Anti-Thrombotic Medications

Drugs can affect coagulation and haemostasis by acting on:

1. Platelet aggregation

2. The coagulation pathway

3. Fibrinolysis

Types of drugs that inhibit thrombus formation include:

1. Antiplatelet agents

   • Salicylate / Selective COX-1 inhibitor (Aspirin)

   • Phosphodiesterase inhibitor (Dipyridamole)

     • Synergistic effect with aspirin; commonly used in combination

   • P2Y₁₂ inhibitor (Clopidogrel, Prasugrel, Ticagrelor)

     • 10-40% of population will have a reduced response to Clopidogrel due to pharmacogenomic variability

   • GP IIb/IIIa inhibitors (Eptifibatide, Tirofiban)

     • Synergistic effect with aspirin commonly used in combination

   • Inhibitors of platelet function are mostly used short-term in settings where monitoring of prothrombin time (PT), activated partial thromboplastin time (aPTT), CrCl, platelet count, haemoglobin and haemotocrit is provided.

2. Anticoagulants

   • Heparins (low molecular weight heparins: dalteparin, danaparoid, enoxaparin, nadroparin)

     • These drugs are large molecules with poor oral bioavailability, so must be administered parenteraly through subcutaneous or intravenous routes to achieve therapeutic effects.

     • Heparin is administered as continuous IV infusion, usually in a hospital with the dose individualised based on the aPTT

     • LMWH and fondaparinux are administered once or twice daily by subcutaneous injection which can be self-administered from pre-filled syringes

     • Dose is based on body weight and monitoring of their anticoagulant effect is not usually required

     • The rapid onset and offset of heparin are useful for patients who require anticoagulation during and after surgery

     • Parenteral administration limits their clinical use

   • Synthetic heparin (Fondaparinux)

   • Vitamin K antagonists (Warfarin)

   • Direct thrombin inhibitors (DOACs) (Dabigatran)

     • DOACs have many advantages over warfarin, like more predictable pharmacokinetics, faster onset and offset, less need for regular monitoring and fewer drug interactions

     • As the DOACs work directly in the blood stream at the site of clot formation, they start working within 12-16 hours of the first dose. This rapid onset is also associated with rapid offset, which allows for significant reduction of effect if the drug is temporarily stopped prior to surgery

     • Regular monitoring is not required due to the more predictable pharmacokinetics of DOACs

     • A drawback is only one DOAC, dabigatran, currently has a specific antidote although others are in the pipeline

     • Antidotes are only required prior to major surgery or in overdose, it is not relevant to dental practice

   • Factor Xa inhibitors (Apixaban, Rivaroxaban) are effective anticoagulants as they prevent the formation of thrombin (rather than blocking the effect of thrombin) and work at the amplification site of the coagulation process. As they inhibit both free Factor Xa and Factor Xa interacting with platelets they are called ‘direct’ oral anticoagulants

   • Do not cause acute GI haemorrhage per se, but their use may increase the risk of bleeding in patients with pre-existing conditions

3. Thrombolytics

4. Selective NSAIDS

   • Aspirin is a COX-1 selective non-steroidal anti-inflammatory drug

   • Corticosteroids in the usual therapeutic doses have no influence on GI hemorrhage; however, caution should still be exercised as they can exacerbate existing conditions.

   • COX-2 specific inhibitors have less effect on the COX-1 enzyme in the gastric mucosa, but still produce gastric mucosal damage although less than with other conventional NSAIDs

   • COX-2 specific inhibitors are often preferred in patients at a higher risk for gastrointestinal complications, as they provide anti-inflammatory effects while minimising the adverse effects associated with COX-1 inhibition

   • Use of COX-2 specific inhibitors however is limited by concern regarding cardiovascular side effects

5. Non-selective NSAIDs

   • Most frequently used drugs are: diclofenac, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, naproxen, piroxicam

   • Reversibly binds to COX-1 on platelets (unlike aspirin which binds irreversibly) causing inhibition of TXA2 production and platelet aggregation, which can lead to increased bleeding risk

   • NSAID-associated bleeding can occur anywhere in the body but the most likely location is in the GI tract

   • Short half-life NSAIDs such as ibuprofen does not produce a clinically significant risk of postoperative bleeding

   • Continuous use of non-selective NSAIDs prior to a procedure can contribute to increased risk of intra- and postoperative bleeding, especially in patients with other risk factors

   • Inhibits COX pathway, which also depletes mucosal prostaglandins, which leads to gastric mucosal damage from targeting COX-1 enzymes found there, increasing the risk of gastrointestinal bleeding, especially in patients with a history of ulcers or those taking other medications that affect gastric mucosa

     • 50% of patients taking regular NSAIDs (even 75 mg/day) will develop gastrointestinal (duodenal, gastric) mucosal damage (erosions, ulcers)

     • 30% will have ulcers on endoscopy

     • 5% (a small proportion) will have symptoms

     • 1-2% will have a major problem i.e. GI bleed

     • H. pylori and NSAIDs are independent and synergistic risk factors for the development of ulcers, highlighting the importance of careful management in patients on anti-thrombotic therapy

