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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cyklokapron: 1000 mg/10 mL (10 mL)
Generic: 1000 mg/10 mL (10 mL)
Solution, Intravenous [preservative free]:
Generic: 1000 mg/10 mL (10 mL)
Lysteda: 650 mg
Generic: 650 mg
Brand Names: U.S.
- Antifibrinolytic Agent
- Antihemophilic Agent
- Hemostatic Agent
- Lysine Analog
Forms a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis; it also inhibits the proteolytic activity of plasmin
With reduction in plasmin activity, tranexamic acid also reduces activation of complement and consumption of C1 esterase inhibitor (C1-INH), thereby decreasing inflammation associated with hereditary angioedema.
Vd: 9 to 12 L; CSF levels are 10% of plasma
Urine (>95% as unchanged drug)
Time to Peak
Oral: 2.5 hours (range: 1 to 5 hours)
~2 to 11 hours
~3%, primarily to plasminogen
Special Populations: Renal Function Impairment
Following administration of a single IV injection, urinary excretion declines as renal function decreases.
Special Populations: Children
The Cmax and AUC values after a single oral dose of 1300 mg in adolescent females were 20% to 25% less than those in adult females given the same dose.
Use: Labeled Indications
Cyclic heavy menstrual bleeding (oral): Treatment of cyclic heavy menstrual bleeding.
Tooth extraction in patients with hemophilia (injection): Short-term use (2 to 8 days) in hemophilia patients to reduce or prevent hemorrhage and reduce need for replacement therapy during and following tooth extraction
Bleeding: Treatment and/or prophylaxis of bleeding as a result of increased local fibrinolysis (hyperfibrinolysis) associated with cervical conization, dental extraction in patients with coagulopathies (in conjunction with antihemophilic factor), epistaxis, hyphema, or menorrhagia (hypermenorrhea).
Hereditary angioedema: Treatment of hereditary angioedema.
Trauma-associated hemorrhage; Traumatic hyphema; Bleeding associated with dental procedures in patients on oral anticoagulant therapy (topical mouth rinse); prevention of bleeding associated with cardiac surgery, craniosynostosis surgery, extracorporeal membrane oxygenation (ECMO), orthognathic surgery, spinal surgery (eg, spinal fusion), hip fracture surgery, total hip replacement surgery, total knee replacement surgery, or transurethral prostatectomy; reduction of blood loss associated with cesarean delivery; hereditary angioedema (long-term prophylaxis)
Injection: Hypersensitivity to tranexamic acid or any component of the formulation; acquired defective color vision; active intravascular clotting; subarachnoid hemorrhage
Oral: Hypersensitivity to tranexamic acid or any component of the formulation; active thromboembolic disease (eg, cerebral thrombosis, DVT, or PE); history of thrombosis or thromboembolism, including retinal vein or retinal artery occlusion; intrinsic risk of thrombosis or thromboembolism (eg, hypercoagulopathy, thrombogenic cardiac rhythm disease, thrombogenic valvular disease); concurrent use of combination hormonal contraception
Canadian labeling: Injection, oral: Hypersensitivity to tranexamic acid or any component of the formulation; acquired defective color vision; history or risk of thrombosis (unless concurrent anticoagulation therapy is possible); active thromboembolic disease (eg, deep vein thrombosis, pulmonary embolism, cerebral thrombosis); subarachnoid hemorrhage; hematuria
Cyclic heavy menstrual bleeding: Oral: 1,300 mg 3 times daily (3,900 mg/day) for up to 5 days during monthly menstruation
Tooth extraction in patients with hemophilia (in combination with appropriate factor replacement therapy): IV: 10 mg/kg immediately before surgery, then 10 mg/kg 3 to 4 times daily; may be used for 2 to 8 days
