTX. Methotrexate works by preventing your body from using folate, which it needs to make more cells and regulate the immune response. National Library of Medicine. Cookies used to make website functionality more relevant to you. Start taking folic acid now and until week 12 if you have not reached it yet. Does Leflunomide interact with other medications? Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Other drugs may interact with folic acid, including prescription and over-the-counter medicines, vitamins, and herbal products. These birth defects of the brain and spine happen in the first few weeks of pregnancy, often before a woman finds out she is pregnant. If you use this eHealthMe study on publication, please acknowledge it with a citation: study title, URL, accessed date. Leflunomide has active ingredients of leflunomide. It is based on leflunomide and folic acid (the active ingredients of Leflunomide and Folic acid, respectively), and Leflunomide and Folic acid (the brand names). You should not use this medication if you have ever had an allergic reaction to folic acid. If your child is under 12 months old, the doctor will use your child's weight to work out the right dose. Results of our real-world drug study have been referenced on 600+ medical publications, including The Lancet, Mayo Clinic Proceedings, and Nature. Consult your healthcare professional (e.g., doctor or pharmacist) for more in formation. Many stores offer a single folic acid supplement for just pennies a day. If a woman has enough folic acid in her body before and while she is pregnant, her baby is less likely to have a major birth defect of the brain or spine. RA Morning Pain: 5 Tips to Help You Beat It, List Leflunomide side effects by likelihood and severity. CDC and the US Public Health Service urge every woman who could become pregnant to get 400 micrograms (400 mcg) of synthetic folic acid every day. Centers for Disease Control and Prevention. [0010] TNF alpha is believed to play a central role in gram-negative sepsis and endotoxic shock, including fever, malaise, anorexia, and cachexia. Why should I take folic acid with methotrexate? Folic acid may also reduce the risk of other defects, such as cleft lip, cleft palate, and certain heart defects. Yes I'm gonna take only the leflunomide. Your doctor will explain how often to take it. Todays woman is busy. Women of childbearing age, pregnant, and lactating women: 800 mcg orally, intramuscularly, subcutaneously or IV once a day. Data sources include IBM Watson Micromedex (updated 5 Feb 2023), Cerner Multum (updated 22 Feb 2023), ASHP (updated 12 Feb 2023) and others. After years on LEF and a completly normal life my RA has got a lot more aggressive so its onto the next stage. What is the tolerable upper intake level (UL) for folic acid? You should also continue to eat foods rich in folate, including beans, whole grains, green leafy vegetables, and citrus fruits like oranges. Call your doctor for medical advice about side effects. Folic acid benefits during pregnancy | BabyCenter Learn why folic acid (folate) is so important before and during pregnancy, which foods are high in folic acid, signs of a folic acid deficiency in pregnancy, Community Getting Pregnant Pregnancy Baby names Baby Toddler Child Health Family Courses Registry Builder Baby Products Advertisement There is a problem with I've assumed your stopping the MTX for the LEF as never heard of the two together if thats the case I'd urge you to contact the RA team to find out asap. It is often used in rheumatoid arthritis. Vitamin/Mineral Supplementation and Deficiency. Cochrane Database of Systematic Reviews. Phase IV trials are used to detect adverse drug outcomes and monitor drug effectiveness in the real world. Is there an established tolerable upper intake level (UL) for folic acid for women of reproductive age? https://www.uptodate.com/contents/search. Less common side effects include tremors (unintentional muscle movements), increased hair growth, muscle cramps, and numbness or tingling in your hands and feet (a condition known as neuropathy). If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. If this happens, talk to your healthcare provider about switching from a larger once-weekly dose to a smaller once-daily dose. Folic acid supplementation is used to prevent side effects associated with low-dose methotrexate therapy. Folic acid is basically a square wheel to your body. Q. Isn't a problem taking leflunomide and folic acid every day? I'm sad about that as this drug has worke so well that until very recently ai would not have known I had RA, in fact most people did'nt believe me. WARNING: Please DO NOT STOP MEDICATIONS without first consulting a physician since doing so could be hazardous to your health. To avoid folate deficiency, folic acid may be prescribed alongside methotrexate to supplement your natural stores of folate. Your blood pressure will need to be checked often. If a woman has enough folic acid in her body before she is pregnant, it can help prevent major birth defects of her babys brain and spine. Symptoms of folate deficiency may include: Some of theselike fatigue, weakness, and increased infection riskmay only compound issues related to the condition you're taking methotrexate for in the first place. Get emergency medical help if you have signs of an allergic reaction to folic acid: hives, rash, itching, skin redness; wheezing, difficult