Aspirin 81 mg (Bayer Aspirin Low Dose) — most widely used LDA formulation in North America · Ecotrin (enteric-coated aspirin 81 mg and 325 mg) — note: enteric coating delays and reduces peak absorption; some evidence suggests plain (non-enteric) aspirin may produce more reliable antiplatelet effect · Disprin (dispersible aspirin 75 mg) — widely used in UK and Commonwealth countries for LDA · Micropirin 75 mg (modified-release aspirin) — UK formulation · Cardiprin 100 mg — Australia · Aspro Clear (effervescent aspirin) — UK/Europe · Nu-Seals 75 mg and 300 mg (enteric-coated) — UK · Acetylsalicylic acid (generic, multiple manufacturers) — 75 mg, 81 mg, 100 mg, 150 mg, 300 mg, 325 mg, 500 mg tablets available globally · Note: Plain (non-enteric-coated) aspirin 75–150 mg is pharmacokinetically preferred for antiplatelet effect in pregnancy — enteric coating delays absorption and may reduce peak platelet inhibition, though steady-state platelet inhibition at once-daily dosing is equivalent with either formulation in most studies
Clinical safety rating: caution
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Irreversibly inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) via acetylation, reducing prostaglandin and thromboxane A2 synthesis. Also activates lipoxin biosynthesis (inflammation resolution).
| Metabolism | Hepatic metabolism via hydrolysis by esterases to salicylic acid; salicylic acid undergoes conjugation with glycine (salicyluric acid) and glucuronic acid. CYP450 minimally involved. Excretion primarily renal (alkaline urine accelerates excretion). |
| Excretion | Renal excretion of salicylates (75-85% as salicyluric acid, 10% as free salicylic acid, 5-10% as glucuronide conjugates); dose-dependent, with renal clearance decreasing at higher doses due to saturation of metabolic pathways. Biliary/fecal elimination is minimal (<5%). |
| Half-life | 30 minutes for aspirin (parent drug); salicylic acid: 2-3 hours after low doses, 15-30 hours after high doses due to saturable metabolism and renal reabsorption. Clinical context: prolonged half-life in overdose, renal impairment, and elderly patients. |
| Protein binding | 80-90% bound to albumin (dose-dependent: lower binding at higher concentrations due to saturation). |
| Volume of Distribution | 0.15-0.2 L/kg for aspirin; 0.1-0.2 L/kg for salicylic acid. Clinical meaning: distributes into most body tissues and crosses placenta; increased Vd in acidosis due to trapping of ionized salicylate. |
| Bioavailability | 50-75% (oral) due to first-pass metabolism in gut and liver; complete with IV administration; rectal absorption is erratic (80% relative to oral). |
| Action Class | NSAID's- Non-Selective COX 1&2 Inhibitors (Salicylates) |
325-650 mg PO q4-6h prn; max 4 g/day
| Renal impairment | GFR 10-50: 50% dose increase interval; GFR <10: avoid or extend interval to q12h |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B/C: avoid use |
| Pediatric use | 10-15 mg/kg PO q4-6h; max 60 mg/kg/day; avoid in viral illness due to Reye syndrome risk |
| Geriatric use | Start at lowest effective dose; monitor renal function and bleeding risk; avoid if CrCl <30 mL/min |
| 1st trimester | Low-dose aspirin (75–150 mg/day): Safe and recommended. Initiate between 12+0 and 16+0 weeks (optimally by 12–13 weeks based on ASPRE data) for preeclampsia prevention in women meeting high-risk criteria (prior preeclampsia, chronic hypertension, diabetes, renal disease, autoimmune disease, multifetal gestation, or combined first-trimester screening-based risk ≥1:100). Evening bedtime dosing preferred. No increased risk of miscarriage at LDA doses — reassuring data from ASPRE (n=1,776) and the CLASP trial. High-dose aspirin: some case-control studies have associated first-trimester high-dose NSAID/aspirin use with gastroschisis and cardiac septal defects; data are not conclusive but the precautionary principle applies. Paracetamol is the preferred analgesic in T1. Aspirin should not be used for fever management in T1 (or any trimester) when paracetamol is available. |