Cervical conization: Oral: 1,000 mg to 1,500 mg every 8 to 12 hours for 12 days post-operatively
Epistaxis: Oral: 1,000 mg to 1,500 mg every 8 to 12 hours for 10 days
Hyphema: Oral: 1,000 mg to 1,500 mg every 8 to 12 hours for 7 days
Dental surgery in patients with coagulopathies:
IV: 10 mg /kg as a single dose 2 hours prior to procedure (in conjunction with Factor VIII and IX); following procedure, administer oral tranexamic acid for 6 to 8 days
Oral: 25 mg /kg as a single dose 2 hours prior to procedure (in conjunction with Factor VIII and IX); following procedure, administer 25 mg/kg 3 to 4 times daily for 6 to 8 days
HAE: Oral: 1,000 mg to 1,500 mg 2 to 3 times daily; treat intermittently for several days or if needed treat continuously
Menorrhagia: Oral: 1,000 mg to 1,500 mg 3 to 4 times daily for several days (initiate only when heavy bleeding has started)
Elective cesarean section, blood loss reduction (off-label use): IV: 1,000 mg over 5 minutes at least 10 minutes prior to skin incision (Gungorduk 2011)
Hereditary angioedema (HAE) (off-label use in US):
Long-term prophylaxis: Oral: 1,000 to 1,500 mg 2 to 3 times daily; reduce to 500 mg/dose once or twice daily when frequency of attacks reduces (Gompels 2005; Levy 2010) or 25 mg/kg/dose administered 2 to 3 times daily (Bowen 2004)
Short-term prophylaxis (eg, for dental work): Oral: 75 mg/kg/day divided 2 to 3 times daily for 5 days before and 2 days after the event (Bowen 2004) or 1,000 mg 4 times daily for 48 hours before and after procedure (Gompels 2005)
Treatment of acute HAE attack: Oral, IV: 25 mg/kg/dose (maximum single dose: 1,000 mg) every 3 to 4 hours (maximum: 75 mg/kg/day) (Bowen 2004) or 1,000 mg 4 times daily for 48 hours (Gompels 2005)
Hip fracture surgery, blood conservation (off-label use): IV: 15 mg/kg administered at the time of skin incision followed by a second dose (15 mg/kg) 3 hours later (Zufferey 2010). Additional data may be necessary to further define the role of tranexamic acid in this setting.
Orthognathic surgery, blood loss reduction (off-label use): IV: 20 mg/kg over 15 minutes prior to incision (Choi 2009)
Perioperative blood loss reduction in bilateral total knee arthroplasty (off-label use): IV:
Three-dose regimen: 10 mg/kg administered as a slow IV infusion 30 minutes before tourniquet deflation for the first operation, 30 minutes before tourniquet deflation for the second operation, and 3 hours after commencement of the second dose (Kim 2014).
Two-dose regimen: 10 or 15 mg/kg administered over 10 minutes before deflation of the first tourniquet, with the second dose administered 3 hours after the first dose (MacGillivray 2011).
Perioperative blood loss reduction in unilateral total knee arthroplasty (off-label use): IV:
Intra- and postoperative regimen: 10 mg/kg at least 10 to 30 minutes prior to tourniquet release (deflation) and 10 mg/kg at 3 hours after the first dose (Alvarez 2008; Camarasa 2006; Maniar 2012). Instead of the second dose, a postoperative infusion may be administered at 1 mg/kg/hour for 6 hours (Alvarez 2008).
Pre- and intraoperative regimen: 10 mg/kg at least 20 minutes or immediately before tourniquet inflation and repeated at least 15 minutes prior to deflation or immediately after release of tourniquet (Lozano 2008; Maniar 2012).
Pre-, intra-, and postoperative regimen: 10 mg/kg at least 20 minutes before tourniquet inflation, repeated at least 15 minutes prior to deflation and postoperatively at 3 hours after the second dose (Maniar 2012).
Prevention of dental procedure bleeding in patients on oral anticoagulant therapy (off-label use): Oral rinse: 4.8% solution: Hold 10 mL in mouth and rinse for 2 minutes then spit out. Repeat 4 times daily for 2 days after procedure. Note: Patient should not eat or drink for 1 hour after using oral rinse (Carter 2003).
