# Safety & Interactions

Aspirin has a familiar safety profile.

Cancer settings still change the risk picture.

This should be treated as a medication decision, not a casual add-on.

### General tolerability

Common issues include:

* stomach irritation
* reflux or dyspepsia
* easy bruising

More serious concerns include:

* gastrointestinal bleeding, which can occur without warning pain
* haemorrhagic complications in already fragile patients
* interaction-related bleeding risk

Low-dose aspirin does not show a strong fatal-bleeding signal in many trials.

That is reassuring. It does **not** mean there is no individual risk.

### Practical cautions

| Risk factor                                    | Why it matters                                                                  |
| ---------------------------------------------- | ------------------------------------------------------------------------------- |
| Prior ulcer or GI disease                      | Raises the risk of GI bleeding.                                                 |
| Older age                                      | Makes the benefit-risk balance less favourable in general prevention settings.  |
| Anticoagulants such as warfarin or rivaroxaban | Adds bleeding risk and needs clinician review.                                  |
| Other NSAIDs such as ibuprofen or naproxen     | Raises GI risk and complicates daily aspirin use.                               |
| Some chemotherapy regimens                     | Thrombocytopenia or mucosal injury can make bleeding more clinically important. |
| Alcohol use                                    | Can worsen gastric irritation and bleeding risk.                                |

### Clinical positioning

Aspirin deserves the same review as any other active drug.

The case for discussion is strongest where there is real biomarker or syndrome context, such as **PIK3CA-mutated colorectal cancer** or **Lynch syndrome**.

For broad primary prevention in healthy older adults, recent evidence does **not** support low-dose aspirin as a general cancer-prevention strategy.

### Practical takeaway

The main safety issue is bleeding.

The main interaction issue is stacking aspirin with other drugs that also raise bleeding risk.

If aspirin is being considered during active treatment, the most useful questions are:

1. Is bleeding risk already elevated by the cancer, the treatment, or current labs?
2. Is the patient also using an anticoagulant, NSAID, or other drug that shifts the balance?
3. Is there a tumour subtype or syndrome where aspirin has a stronger evidence base?

### Key References

* García Rodríguez LA et al. (2011). Long Term Use of Aspirin and the Risk of Gastrointestinal Bleeding (dose-dependent risk; multivariate RR 1.43; highest with >14 tablets/week). BMJ 343:d5225. [https://pmc.ncbi.nlm.nih.gov/articles/PMC3086018/\[^45\]](https://pmc.ncbi.nlm.nih.gov/articles/PMC3086018/\[%5E45])
* Valkhoff VE et al. (2016). Bleeding Risk with Long-Term Low-Dose Aspirin (NSAIDs, clopidogrel, SSRIs all increase bleeding; PPI use protective). PLOS ONE 11(8):e0160046. [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160046\[^46\]](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160046\[%5E46])
* Lanas A et al. (2007). Association between aspirin and upper gastrointestinal complications: systematic review. Aliment Pharmacol Ther 26(2):187–202. [https://pmc.ncbi.nlm.nih.gov/articles/PMC2014603/\[^47\]](https://pmc.ncbi.nlm.nih.gov/articles/PMC2014603/\[%5E47])
* Bhatt DL et al. (2018). Helicobacter pylori doubles bleeding risk in aspirin users (co-presence of H. pylori >2× risk of upper GI bleed). RACGP News GP Sep 2018. [https://www1.racgp.org.au/newsgp/clinical/aspirin-doubles-bleeding-risk-for-people-with-comm\[^48\]](https://www1.racgp.org.au/newsgp/clinical/aspirin-doubles-bleeding-risk-for-people-with-comm\[%5E48])

ASPREE Investigator Group (2021). Aspirin Use With Cancer Incidence and Survival (ASPREE trial: increased cancer-associated death in elderly ≥65 with late-stage disease — important safety caveat). JAMA Network Open 4(1):e2033622. [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775219\[^7\]](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775219\[%5E7])

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