NSAIDs for sickle cell disease

Last updated Aug. 13, 2024, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD

What are NSAIDs?

Nonsteroidal anti-inflammatory drugs, or NSAIDs, are a class of anti-inflammatory, fever-reducing medications that are commonly used to help relieve pain in people with sickle cell disease (SCD).

There are many different types of NSAIDs, including common over-the-counter pain relievers, such as ibuprofen and aspirin, as well as others that are only available with a medical prescription.

However, these medicines, which are available in a wide range of strengths and formulations, are associated with toxic effects on multiple organs and systems in the body, including the digestive and cardiovascular systems, as well as the kidneys. For this reason, NSAIDs may not be recommended for patients with underlying conditions affecting these organs and systems. A healthcare provider will take this risk profile into account when deciding if NSAIDs are appropriate for a specific patient.

When are NSAIDs used in SCD?

NSAIDs, along with other medications and interventions, are a standard part of pain management for people with SCD who are experiencing a vaso-occlusive crisis (VOC) or other forms of acute disease-related pain.

VOCs occur when the sickle-shaped red blood cells that give SCD its name obstruct blood vessels, ultimately compromising blood flow to certain parts of the body. The blockage of blood flow that occurs during a VOC leads to inflammation in the affected tissue, resulting in episodes of acute pain.

In addition to acute pain, SCD patients may experience chronic pain arising from other conditions or SCD-related complications, including bone degeneration or leg ulcers.

Acute pain

The American Society of Hematology (ASH) recommends that a short course (5-7 days) of NSAIDs be given alongside opioids to help manage acute pain in adults and children with SCD.

The decision of whether to use NSAIDs, and if so, the specific medication or class of medications to be given, will be determined by a healthcare professional based on a patient-specific assessment of harms, which includes assessing the risk of kidney, vascular, and gastrointestinal toxicity.

In some cases, the potential benefits of NSAIDs for acute pain may not outweigh their risks. This may be the situation, for example, for patients with or at risk of developing certain underlying conditions, such as peptic ulcer disease and kidney function impairments. SCD patients receiving NSAIDs also should be closely monitored for the development of possible side effects.

Chronic pain

NSAIDs also may be given routinely to help manage chronic pain in people with sickle cell disease. Management of such pain in SCD is highly personalized, and specific regimens vary widely depending on the needs of the individual.

The ASH guidelines recommend the use of NSAIDs and a class of antidepressants known as serotonin and norepinephrine reuptake inhibitors (SNRIs) for managing chronic pain associated with bone degeneration in adults with SCD. Nevertheless, the recommendations stress that there’s not much hard evidence for how best to manage chronic SCD pain, so decisions need to be made on a case-by-case basis.

How do NSAIDs work?

NSAIDs are a class of anti-inflammatory medications that work by blocking an enzyme called cyclooxygenase (COX). There are two versions of the COX enzyme, named COX-1 and COX-2, and existing NSAIDs vary in their ability to inhibit each version of the protein.

COX-1 is widely produced throughout the body under normal conditions. This specific form of the enzyme helps regulate kidney function, control blood clotting, and maintain the health of the gastrointestinal lining. COX-2, meanwhile, is pro-inflammatory and is only produced at times of active inflammation. Blocking COX-2 is the main way through which NSAIDs work to reduce inflammation and ease pain.

The vast majority of NSAIDs, including over-the-counter pain relievers such as ibuprofen, block both the COX-1 and COX-2 forms of the COX enzyme. There also are a few NSAIDs that specifically block COX-2, but not COX-1.

Benefits of NSAIDs

The main benefits of NSAIDs for sickle cell disease are related to pain relief. NSAIDs are commonly used to help ease pain in SCD patients who are experiencing acute pain episodes, such as a VOC, and also may be used in the long-term management of chronic pain.

In addition to controlling pain, NSAIDs may help reduce the use of highly addictive opioids, and may decrease a patient’s length of stay at a hospital or clinic.

Risks and side effects

As with any medication, the use of NSAIDs carries the risk of possible side effects and complications. The most common NSAID side effects include:

• digestive complaints, such as gas, bloating, nausea or vomiting, diarrhea, constipation, stomach pain, and heartburn
• lightheadedness, dizziness, or mild headache
• trouble with concentration and/or balance.

