Drug Detail:Dupixent (Dupilumab [ doo-pil-us-mab ])
Drug Class: Interleukin inhibitors
1. How it works
- Dupixent is a brand (trade) name for dupilumab which may be used to reduce inflammation associated with asthma, eczema, and some other conditions.
- Dupixent (dupilumab) blocks the inflammatory response by binding to the interleukin-4Rα subunit which is shared by the interleukin-4 (IL-4) and IL-13 receptor complexes. Interleukins are naturally occurring cytokines. Cytokines are substances released by cells of the immune system that influence other cells. Multiple cell types in the immune system express IL-4Rα, such as mast cells, eosinophils, macrophages, lymphocytes, epithelial cells, and goblet cells. These release substances such as histamine, eicosanoids, cytokines, etc, that are involved in inflammation. Blocking IL-4Rα with Dupixent inhibits the IL-4 and IL-13 induced inflammatory response in eczema, nasal polyps, and eosinophilic esophagitis. The exact mechanism of Dupixent in asthma is not well defined.
- Dupixent belongs to the class of medicines known as interleukin inhibitors. It may also be called a human monoclonal antibody or a biologic.
2. Upsides
- May be used to treat moderate-to-severe eczema (atopic dermatitis) in adults and children aged 6 months and older when other topical therapies are not effective or advisable. May be used with or without topical corticosteroids.
- May also be used for moderate-to-severe eosinophilic asthma (this is asthma associated with high levels of white blood cells known as eosinophils) or oral corticosteroid-dependent asthma as an add-on maintenance treatment in adults and children aged 6 years of age and older. Dupixent does NOT treat an asthma attack.
- Can be used in addition to other treatments for chronic rhinosinusitis associated with nasal polyps in adults and eosinophilic esophagitis in adults and children aged 12 years and older, who weigh at least 40 kg.
- Is the first treatment (and currently the only) treatment approved to treat Prurigo Nodularis, a chronic, debilitating skin disease that has a significant impact on a person's quality of life.
- Steroid-free.
- Administered by subcutaneous injection (under the skin).
- Available as a pre-filled syringe or pre-filled pen. The pre-filled pen is only for use in patients 12 years of age and older. The pre-filled pen contains a 300 mg dose. The pre-filled syringe comes in doses of 200 mg or 300 mg.
- People prescribed Dupixent can be taught how to self-administer the injection.
- Usually given every two weeks (every other week). In children weighing 15kg to less than 30kg, it is recommended Dupixent be given every four weeks.
- Not considered an immunosuppressant because it does not suppress the immune system.
- Not a cure for eczema but it does reduce symptoms (such as itching, rash, flare frequency) in two-thirds to three-fourths of people prescribed it. But there does appear to be a subset of people who only partially respond to Dupixent (partial responders), or who respond initially, and then their symptoms return (non-durable responders).
3. Downsides
If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:
- Injection site reactions (such as redness, pain, swelling at the injection site), conjunctivitis and other eye problems (such as dry eyes, itchy eyes, or keratitis), and herpes (eg, cold sores) infections are the most common side effects reported.
- Although weight gain is not listed as a side effect in the product information, a published case series comparing twelve people prescribed Dupixent to 8 people prescribed methotrexate reported significant weight gain in those people prescribed Dupixent (an average of 6.1kg over one year; the amount of weight gained ranged from 0.1kg to 18.0kg) compared with no weight gain or a loss of weight in those prescribed methotrexate. Anecdotally, people posting on blog sites have also reported weight gain as a side effect.
- Postmarketing, there are several reports of painful joints, tendinitis, and arthritic-like pain associated with Dupixent. Naproxen may be given as treatment for Dupixent-associated joint pain, followed by methotrexate if naproxen is ineffective. Consideration should be given to discontinuing Dupixent if the joint pain persists despite treatment or is particularly severe.
- Dupixent, like other biologics, should be monitored for effectiveness and side effects. A lack of response, loss of response, or severe side effects may warrant switching to a different biologic or the addition of other treatments. Corticosteroids should not be discontinued abruptly when Dupixent is started; rather, they should be reduced gradually and performed under the supervision of a doctor.
- Must be kept refrigerated at between 2°C to 8°C [36°F to 46°F]). Store in the original carton to protect from light. May be kept at room temperature of up to 77ºF (25ºC) for up to 14 days. Do not shake, heat, freeze, or put the pens in direct sunlight. Once stored at room temperature, do not place back in the refrigerator and discard Dupixent if not used within 14 days.
- Before starting treatment with Dupixent, ensure all patients have received all their appropriate immunizations for their age as recommended by National guidelines. It is important people administered Dupixent DO NOT receive live vaccines.
- Serious hypersensitivity reactions (such as serum sickness and urticaria) have been reported in less than 1% of people administered Dupixent. If a reaction occurs, discontinue Dupixent and initiate appropriate treatment. There is also the potential for immunogenicity and antibody formation. Up to week 52, approximately 5% of people treated with Dupixent developed antibodies to it; 2% of these antibodies were classified as neutralizing.
- There is not enough data to know the effect Dupixent has during pregnancy on the unborn child, but it is known that human IgG antibodies cross the placental barrier. Weigh up risks of uncontrolled disease versus benefits of Dupixent treatment. Enroll women who become pregnant while taking Dupixent on the pregnancy exposure registry call 1-877-311-8972. There are no data on the effect of Dupixent during lactation.
- No generic form of Dupixent is available.
Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects
4. Tips
- Dupixent comes as a single-use prefilled syringe (with a needle shield) or as a pre-filled pen. It is supplied in a carton with two pens or syringes in each package and is given as a subcutaneous (under the skin) injection.
- Dupixent is usually administered every other week (every second week).
