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): 4,500 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): 2,250 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.
Mechanical prosthetic heart valve (aortic or mitral position) to bridge anticoagulation (off-label use):
Note: Bridging during intervals of subtherapeutic anticoagulation should be considered for patients with mechanical mitral or tricuspid valve replacement; however, for patients with mechanical aortic valve replacement, bridging is not required unless an additional thromboembolic risk factor is present or patient has an older generation mechanical aortic valve (ACC/AHA [Otto 2021]).
SUBQ: 175 anti-Xa units/kg once daily (ACCP [Douketis 2012]).
Venous thromboembolism prophylaxis:
Bariatric surgery, moderate to high venous thromboembolism risk (off-label use): Based on limited evidence: SUBQ: Initial: 75 anti-Xa units/kg once daily starting on postoperative day 1 (minimum dose: 4,500 anti-Xa units once daily and maximum dose: 14,000 anti-Xa units once daily); round dose to the closest possible syringe size; duration of therapy is typically 10 days postoperatively (Douketis 2018; Tseng 2018). Note: Optimal duration of prophylaxis is unknown, but is usually continued until hospital discharge and may be extended for up to 6 weeks postoperatively depending upon venous thromboembolism (VTE) risk. There is no consensus on indications for extended prophylaxis following bariatric surgery (Lim 2021).
Total hip arthroplasty:
Preoperative initiation regimen: SUBQ: 50 anti-Xa units/kg given 2 hours preoperatively, followed by 50 anti-Xa units/kg once daily (manufacturer's labeling); guidelines recommend initiation of a low molecular weight heparin (eg, tinzaparin) ≥12 hours preoperatively (ACCP [Falck-Ytter 2012]); clinical practice may differ on timing of initiation, refer to institutional protocols.
Postoperative initiation regimen: SUBQ: 75 anti-Xa units/kg once daily, with initial dose given ≥12 hours postoperatively (ACCP [Falck-Ytter 2012]; manufacturer's labeling); clinical practice may differ on timing of initiation, refer to institutional protocols.
Duration of therapy: Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days (ACCP [Falck-Ytter 2012]).
Total knee arthroplasty: SUBQ: 75 anti-Xa units/kg once daily, with initial dose given ≥12 hours preoperatively or ≥12 hours postoperatively (ACCP [Falck-Ytter 2012]; manufacturer's labeling). Body weight dosing using prefilled syringes may also be considered, refer to manufacturer labeling for detailed dosing recommendations.
Duration of therapy: Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days (ACCP [Falck-Ytter 2012].
Medical patients with acute illness at moderate and high risk for venous thromboembolism (off-label use): SUBQ: 4,500 anti-Xa units once daily; continue for length of hospital stay or until patient is fully ambulatory and risk of VTE has diminished (ACCP [Kahn 2012]; Thrombosis Canada 2020). Extended prophylaxis beyond acute hospital stay is not routinely recommended (ACCP [Kahn 2012]; Sharma 2012). However, in high-risk coronavirus disease 2019 (COVID-19) patients who are discharged from the hospital, some experts would consider extended prophylaxis with a direct oral anticoagulant (DOAC) (eg, rivaroxaban) (Cuker 2021).
General surgery: SUBQ: 3,500 anti-Xa units once daily, with initial dose given 2 hours prior to surgery and then continued postoperatively for 7 to 10 days.
Venous thromboembolism treatment:
Note: For timing of initiating oral anticoagulant, see Transitioning between anticoagulants.
Deep vein thrombosis and/or pulmonary embolism treatment: SUBQ: 175 anti-Xa units/kg once daily.
Duration of therapeutic anticoagulation (first episode, general recommendations): Optimal duration of therapy is unknown and depends on many factors, such as whether provoking events were present, patient risk factors for recurrence and bleeding, and individual preference.
Provoked venous thromboembolism: 3 months (provided the provoking risk factor is no longer present) (ACCP [Stevens 2021]).
Unprovoked venous thromboembolism or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of VTE recurrence and bleeding (ACCP [Stevens 2021]; ISTH [Baglin 2012]).
Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals.
Venous thromboembolism treatment in patients with active cancer:
Months 1 to 6: SUBQ: Initial: 175 anti-Xa units/kg once daily for a total duration of 3 to 6 months (ASCO [Key 2020]; Bauer 2019).
Maintenance beyond 6 months: ACCP and ASCO guidelines for VTE prophylaxis/treatment recommend considering continuing anticoagulation beyond 6 months in select patients due to the persistent high risk of recurrence in those with active cancer; consider risk vs benefit of bleeding and recurrence (ACCP [Stevens 2021]; ASCO [Key 2020]).
Transitioning between anticoagulants: Note: This provides general guidance on transitioning between anticoagulants; also refer to local protocol(s) for additional detail:
Transitioning from another anticoagulant to tinzaparin:
Transitioning from therapeutic IV unfractionated heparin infusion to therapeutic-dose tinzaparin: Discontinue unfractionated heparin (UFH) and begin tinzaparin within 1 hour. Note: If aPTT is not in therapeutic range at the time UFH is discontinued, consult local protocol (Nutescu 2007).
Transitioning from tinzaparin to another anticoagulant:
Transitioning from therapeutic-dose tinzaparin to therapeutic IV unfractionated heparin infusion: Start IV UFH (rate based on indication) 1 to 2 hours before the next dose of tinzaparin would have been due. Note: Omit IV UFH loading dose (Nutescu 2007).
