(tin ZA pa rin)
Treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) (except in patients with severe hemodynamic instability); prevention of venous thromboembolism (VTE) following orthopedic surgery or following general surgery in patients at high risk of VTE; prevention of clotting in indwelling intravenous lines and extracorporeal circuit during hemodialysis (in patients without high bleeding risk)
Hypersensitivity to tinzaparin sodium, heparin or other low molecular weight heparins (LMWH), or any component of the formulation; active bleeding; history of confirmed or suspected immunologically mediated heparin-induced thrombocytopenia (HIT) or positive in vitro platelet-aggregation test in the presence of tinzaparin; acute or subacute endocarditis; generalized hemorrhage tendency and other conditions involving increased risks of hemorrhage (eg, severe hepatic insufficiency, imminent abortion); hemophilia or major blood clotting disorders; acute cerebral insult or hemorrhagic cerebrovascular accidents without systemic emboli; uncontrolled severe hypertension; diabetic or hemorrhagic retinopathy; injury or surgery involving the brain, spinal cord, eyes or ears; spinal/epidural anesthesia in patients requiring treatment dosages of tinzaparin; use of multidose vials containing benzyl alcohol in children <2 years of age, premature infants, and neonates
Note: Use of tinzaparin in patients with current HIT or HIT with thrombosis is not recommended and considered contraindicated due to high cross-reactivity to heparin-platelet factor-4 antibody (Guyatt [ACCP], 2012; Warkentin, 1999).
Note: 1 mg of tinzaparin equals 70 to 120 units of anti-Xa activity
DVT and/or PE treatment: SubQ: 175 anti-Xa units/kg once daily. The 2012 Chest guidelines recommend starting warfarin on the first or second treatment day and continuing tinzaparin until INR is ≥2 for at least 24 hours (usually 5 to 7 days) (Guyatt 2012). Body weight dosing using prefilled syringes may also be considered. Refer to manufacturer labeling for detailed dosing recommendations.
Obesity: Use actual body weight to calculate dose; dose capping is not recommended (Nutescu 2009).
DVT prophylaxis: SubQ:
Obesity:Note: In morbidly obese patients (BMI ≥40 kg/m2), increasing the prophylactic dose by 30% may be appropriate for some indications (Nutescu 2009).
Hip replacement surgery:Note: The American College of Chest Physicians recommends initiation of LMWH ≥12 hours preoperatively or ≥12 hours postoperatively; extended duration up to 35 days suggested (Guyatt 2012).
Preoperative regimen: 50 anti-Xa units/kg given 2 hours preoperatively followed by 50 anti-Xa units/kg once daily for 7 to 10 days
Postoperative regimen: 75 anti-Xa units/kg once daily, with initial dose given postoperatively and continued for 7 to 10 days
Knee replacement surgery: 75 anti-Xa units/kg once daily, with initial dose given postoperatively and continued for 7 to 10 days. Note: The American College of Chest Physicians recommends initiation of LMWH ≥12 hours preoperatively or ≥12 hours postoperatively; extended duration of up to 35 days suggested (Guyatt 2012). Body weight dosing using prefilled syringes may also be considered. Refer to manufacturer labeling for detailed dosing recommendations.
General surgery: 3500 anti-Xa units once daily, with initial dose given 2 hours prior to surgery and then continued postoperatively for 7 to 10 days
Anticoagulant in extracorporeal circuit during hemodialysis (recommendations apply to stable patients with chronic renal failure): IV:
Dialysis session ≤4 hours (no hemorrhage risk): Initial bolus (via arterial side of circuit or IV): 4500 anti-Xa units at beginning of dialysis; typically achieves plasma concentrations of 0.5 to 1 anti-Xa units/mL; may give larger bolus for dialysis sessions >4 hours. For subsequent dialysis sessions, may adjust dose as necessary in increments of 500 anti-Xa units based on previous outcome.
Dialysis session ≤4 hours (hemorrhage risk): Initial bolus (IV only): 2250 anti-Xa units at beginning of dialysis (do not add to dialysis circuit). A smaller second IV dose may be administered during dialysis sessions >4 hours. For subsequent dialysis sessions, adjust dose as necessary to achieve plasma concentrations of 0.2 to 0.4 anti-Xa units/mL.
