Can You Take Celecoxib with Pregabalin?
A plain-English look at the major interaction between Celecoxib (Celebrex) and Pregabalin (Lyzalon) — what it means, why it happens, and what to talk to your doctor or pharmacist about.
Taking Celecoxib (Celebrex) with Pregabalin (Lyzalon) is a major drug interaction that should be avoided. Respiratory depression, excessive sedation, overdose. Additive CNS depression. Gabapentinoids potentiate opioid-induced respiratory depression even at therapeutic doses.
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Key Takeaways
- Interaction severity: Major
- Risk: Respiratory depression, excessive sedation, overdose.
- Mechanism: Additive CNS depression. Gabapentinoids potentiate opioid-induced respiratory depression even at therapeutic doses.
- Celecoxib: S4 in Australia, low risk
- Pregabalin: S4 in Australia, moderate risk
- Claims action: Flag for immediate prescriber review. Document intervention in claim file.
Celecoxib vs Pregabalin at a Glance
| Property | Celecoxib | Pregabalin |
|---|---|---|
| Brand names | Celebrex, Celecoxib Sandoz, Celecoxib GH | Lyzalon, Pregabalin Sandoz, APO-Pregabalin |
| Drug class | opioid | gabapentinoid |
| Risk level | low | moderate |
| TGA Schedule (AU) | S4 | S4 |
Why Is This Combination Dangerous?
Additive CNS depression. Gabapentinoids potentiate opioid-induced respiratory depression even at therapeutic doses.
Regulatory Guidance by Jurisdiction
Australia TGA / SIRA / WorkSafe
The TGA and Australian Medicines Handbook classify this as a major drug interaction requiring immediate intervention.
The TGA has issued safety communications about the risk of respiratory depression when gabapentinoids are combined with opioids. WorkSafe Victoria Drugs of Dependence Guidelines require monitoring for this combination.
United Kingdom NICE / MHRA / FPM
The MHRA has issued Drug Safety Updates warning about the risk of respiratory depression and death when gabapentinoids are combined with opioids. NICE CG173 (Neuropathic Pain) recommends gabapentinoids as monotherapy, not in combination with opioids.
United States FDA / CDC / State WC
The FDA has added warnings to gabapentinoid labels about serious breathing difficulties when taken with opioids. The CDC opioid guidelines recommend caution with concurrent CNS depressant use. Some state formularies require prior authorization for this combination.
What Claims Professionals Should Do
- Flag immediately as a high-risk prescribing pattern in the claim file
- Request urgent prescriber review with documented clinical justification for the combination
- Consider an independent medical examination if the prescriber cannot provide adequate justification
- Assess work capacity impact as the combination significantly increases sedation and impairment risk
- Document all interventions for audit trail and compliance purposes
- Check Reasonable and Necessary status for both medications against the compensable injury
Clinical reference
A clinical summary of Celecoxib and Pregabalin drawn from regulator advisories, national guidelines, and authoritative drug references. Read this if you want the deeper clinical picture before talking to your prescriber or pharmacist.
Severity assessment
Moderate. The co-administration of celecoxib and pregabalin may lead to additive central nervous system (CNS) depressant effects and potentially exacerbate renal impairment or peripheral edema.
Mechanism (plain English)
Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that works by reducing inflammation and pain. It primarily acts by blocking an enzyme called cyclooxygenase-2 (COX-2). Pregabalin is an anticonvulsant and neuropathic pain agent that works by binding to a specific site in the brain and spinal cord, which reduces the release of certain pain-signaling chemicals. Both drugs can cause side effects such as dizziness and drowsiness. Celecoxib can also affect kidney function, and pregabalin is mainly removed from the body by the kidneys. Therefore, if kidney function is reduced by celecoxib, pregabalin levels in the body could increase, leading to more side effects. Additionally, both drugs can cause fluid retention (edema).
Evidence level
Theoretical. While there are no specific regulator advisories or case reports detailing a direct interaction between celecoxib and pregabalin, the potential for additive adverse effects is based on the known pharmacodynamic profiles of both drugs and the pharmacokinetic profile of pregabalin, which is renally excreted [1] [2].
Top regulator advisories (cite verbatim or close paraphrase)
- TGA (Australia): No pair-specific public advisory found. Applicable product information for celecoxib (e.g., CELEBREX) warns about renal effects and fluid retention [3]. Applicable product information for pregabalin (e.g., LYRICA) warns about central nervous system depressant effects, dizziness, somnolence, and peripheral edema [4].