     • The odds ratio (OR) for the incidence of peptic ulcer was 61.1

   • Prophylactic use of PPI with NSAID is indicated for all high-risk patients, i.e. > 65 years, history of peptic ulcer (particularly those with complications), on therapy with corticosteroids or anticoagulants, has co-morbidity (cardiac failure, IHD, chronic kidney disease, malignant disease, chronic liver disease)

6. Serotonergic antidepressants

   • Antidepressants which inhibit serotonin reuptake can impair platelet aggregation by inhibiting the reuptake of serotonin on platelets, potentially increasing the risk of bleeding in patients already taking anti-thrombotic medications

   • Serotonin is a factor involved in platelet aggregation but platelets are unable to make their own serotonin so they acquire it from the bloodstream. This means that any alterations in serotonin levels, such as those caused by serotonergic antidepressants, can significantly affect platelet function and increase bleeding risk

   • The main bleeding risk associated with selective serotonin reuptake inhibitors (SSRIs) is GI bleeding. Estimated risk is 1.55 to 3.6 times higher than that of non-users

   • Venlafaxine (SNRI) and its active metabolite desvenlafaxine (SNRI) have also been shown to increase bleeding risk

   • The combination of SSRI and NSAID increases the risk of bleeding between 4.25 and 12.2 times

   • Since antidepressants can’t be abruptly ceased prior to surgery, their additional bleeding risk should be considered when contemplating use of NSAIDs for postoperative pain management in people taking SSRIs or SNRIs

   • As antidepressants must be ceased gradually over several weeks, they should not be stopped prior to dental procedures unless there was a very high risk of bleeding with potential catastrophic consequences

   • Antidepressants are rarely ceased prior to surgery due to high risk of withdrawal syndrome. If indicated, withdrawal should be done under close medical supervision with gradual dose tapering over 2-4 weeks as outlined in Therapeutic Guidelines Psychotropic

7. Medications associated with thrombocytopenia e.g. cytotoxics, immunomodulators

   • Thrombocytopenia is a reduced platelet count, which is typically defined as a platelet count of < 150 × 10⁹/L and can lead to increased bleeding risk during surgical procedures (usual reference range 15-450 × 10⁹/L)

   • Drug-induced thrombocytopenia (DITP) is an adverse effect associated with > 300 different drugs, including certain antibiotics, antiepileptics, and non-steroidal anti-inflammatory drugs (NSAIDs)

   • Mechanisms responsible for DITP include:

     1. Inhibition of platelet production in the bone marrow

     2. Increased destruction of circulating platelets in the blood stream by the formation of drug-induced platelet antibodies

     3. Increased elimination from the blood stream via the spleen

     4. Myelosuppression by antineoplastic agents causing depletion of all blood cell lines or specific to megakaryocytopoiesis

   • Signs of drug-induced thrombocytopenia:

     • Severe bleeding seen as purpura, petechiae, ecchymosis, easy bruising, prolonged bleeding from cuts

     • < 20 × 10⁹/L is considered severe thrombocytopenia and associated with major bleeding

     • DITP usually occurs around 5-10 days after starting the offending drug but some can induce thrombocytopenia hours after administration e.g. GP IIa/IIIb inhibitors (abciximab, eptifibatide) and heparin

   • Heparin is the most common drug associated with thrombocytopenia but is managed differently as it is also associated with a prothrombotic state

   • Conventional cytotoxic drugs, antineoplastic agents and targeted therapies are also typically associated with thrombocytopenia

   • Other drugs like quinine, GP IIb/IIIa inhibitors, some cephalosporins, and anticonvulsants are also rarely associated

   • Before any invasive procedure, the most recent blood test should be assessed to evaluate platelet count is within the standard range > 150 × 10⁹/L

8. Complementary medicines with antithrombotic effects e.g. garlic gingko biloba

   • Dong quai

   • Evening primrose

   • Fish oil

   • Garlic

   • Ginger

   • Ginkgo

   • Ginseng

   • Glucosamine

   • Turmeric

   • As platelets take up to 2 weeks to regenerate, the complementary medicines should be stopped 10-14 days prior to the procedure

Tranexamic Acid (TXA)

• Is an antifibrinolytic, pro-thrombotic agent used to manage bleeding in patients on warfarin (vitamin K antagonists)

• Is a synthetic derivative of lysine and works by preventing lysine from binding to plasminogen, inhibiting the activation of plasmin by plasminogen

• Plasmin breaks down the fibrin polymers in the blood clot (hence TXA works as an antifibrinolytic)

• When applied topically for oral surgery, TXA has low systemic absorption, making it an effective option for controlling localized bleeding while minimizing the risk of systemic side effects.