Refer to adult dosing. Increased sensitivity to tinzaparin in elderly patients may be possible due to a decline in renal function. Use is not recommended in patients >70 years of age with renal impairment.
Note: 1 mg of tinzaparin equals 70-120 units of anti-Xa activity
VTE treatment (off-label use; Monagle, 2012): SubQ: Infants, Children, and Adolescents: Note: May initiate a vitamin K antagonist on day 1 of tinzaparin therapy; discontinue tinzaparin on day 6 or later if INR is not >2.
Birth to 2 months: 275 anti-Xa units/kg once daily
2-12 months: 250 anti-Xa units/kg once daily
1-5 years: 240 anti-Xa units/kg once daily
5-10 years: 200 anti-Xa units/kg once daily
10-16 years: 175 anti-Xa units/kg once daily
CrCl ≥30 mL/minute: No dosage adjustment provided in manufacturer 's labeling; however, primarily undergoes renal elimination. Clearance is decreased in renal impairment; use with caution.
CrCl <30 mL/minute: Manufacturer 's labeling suggests that a reduction in dose be considered but does not provide specific dose recommendations. Use with caution.
No dosage adjustment provided in manufacturer 's labeling. Does not undergo hepatic metabolism; however, has been associated with transient increases in transaminase levels; use with caution.
Patient should be lying down or sitting. Administer by deep SubQ injection into the lower abdomen, outer thigh, lower back, or upper arm. Injection site should be varied daily. To minimize bruising, do not rub the injection site. In hemodialysis patients, may be administered IV (patients with high or low hemorrhage risk) or added to the dialyzer circuit (patients with low hemorrhage risk).
Store at 15 � �C to 25 � �C (59 � �F to 77 � �F).
5-ASA Derivatives: May enhance the adverse/toxic effect of Heparin (Low Molecular Weight). Specifically, the risk for bleeding/bruising may be increased. Monitor therapy
ACE Inhibitors: Heparin (Low Molecular Weight) may enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Aliskiren: Heparin (Low Molecular Weight) may enhance the hyperkalemic effect of Aliskiren. Monitor therapy
Angiotensin II Receptor Blockers: Heparin (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy
Antithrombin: May enhance the anticoagulant effect of Heparin (Low Molecular Weight). Monitor therapy
Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination
Canagliflozin: Heparin (Low Molecular Weight) may enhance the hyperkalemic effect of Canagliflozin. Monitor therapy
Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy
Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination
Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy
Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Consider therapy modification
Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination
Eplerenone: Heparin (Low Molecular Weight) may enhance the hyperkalemic effect of Eplerenone. Monitor therapy
Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification
Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Monitor therapy
Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification
Ibritumomab: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding. Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy
Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy
Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy
Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination
Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Palifermin: Heparin (Low Molecular Weight) may increase the serum concentration of Palifermin. Monitor therapy
Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Pentoxifylline: May enhance the anticoagulant effect of Heparin (Low Molecular Weight). Monitor therapy
Potassium Salts: Heparin (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium Salts. Monitor therapy
Potassium-Sparing Diuretics: Heparin (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy
Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy
Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination
Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy
Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Anticoagulants may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased. Monitor therapy
Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination
CBC (at baseline then twice weekly throughout therapy); renal function (use Cockcroft-Gault formula); hepatic function; potassium (baseline in patients at risk for hyperkalemia, monitor regularly if duration >7 days); stool for occult blood. Routine monitoring of anti-Xa levels is generally not recommended; however, anti-Xa levels may be beneficial in certain patients (eg, children, obese patients, patients with severe renal insufficiency receiving therapeutic doses, and possibly pregnant women receiving therapeutic doses) (Guyatt, 2012). Peak anti-Xa levels are measured 4-6 hours after administration. Monitoring of PT and/or aPTT is not of clinical benefit.
As with all anticoagulants, bleeding is the major adverse effect of tinzaparin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables. Note: Incidence not always reported.
