Apixaban

Mechanism

Aspirin irreversibly blocks platelet cyclooxygenase; apixaban directly inhibits factor Xa. Dual antithrombotic action roughly doubles major bleeding risk versus apixaban alone.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

Combine only for strict indications: after coronary stenting or in acute coronary syndrome. Limit aspirin to 75–100 mg/day, and dual therapy to 1–6 months. PPI cover with pantoprazole is mandatory.

Mechanism

Amiodarone moderately blocks P-glycoprotein and CYP3A4 – two apixaban clearance routes. Apixaban plasma levels rise by about 50%, with a modest bleeding risk increase.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

The combination is acceptable without dose change in patients with atrial fibrillation. In elderly patients weighing ≤60 kg or with serum creatinine ≥133 µmol/L, reduce apixaban to 2.5 mg twice daily. PPI cover with pantoprazole is advisable.

Mechanism

Clarithromycin blocks CYP3A4 and P-glycoprotein – two apixaban clearance routes. Apixaban levels rise by about 60%, and bleeding risk increases.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

Avoid where possible. Alternative antibiotics: azithromycin or doxycycline. If clarithromycin is required, reduce apixaban to 2.5 mg twice daily only when at least two of these apply: age ≥80, weight ≤60 kg, serum creatinine ≥133 µmol/L.

Mechanism

Apixaban directly inhibits factor Xa; clopidogrel blocks the platelet P2Y12 receptor. The two antithrombotic mechanisms add up.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

Dual therapy is used after acute coronary syndrome or stenting in atrial fibrillation, generally for no more than 1–6 months. Apixaban dose is selected according to age, weight, and renal function. PPI cover with pantoprazole is mandatory.

Mechanism

Dexamethasone is a CYP3A4 and P-glycoprotein inducer. It reduces apixaban (a substrate of both) levels by 30–50%, raising thrombotic event risk.

Symptoms

The patient feels no symptoms. Stroke risk in atrial fibrillation rises, as do deep vein thrombosis and pulmonary embolism risks.

Management

For prolonged systemic dexamethasone, do not increase apixaban (no titration data); switch to warfarin with INR monitoring instead. For short dexamethasone pulse therapy (1–3 days), no clinically significant effect.

Mechanism

Apixaban inhibits factor Xa; diclofenac injures the gastric mucosa and reduces platelet aggregation. Diclofenac additionally raises cardiovascular event risk, which matters in atrial fibrillation patients.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

Avoid where possible. If diclofenac is needed for a short course, use the minimum effective dose for no more than 5–7 days under pantoprazole cover. For chronic analgesia, choose paracetamol, celecoxib, or topical NSAIDs.

Mechanism

Dronedarone is a strong P-glycoprotein and CYP3A4 inhibitor – two apixaban clearance routes. Apixaban plasma levels rise by 30–60%; bleeding risk increases.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black stools, blood in urine. Severe cases include gastrointestinal or intracranial haemorrhage.

Management

The combination is acceptable without dose change in patients under 80, weight above 60 kg, serum creatinine below 133 µmol/L. In older patients with two of these factors, reduce apixaban to 2.5 mg twice daily.

Mechanism

Efavirenz induces CYP3A4 and P-gp. Apixaban falls 50% – stroke risk in AF.

Symptoms

Ischemic stroke or recurrent VTE.

Management

Alternative ARV – dolutegravir, or alternative anticoagulant – warfarin with INR 2.5-3.5.

Mechanism

Escitalopram (SSRI) depletes the platelet serotonin pool, impairing primary haemostasis. Apixaban inhibits factor Xa. Combined, GI bleeding risk rises 1.5- to 2-fold.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black tarry stools, blood in urine. Severe cases include gastrointestinal or intracranial haemorrhage.

Management

The combination is acceptable. PPI cover with pantoprazole is mandatory. Alternative antidepressants with minimal platelet effect: mirtazapine or agomelatine.

Mechanism

Apixaban inhibits factor Xa; ibuprofen (NSAID) injures the gastric mucosa and transiently inhibits platelet aggregation. The GI bleeding risk is additive.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

Avoid where possible. If a short ibuprofen course is needed, use the minimum effective dose for no more than 5–7 days under pantoprazole cover. For chronic analgesia, choose paracetamol, a selective COX-2 inhibitor (celecoxib), or topical NSAIDs.

Mechanism

Apixaban inhibits factor Xa, while ketorolac is the most potent available NSAID. Ketorolac injures the gastric mucosa and inhibits platelet aggregation. Massive GI bleeding risk increases several-fold. FDA Toradol Section 4.3 lists anticoagulants as contraindications.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

The combination is not prescribed. For analgesia in a patient on apixaban, use paracetamol (up to 3 g/day), metamizole, or a short opioid course. Ketorolac courses never exceed 5 days under any circumstances.

Mechanism

Apixaban is a direct factor Xa inhibitor; meloxicam blocks platelet function and injures the GI mucosa. Additive GI bleeding risk increases 2- to 3-fold.

Symptoms

Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.

Management

Avoid prolonged combination. If meloxicam is needed for a short course, use the minimum effective dose for 5–7 days with pantoprazole cover. For chronic analgesia: paracetamol or celecoxib.

Mechanism

Similar to apixaban + meloxicam. Additive GI bleeding risk with an anticoagulant and NSAID.

Symptoms

Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.

Management

Avoid prolonged combination. If naproxen is needed for a short course, use the minimum effective dose for 5–7 days with pantoprazole cover. For chronic analgesia: paracetamol or celecoxib.

Mechanism

Rifabutin is a moderate CYP3A4 + P-gp inducer (2-3 fold weaker than rifampicin). Apixaban falls 30-40%. Lower risk than with rifampicin but still significant.

Symptoms

Reduced anticoagulation, thrombosis risk.

Management

If possible – warfarin to INR 2.0-3.0.

Mechanism

Sertraline (SSRI) depletes the platelet serotonin pool and impairs primary haemostasis. Combined with apixaban, upper GI bleeding risk roughly doubles.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

The combination is acceptable when antidepressant therapy is needed. PPI cover with pantoprazole is advisable. Alternative antidepressants with minimal platelet effect: mirtazapine or agomelatine.