• It has not been shown to be effective in reducing bleeding in patients on other antithrombotics, including DOACs

• Recommended use is 4.8% concentration applied topically at the surgical site, followed by use as a mouthwash for 2 days post procedure as an adjunctive measure for patients taking warfarin

Anti-thrombotic medications and their mechanisms of actions:

1. Aspirin (acetylsalicylic acid) (Brand names: Astrix, Cartia, etc)

• Indication for Use: Cardiovascular protection, reduces risk of heart attack and stroke. Aspirin is no longer recommended for primary prevention of CVD because clinical trials have shown that the benefit of aspirin for primary prevention of CV events is outweighed by the risk of bleedingin individuals without a history of cardiovascular disease. Therefore, it is typically prescribed only for secondary prevention in patients who have already experienced a cardiovascular event. It has antiplatelet, antipyretic and analgesic properties

• Mode of Action: Inhibits platelet aggregation by irreversibly acetylating cyclooxygenase-1 (COX-1) enzyme on the surface of platelets, leading to decreased thromboxane A2 (TXA2) production which is essential for platelet activation and aggregation. As aspirin’s inactivation of platelet activity is permanent, it lasts for the remaining lifetime of the platelet which is 7-10 days

• Drug Class: Antiplatelet agent | Salicylate

• Mode of Administration: Oral

• Half-life: Approximately 15-20 minutes

• Effect Duration: 7-10 days due to permanent inactivation of platelet function rather than affecting its half-life. Recovery of platelet function occurs once sufficient new platelets are formed after the drug is discontinued - generally a further 10 days

• Surgical Guidelines: Generally advised to discontinue 5-7 days before surgery. Recommence 24 hours after surgery, unless contraindicated.

• Reversal Agents: No specific reversal agent, manage bleeding as necessary.

2. Dipyridamole (Brand names: Persantin, Asasantin)

• Indication for Use: Prevention of thromboembolism, TIA, ischaemic stroke

• Mode of Action: Reversibly inhibits platelet aggregation by:

  1. Inhibiting adenosine reuptake into erythrocytes and endothelial cells, allowing for increased adenosine binding on platelets, resulting in an increased blood flow and reduced platelet aggregation, increased vasodilation

  2. Inhibiting the enzyme phosphodiesterase (PDE), resulting in increased cAMP levels in platelets, reducing their ability to aggregate and form clots

  • When used alone, has a weak, reversible antiplatelet effect that is lost after ~24 hrs following cessation; however, when combined with other antiplatelet agents, this effect can be enhanced, providing a more substantial inhibition of platelet aggregation and reducing the risk of thrombotic events.

• Drug Class: Antiplatelet agent

• Mode of Administration: Oral

• Half-life: Approximately 10-12 hours

• Surgical Guidelines: May continue during surgery depending on the procedure; assess bleeding risk

• Reversal Agents: No specific reversal agents.

3. Clopidogrel (Brand names: Plavix, Iscover)

• Indication for Use: Prevention of blood clots in patients with a history of heart attack or stroke

• Mode of Action: A P2Y12 receptor antagonist that inhibits ADP-induced platelet activation, leading to decreased platelet aggregation. This action can last beyond the drug's half-life due to irreversible binding to the receptor.

• Drug Class: Antiplatelet agent

• Mode of Administration: Oral

• Half-life: Approximately 6 hours (active metabolite longer)

• Surgical Guidelines: Discontinue 5-7 days before surgery, resumption depends on bleeding risk

• Reversal Agents: No specific antidote, platelet transfusions may be used in emergencies.

4. Prasugrel (Brand name: Effient)

• Indication for Use: Prevention of thrombotic cardiovascular events

• Mode of Action: A potent P2Y12 inhibitor that irreversibly binds to the ADP receptor on platelets, leading to reduced platelet activation and aggregation even after drug clearance.

• Drug Class: Antiplatelet agent

• Mode of Administration: Oral

• Half-life: Approximately 7 hours

• Surgical Guidelines: Discontinue 7 days before surgery; may resume 24 hours post-surgery, depending on bleeding risk

• Reversal Agents: No specific reversal agent, consider platelet transfusion if necessary.

5. Ticagrelor (Brand name: Brilanta)

• Indication for Use: Protection against thrombotic events

• Mode of Action: A reversible P2Y12 receptor antagonist that inhibits ADP-mediated platelet activation, providing a rapid and potent antiplatelet effect. Unlike clopidogrel, it does not require metabolic activation.

• Drug Class: Antiplatelet agent

• Mode of Administration: Oral

• Half-life: Approximately 12 hours

• Surgical Guidelines: Discontinue 5 days before surgery; resumption depends on bleeding and thrombotic risk

• Reversal Agents: No specific reversal agents; manage bleeding accordingly.

6. Low Molecular Weight Heparins (LMWH) (Brand names: Dalteparin, Danaparoid, Enoxaparin)

• Background: Heparin comprises a family of mucopolysaccharides naturally present in mast cells. LMWH are fragments of heparin that provide anticoagulation with a more predictable response and longer half-life compared to unfractionated heparin. Heparin, LMWHs and fondaparinux have no intrinsic anticoagulant activity

• The rapid onset and offset of heparin are useful for patients who require anticoagulation during and after surgery

• Parenteral application limits their clinical use

• Indication for Use: Prevention and treatment of thromboembolic disorders, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

• Mode of Action: Bind to and activate antithrombin III, an endogenous anticoagulant, leading to inhibition of clotting Factors Xa, IIa (thrombin) and some serine proteases in the coagulation cascade, preventing clot formation. While LMWH activates antithrombin IIII, it predominantely inhibits Factor IIa only

• Drug Class: Anticoagulant.