Other risks associated with the use of NSAIDs may include:

• damage to the digestive tract (e.g. peptic ulcer disease, gastrointestinal bleeding)
• kidney damage and inflammation
• fluid and electrolyte disorders
• liver toxicity
• heart problems (e.g. heart attack, abnormal blood clotting)
• abnormal bleeding.

Due to the risk of damage to the kidneys, heart, and digestive tract, caution is necessary if using NSAIDs in people with underlying health problems affecting these organs. In particular, the use of these medications may not be recommended to patients with a history of peptic ulcer disease, liver or kidney disease, bleeding disorders, and cardiovascular disease.

The specific risks associated with the use of NSAIDs will vary depending on the specific medication, as well as the patient’s genetic background and underlying health issues. This risk will be assessed by a physician when deciding if NSAIDs should be used to treat a specific patient.

Pregnancy and breastfeeding

NSAIDs are generally not recommended to be used during pregnancy, because they can cause problems with organ development in the fetus.

The U.S. Food and Drug Administration (FDA) specifically recommends that NSAIDs be avoided by pregnant women from the 20th week of gestation onward due to the risk of serious kidney problems in the fetus, which can reduce the levels of amniotic fluid (a condition also known as oligohydramnios). This, in turn, can result in complications, including fetal malformations, premature delivery, and miscarriage.

Pregnant women should therefore not take NSAIDs at 20 weeks or later into the pregnancy unless they have been specifically advised to do so by a healthcare professional. The FDA also states that clinicians should avoid prescribing NSAIDs to pregnant women, particularly after the 30th week of gestation. In cases where these medications are deemed necessary, they should be used at the lowest effective dose and for the shortest time possible.

Limited data are available on the use of NSAIDs during breastfeeding. In general, if NSAIDs are deemed necessary, efforts should be made to minimize the infant’s exposure to the medication. This can be achieved by opting to use the lowest possible effective dose for the shortest time possible. NSAIDs that are eliminated faster from the body, such as ibuprofen, are generally preferred in this situation over others that remain in circulation in the body for longer periods of time.

NSAIDs used in SCD

NSAIDs can be broadly classified into two categories:

• nonselective NSAIDs, which block both COX-1 and COX-2
• selective NSAIDs that block COX-2, but don’t affect COX-1.

Selective NSAIDs are generally associated with a lower risk of digestive side effects, but their use has also been linked to an increased risk of heart problems compared with nonselective NSAIDS.

NSAIDs are mainly taken by mouth, though in some situations, such as during emergency treatment in a hospital, they may be given via injection or other routes.

Guidelines for SCD management don’t recommend any one particular NSAID as the best option for most patients. Instead, the selection of which NSAID should be used depends on the individual’s specific situation and on which medications are available.

Nonselective NSAIDs

Several common nonselective NSAIDs may be used to help ease pain in people with SCD:

• Ibuprofen (sold as Advil and others) is a commonly used over-the-counter medication that’s available in various oral formulations, including tablets, capsules, and suspension. It can be given alone or in combination with other agents. Intravenous or into-the-vein formulations also are available. Ibuprofen is said to be one of the most commonly used NSAIDs to treat acute pain in SCD.
• Aspirin (sold as Excedrin and others) is another commonly used over-the-counter medicine that’s sold alone and in combination with other analgesics. It usually is available in the form of oral tablets and capsules.
• Naproxen (sold as Naprosyn and others) also is an over-the-counter medication that’s sold alone or in combination with other agents. It is available in the form of conventional and extended-release tablets, capsules, and as an oral suspension.
• Ketorolac (available as generics) is another option that’s available in various formulations, including oral and injectable forms. Intravenous ketorolac was found to be effective when used as a first-line treatment in emergency departments to manage acute pain in children with SCD.
• Diclofenac (sold as Zipsor and others) also is available in several formulations, including oral, injectable, and topical forms.

Selective NSAIDs

In the U.S., there is only one available selective NSAID: the prescription therapy celecoxib (sold as Celebrex and others). This medication is sold in the form of oral capsules or as an oral solution. Celecoxib also is sold as part of a combined medication along with the opioid tramadol.

Other COX-2-specific NSAIDs, such as etoricoxib, are not approved for use in the U.S. but may be available in other countries.

Sickle Cell Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.