- Do not attempt to self-administer Dupixent until you have been shown how to do so by a healthcare professional. Adults should supervise children 12 years of age and older. In children younger than 12 years of age, Dupixent should be given by an adult parent or caregiver. The injection can be administered into the thigh or stomach, except for the 2 inches (5 cm) around the belly button. If a caregiver injects the dose, they can also use the outer area of the upper arm. Choose a different injection site for each injection. DO NOT inject Dupixent into skin that is tender, damaged, bruised, or scarred.
- Clean the injection site with an alcohol wipe. Let your skin dry before injecting. Remove the green cap. Hold the pen so that you can see the window. Place the yellow needle cover on your skin at approximately a 90-degree angle. Press and hold the pre-filled pen firmly against your skin until you cannot see the yellow needle cover. There will be a “click” when the injection starts, and the window will start to turn yellow. Keep pressing the pen against your skin and watch the window. The window will turn completely yellow, and you will hear a 2nd “click”. Keep pressing the pen against your skin and count to 5 to make sure you get your full dose. After you have completed your injection pull straight up to remove the pen from the skin. The yellow needle cover will cover the needle. If you see any blood at the site, lightly dab a cotton ball or gauze pad. Do not rub your skin after the injection. If the window does not turn completely yellow, remove the pen and call your healthcare provider. Do not give yourself a second dose without speaking to your healthcare provider. Put your used pen into an FDA-approved sharps disposal container right away after use. Do not throw the pens in the trash.
- Store unused Dupixent Pre-filled Pens in the refrigerator between 36ºF and 46ºF (2ºC and 8ºC). Store in the original carton to protect from light. Take Dupixent out of the refrigerator 30 to 45 minutes before injecting and place it on a bench to allow it to warm up to room temperature. If necessary, Dupixent may be kept at room temperature (77ºF [25ºC]) for up to 14 days. Do not shake, heat, freeze, or put the pens in direct sunlight. Keep Dupixent Pre-filled Pens and all medicines out of the reach of children.
- Side effects, such as injection site reactions, eye problems (such as conjunctivitis or eye inflammation), and cold sores on the lips and mouth (oral herpes) are common with Dupixent; however, most of these side effects can be managed effectively with other treatments, such as eye drops or anti-virals, allowing people to continue with Dupixent, especially if it offers them significant benefits.
- Associated with several different eye problems, including conjunctivitis, blepharitis, dry eyes, itchy eyes, and keratitis. The cause is because Dupixent works by blocking two inflammatory proteins, IL-4 and IL-13. Goblet cells, which are responsible for creating mucus in the eye and ensuring the stability of tears, are also stimulated by IL-13. So when Dupixent blocks IL-13 which helps resolve the symptoms of AD and asthma, it also lowers the numbers of epithelial goblet cells, leading to inflammation and eye problems. Most of the time the inflammation is not too severe, but in some people, Dupixent may need to be discontinued. Most eye problems respond to standard treatments (eg, ophthalmic antibiotics for bacterial conjunctivitis).
- Seek urgent medical attention if you experience shortness of breath, facial or throat tightness after being administered Dupixent. Tell your doctor if you experience any other side effects, such as eye conditions, herpes infections, or weight gain.
- Tell other health professionals that you are being administered Dupixent. Before you start Dupixent, all your vaccinations should be up to date. While you are receiving Dupixent, you should not receive any live vaccines (such as the MMR vaccine or the chickenpox vaccine).
- It is not known how Dupixent affects a developing baby but your doctor may consider using it during pregnancy if the benefits outweigh the risks. Tell your doctor immediately if you become pregnant while being administered Dupixent.
5. Response and effectiveness
- For eczema in adults and adolescents, Dupixent works within 2 to 4 weeks to relieve itching and within 16 weeks a significant improvement in the condition of the skin is noticed.
- In studies of children aged 6 to 11 years with severe eczema, 4.5 times more children using Dupixent had reduced itching compared to those using a placebo (an inactive medicine). In addition, twice as many children on Dupixent saw clear or almost clear skin improvements.
- For asthma, some improvement in lung function was seen by two weeks which was significant within 12 weeks and sustained through 52 weeks. Severe breathing exacerbations were reduced by up to 81%. About 86% of people reduced or eliminated their oral steroid dose.
- Adults with uncontrolled chronic rhinosinusitis with nasal polyps had an improved ability to smell in as little as 2 weeks. In addition, over 80% fewer patients required nasal polyp surgery in 24-week and 52-week clinical trials.
- The manufacturer reports that it takes 16 weeks of treatment with Dupixent to reach steady-state levels.
6. Interactions
Medicines that interact with Dupixent may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Dupixent. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.
Common medications that may interact with Dupixent include:
- etanercept
- herbals, such as brewers yeast
- immunosuppressants (such as azathioprine, cyclosporine, or tacrolimus)
- live vaccines and some other vaccines, such as BCG, cholera, measles, or hepatitis b vaccines
- medications used to treat multiple sclerosis, such as fingolimod
- other biologics, such as adalimumab, golimumab, or infliximab
- probiotics, such as bifidobacterium lactobacillus
- warfarin
- zinc.
There is a potential for any medication that is metabolized by CYP450 enzymes, particularly those with a narrow therapeutic index (such as cyclosporine or warfarin) to interact with Dupixent. This is because the formation of CYP450 enzymes can be altered by increased levels of certain cytokines (such as IL-13) during chronic inflammation. Because Dupixent stops IL-4 and IL-13 from interacting with their receptors, this could normalize the formation of CYP450 enzymes. Monitor for any change in effect and consider any dosage modification.
Note that this list is not all-inclusive and includes only common medications that may interact with Dupixent. You should refer to the prescribing information for Dupixent for a complete list of interactions.