• Mode of Administration: Subcutaneous (SC).

• Half-life: Approximately 2-4 hours (varies by specific drug).

• Bioavailability: Approximately 87-100% (higher than unfractionated heparin due to reduced interactions with plasma proteins).

• Maximum Effect Time: 3-5 hours.

• Effect Duration: 12-24 hours after administration.

• Surgical Guidelines: Typically, LMWH is discontinued 24 hours before surgery and can be restarted 24 hours post-surgery, provided there are no bleeding complications.

• Reversal Agent: Protamine sulfate can partially reverse the effects, but it is not as effective as with unfractionated heparin.

• Monitoring Parameters: Complete blood count (CBC) for platelet count, renal function tests, anti-factor Xa, aPTT, and signs of bleeding. Regular monitoring may be necessary in patients with renal impairment or those at high risk for bleeding complications.

7. Fondaparinux

• Indications:

  • Prevention of deep vein thrombosis (DVT) in patients undergoing surgery (hip replacement, knee replacement, abdominal surgery).

  • Treatment of DVT and pulmonary embolism (PE) in conjunction with warfarin.

  • Prevention of thromboembolic disorders in patients with acute coronary syndrome (ACS).

• Mode of Action:

  • Fondaparinux is a synthetic pentasaccharide that selectively inhibits Factor Xa in the coagulation cascade.

  • By binding to antithrombin III, fondaparinux enhances its ability to inactivate Factor Xa, which prevents the conversion of prothrombin to thrombin, thereby reducing thrombus formation.

• Half-Life: Approximately 17 hours.

• Bioavailability: Approximately 100% (when administered subcutaneously).

• Maximum Effect: Achieved within 2-3 hours after subcutaneous administration.

• Effect Duration: Anticoagulant effects last for approximately 24-48 hours after the last dose.

• Surgical Guidelines: Discontinue at least 24 hours before surgery; can be resumed 48 hours post-surgery if no bleeding complications arise.

• Reversal Agents: There is no specific reversal agent for fondaparinux; manage bleeding as needed.

• Monitoring: Routine monitoring of anticoagulation levels is not required; however, watch for signs of bleeding, and renal function should be assessed periodically, especially in patients with renal impairment.

8. Heparin

• Indications:

  • Prevention and treatment of thromboembolic disorders, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

  • Management of acute coronary syndrome (ACS).

  • Prevention of clot formation during surgical procedures and in patients undergoing dialysis.

• Mode of Action:

  • Heparin works by binding to and activating antithrombin III, an endogenous anticoagulant, leading to inhibition of coagulation factors, primarily Factor Xa and thrombin (Factor IIa), thereby preventing the formation of clots.

• Half-Life: Approximately 1-2 hours (varies based on dose and patient factors).

• Bioavailability: Variable, generally around 30% (due to significant binding to plasma proteins and cellular components).

• Maximum Effect: Achieved within 30 minutes after intravenous (IV) administration.

• Effect Duration: Anticoagulant effects last approximately 2-6 hours after a dose, depending on the dose and route of administration.

• Surgical Guidelines: Discontinue heparin at least 4-6 hours before surgery; can be restarted 24 hours post-surgery if no bleeding complications are present.

• Reversal Agents: Protamine sulfate is used as a reversal agent for heparin; it can reverse its effects, but the efficacy depends on the amount of heparin administered.

• Monitoring: APTT (activated partial thromboplastin time) is commonly monitored to ensure therapeutic levels; also monitor for signs of bleeding and platelets (to assess for heparin-induced thrombocytopenia).

9. Warfarin

• Background:

  • Warfarin use is declining in the community due to preference for the new DOACs, which act more quickly and more predictably and don’t require regular anticoagulation monitoring

  • Warfarin has a narrow therapeutic index, and due to genetic, drug and dietary interactions, works slightly differently in everyone

  • S-warfarin is 4 times more potent than R-warfarin

  • Foods, drinks and nutritional supplements containing signification concentrations of vitamin K, including green leafy vegetables (such as spinach and kale), can interfere with warfarin's effectiveness and lead to fluctuations in INR levels. Therefore, patients on warfarin must maintain a consistent diet and communicate any changes in their eating habits to their healthcare provider. In contrast, DOACs, such as apixaban and rivaroxaban, offer a more stable anticoagulation effect without the need for dietary restrictions, making them a more convenient option for many patients.

  • Pharmacogenomic variation in the enzymes CYP2C9 and VKORC also affect the clinical response to warfarin and duration of action and offset

  • Penicillin antibiotics can increase the INR

• Indications:

  • Prevention and treatment of thromboembolic disorders, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

  • Atrial fibrillation to reduce the risk of stroke.

  • Prevention of thromboembolic complications in patients with mechanical heart valves.

  • For most indications, warfarin is usually prescribed in a dose to reach an INR between 2 and 3.5

• Mode of Action:

  • Warfarin inhibits vitamin K epoxide reductase in the liver, decreasing the synthesis of vitamin K-dependent clotting factors (Factors II, VII, IX, and X) and proteins C and S, thus leading to a reduction in overall coagulation activity.