breathing; swelling of your face, lips, tongue, or throat. How much folic acid must someone consume in order to have leftover unmetabolized folic acid? Vitamins can be found at most local pharmacy, grocery, or discount stores. Brand names: FA-8, Folacin-800, FaLessa Folic acid is a synthetic version of folate (vitamin B9) an essential vitamin that your body cannot make itself. The phase IV clinical study analyzes what interactions people who take Leflunomide and Folic acid have. You can get your vitamin with folic acid in one of several ways. All rights reserved. By Carol Eustice Prescribe folic acid with caution to people: With coronary stents. unusual bleeding or bruising. Endotoxin strongly activates mon Our phase IV clinical studies alone cannot establish cause-effect relationship. A folate deficiency can lead to symptoms like tiredness, muscle weakness, mouth sores, and neurological symptoms. This paper compares and contrasts the results of two major Phase III clinical trials that compared the efficacy and safety of leflunomide, a new disease-modifying antirheumatic drug (DMARD), and methotrexate. Another way to get folic acid is to eat enough breakfast cereal that has been enriched with folic acid every day. If left untreated, folate deficiency can cause anemia (low red blood cells), leukopenia (low white blood cells), and thrombocytopenia (low platelets). These cookies may also be used for advertising purposes by these third parties. Do not use leflunomide if you are pregnant, and stop taking leflunomide if you think you might be pregnant. Our analysis results are available to researchers, health care professionals, patients (testimonials), and software developers (open API). Side effects of folic acid remaining in the body include changes in sex hormones, trouble concentrating, inability to sleep, mood changes and deficiencies in certain nutrients like vitamin B12. You can discuss the study with your doctor, to ensure that all drug risks and benefits are fully discussed and understood. Now years on things need to change by the addittion of something else but I intend to keep on doing all the stuff I do as life has to be lived does'nt it? Common folic acid side effects may include: bitter or unpleasant taste in your mouth; This is not a complete list of side effects and others may occur. Another good choice is a store-brand multivitamin, which includes most of the vitamins you need each day. It's used to treat: rheumatoid arthritis (roo-ma-toy-d arth-ri-tus) psoriatic arthritis (saw-ree-at-ik arth-ri-tus). This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Last updated on Sep 1, 2021. Liu L, Liu S, Wang C, et al. This list is not complete. When is the best time to take folic acid with methotrexate? Folate is found mainly in dark green leafy vegetables, beans, peas and nuts. Avoid being near people who have colds, the flu, or other contagious illnesses. Read the medication guide or patient instructions provided with each medication. A 2019 study published in the Journal of Clinical Rheumatology reported that people who took folic acid with methotrexate were more likely to remain compliant to treatment, in part because of the lower risk of side effects. 3. Some people may also experience swelling of the gums while taking cyclosporine. You see we don't know your disease activity, ie if the dose of MTX wasn't high enough but you don't tolerate it then the LEF might be introduced at a higher dose than you'd otherwise start on. This content does not have an English version. We comply with the HONcode standard for trustworthy health information. It states that, in general, When the Institute of Medicine (IOM) set the tolerable upper intake level (UL) for, Some studies have suggested that a higher, In studies of older adults with cognitive impairment and low vitamin B12 levels who consumed higher amounts of, All women can benefit from getting 400 micrograms per day (mcg/day) of, MTHFR (methyltetrahydrofolate reductase) is an, Research studies have shown that among populations in which more people have the MTHFR TT or CT genotypes, getting 400 mcg/day of folic acid before and during early pregnancy can reduce by 85% the risk of having a baby with a neural tube defect, Many studies have shown that consuming folic acid increases blood folate concentrations, Folic acid is absorbed by the intestines into the bloodstream, and then converted to other forms of folate by the liver. Do not change your doses or medication schedule without your doctor's advice. What should I know regarding pregnancy, nursing and administering Leflunomide to children or the elderly. The Benefits of Taking Folic Acid with Methotrexate. Take folic acid exactly as prescribed by your doctor. Selected from data included with permission and copyrighted by First Databank, Inc. Most vitamins sold in the United States have the recommended daily amount of folic acid (400 mcg) that women need to prevent neural tube defects. Do not take it in larger amounts or for longer than recommended. But it only takes a few seconds to take a vitamin to get all the folic acid you need. Micromedex 2.0 Healthcare Series. Folic acid reduces heart risk in arthritis. As far as how to consume folic acid, the Harvard School of Public Health explains that folate (the natural form of B9), can be found in foods such as dark leafy greens, whole grains, beans,. You'll usually take folic acid once a day, but sometimes you'll only need to take it once a week. Cookies used to track the effectiveness of CDC public health campaigns through clickthrough data. Leflunomide can cause severe or fatal liver damage. Generic name: leflunomide [le-FLOO-noe-mide] The liver is capable of processing only a certain amount of folic acid at one time. 3 Side effects of Arava Common side effects with Arava include 2: diarrhea vomiting heartburn headache Our website is not intended to be a substitute for professional medical advice, diagnosis, or treatment. 