Prevention of perioperative bleeding associated with cardiac surgery (off-label use): IV: Loading dose of 30 mg/kg over 30 minutes (total loading dose includes a test dose administered over the first 10 minutes followed by the remainder of dose) prior to incision, followed by 16 mg/kg/hour until sternal closure; add an additional 2 mg/kg to cardiopulmonary bypass circuit (Fergusson 2008)
Loading dose of 10 mg/kg over 20 minutes prior to incision followed by 2 mg/kg/hour continued for 2 hours after transfer to ICU; add a prime dose of 50 mg for a 2.5 L cardiopulmonary bypass circuit; maintenance infusion adjusted for renal insufficiency (Nuttall 2008)
Loading dose of 10-15 mg/kg over 10 to 15 minutes, followed by 1 to 1.5 mg/kg/hour. The authors suggest adding 2 to 2.5 mg/kg to cardiopulmonary bypass circuit; however, amounts have varied widely in clinical trials (Gravlee 2008).
Prevention of perioperative bleeding associated with spinal surgery (eg, spinal fusion) (off-label use): IV: 2,000 mg over 20 minutes prior to incision followed by 100 mg/hour during surgery and for 5 hours postoperatively (Elwatidy 2008) or 10 mg/kg prior to incision followed by 1 mg/kg/hour for the remainder of the surgery; discontinue at time of wound closure (Wong 2008)
Total hip replacement surgery, blood conservation (off-label use): IV: 10 to 15 mg/kg (or 1,000 mg) administered over 5 to 10 minutes immediately before the operation or 15 minutes before skin incision; the preoperative dose may be followed by 10 mg/kg administered 3 to 12 hours after the operation. Postoperative doses ranged from a 10 mg/kg IV bolus (or 1,000 mg) to a 1 mg/kg/hour infusion over 10 hours (Gandhi 2013; Oremus 2014).
Note: Multiple regimens have been evaluated in varying degrees of evidence quality. The regimen listed here reflects the more commonly used dosing based on a number of prospective randomized controlled trials (Johansson 2005; McConnell 2011; Niskanen 2005; Oremus 2014). Metaanalyses have also been conducted demonstrating significant reduction in blood loss perioperatively without an increased risk of thromboembolic events (Gandhi 2013; Sukeik 2011; Zhou 2013). The use of intra-articular tranexamic acid (ie, 1,000 mg/50 mL of NaCl 0.9% sprayed into the wound at the end of the procedure) has also been evaluated demonstrating effectiveness (Alshryda 2014a; Alshryda 2014b).
Transurethral prostatectomy, blood loss reduction (off-label use): Oral: 2,000 mg 3 times daily on the operative and first postoperative day (Rannikko 2004)
Trauma-associated hemorrhage (off-label use): IV: Loading dose: 1,000 mg over 10 minutes, followed by 1,000 mg over the next 8 hours. Note: Clinical trial included patients with significant hemorrhage (SBP <90 mm Hg, heart rate >110 bpm, or both) or those at risk of significant hemorrhage. Treatment began within 8 hours of injury; however, every effort should be made to give as soon as possible (ideally within 3 hours of injury since treatment beyond 3 hours has been shown to be significantly less effective and may be associated with harm) (CRASH-2 Trial Collaborators 2010; CRASH-2 Trial Collaborators 2011).
Traumatic hyphema (off-label use): Oral: 25 mg/kg administered 3 times daily for 5 to 7 days (Rahmani, 1999; Vangsted, 1983; Varnek, 1980). Note: This same regimen may also be used for secondary hemorrhage after an initial traumatic hyphema event.
Refer to adult dosing.
Cyclic heavy menstrual bleeding: Children ≥12 years (postmenarche) and Adolescents: Oral: US labeling: Refer to adult dosing.