| 2nd trimester | Low-dose aspirin: Safe. Continue LDA throughout T2 for preeclampsia prevention and APS management. No ductal or renal fetal toxicity at low doses — prostaglandin inhibition insufficient at 75–150 mg to affect ductal tone or fetal renal function. Monitor uterine artery Doppler at 20–24 weeks as part of preeclampsia surveillance. High-dose aspirin (≥325 mg): should be avoided after 20 weeks per FDA 2020 Drug Safety Communication. If NSAID-level aspirin was used before 20 weeks, reassess and discontinue or switch to paracetamol. If continued between 20–30 weeks for compelling indications (rare), serial ultrasound for amniotic fluid volume and ductal Doppler is recommended per FDA guidance. |
| 3rd trimester | Low-dose aspirin: Continue until 36 weeks (ACOG) or 37 weeks (some guidelines) if prescribed for preeclampsia prevention, then discontinue to reduce bleeding risk at delivery. Women with APS or mechanical heart valves may continue under specialist guidance with anaesthetic team communication. Neuraxial anaesthesia (epidural/spinal) is generally considered safe with LDA alone per OAA/AAGBI and ASRA guidelines — no mandatory washout period required for 75–100 mg/day if no other anticoagulants co-prescribed. High-dose aspirin: absolutely contraindicated in T3. After 32 weeks, the risk of premature ductal arteriosus closure is high and the ductus is exquisitely sensitive to prostaglandin inhibition — even short courses of analgesic-dose aspirin can cause rapid and potentially irreversible ductal constriction, neonatal pulmonary hypertension, and death. Additionally, high-dose aspirin inhibits myometrial prostaglandin synthesis, potentially prolonging labour and increasing postpartum haemorrhage risk. |
■ FDA Black Box Warning
Reye syndrome risk in children and adolescents with viral illness (e.g., influenza, chickenpox); avoid in patients aged <16 years with viral infection unless specifically indicated (e.g., Kawasaki disease). Use of NSAIDs after coronary artery bypass graft (CABG) surgery is contraindicated.
| Serious Effects |
Known hypersensitivity to aspirin or salicylates — including aspirin-exacerbated respiratory disease (AERD / Samter's triad: aspirin hypersensitivity, asthma, and nasal polyposis); aspirin may trigger life-threatening bronchospasm in AERD patients.Known hypersensitivity to other NSAIDs with cross-reactivity to aspirin.High-dose aspirin (≥325 mg) after 32 weeks gestation: contraindicated due to high risk of premature closure of the ductus arteriosus, neonatal pulmonary hypertension, and peripartum haemorrhage. This is an absolute contraindication regardless of indication.Active peptic ulcer disease or significant GI bleeding — aspirin exacerbates mucosal damage and impairs platelet-mediated haemostasis; even LDA increases GI bleeding risk in the presence of active ulceration.Haemophilia or other hereditary coagulation disorders — aspirin's antiplatelet effect combined with coagulopathy creates an unacceptable haemorrhagic risk.Concomitant anticoagulation with therapeutic-dose warfarin or direct oral anticoagulants (DOACs) without specific indication for dual therapy (e.g., mechanical heart valve + APS) — risk of serious haemorrhage is substantially elevated; DOACs are generally contraindicated in pregnancy separately.Severe hepatic failure (Child-Pugh C) — impaired coagulation factor synthesis plus aspirin antiplatelet effect creates high haemorrhagic risk; aspirin also hepatotoxic at high doses.Severe renal impairment (eGFR <10 mL/min) — aspirin further reduces renal prostaglandin-dependent blood flow and may precipitate acute kidney injury; salicylate accumulation risk due to impaired excretion.Concomitant methotrexate use at doses >15 mg/week — aspirin inhibits renal tubular secretion of methotrexate, raising methotrexate levels to potentially toxic concentrations (haematological and hepatic toxicity). Note: methotrexate is contraindicated in pregnancy independently.