- MHRA / NICE (UK): No pair-specific public advisory found. General guidance for NSAIDs (like celecoxib) advises caution with other drugs that can cause renal impairment or fluid retention. General guidance for pregabalin advises caution with other CNS depressants due to additive effects.
- FDA / CDC (US): No pair-specific public advisory found. The FDA prescribing information for celecoxib (CELEBREX) notes potential for renal toxicity, hypertension, heart failure, and edema, and interactions with drugs affecting hemostasis, ACE inhibitors, ARBs, beta-blockers, diuretics, and digoxin [1]. The FDA prescribing information for pregabalin (LYRICA) warns of respiratory depression, dizziness, somnolence, and peripheral edema, especially when used with concomitant CNS depressants [2].
- EMA (Europe): No pair-specific public advisory found. Similar warnings regarding CNS depression, peripheral edema, and renal excretion are present in European product information for both drugs.
Clinical risk factors that elevate the danger
- Elderly patients: Increased susceptibility to CNS depressant effects and reduced renal function.
- Patients with pre-existing renal impairment: Increased risk of pregabalin accumulation and celecoxib-induced renal deterioration.
- Patients with pre-existing heart failure or hypertension: Increased risk of fluid retention and exacerbation of cardiovascular conditions due to celecoxib.
- Concomitant use of other CNS depressants: (e.g., opioids, benzodiazepines, alcohol) increases the risk of severe sedation and respiratory depression with pregabalin.
- High doses of either drug: Increases the likelihood and severity of dose-dependent adverse effects.
What a patient should be told
- Risk of increased drowsiness and dizziness: Both medications can make you feel sleepy or dizzy. Combining them can make these effects worse, impacting your ability to drive or operate machinery safely. Be very careful until you know how these medicines affect you.
- Do not stop suddenly: Do not stop taking either medication without talking to your doctor or pharmacist first. Suddenly stopping pregabalin can lead to withdrawal symptoms or seizures.
- Warning signs to watch for: Be aware of signs of excessive drowsiness, confusion, difficulty breathing, unusual swelling in your hands, feet, or ankles, or any changes in how you urinate. Report these to your doctor immediately.
- Discuss alternatives: If you are concerned about these risks, talk to your doctor or pharmacist about whether there are alternative treatments or dose adjustments that might be safer for you.
- Urgent care triggers: Seek immediate medical attention if you experience severe difficulty breathing, extreme dizziness or fainting, severe swelling of the face or throat, or any signs of an allergic reaction.
Top 3 sources (with full citation)
- FDA. CELEBREX (celecoxib) capsules, for oral use. Revised: 11/2024. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2d6675e4-5859-4be2-8037-a20ce9f707aa
- FDA. PREGABALIN capsule. Revised: 7/2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cf7b4b67-b017-47ac-af3f-bde5bd07bb0c
- Therapeutic Goods Administration (TGA). CELEBREX (celecoxib) Product Information. Last updated: 21 October 2022. https://www.tga.gov.au/resources/artg-entry/80249
Notes for the reviewing pharmacist
This interaction is primarily based on additive pharmacodynamic effects and potential pharmacokinetic considerations related to renal function. While no specific drug-drug interaction studies for celecoxib and pregabalin were found, the individual drug labels highlight overlapping adverse effects (CNS depression, peripheral edema) and celecoxib's potential to impact renal function, which is critical for pregabalin elimination. Therefore, careful monitoring for increased sedation, dizziness, and signs of renal impairment or worsening edema is warranted, particularly in vulnerable patient populations. The absence of a specific regulator-flagged interaction for this pair does not negate the clinical relevance of these additive effects. Patient education should emphasize symptom recognition and the importance of not discontinuing medication abruptly. Consideration of alternative agents or dose adjustments should be made for patients at higher risk. The TGA links provided are to the ARTG entries, as direct links to the full Product Information documents were not readily available through a quick search; a pharmacist might need to access these via a subscription service or a more in-depth search of the TGA website. The FDA links are to DailyMed, which provides the full prescribing information.
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Related Resources
Important: This page is general health information, not personal medical advice. If you have questions about your medication — including starting it, stopping it, changing the dose, or combining it with something else — speak with your doctor or pharmacist. For an emergency or suspected overdose, call your local emergency number or poison information service immediately. Information is drawn from regulator and clinical guideline sources (TGA, FDA, MHRA, NICE, PBS, CDC); see our methodology for details.