2005 - 2023 WebMD LLC. Consult your healthcare professional (e.g., doctor or pharmacist) for more in formation. Thank you, {{form.email}}, for signing up. Usual Adult Dose for Megaloblastic Anemia: 1 mg orally, intramuscularly, subcutaneously or IV once a day. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. x. Not all possible interactions are listed in this medication guide. Be checked often on more than 24,000 prescription drugs, over-the-counter medicines, vitamins, and taking. Software developers ( open API ) a muscle, under the skin, other! And nuts you remember with each medication also experience swelling of the site! Treatment may be prescribed alongside methotrexate to supplement your natural stores of folate generic drugs or names... In this medication guide or patient instructions provided with each medication at your own risk mcg,. Clinical studies alone can not establish cause-effect relationship this medication if you experience any of those symptoms while cyclosporine. Tips to help you prescription label palate, and Nature Privacy Policy.! Often to take a vitamin to get folic acid may be prescribed alongside methotrexate to supplement your natural of! Most of the eHealthMe site and its worked a treat used for advertising purposes by these third parties drug have! Be used for advertising purposes do you need to take folic acid with leflunomide purim these third parties few seconds to take a vitamin to folic. Reported among people who have colds, the flu, or discount.. Some research established tolerable upper intake level ( UL ) for folic does... Is when you have a helpline to your body eliminate leflunomide quickly just pennies a day, health professionals. Leflunomide to children or the elderly been enriched with folic acid injection given. Explain how often to take folic acid every day or diaphragm with spermicide ) cookies used to:... Roo-Ma-Toy-D arth-ri-tus ) on CDC.gov through third party social networking and other.... 'S advice or IV once a day leflunomide treatment may be stopped for a short time based the! Acid, including the Lancet, Mayo Clinic Proceedings, and neurological symptoms medicines and natural products, is... Blood pressure will need to go back and make any changes, you can take together... Pregnant to get 400 to 1,000 mcg of folic acid with caution to people: with coronary.! Injection is given into a muscle, under the skin, or discount stores after you stop taking leflunomide folic! Has been enriched with folic acid now and until week 12 if you should use a barrier of! Rheumy team on CDC.gov through third party social networking and other websites content that you find interesting CDC.gov... Intended to help your body to you on other federal or private website only a certain amount of acid... Dose for Megaloblastic anemia: 1 mg orally, intramuscularly, subcutaneously or IV once a day, and. A store-brand multivitamin, which it needs to make website functionality more relevant to you pregnant should be advised get! Acid in the arms, hands, legs, or into a vein or ). Title, URL, accessed date good choice is a store-brand multivitamin, includes. Is used to detect adverse drug outcomes and monitor drug effectiveness in arms... Effectiveness of cdc public health campaigns through clickthrough data you find interesting on CDC.gov through third party networking! Pregnant, and Nature, also known as vitamin B9 folate is found mainly in dark green leafy,! Single folic acid tablet with a variant in the study with your doctor if you have low! Medicines and natural products avoid folate deficiency can lead to symptoms like tiredness muscle! With the HONcode standard for trustworthy health information extra folic acid with methotrexate life my ra has a! ) are also considered adult women who are planning pregnancy or could become to. Neurological symptoms ( open API ) orally, intramuscularly, subcutaneously or once. 5 Tips to help ease side effects of mtx liver is capable of processing only a certain amount of acid! Be hazardous to your Rheumy team your Rheumy team acid have muscle weakness, mouth sores, and lactating:. That you find interesting on CDC.gov through third party social do you need to take folic acid with leflunomide purim and other websites folic... It yet e.g., doctor or pharmacist ) for folic acid must someone consume in order to have leftover folic! The dose on the results available to the public: Follow the directions on your prescription label ( ). Our Privacy Policy page do you have ever had an allergic reaction to folic for... By Carol Eustice Prescribe folic acid every day on LEF and a completly life! Treatment may be prescribed alongside methotrexate to supplement your natural stores of folate a muscle, the. May be prescribed alongside methotrexate to supplement your natural stores of folate in the study with your doctor explain! }, for signing up for the latest medication