Loading safety data…
| Onset of Action | Analgesic/antipyretic: 30-40 minutes (oral). Antiplatelet: 60 minutes (oral); immediate with chewing or IV administration (immediate). |
| Duration of Action | Analgesic/antipyretic: 3-4 hours (oral). Antiplatelet: 7-10 days (irreversible COX-1 inhibition, platelet lifespan). |
| Molecular Weight | Aspirin (acetylsalicylic acid): 180.16 g/mol. The low molecular weight facilitates rapid GI absorption and efficient placental transfer. Salicylate (the primary active metabolite): 138.12 g/mol. |
Clinical note
Aspirin has a profoundly dose-dependent safety and indication profile in pregnancy that mandates clear clinical distinction between low-dose (75–100 mg/day, antiplatelet) and high-dose (≥325 mg, analgesic/anti-inflammatory) use. Low-dose aspirin (LDA) is a cornerstone intervention in obstetric medicine: ACOG, USPSTF (Grade B recommendation), WHO, NICE, and FIGO all recommend initiating LDA at 12–16 weeks gestation (optimally before 16 weeks, ideally by 12 weeks) in women at increased risk of preeclampsia, reducing its incidence by approximately 10–24% overall and by up to 62% when initiated before 16 weeks in high-risk women (ASPRE trial). LDA is also used for antiphospholipid syndrome (APS), prevention of recurrent pregnancy loss in APS, and thromboprophylaxis in specific haematological conditions. High-dose aspirin functions as a full NSAID and carries the class risks of premature closure of the ductus arteriosus (particularly after 20 weeks, critically so after 32 weeks), fetal renal impairment, oligohydramnios, inhibition of labour, and maternal and fetal haemostatic compromise. High-dose aspirin should be avoided after 20 weeks of gestation and is contraindicated after 32 weeks. The FDA issued a Drug Safety Communication in 2020 strengthening warnings against NSAID use (including high-dose aspirin) from 20 weeks onwards.
| Placental transfer | Yes — aspirin and its primary metabolite salicylate cross the placenta readily by passive diffusion, facilitated by aspirin's low molecular weight (180 g/mol) and moderate lipophilicity. Umbilical cord blood salicylate concentrations approximate maternal plasma levels, with cord:maternal ratios approaching 1.0 with sustained maternal exposure. Fetal plasma protein binding of salicylate is lower than maternal (fetal albumin has reduced salicylate-binding affinity), resulting in higher free salicylate fractions in fetal plasma — potentially amplifying fetal exposure relative to total plasma concentrations. At low doses (75–100 mg/day), transplacental salicylate exposure is clinically minimal and does not cause measurable fetal platelet inhibition at term under standard monitoring. At analgesic doses, particularly with prolonged use, fetal salicylate accumulation can occur. Aspirin itself (the acetylated form) is rapidly hydrolysed to salicylate in plasma and at the intestinal wall, so the primary transplacental species is salicylate rather than aspirin per se. |
| Breastfeeding | Aspirin is excreted into breast milk as salicylate. Following a single 650 mg maternal dose, peak milk salicylate concentrations of approximately 1.1–10 mg/L have been reported, with milk:plasma ratios of approximately 0.03–0.08. At low doses (75–100 mg/day), infant salicylate exposure via breast milk is minimal and the relative infant dose (RID) is estimated to be well below 1% of the maternal weight-adjusted dose — considered negligible. The primary concern with aspirin in breastfeeding is the theoretical risk of Reye syndrome — a rare but serious condition of hepatic encephalopathy associated with salicylate exposure during viral illness (influenza, varicella) in infants and children. No cases of Reye syndrome have been specifically attributed to breast milk aspirin exposure at low doses, but the theoretical risk is the basis for caution. Practical guidance: low-dose aspirin (75–100 mg/day) for maternal indications (preeclampsia prevention, APS, cardiac) is compatible with breastfeeding. High-dose or repeated analgesic-dose aspirin should be avoided — use paracetamol (acetaminophen) instead. Avoid breastfeeding during maternal influenza or varicella illness if taking any aspirin dose. Monitor infant for unusual bruising or bleeding (theoretical antiplatelet effect via breast milk is negligible at low doses but theoretically possible at high doses). |
