Why Does My DUPIXENT Injection Hurt So Bad? An In-Depth Guide

October 12, 2025 •

5 min read

In clinical trials for atopic dermatitis, injection site reactions, including pain, were reported by 10% of patients receiving DUPIXENT [1.4.1]. If you're wondering, 'Why does my DUPIXENT injection hurt so bad?', several factors from medication temperature to injection technique could be the cause.

Quick Summary

Pain during DUPIXENT injections is a common concern. The discomfort can be attributed to the medication's temperature, its volume, injection speed, and individual technique. Simple measures can significantly reduce this pain.

Key Points

Temperature is Critical: Injecting cold DUPIXENT directly from the fridge is a major cause of pain; let it warm to room temperature for 30-45 minutes [1.2.7].
Technique Matters: Injecting slowly, at the correct angle (45° for syringe, 90° for pen), and into a proper site can significantly reduce discomfort [1.3.6].
Rotate Injection Sites: Avoid soreness and tissue damage by alternating between the thigh and abdomen, staying 2 inches away from the navel [1.2.7].
Numb the Area: Using an ice pack before the injection or asking a doctor about topical numbing creams can help dull the initial pinch [1.3.2].
Syringe vs. Pen: The syringe allows manual control over injection speed which may reduce pain, while the pen is often easier to use but has a fixed injection rate that some find painful [1.7.5].
Don't Rub the Site: After the injection, avoid rubbing the area to prevent irritation and bruising; a cold compress can be used for relief [1.3.1].
Stomach May Be Less Painful: Many users report that injecting into the subcutaneous tissue of the abdomen is less painful than the thigh [1.2.4].

Understanding DUPIXENT and Its Purpose

DUPIXENT (dupilumab) is a biologic medication used to treat several inflammatory conditions, including moderate-to-severe atopic dermatitis (eczema), asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and prurigo nodularis [1.6.1, 1.7.3]. It works by targeting and blocking two specific proteins, Interleukin-4 (IL-4) and Interleukin-13 (IL-13), which are key drivers of the underlying inflammation in these diseases [1.2.3]. Unlike immunosuppressants, DUPIXENT calms an overreactive part of the immune system without suppressing it entirely [1.2.7]. Because it is a protein-based therapy, it must be administered as a subcutaneous (under the skin) injection to be effective [1.7.3]. While highly effective, a common complaint from users is the pain associated with the injection itself.

Key Reasons for Injection Pain

Several factors contribute to the discomfort experienced during a DUPIXENT injection. Understanding these can help you pinpoint the cause of your pain and take steps to mitigate it.

Medication Temperature: Injecting DUPIXENT straight from the refrigerator is a primary cause of pain and a burning sensation [1.2.7]. Cold liquid entering the subcutaneous tissue is more likely to cause discomfort. The manufacturer recommends allowing the pen or syringe to warm to room temperature for at least 30-45 minutes before injection, depending on the dosage [1.2.4].
Volume and Viscosity: The DUPIXENT injection involves delivering a 2 mL volume of solution (for the 300mg dose) under the skin [1.5.4]. This volume can cause a sensation of pressure and stretching in the tissue, leading to pain. While not excessively thick, the solution has a certain viscosity, and pushing it too quickly can exacerbate discomfort [1.5.1].
Injection Speed: Pushing the plunger too fast or, in the case of the auto-injector pen, the fixed rate of injection can cause a burning sensation [1.2.7]. A slower, more controlled injection allows the tissue to accommodate the fluid more gradually. Studies have noted that the pre-filled pen, while easier to use, may cause more pain than the syringe, potentially due to the rapid injection speed [1.7.5].
Injection Site and Technique: The location and method of injection play a crucial role. Injecting into a muscle instead of the subcutaneous fat layer, using an incorrect angle, or injecting into scarred, bruised, or tender skin can significantly increase pain [1.3.1, 1.3.6]. Repeatedly using the same spot can also lead to soreness and tissue damage [1.2.7]. Many users report that the stomach is a less painful injection site than the thigh [1.2.7].
Needle Gauge: DUPIXENT uses a 27-gauge needle, which is relatively thin [1.5.2]. However, individual pain perception and anxiety about needles can still be a factor.

Pen vs. Syringe: A Pain Comparison

DUPIXENT is available in both a pre-filled auto-injector pen and a pre-filled syringe. The choice between them can impact the injection experience.