• Half-Life:

  • Approximately 36-42 hours (subject to considerable variation).

• Bioavailability:

  • Approximately 100% when administered orally, but can vary based on individual factors.

• Maximum Effect:

  • Anticoagulant effect generally reaches its peak after 72-96 hours post-administration, as it depends on the depletion of existing clotting factors.

• Effect Duration:

  • Anticoagulant effects can last for 2-5 days after stopping the medication, depending on the patient's metabolism and the specific dose taken.

• Surgical Guidelines:

  • Typically, warfarin is discontinued 5 days before surgery; bridging anticoagulation may be used based on individual risk factors.

• Reversal Agents:

  • Vitamin K i.e. phytomenadione (oral or intravenous) can be used to reverse the effects of warfarin; prothrombin complex concentrates can be used for rapid reversal in urgent situations.

• Monitoring:

  • International Normalized Ratio (INR) is monitored regularly to ensure therapeutic levels; adjustments in dosage are made based on INR results.

  • INR should be checked within 24 hours before a procedure

  • INR < 4 is unlikely to cause any significant postoperative bleeding; however, if the INR is between 4 and 5, additional precautions should be taken, including possible reversal of anticoagulation

  • Other factors should also be considered like other drugs, underlying medical conditions and the procedure itself that may influence bleeding risk

  • The INR will only indicate the prolonged bleeding time due to warfarin. It does not reflect changes in platelet function, so if the patient is on antiplatelet agents these drugs will also elevate the patient’s bleeding risk without increasing the INR

10. Dabigatran (Brand name: Pradaxa)

• Background: Dabigatran etexilate is the pro-drug presented in the medication, which has no pharmacological activity and poor oral bioavailability (3-7%) so relatively high doses are given to ensure adequate efficacy. After oral administration and absorption, it undergoes transformation in the liver and plasma to dabigatran, which is the active form and confers the anticoagulant effect

• Dabigatran etexilate is a substrate of p-glycoprotein transport so other drugs that are substrates or inhibitors of p-glycoprotein can affect its gastrointestinal absorption and plasma concentrations; therefore, careful consideration must be given when co-administering these medications to avoid potential interactions that could lead to either increased bleeding risk or reduced efficacy

• It produces a more predictable and much faster clinical effect than warfarin

• ~80% of dabigatran is renally excreted so patients with impaired renal function require a lower dose, and dabigatran is contraindicated in patients with severe renal impairment (Cr/Cl < 30ml/min). Additionally, monitoring renal function is essential during treatment to ensure patient safety and to adjust dosages accordingly

• Indication for Use: Anticoagulation for atrial fibrillation and prevention of thromboembolism

• Mode of Action: Direct thrombin inhibitor (free, fibrin-bound and thrombin-induced platelet prevents conversion of fibrinogen to fibrin, effectively blocking the clotting process at the final step. This leads to reduced thrombus formation

• Drug Class: Direct oral anticoagulant (DOAC)

• Mode of Administration: Oral

• Half-life: Approximately 12-17 hours

• Surgical Guidelines: Discontinue 1-2 days before surgery (varies based on renal function); recommence after hemostasis

• Reversal Agents: Idarucizumab (Praxbind) for urgent reversal

  • It is a humanised monoclonal antibody specifically made as the antidote to dabigatran

  • Can be administered as an IV infusion or bolus IV injection

  • It binds to dabigatran in the blood stream, reversing the effect of dabigatran within 5 mins

  • It is generally used prior to emergency surgery to reduce the risk of major intraoperative bleeding

• Bioavailability:

  • Approximately 6.5% (lower due to extensive first-pass metabolism).

• Maximum Effect:

  • Achieved within 1-3 hours after administration.

• Effect Duration:

  • Anticoagulant effects can last approximately 24 hours.

• Monitoring:

  • Routine monitoring of anticoagulation levels is not required; however, renal function should be assessed periodically, especially in patients with renal impairment.

12. Rivaroxaban (Brand name: Xarelto)

• Background: rivaroxaban is a substrate for p-glycoprotein in the gut wall, and around 2/3rds undergoes hepatic metabolism by several CYP enzymes (including CYP3A4, CYP2J2 and others), hence it is subject to many drug interations that may affect its efficacy and safety profile. Careful consideration of concomitant medications is essential to avoid potential adverse effects

• Indication for Use: Anticoagulation for atrial fibrillation and deep vein thrombosis

• Mode of Action: Selectively inhibits Factor Xa, interrupting the coagulation cascade and preventing the formation of thrombin, thus inhibiting clot formation.

• Drug Class: Direct oral anticoagulant (DOAC)

• Mode of Administration: Oral

• Half-life: Approximately 5-9 hours

• Surgical Guidelines: Discontinue 24 hours before surgery for minor and 48 hours for major; recommence after hemostasis

• Reversal Agents: Andexanet alfa for urgent reversal

• Bioavailability: > 80% (highly affected by food)

• Maximum Effect: Achieved within 2-4 hours after administration

• Effect Duration: Anticoagulant effects last approximately 24 hours

• Monitoring: Routine monitoring of anticoagulation levels is not required; however, renal function should be assessed periodically, especially in patients with renal impairment.