>10%:
Hepatic: ALT increased ( ≤13%)
Local: Injection site hematoma
1% to 10%:
Cardiovascular: Chest pain (2%), angina pectoris ( ≥1%), arrhythmia ( ≥1%), coronary thrombosis/MI ( ≥1%), dependent edema ( ≥1%), thromboembolism ( ≥1%)
Central nervous system: Fever (2%), headache (2%), pain (2%)
Dermatologic: Bullous eruption ( ≥1%), erythematous rash ( ≥1%), maculopapular rash ( ≥1%), skin necrosis ( ≥1%)
Gastrointestinal: Nausea (2%), abdominal pain (1%), constipation (1%), diarrhea (1%), vomiting (1%)
Genitourinary: Urinary tract infection (4%)
Hematologic: Bleeding events (major events including intracranial, retroperitoneal, or bleeding into a major prosthetic joint: ≤3%; hemorrhage site not specified (2%); other bleeding events reported at an incidence of ≥1% include anorectal bleeding, GI hemorrhage, hemarthrosis, hematemesis, hematuria, hemopericardium, injection site bleeding, melena, purpura, intra-abdominal bleeding, vaginal bleeding, wound hemorrhage), granulocytopenia ( ≥1%), thrombocytopenia ( ≥1%)
Hepatic: AST increased (9%)
Local: Injection site cellulitis ( ≥1%)
Neuromuscular & skeletal: Back pain (2%)
Respiratory: Epistaxis (2%), dyspnea (1%)
Miscellaneous: Allergic reaction ( ≥1%), neoplasm ( ≥1%)
<1% (Limited to important or life-threatening): Agranulocytosis, angioedema, anaphylactoid reaction, GGT increased, hemoptysis, hypoaldosteronism, hyperkalemia, LDH increased, lipase increased, metabolic acidosis, ocular hemorrhage, osteopenia, osteoporosis, priapism, pruritus, rash, spinal epidural hematoma, Stevens-Johnson syndrome, thrombocytosis, toxic epidermal necrolysis, urticaria
Concerns related to adverse effects:
- Bleeding: Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding. Risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; severe uncontrolled hypertension; history of hemorrhagic stroke; or use shortly after brain, spinal, or ophthalmology surgery; those concomitantly treated with drugs that increase the risk of bleeding (eg, antiplatelet agents, anticoagulants); recent GI bleeding; thrombocytopenia or platelet defects; severe liver disease; hypertensive or diabetic retinopathy; or in patients undergoing invasive procedures. Withhold or discontinue for minor bleeding. Protamine infusion may be necessary for serious bleeding (consult Protamine monograph for dosing recommendations).
- Hyperkalemia: Monitor for hyperkalemia. Heparin can cause hyperkalemia by suppressing aldosterone production; similar reactions could occur with LMWHs. Most commonly occurs in patients with risk factors for the development of hyperkalemia (eg, renal dysfunction, concomitant use of potassium-sparing diuretics or potassium supplements, hematoma in body tissues).
- Thrombocytopenia: Cases of thrombocytopenia including thrombocytopenia with thrombosis have occurred. Use with caution in patients with history of thrombocytopenia (drug-induced or congenital) or platelet defects; monitor platelet count closely. Use is contraindicated in patients with history of confirmed or suspected heparin-induced thrombocytopenia (HIT) or positive in vitro test for antiplatelet antibodies in the presence of tinzaparin. Discontinue therapy and consider alternative treatment if platelets are <100,000/mm3 and/or thrombosis develops.
- Thrombocytosis: Asymptomatic thrombocytosis has been observed with use, particularly in patients undergoing orthopedic surgery or with concurrent inflammatory process; discontinue use with increased platelet counts and evaluate the risks/necessity of further therapy.
Disease-related concerns:
- GI ulceration: Use with caution in patients with history of GI ulcer.
- Hepatic impairment: Use with caution in hepatic impairment; associated with transient, dose-dependent increases in AST/ALT which typically resolve within 2-4 weeks of therapy discontinuation.
- Prosthetic heart valves: Prosthetic valve thrombosis has been reported in patients receiving thromboprophylaxis therapy with LMWHs. Pregnant women may be at increased risk.
- Renal impairment: Use with caution in renal impairment; clearance is decreased in patients with CrCl ≤50 mL/minute; consider dosage reduction in patients with CrCl <30 mL/minute.