Hereditary angioedema (HAE) or bleeding due to fibrinolysis (excludes menorrhagia): Oral: Canadian labeling: 25 mg/kg 2 to 3 times per day
HAE (off-label use in US): Oral:
Long-term prophylaxis: 20 to 40 mg/kg/day in 2 to 3 divided doses (maximum dose: 3,000 mg daily) (Farkas 2007) or 50 mg/kg/day (or 1,000 to 2,000 mg daily; depending on age and size of patient); may consider alternate-day regimen or twice-weekly regimen when frequency of attacks reduces; diarrhea may be a dose-limiting side effect (Gompels 2005)
Short-term prophylaxis: 20 to 40 mg/kg/day in 2 to 3 divided doses (maximum dose: 3,000 mg daily) (Farkas 2007) or 500 mg 4 times daily (Gompels 2005). Note: For short-term prophylaxis (eg, dental work), initiate 2-5 days before and continue for 2 days after the procedure (Bowen 2004; Gompels 2005).
Prevention of perioperative bleeding associated with cardiac surgery (off-label use): IV: 10 mg/kg given over 30 minutes prior to incision, 10 mg/kg while on cardiopulmonary bypass, and 10 mg/kg administered after protamine reversal (Chauhan 2004a; Chauhan 2004b)
Loading dose of 100 mg/kg over 15 minutes prior to incision, followed by 10 mg/kg/hour infusion (continued until ICU transport); add 100 mg/kg to pump reservoir when cardiopulmonary bypass initiated (Reid, 1997)
Prevention of perioperative bleeding associated with craniosynostosis surgery (off-label use): IV: Loading dose of 50 mg/kg over 15 minutes prior to incision, followed by 5 mg/kg/hour (Goobie 2011) or 15 mg/kg over 15 minutes prior to incision, followed by 10 mg/kg/hour until skin closure (Dadure 2011)
Prevention of perioperative bleeding associated with spinal surgery (eg, spinal fusion) (off-label use): Children and Adolescents: IV: 10 mg/kg given over 15 minutes prior to incision followed by 1 mg/kg/hour for the remainder of the surgery; discontinue at time of wound closure (Neilipovitz 2001; Verma 2010)
100 mg/kg over 15 minutes prior to incision followed by 10 mg/kg/hour until skin closure (Sethna 2005)
30 mg/kg over 20 minutes prior to incision followed by 1 mg/kg/hour during surgery and for 5 hours postoperatively (Elwatidy 2008)
Tooth extraction in patients with hemophilia (in combination with appropriate factor replacement therapy): Children and Adolescents: IV: Refer to adult dosing.
Traumatic hyphema (off-label use): Oral: Refer to adult dosing.
Dosing: Renal Impairment
Tooth extraction in patients with hemophilia:
Serum creatinine 1.36 to 2.83 mg/dL: Maintenance dose of 10 mg/kg/dose twice daily
Serum creatinine 2.83 to 5.66 mg/dL: Maintenance dose of 10 mg/kg/dose once daily
Serum creatinine >5.66 mg/dL: Maintenance dose of 10 mg/kg/dose every 48 hours or 5 mg/kg/dose once daily
Cardiac surgery (the following dose adjustments have been recommended [Nuttall 2008]):
Serum creatinine 1.6 to 3.3 mg/dL: Reduce maintenance infusion to 1.5 mg/kg/hour (based on a 25% reduction from 2 mg/kg/hour)
Serum creatinine 3.3 to 6.6 mg/dL: Reduce maintenance infusion to 1 mg/kg/hour (based on a 50% reduction from 2 mg/kg/hour)
Serum creatinine >6.6 mg/dL: Reduce maintenance infusion to 0.5 mg/kg/hour (based on a 75% reduction from 2 mg/kg/hour)
Canadian labeling (regardless of indication):
Serum creatinine 1.4 to 2.8 mg/dL (120 to 250 micromol/L): 10 mg/kg twice daily
Serum creatinine 2.8 to 5.7 mg/dL (250 to 500 micromol/L): 10 mg/kg every 24 hours
Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): 10 mg/kg every 48 hours
Cyclic heavy menstrual bleeding:
Serum creatinine >1.4 to 2.8 mg/dL: 1,300 mg twice daily (2,600 mg/day) for up to 5 days
Serum creatinine 2.9 to 5.7 mg/dL: 1,300 mg once daily for up to 5 days
Serum creatinine >5.7 mg/dL: 650 mg once daily for up to 5 days
Canadian labeling (regardless of indication):
Serum creatinine 1.4 to 2.8 mg/dL (120 to 250 micromol/L): 15 mg//kg twice daily
Serum creatinine 2.8 to 5.7 mg/dL (250 to 500 micromol/L): 15 mg/kg every 24 hours
Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): 15 mg/kg every 48 hours
Dosing: Hepatic Impairment
US labeling: No dosage adjustment is necessary.
