Top 11 Reasons Why Humira Citrate Free Pen Might be Right For You

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Medically reviewed by, Russell Braun RPH

Humira is the best selling drug in the world based on revenue. It has been a huge leap forward in treating many autoimmune conditions. So why would AbbVie the manufacturer go to the trouble of creating a new formulation that is called Humira citrate free?

The answer is simple, injection site pain.

Humira has been available since 2002 and seen rapid growth in use every year. Unfortunately, many patients had to deal with pain every time they received Humira because of the injection. The pain at injection site could be immediate or similarly linger after the dose had been given. Consequently, the range of pain severity spanned from mild to severe.

1. What does Humira citrate free mean?

Citrate is something that chemists call a buffer. Buffers help keep that acid to base balance in check and maintain a stable pH. This is important because the pH of our body is held in check at 7.4. For that reason, anything that sways too far from 7.4 will irritate the body or cause us to feel pain or sick.

Why does Humira need a buffer?

Humira is a biologic drug. That simply means it is produced inside living organisms. Furthermore, Humira is actually a complex molecule called a protein. These proteins need the same pH as the body and thus a buffer is required so Humira doesn’t breakdown in the syringe before it is used.

2. Why did Humira go citrate free?

Citrate was found to cause some of the pain associated with Humira injection. Therefore, a different buffer was used in the new formulation that does not seem to cause as much pain in clinical trials. In addition some of the other inactive ingredients were removed as well.

3. What is Humira citrate free pen used for?

Humira citrate free still contains adalimumab, which is the active ingredient. Similarly it has the same Food and Drug Administration (FDA) approved uses which are listed in the tables below.


Rheumatoid ArthritisPlaque Psoriasis
Crohn’s DiseaseUlcerative Colitis
Psoriatic ArthritisHidradenitis Suppurativa
Ankylosing SpondylitisPanuveitis


Crohn’s DiseaseJuvenile Idiopathic Arthritis
Hidradenitis Suppurativa (12 years and older)Panuveitis

4. What does Humira do to your body?

Adalimumab, the active ingredient in Humira is a monoclonal antibody (that is what the “mab” potion at the end of adalimumab stands for. A monoclonal antibody looks for one thing in the body and binds to it specifically. That one thing adalimumab is looking to bind to is called TNF-alpha, also known as Tumor Necrosis Factor.

TNF-alpha occurs naturally in the body but is found to be elevated in people with auto-immune diseases. Some examples include rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis to name a few. Humira blocks the effects of TNF-alpha in the body. Consequently, it has been shown to lower inflammatory substances such as C-reactive protein (CRP) and lower erythrocyte sedimentation rate (ESR).

5. What is different about Humira Citrate free pen?

Bye, bye citrate

As noted above the most important difference is that the citrate buffer has been removed. In addition, other inactive ingredients were removed also.

Less fluid to inject

Humira citrate free pen version contains half the volume of fluid. The injection now contains 0.4ml instead of 0.8ml. This smaller amount of fluid also helps prevent injection pain.

The needle is smaller

The new Humira citrate free pen formulation comes with a 29 gauge needle. In contrast, the original Humira injection had a 27 gauge needle. The higher the gauge number, the smaller the size of the needle. Studies have shown that smaller needles can also decrease pain and increase the likelihood that patients will use their medication.

Color of cap numbers

The large numbers on the caps are white on the new pen. Furthermore, these numbers show the patient which end is which. Number one has the needle and goes against the body part being injected and number two is the trigger.

Larger pen window

The window that allows you to see inside the pen has been made larger than the original pen. The pen window is used to view a yellow indicator that lets the patient know when the medication has all been dispensed during the injection. This doesn’t decrease injection pain, but simply makes the pen more user friendly.

Latex has been removed

The needle cover is no longer made with rubber containing latex. Again this does not decrease injection site pain, but instead prevents people with latex allergies from having problems with Humira citrate free pen.

New packaging

Humira citrate free pen now comes in a blue box. This helps pharmacist and patients easily determine which version of Humira they reach for. Another way to confirm the citrate free version is to look for the 29 guage needle designation on the box.

6. What is the same as the old Humira Pen?


Both Humira pen formulations are the exact same size.


Both contain adalimumab, which is the active ingredient in Humira. In addition, the 40mg dose is also the same.

Injection technique

The way that the injection is given remains the same. Consequently, the same areas of the body are still going to be used as well. Patients will not need to learn a new injection method or take another training.

Both need a prescription

Humira citrate free pen is a prescription only medication and that also applies the old formulation. Similarly, if patients want the new citrate free version their doctor must write a new prescription for it. A prescription for the original Humira formulation can’t be filled with citrate free.


Humira citrate free pen should be stored in the refrigerator, not the freezer. They can be stored at room temperature for up to 14 days. After that they should be thrown away.