13. Apixaban (Brand name: Eliquis)

• Background: apixaban is a substrate for p-glycoprotein and is metabolised by CYP3A4 and CYP3A5 so is susceptible to many drug interactions that can affect its efficacy and safety profile. It is crucial to review a patient's medication list thoroughly to prevent adverse effects.

• Renal excretion accounts for the elimination of ~27% of apixaban and it is contraindicated in indivviduals with severe hepatic or renal impairment (CrCl < 15ml/min)

• Indication for Use: Anticoagulation for atrial fibrillation and prevention of thromboembolism

• Mode of Action: Factor Xa inhibitor that blocks thrombin formation, preventing the conversion of fibrinogen to fibrin and hence clot formation.

• Drug Class: Direct oral anticoagulant (DOAC)

• Mode of Administration: Oral

• Half-life: Approximately 12 hours

• Surgical Guidelines: Discontinue 48 hours prior to surgery; can be resumed 24 hours after surgery if no bleeding complications

• Reversal Agents: Andexanet alfa for urgent reversal; Prothrombin complex concentrate may also be considered in certain situations

• Bioavailability: 50% (lower due to extensive first-pass metabolism)

• Maximum Effect: Achieved within 3-4 hours after administration

• Effect Duration: Anticoagulant effects can last approximately 24 hours

• Reversal Agent: Andexanet alfa is a specific reversal agent that neutralises the anticoagulant effects of Factor Xa inhibitors like apixaban. This is not available in Australia

• Monitoring: Routine monitoring of anticoagulation levels is not required; however, renal function should be assessed periodically, especially in patients with renal impairment.

14. Garlic Tablets

• Indication for Use: Cardiovascular health, does not replace anticoagulants

• Mode of Action: Exhibits antiplatelet effects by inhibiting platelet aggregation and may enhance nitric oxide production, contributing to vasodilation.

• Drug Class: Herbal supplement

• Mode of Administration: Oral

• Half-life: Not well-defined, varies by formulation

• Surgical Guidelines: Discontinue 7 days prior to surgery

• Reversal Agents: None recommended.

15. Ginkgo Biloba Tablets

• Indication for Use: Cognitive function enhancement

• Mode of Action: Has antioxidant properties and may inhibit the aggregation of platelets and improve blood circulation through vasodilation.

• Drug Class: Herbal supplement

• Mode of Administration: Oral

• Half-life: Not well understood

• Surgical Guidelines: Discontinue 7 days prior to surgery

• Reversal Agents: None recommended.

16. Dong Quai Tablets

• Indication for Use: Herbal remedy traditionally used for menstrual disorders, menopausal symptoms, and supporting overall women's health.

• Mode of Action: Believed to have estrogenic effects, supporting hormonal balance; may also promote blood circulation.

• Drug Class: Herbal supplement.

• Mode of Administration: Oral (usually in tablet or powder form).

• Half-Life: Not well-defined, varies by formulation and individual metabolism.

• Surgical Guidelines: Discontinue at least 2 weeks prior to surgery to reduce the risk of bleeding.

• Reversal Agents: None specific; manage bleeding as necessary.

• Bioavailability: Variable; depends on the formulation and individual absorption characteristics.

• Maximum Effect: Generally observed after prolonged use; specific timeframes not well-established due to individual variability.

• Effect Duration: Effects may last several days; again, highly variable among individuals.

17. Evening Primrose

• Indication for Use: Used primarily for conditions such as premenstrual syndrome (PMS), skin disorders such as eczema, and to support overall women's health, particularly in relation to hormonal balance.

• Mode of Action: Contains gamma-linolenic acid (GLA), an omega-6 fatty acid that is believed to help regulate hormonal levels and reduce inflammation.

• Drug Class: Herbal supplement.

• Mode of Administration: Oral (usually in capsule or liquid form).

• Half-Life: Not well-defined; varies based on formulation and individual metabolism.

• Surgical Guidelines: Discontinue use at least 2 weeks prior to surgery to minimize the risk of bleeding.

• Reversal Agents: None specific; manage bleeding as necessary.

• Bioavailability: Not well-documented; varies depending on formulation and individual absorption characteristics.

• Maximum Effect: Generally observed after several weeks of use; specific timeframes are not well-established due to individual variability.

18. Ginger

• Indication for Use: Used primarily for digestive issues such as nausea, motion sickness, and loss of appetite. It is also used to alleviate pain and inflammation in conditions like osteoarthritis.

• Mode of Action: Ginger contains bioactive compounds like gingerol that have anti-inflammatory and antioxidant properties. It may work by inhibiting the production of pro-inflammatory cytokines and improving gastrointestinal motility.

• Drug Class: Herbal supplement.

• Mode of Administration: Oral (available in various forms including fresh, dried, powder, and capsules).

• Half-Life: Not well defined; varies among individuals and depends on the form and concentration used.

• Surgical Guidelines: It is generally advisable to discontinue ginger at least 1-2 weeks prior to surgery to minimize bleeding risks, particularly if used in high doses.

• Reversal Agents: None specific; manage bleeding as necessary.