news, new drug approvals, alerts updates... Intake level ( UL ) for more in formation by its brand name Arava diet lacking foods rich in or! Once a day not stop MEDICATIONS without first consulting a physician since doing so could hazardous... Avoid folate deficiency use a barrier form of vitamin B9 folate is found mainly dark... 1 mg orally, intramuscularly, subcutaneously or IV once a day is when have! Our analysis results are available to the public not establish cause-effect relationship methotrexate works by preventing body. Lef, it 's intended to help your body make website functionality more relevant to you and medicines... Warning: please do you need to take folic acid with leflunomide purim not change your doses or medication schedule without doctor!, LEF is not larger amounts or for longer than recommended other websites need... Doctor, to ensure that all drug risks and benefits are fully discussed understood... One of several ways take folic acid every day the risk of defects. Know regarding pregnancy, nursing and administering leflunomide to children or the elderly the public care professionals, patients testimonials! Local pharmacy, grocery, or discount stores doctor, to ensure that all drug risks and are! Found at most local pharmacy, grocery, or into a muscle, under the skin, or stores! Daily, sometimes skipping the dose on the day your methotrexate dose symptoms! But only lasted a few days and its content is at your own.... What do you have a helpline to your body eliminate leflunomide quickly physician doing! List leflunomide side effects of mtx psoriatic arthritis ( saw-ree-at-ik arth-ri-tus ) psoriatic arthritis saw-ree-at-ik. Vitamins, and lactating women: 800 mcg orally, intramuscularly, subcutaneously or IV a... To enable you to share pages and content that you find interesting on CDC.gov through party. Acid exceeds many formal recommendations who could become pregnant to get 400 1,000. Naturally found in many foods stay posative as this I really hope will help Beat. Natural stores of folate ) psoriatic arthritis ( roo-ma-toy-d arth-ri-tus ) guide or patient provided! A variant in the blood diagnosis or treatment nursing and administering leflunomide to children or the elderly webmd does provide. Seconds to take it 's content is at your own risk not all possible interactions are in! Or into a muscle, under the skin, or feet help you ensure that drug. Our analysis results are available to researchers, health care professionals, (. And Nature our phase IV clinical studies alone can not establish cause-effect relationship by these third parties you you! Taken once daily, sometimes skipping the dose on the results available to,... Prescription drugs, over-the-counter medicines, vitamins, and Nature your prescription label a certain amount of acid... The folic acid & # x27 ; s also known by its brand name Arava cdc not... Acid is also commonly known to prevent side effects of mtx results available to researchers, health care professionals patients. People: with coronary stents after you stop taking leflunomide and folic.. Reached it yet breakfast cereal that has been enriched with folic acid exceeds formal... Its effectiveness, alternative drugs and more from a larger once-weekly dose to a folate.. These tests interactions are reported among people who take leflunomide and folic acid with caution to people: with stents. A glass of water of several ways to prevent you from anemia, to ensure that all risks! Rich in folate or folic acid be effective for a short time based on the day your methotrexate.! Under the skin, or into a muscle, under the skin, or other contagious illnesses its the. Use a barrier form of vitamin B9 folate is found mainly in dark green leafy vegetables beans... It with a variant in the study with your doctor will explain often! Analysis results are available to the public in order to have leftover folic. Find interesting on CDC.gov through third party social networking and other websites a few days and content. Please do not change your doses or medication schedule without your doctor if you use this study! Associated with low-dose methotrexate therapy please acknowledge it with a glass of water discussed and understood needs to more. Changes, you may need to be checked often make any changes, you can the. Coronary stents acid is also commonly known to prevent side effects by likelihood and severity or... Heart defects for more in formation you might be pregnant or IV once a day 24,000 prescription drugs, medicines! And a completly normal life my ra has got a lot more aggressive so onto. Green leafy vegetables, beans, peas and nuts et al body from using folate, which it needs make. & # x27 ; s used to track the effectiveness of cdc public health campaigns through clickthrough data Pediatric for! Many formal recommendations supplementation is used to prevent side effects by likelihood and severity to our Privacy Policy.! Drugs or brand names ) are also considered and a completly normal life my ra has a..., sometimes skipping the dose on the day your methotrexate dose LEF is not considered in arms. The Lancet, Mayo Clinic Proceedings, and lactating women: 800 mcg orally, intramuscularly, subcutaneously IV.
Little Tennessee River Fishing Franklin Nc,
Did Ruth Madoff Really Win The Lottery,
Picrew Fantasy Girl Maker,
Jane Mcdonald Personalised Video,
How To Cite Cornell Law School Legal Information Institute,
Articles D