7. Is there proof the new pen causes less pain?

A study published in the Journal Rheumatology and Therapy looked to determine if the Humira citrate free pen caused less injection site pain. They looked at patient reported injection pain measured by an assessment of patients after receiving the injection. They were given the assessment immediately following the injection and 15 minutes later.

There was a statistically significant lower pain score for the Humira citrate free version compared to the older formulation. In addition to being statistically significant it did also appear to be clinically significant as the reduction in pain as nearly 50% of patients reported less pain at both immediately and 15 minutes after the injection.

Important to remember

  1. The study was funded by AbbVie the manufacturer of Humira. This could be important in 2023, see the discussion below on cost.
  2. Staff who conducted the study did not notice any difference in the amount of bruising, swelling, redness and itching between the formulations. Therefore, it is possible these issues may still arise with Humira citrate free.

8. How can I make my Humira Pen less painful?

Regardless of which version of Humira pen you use below are the steps to make sure the injection is as pain free as possible. It is important to remember Humira requires repeated injections normally once per week. Therefore, following proper procedures becomes even more critical.

Humira users click here to get this Infographic emailed to your inbox.

Get training

Your doctor or their staff should be able to provide training. Make sure you pay attention and ask questions. As with anything, the more you do something the better you will become. If you are still unsure after the training call and ask for a refresher.

Collect needed items

  • Humira pen or syringe
  • Alcohol swab
  • Cotton ball or gauze pad
  • Sharps container to discard the used pen or syringe

Wash your hands

Hand washing as always is very important to lower the chances of infection. Your hands have millions of bacteria on them, some good and some bad. Wash before with soap and warm water for at least 30 seconds to prevent a skin infection.

Sit down

This helps to steady the body and hands as you get ready to inject the drug. This is also crucial if you get faint at the thought of needles. Falling after fainting could be painful and dangerous.

Pick the injection site

The abdomen or the thighs are potential sites that can be injected. Most people inject in the abdomen because it is the least painful. Make sure it is two inches away from the belly button and one inch away from the previous injection site. Wipe the area with the alcohol swab.

Pull the caps off

The caps are numbered 1 and 2. Pull 1 off first while holding the pen in the middle. Next pull off cap 2 and place your thumb near the plumb colored activator. Make sure the window on the pen is visible.

Pinch the skin

With the free hand pinch the skin where the injection will be given. Hold the number 1 end of the pen on the skin at a 90 degree angle to the body part being injected.

Press the button

With your finger press the plum colored activator and you will hear a loud click noise. Take a deep breath and then slowly exhale as the medicine is being injected. After 10-15 seconds the window of the pen will have a yellow color indicating the entire dose has been given.

Finally, put everything in it’s place

The cotton ball or gauze should be held on your skin for about 20 seconds to stop any minor bleeding. The pen should be placed in the sharps container.

Key tips

  • If you don’t like needles then the pen is a good idea because you never see the needle.
  • Take the Humira citrate free pen out of the refrigerator at least 30 minutes prior to giving the injection, this allows it to warm up.
  • Never give the injection through clothing.
  • If the skin where planning to inject doesn’t look normal use another site.

8. How much does Humira cost without insurance?

According to GoodRx the cost of a 30 day supply of Humira is $5,490. That comes out to $65,880 per year! With these staggering prices tags even the very wealthy have trouble paying for the drug without assistance. 11 Money Saving Tips to Know before using Humira copay card explains how to get the biggest bang for your buck.

9. What insurance plans cover Humira?

Humira is covered by most insurance plans because it is a very effective drug. However, keep the following in mind.

  • High Deductible Health Plans (HDHPs) can still leave patients with a large out of pocket cost.
  • People with government insurance such as Medicare and Medicaid are not eligible for manufacturer copay coupon offers.
  • No generic will ever become available.
  • Biosimilars, which are like generics will not be available until 2023.

10. What you need to know in 2023!

Humira will finally have biosimilar competition coming in 2023 when it’s patents expire. This will drive down the cost. For much more on that subject check out 7 Intriguing Facts about Humira Generics and Biosimilars. The problem is if you switch to Humira citrate free, there will not be a biosimilar to the citrate free version in 2023! That may mean you have to decide between a cheaper version and the less painful injection. Additionally, your insurance may also require biosimilar use.

Keep this in mind as 2023 approaches.

11. Lifestyle changes

A great way to cope with the auto-immune process that Humira helps treat is to look at lifestyle changes. Changes to the diet can make the body less likely to have inflammatory tendencies. The complete anti-inflammatory diet for beginners is a great resource to explain the relationship between food and inflammation.

Click here to get Dr. Jason Reed’s exclusive list of medication questions you MUST ask your doctor, for FREE!

Share your story!

Have you used Humira pen? Likewise, tell us if you have tried the citrate free version. Was there a difference in injection pain? Please chime in below with your comments and thoughts below.

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