• Bioavailability: Varies depending on the formulation and individual absorption.

• Maximum Effect: Generally observed within 1-2 hours after ingestion for nausea; effects on inflammation may take longer with regular use.

• Effect Duration: The effects may last for several hours, but it may take regular use over days or weeks to observe a significant impact on chronic conditions.

19. Ginseng

• Indication for Use: Commonly used to enhance energy levels, reduce fatigue, improve cognitive function, and boost the immune system. It is also used to reduce stress and improve overall well-being.

• Mode of Action: Ginseng contains active compounds called ginsenosides which are believed to exert adaptogenic effects, helping the body to adapt to stress and enhancing physical and mental performance. It may also have anti-inflammatory and antioxidant properties.

• Drug Class: Herbal supplement.

• Mode of Administration: Oral (available in forms such as capsules, tablets, teas, and extracts).

• Half-Life: Not well-defined; varies among individuals and depends on the specific formulation used.

• Surgical Guidelines: Discontinue at least 1-2 weeks prior to surgery to minimize the risk of bleeding.

• Reversal Agents: None specific; manage bleeding as necessary.

• Bioavailability: Varies depending on the formulation and individual absorption characteristics.

• Maximum Effect: Effects on energy and cognitive function may be observed within a few hours after administration, but benefits might become more evident after prolonged use.

• Effect Duration: The effects may last several hours, with cumulative benefits noticed with continued use

20. Glucosamine

• Indication for Use: Commonly used to treat osteoarthritis and joint pain, helping to alleviate symptoms and improve joint function.

• Mode of Action: Glucosamine is an amino sugar that serves as a building block for cartilage. It is believed to help in the synthesis of glycosaminoglycans, which are essential for cartilage and joint health, potentially reducing inflammation and promoting cartilage repair.

• Drug Class: Herbal supplement (also categorized as a dietary supplement).

• Mode of Administration: Oral (available in capsule, tablet, or powder form).

• Half-Life: Generally around 1.5 to 2 hours, but this can vary depending on individual metabolism.

• Surgical Guidelines: It is advisable to discontinue glucosamine at least 1-2 weeks prior to surgery to minimize bleeding risks.

• Reversal Agents: None specific; manage bleeding as necessary.

• Bioavailability: Approximately 25% when administered orally, due to significant first-pass metabolism.

• Maximum Effect: May take several weeks to months of consistent use to observe significant effects on joint health and function.

• Effect Duration: Effects can last for several hours after administration

21. Turmeric

• Indication for Use: Commonly used for its anti-inflammatory and antioxidant properties; it may help with conditions such as arthritis, digestive disorders, and skin issues. Turmeric is also used to support overall health and boost the immune system.

• Mode of Action: Contains curcumin, which inhibits inflammatory pathways by blocking the activity of various mediators and enzymes involved in inflammation. It has antioxidant properties that help neutralize free radicals.

• Drug Class: Herbal supplement.

• Mode of Administration: Oral (available in forms such as capsules, powder, or as a spice in food).

• Half-Life: Approximately 1-2 hours, but effects may last longer due to cumulative benefits with regular use.

• Surgical Guidelines: It is generally advisable to discontinue turmeric at least 2 weeks prior to surgery to minimize the risk of bleeding, particularly in high doses.

• Reversal Agents: None specific; manage bleeding as necessary.

• Bioavailability: Low bioavailability; it is often recommended to consume turmeric with black pepper (which contains piperine) to enhance absorption.

• Maximum Effect: The maximum effect is usually observed after regular use over several weeks.

• Effect Duration: The effects may vary, but frequent use can contribute to longer-term health benefits.

22. Fish Oil

• Indication for Use: Fish oil is commonly used for cardiovascular benefits, including lowering triglyceride levels, and to support overall heart health. It is also used for inflammatory conditions, such as rheumatoid arthritis, and may help reduce symptoms of attention deficit hyperactivity disorder (ADHD) and improve cognitive function.

• Mode of Action: The omega-3 fatty acids in fish oil, particularly EPA and DHA, are thought to exert beneficial effects by reducing inflammation, lowering triglyceride levels, and promoting healthy blood vessel function.

• Drug Class: Nutritional supplement / Herbal supplement.

• Mode of Administration: Oral (available in forms including liquid, capsules, and tablets).

• Half-Life: Not well-defined; varies among individuals and depends on the specific formulation and dosage.

• Surgical Guidelines: Discontinue use at least 1-2 weeks prior to surgery to minimize the risk of bleeding.

• Reversal Agents: None specific; manage bleeding as necessary.

• Bioavailability: Variable; depends on the formulation and can be affected by individual absorption characteristics.

23. Ibuprofen (Brand names: Nurofen, Brufen)

• Indication for Use: Pain relief, anti-inflammatory

• Mode of Action: Nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX-1 and COX-2 enzymes, leading to reduced synthesis of prostaglandins and pain relief.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)

• Mode of Administration: Oral

• Half-life: Approximately 2-4 hours

• Surgical Guidelines: Discontinue 24-48 hours prior to surgery, resume as tolerated post-surgery

• Reversal Agents: None needed; manage bleeding as necessary.