Canadian labeling: There are no dosage adjustments provided in the manufacturer’s labeling.
Tranexamic acid doses may be diluted in 50 to 250 mL of NS or D5W (Trissels 2015). According to the manufacturer, tranexamic acid may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and dextran solutions.
A 5% (50 mg/mL) oral solution may be prepared by diluting 5 mL of 10% (100 mg/mL) tranexamic acid injection with 5 mL sterile water. Label “refrigerate”. Stable for 5 days refrigerated.
A 25 mg/mL oral suspension may be prepared with tablets. Place one 500 mg tablet (strength not available in U.S.) into 20 mL water and let stand ~2 to 5 minutes. Begin stirring and continue until the tablet is completely disintegrated, forming a fine particulate suspension (dispersion time for each 500 mg tablet is ~2 to 5 minutes). Administer immediately after preparation.Lam MS, "Extemporaneous Compounding of Oral Liquid Dosage Formulations and Alternative Drug Delivery Methods for Anticancer Drugs," Pharmacotherapy 2011, 31(2):164-92.21275495
Injection: May be administered by direct IV injection at a maximum rate of 100 mg/minute (Crash-trial collaborators 2010; Elwatidy 2008); use plastic syringe only for IV push
In general, do not inject more rapidly than 1 mL/minute to avoid hypotension.
Oral: Administer without regard to meals. Swallow tablet whole; do not break, chew, or crush.
See Trissel’s IV Compatibility Database
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Injection: The diluted mixture may be stored for up to 4 hours at room temperature. However, solutions prepared in NS are chemically stable for up to 180 days at room temperature (McCluskey 2014). Solutions prepared in D5W should be used within the same day of preparation (Trissels 2015). In another study, tranexamic acid (undiluted) was shown to be chemically stable for up to 12 weeks when stored at -20°C, 4°C, 22°C, and 50°C; freezing tranexamic acid in original ampuls is unacceptable due to cracking of the ampuls (de Guzman 2013). Freezing tranexamic acid in original vials has not been evaluated.
Anti-inhibitor Coagulant Complex (Human): Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human). Avoid combination
Contraceptives (Estrogens): May enhance the thrombogenic effect of Tranexamic Acid. Avoid combination
Contraceptives (Progestins): May enhance the thrombogenic effect of Tranexamic Acid. Avoid combination
Fibrinogen Concentrate (Human): Antifibrinolytic Agents may enhance the adverse/toxic effect of Fibrinogen Concentrate (Human). Specifically, the risk for thrombosis may be increased. Fibrinogen Concentrate (Human) may enhance the adverse/toxic effect of Antifibrinolytic Agents. Specifically, the risk for thrombosis may be increased. Monitor therapy
Tretinoin (Systemic): May enhance the thrombogenic effect of Antifibrinolytic Agents. Monitor therapy
Injection: Frequency not defined.