Special populations:
- Elderly: Use with caution due to increased bleeding risks. Use is not recommended in patients >70 years of age with renal impairment. In a trial terminated early, an increase in all-cause mortality has been observed in patients ≥70 years (mean age: >82 years) with CrCl ≤60 mL/minute treated with tinzaparin compared to unfractionated heparin for acute DVT and/or PE (Leizorovicz, 2011).
- Extreme body weights: Use with caution in patients <45 kg or >120 kg; limited experience in these patients. Individualized clinical and laboratory monitoring are recommended.
Dosage form specific issues:
- Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and should not be used in pregnant women. In neonates, large amounts of benzyl alcohol ( ≥99 mg/kg/day) have been associated with a potentially fatal toxicity ( "gasping syndrome " �); the "gasping syndrome " � consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer 's labeling.
- Porcine intestinal mucosa: This product is derived from porcine intestinal mucosa and should not be used in patients allergic to pork products.
- Sodium metabisulfite: Some dosage forms contain sodium metabisulfite which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people; this is observed more frequently in asthmatics.
Other warnings/precautions:
- Administration: For subcutaneous use only; do not administer IM and avoid IM administration of other medications due to the risk of hematoma formation.
- Conversion to other products: Not to be used interchangeably (unit for unit) with heparin or any other low molecular weight heparins.
- Neuraxial anesthesia: Spinal or epidural hematomas, including subsequent paralysis, may occur with recent or anticipated neuraxial anesthesia (epidural or spinal) or spinal puncture in patients anticoagulated with LMWH or heparinoids. Consider risk versus benefit prior to spinal procedures; risk is increased by the use of concomitant agents which may alter hemostasis, the use of indwelling epidural catheters for analgesia, a history of spinal deformity or spinal surgery, as well as traumatic or repeated epidural or spinal punctures. Avoid invasive spinal procedures for 12 hours following tinzaparin administration and withhold the next tinzaparin dose for at least 2 hours after the spinal procedure. Patient should be observed closely for bleeding and signs and symptoms of neurological impairment if therapy is administered during or immediately following diagnostic lumbar puncture, epidural anesthesia, or spinal anesthesia.
Teratogenic events were not observed in animal reproduction studies. Tinzaparin does not cross the human placenta. A pharmacokinetic study in pregnant women found no dose adjustment was needed during pregnancy. Vaginal bleeding was reported in ~10% of pregnant patients during tinzaparin therapy. LMWH is recommended over unfractionated heparin for the treatment of acute venous thromboembolism (VTE) in pregnant women. LMWH is also recommended over unfractionated heparin for VTE prophylaxis in pregnant women with certain risk factors. LMWH should be discontinued prior to induction of labor or a planned cesarean delivery. When choosing therapy, fetal outcomes (ie, pregnancy loss, malformations), maternal outcomes (ie, VTE, hemorrhage), burden of therapy, and maternal preference should be considered (Guyatt, 2012). Contains benzyl alcohol; use with caution in pregnant women due to association with gasping syndrome in premature infants.
Tinzaparin is a low molecular weight heparin (average molecular weight ranges between 5500 and 7500 daltons, distributed as <2000 daltons [<10%], 2000-8000 daltons [60% to 72%], and >8000 daltons [22% to 36%]) that binds antithrombin III, enhancing the inhibition of several clotting factors, particularly factor Xa. Tinzaparin anti-Xa activity (70-120 units/mg) is greater than anti-IIa activity (~55 units/mg) and it has a higher ratio of antifactor Xa to antifactor IIa activity compared to unfractionated heparin. Low molecular weight heparins have a small effect on the activated partial thromboplastin time.
Slow; absorption half-life ~3 hours after subcutaneous administration
4 L
Does not undergo hepatic metabolism
Urine
2-3 hours
4-6 hours
Detectable anti-Xa activity persists for 24 hours
82 minutes; prolonged in renal impairment
- 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 injection site irritation. Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds, coughing up blood, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get bigger, or any bleeding that is very bad or that will not stop), signs of nerve problems (back pain, numbness, or tingling, muscle weakness, paralysis, or urinary incontinence), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), 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), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), severe dizziness, passing out, fall or crash hitting head, severe headache, burning or numbness feeling, angina, arrhythmia, or severe loss of strength and energy (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.