• Bioavailability: Approximately 80-100% when administered orally.

• Maximum Effect: Usually reached within 1-2 hours after administration.

• Effect Duration: Generally lasts for 4-8 hours depending on the dose and individual factors.

24. Diclofenac (Brand names: Voltaren)

• Indication for Use: Pain relief, anti-inflammatory

• Mode of Action: NSAID that inhibits both COX-1 and COX-2 enzymes, reducing prostaglandin E2 levels associated with inflammation and pain.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)

• Mode of Administration: Oral, topical

• Half-life: Approximately 1-2 hours

• Surgical Guidelines: Discontinue 24 hours prior to surgery

• Reversal Agents: None; manage bleeding using conservative measures.

• Bioavailability: Approximately 80-100% when administered orally.

• Maximum Effect: Usually reached within 1-2 hours after administration.

• Effect Duration: Generally lasts for 4-8 hours depending on the dose and individual factors.

25. Ketorolac (Brand name: Toradol)

• Indication for Use: Short-term management of pain

• Mode of Action: NSAID that non-selectively inhibits COX enzymes, leading to decreased formation of pain mediators, prostaglandins, and inflammatory responses.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)

• Mode of Administration: Oral, parenteral

• Half-life: Approximately 5 hours

• Surgical Guidelines: Discontinue 24 hours before surgery

• Reversal Agents: None; manage bleeding as required.

• Bioavailability: Approximately 100% when administered intravenously; oral bioavailability is around 90%.

• Maximum Effect: Usually reached within 1-2 hours after administration.

• Effect Duration: Generally lasts for 4-6 hours, but may differ based on individual factors.

26. Indomethacin (Brand names: Indocid, Inza)

• Indication for Use: Pain and inflammation

• Mode of Action: Non-selective NSAID that inhibits COX-1 and COX-2 enzymes, reducing prostaglandin synthesis and thus alleviating inflammation and pain.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)

• Mode of Administration: Oral, rectal

• Half-life: Approximately 4.5 hours

• Surgical Guidelines: Discontinue 48 hours prior to surgery

• Reversal Agents: None; bleeding should be managed as necessary.

• Bioavailability: Approximately 90%.

• Maximum Effect: Usually achieved within 2-4 hours after administration.

• Effect Duration: Generally lasts for 4-6 hours, though longer effect duration may be observed with sustained-release formulations.

27. Naproxen (Brand name: Naprosyn)

• Indication for Use: Pain relief, anti-inflammatory

• Mode of Action: NSAID that inhibits the COX enzymes, leading to decreased synthesis of prostaglandins, which are responsible for pain and inflammation.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)

• Mode of Administration: Oral

• Half-life: Approximately 12-17 hours

• Surgical Guidelines: Discontinue 48 hours before surgery

• Reversal Agents: None; monitor and manage bleeding.

• Bioavailability: Approximately 95% when administered orally.

• Maximum Effect: Usually reached within 2-4 hours after administration.

• Effect Duration: Generally lasts for 8-12 hours, depending on the dose and individual factors.

• Bioavailability: Approximately 95% when administered orally.

• Maximum Effect: Usually reached within 2-4 hours after administration.

• Effect Duration: Generally lasts for 8-12 hours, depending on the dose and individual factors.

28. Mefenamic Acid

• Indication for Use: Pain relief; commonly used for the treatment of mild to moderate pain, such as menstrual pain, and for inflammatory conditions.

• Mode of Action: NSAID that inhibits COX-1 and COX-2 enzymes, reducing the production of prostaglandins which are responsible for pain and inflammation.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID).

• Mode of Administration: Oral (available in capsules and tablets).

• Half-Life: Approximately 2.5 hours.

• Surgical Guidelines: Discontinue 24 hours before surgery to minimize the risk of bleeding.

• Reversal Agents: None; manage bleeding as necessary.

• Bioavailability: Approximately 90% when administered orally.

• Maximum Effect: Usually reached within 2-4 hours after administration.

• Effect Duration: Generally lasts for 6-8 hours.

29. Meloxicam (Brand name: Mobic)

• Indication for Use: Pain relief, anti-inflammatory

• Mode of Action: Preferentially inhibits COX-2 over COX-1, resulting in analgesic and anti-inflammatory effects with potentially fewer gastrointestinal side effects.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)

• Mode of Administration: Oral

• Half-life: Approximately 15 hours

• Surgical Guidelines: Discontinue 48 hours prior to surgery

• Reversal Agents: None; handling of bleeding is required.

• Bioavailability: Approximately 89% when administered orally.

• Maximum Effect: Usually reached within 4-6 hours after administration.

• Effect Duration: Generally lasts for 24 hours, allowing for once-daily dosing.

30. Piroxicam (Brand name: Feldene)

• Indication for Use: Pain relief, anti-inflammatory

• Mode of Action: Nonselective NSAID that inhibits both COX-1 and COX-2 enzymes, resulting in anti-inflammatory and analgesic effects.

• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)

• Mode of Administration: Oral

• Half-life: Approximately 50 hours

• Surgical Guidelines: Discontinue 1 week prior to surgery

• Reversal Agents: None; manage bleeding as necessary.