| Lactation Rating | L3 — Moderately safe for low-dose (75–100 mg/day); L4 — Possibly hazardous for high-dose or prolonged use (Hale's Lactation Risk Category). Low-dose aspirin is widely considered compatible with breastfeeding by WHO, AAP (historically listed as compatible), and most obstetric formularies. High-dose aspirin should be avoided in breastfeeding mothers. |
| Teratogenic Risk | First trimester: Crosses placenta; case-control studies suggest small increased risk of gastroschisis (OR 1.5-2.0) with use near conception; avoid if possible. Second trimester: Relatively safe at low doses (e.g., 81 mg), but high doses associated with premature ductus arteriosus constriction and oligohydramnios. Third trimester: Contraindicated after 30 weeks due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal bleeding (platelet dysfunction). |
| Fetal Monitoring | Maternal: Periodic blood pressure, urine protein for preeclampsia surveillance. Fetal: Ultrasound for ductus arteriosus patency and amniotic fluid index if used in third trimester. In high-dose or chronic use, monitor fetal growth and placental function. |
| Fertility Effects | Aspirin may impair female fertility by inhibiting prostaglandin synthesis, which is essential for ovulation and embryo implantation. Use for analgesia doses may reduce fertility; low-dose aspirin for antiplatelet effects may have no adverse impact. Male fertility: No significant adverse effects reported. |
| Precautions | Increased bleeding risk (GI, intracranial) especially with alcohol use, anticoagulants, or other NSAIDs, GI adverse effects: dyspepsia, gastritis, peptic ulcer disease (use with PPI if high risk), Reye syndrome (children/adolescents with viral illness), Hypersensitivity reactions (including asthma exacerbation, anaphylaxis), Surgery: discontinue 5-7 days prior (bleeding risk) unless cardiovascular indication, Pregnancy: avoid in third trimester (premature closure of ductus arteriosus, oligohydramnios); may be used for preeclampsia prevention in first/second trimesters under guidance, Renal impairment: can reduce renal function; avoid in severe renal failure, Hepatic impairment: risk of salicylate toxicity; reduce dose |
| Food/Dietary | Avoid alcohol; combination increases risk of gastric mucosal injury and bleeding. No specific dietary restrictions, but taking with food can mitigate GI irritation. High-dose aspirin may reduce vitamin C absorption and increase excretion; consider adequate vitamin C intake. No interaction with grapefruit juice. |
| Clinical Pearls | Aspirin irreversibly acetylates cyclooxygenase-1 (COX-1), inhibiting thromboxane A2 synthesis and platelet aggregation for the platelet's lifespan (7-10 days). Low-dose (75-100 mg/day) is preferred for cardioprotection. Avoid in children with viral illness due to Reye's syndrome risk. Enteric coating reduces GI irritation but may delay absorption, making chewable or immediate-release preferred for acute MI. Monitor for bleeding, especially in elderly or those on anticoagulants. Discontinue 7 days before elective surgery. |
| Patient Advice | Take with food or a full glass of water to reduce stomach upset. · Do not crush or chew enteric-coated tablets; swallow whole. · If you miss a dose, take it as soon as you remember unless it's almost time for the next dose; do not double the dose. · Seek medical attention for signs of bleeding: black/tarry stools, blood in urine or vomit, easy bruising, or prolonged bleeding from cuts. · Avoid alcohol while taking aspirin as it increases risk of stomach bleeding. · Tell all healthcare providers you are taking aspirin, especially before surgery or dental procedures. · Do not give aspirin to children or teenagers with flu-like symptoms or chickenpox due to risk of Reye's syndrome. · If taking for heart attack prevention, do not stop suddenly without consulting your doctor. |