Cardiovascular: Hypotension (with rapid IV injection)
Central nervous system: Dizziness
Dermatologic: Allergic dermatitis
Endocrine & metabolic: Menstrual disease (unusual menstrual discomfort)
Gastrointestinal: Diarrhea, nausea, vomiting
Ophthalmic: Blurred vision
Central nervous system: Headache (50%)
Gastrointestinal: Abdominal pain (20%)
Neuromuscular & skeletal: Back pain (21%), myalgia (11%)
Respiratory: Nasal signs and symptoms (25%; including sinus symptoms)
1% to 10%:
Central nervous system: Fatigue (5%)
Hematologic & oncologic: Anemia (6%)
Neuromuscular & skeletal: Arthralgia (7%), muscle cramps (≤7%), muscle spasm (≤7%)
All formulations: <1% (Limited to important or life-threatening): Allergic skin reaction, anaphylactic shock, anaphylactoid reaction, cerebral thrombosis, deep vein thrombosis, diarrhea, dizziness, nausea, pulmonary embolism, renal cortical necrosis, retinal artery occlusion, retinal vein occlusion, seizure, ureteral obstruction, visual disturbances (including impaired color vision and vision loss), vomiting
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypersensitivity reactions: Severe hypersensitivity reactions have rarely been reported. A case of anaphylactic shock has also been reported in a patient who received an IV bolus of tranexamic acid.
• Ocular effects: Visual defects (eg, color vision change, visual loss) and retinal venous and arterial occlusions have been reported; discontinue treatment if ocular changes occur; prompt ophthalmic examination should be performed by an ophthalmologist. Use of the injection is contraindicated in patients with acquired defective color vision. Ligneous conjunctivitis has been reported with the oral formulation, but resolved upon discontinuation of therapy.
• Seizure: Seizures have been reported with use; most often with intraoperative use (eg, open chamber cardiac surgery) and in older patients (Murkin 2010). The mechanism by which tranexamic acid use results in seizures may be secondary to neuronal gamma aminobutyric acid (GABA) inhibition.
• Thrombotic events: Venous and arterial thrombosis or thromboembolism, including central retinal artery/vein obstruction, has been reported. Use the injection with caution in patients with thromboembolic disease; oral formulation is contraindicated in patients with a history of or active thromboembolic disease or with an intrinsic risk of thromboembolic events (eg, thrombogenic valvular disease, thrombogenic cardiac rhythm disease, hypercoagulopathy).
• Ureteral obstruction: Use the injection with caution in patients with upper urinary tract bleeding, ureteral obstruction due to clot formation has been reported.
• Disseminated intravascular coagulation (DIC): Use with extreme caution in patients with DIC requiring antifibrinolytic therapy; patients should be under strict supervision of a health care provider experienced in treating this disorder.
• Renal impairment: Use with caution in patients with renal impairment; dosage modification necessary.
• Subarachnoid hemorrhage: Use oral formulation with caution in patients with subarachnoid hemorrhage; cerebral edema and infarction may occur. Use of the injection is contraindicated.
• Vascular disease: Use with caution in patients with uncorrected cardiovascular or cerebrovascular disease due to the complications of thrombosis.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Ophthalmic examination (visual acuity, color vision, eye-ground, and visual fields) at baseline and regular intervals during the course of therapy in patients being treated for longer than several days; signs/symptoms of hypersensitivity reactions, seizures, thrombotic events, and ureteral obstruction
Pregnancy Risk Factor
Adverse events have not been observed in animal reproduction studies. Tranexamic acid crosses the placenta and concentrations within cord blood are similar to maternal concentrations. Tranexamic acid has been evaluated for the treatment of postpartum hemorrhage (Ducloy-Bouthors 2011; Gungorduk 2011). Oral tranexamic acid (Lysteda) is not indicated for use in pregnant women.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience abdominal pain, back pain, muscle pain, joint pain, rhinitis, muscle cramps, nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; fast heartbeat; or coughing up blood), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), severe headache, bruising, bleeding, vision changes, eye pain, severe eye irritation, angina, severe loss of strength and energy, seizures, severe dizziness, or passing out (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.