Feature	Pre-filled Pen	Pre-filled Syringe
Needle Visibility	Needle is hidden from view [1.7.1].	Needle is visible before injection [1.7.2].
Injection Control	Automatic injection at a fixed rate once activated [1.7.3].	Manual control over injection speed via the plunger [1.7.3].
Ease of Use	Generally considered easier to use and preferred by many patients for convenience [1.7.1, 1.7.5].	Requires manual dexterity to hold, inject, and push the plunger [1.7.3].
Reported Pain	Some studies and users report more pain, possibly due to the fast, automated injection speed [1.7.5].	May be less painful as the user can control the speed of injection [1.2.7].
Approved Age	Ages 2 and older [1.7.4].	Ages 6 months and older [1.7.4].

Proven Strategies to Minimize Injection Pain

Fortunately, there are many effective techniques to make your DUPIXENT injection experience more comfortable. It may take some experimentation to find what works best for you.

Preparation is Key

Warm It Up: This is the most crucial step. Take the DUPIXENT pen or syringe out of the refrigerator and let it sit at room temperature on a flat surface for at least 30 minutes (for the 200mg dose) or 45 minutes (for the 300mg dose) [1.3.6]. Do not try to warm it in a microwave, hot water, or direct sunlight [1.8.2].
Choose the Right Site: Rotate your injection sites between the thigh and abdomen (staying at least 2 inches away from the belly button) [1.8.1]. If a caregiver is administering the shot, the upper arm is also an option [1.8.1]. Avoid any areas that are bruised, scarred, tender, or damaged [1.3.4]. Many patients find the abdomen to be less painful than the thigh [1.2.4].
Numb the Area: Before cleaning the site, apply an ice pack or cold compress for a few minutes to numb the skin [1.3.2]. Alternatively, you can ask your doctor about using an over-the-counter topical numbing cream (like one containing lidocaine) [1.3.2].

Proper Injection Technique

Clean and Dry: Clean the chosen site with an alcohol wipe and let it air dry completely. Injecting through wet alcohol can cause a stinging sensation [1.2.2].
Inject Slowly and Steadily: If using the syringe, push the plunger slowly and consistently [1.2.7]. This gives the tissue time to expand and absorb the medication, reducing the burning feeling. While you can't control the speed of the pen, ensuring you are relaxed can help.
Use the Correct Angle: The pre-filled syringe should be inserted at a 45-degree angle, while the pen should be held firmly against the skin at a 90-degree angle [1.3.6].
Relax: Tensing the muscles at the injection site can make the pain worse. Take a deep breath and try to relax the area before and during the injection [1.3.2].

After the Injection

Don't Rub: It's important not to rub the injection site afterward, as this can increase irritation and bruising [1.3.1].
Apply a Cold Compress: If you experience pain, swelling, or itching, applying a cold compress can provide relief [1.3.1].
OTC Pain Relievers: If needed, over-the-counter pain medications like ibuprofen or acetaminophen may help, but consult your doctor first [1.3.1].

Conclusion

While the question, "Why does my DUPIXENT injection hurt so bad?" is a common and valid one, the pain is manageable. The discomfort is typically caused by a combination of the medication's temperature, volume, and injection technique. By taking simple preparatory steps like warming the medication, choosing the right site, and using numbing agents, and by focusing on a slow, steady injection technique, you can significantly reduce or even eliminate injection pain. Always follow the training provided by your healthcare provider and consult them about any persistent or severe injection site reactions [1.3.6].

For detailed, step-by-step visual instructions, consider visiting the official DUPIXENT® Injection Support Center.

Frequently Asked Questions

A burning sensation is often caused by injecting the medication when it's too cold, injecting it too quickly, or if the alcohol used to clean the site hasn't fully dried [1.2.7, 1.2.2].

Many patients report that the stomach is the least painful injection site for DUPIXENT. However, pain perception is individual, so it's best to rotate sites and see what works for you [1.2.7].

To make the injection less painful, let the medication reach room temperature, choose a different injection site each time, inject slowly (with the syringe), and consider numbing the area with ice beforehand [1.3.6].

The pre-filled syringe may cause less pain because you can control the injection speed. Some studies have found the pre-filled pen, while easier to use, is associated with more pain due to its automated, rapid injection [1.7.5].

Minor lumps or bruising can be normal. This can happen if the injection angle is off or the site is sensitive. If you have persistent lumps, severe swelling, or signs of infection, you should contact your healthcare provider [1.2.7].

No, you should only let it warm up naturally at room temperature for the recommended 30-45 minutes. Do not use any heat sources like microwaves, hot water, or direct sunlight, as this can damage the medication [1.8.2].

Yes, injection site reactions, including pain, redness, swelling, and itching, are among the most common side effects of DUPIXENT. These reactions are typically mild and resolve on their own [1.6.3, 1.3.1].