Transitioning from prophylactic tinzaparin to therapeutic IV unfractionated heparin: UFH should be started without delay. A UFH bolus/loading dose may be used if indicated.
Transitioning from therapeutic-dose tinzaparin to warfarin: Start warfarin and continue tinzaparin until INR is within therapeutic range (Wittkowsky 2018). Note: Overlap tinzaparin with warfarin until INR is ≥2 for at least 2 measurements taken ~24 hours apart (duration of overlap is ~5 days) (ACCP [Ageno 2012]).
Transitioning from therapeutic-dose tinzaparin to a direct oral anticoagulant: Start direct oral anticoagulant within 2 hours prior to the next scheduled dose of tinzaparin.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, primarily undergoes renal elimination and clearance is decreased in renal impairment; use with caution.
CrCl <30 mL/minute: Evidence suggests no accumulation in patients with CrCl ≥20 mL/minute, but there are limited data available in patients with a CrCl <20 mL/minute. While the manufacturer recommends that a dose reduction be considered in patients with CrCl <30 mL/minute, there are no specific dosage adjustments provided in the manufacturer's labeling; use with caution.
Hemodialysis: Not dialyzable (NCS/SCCM [Frontera 2016])
There are no dosage adjustments provided in the manufacturer's labeling. Does not undergo hepatic metabolism; however, has been associated with transient increases in transaminase levels; use with caution.
Note: 1 mg of tinzaparin equals 70 to 120 units of anti-Xa activity
Deep vein thrombosis and/or pulmonary embolism treatment (off-label dose) (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 to 12 months: 250 anti-Xa units/kg once daily
1 to 5 years: 240 anti-Xa units/kg once daily
5 to 10 years: 200 anti-Xa units/kg once daily
10 to 16 years: 175 anti-Xa units/kg once daily
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric specific recommendations; based on experience in adult patients, use with caution; tinzaparin primarily undergoes renal elimination and clearance is decreased in renal impairment.
There are no pediatric specific recommendations; based on experience in adult patients, use with caution; does not undergo hepatic metabolism; however, has been associated with transient increases in transaminase levels.
Refer to adult dosing; clearance of tinzaparin may be reduced in elderly patients. Increased sensitivity to tinzaparin in elderly patients may be possible due to a decline in renal function. Avoid use in patients >70 years of age with renal impairment (Leizorovicz 2011).
Note: Specific dosing recommendations may not be available for all indications.
Venous thromboembolism prophylaxis:
BMI 30 to 39 kg/m2: Use standard prophylaxis dosing.
BMI ≥40 kg/m2: Increase standard prophylaxis dose by 30% (Nutescu 2009); however, the ideal dose is unknown.
Venous thromboembolism treatment: Use actual body weight to calculate dose; a fixed upper dose limit is not recommended; however, increased monitoring and dosage adjustment based on anti-Xa levels may be considered (Nutescu 2009).
Yes
Innohep is manufactured from products derived from porcine intestinal mucosa.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injectable, Subcutaneous:
Innohep: 10000 units/mL (2 mL); 20000 units/mL (2 mL) [contains benzyl alcohol, sodium metabisulfite]
Solution Prefilled Syringe, Subcutaneous:
Innohep: 2500 units/0.25 mL (0.25 mL); 3500 units/0.35 mL (0.35 mL); 4500 units/0.45 mL (0.45 mL)
Innohep: 8000 units/0.4 mL (0.4 mL); 10,000 units/0.5 mL (0.5 mL); 12,000 units/0.6 mL (0.6 mL); 14,000 units/0.7 mL (0.7 mL); 16,000 units/0.8 mL (0.8 mL); 18,000 units/0.9 mL (0.9 mL) [contains sodium metabisulfite]
SubQ: Patient should be lying down or sitting. Administer by deep SubQ injection into the lower abdomen (avoiding navel area), outer thigh, lower back, or upper arm. Do not administer IM. Injection site should be varied daily. To minimize bruising, do not rub the injection site.
During hemodialysis, may be administered into the arterial side of the dialyzer circuit or IV in patients with no hemorrhage risk. In patients at risk of hemorrhage, administer IV only (do not add to the dialyzer circuit).
SubQ: For SubQ administration; do not administer IM. Administer by deep SubQ injection; in adults, it is recommended to alternate between the lower abdomen (avoiding navel area), outer thigh, lower back, or upper arm. Injection site should be varied daily. To minimize bruising, do not rub the injection site.
Note: Not available in the United States.
Anticoagulation in extracorporeal circuit during hemodialysis: Prevention of clotting in indwelling intravenous lines and extracorporeal circuit during hemodialysis (in patients without high bleeding risk).
Deep vein thrombosis/pulmonary embolus (treatment): Treatment of deep vein thrombosis and/or pulmonary embolism.
Postoperative thromboprophylaxis: Prevention of venous thromboembolism (VTE) following orthopedic surgery or following general surgery in patients at high risk of VTE.
Mechanical prosthetic heart valve (aortic or mitral position) to bridge anticoagulation; Venous thromboembolism prophylaxis, bariatric surgery (moderate to high venous thromboembolism risk); Venous thromboembolism prophylaxis, medical patients with acute illness at moderate and high risk for venous thromboembolism
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Tinzaparin may be confused with Tinza (international brand name for nizatidine).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
1% to 10%:
Cardiovascular: Chest pain (2%)
Dermatologic: Skin rash (1%)
Gastrointestinal: Constipation (1%), nausea (2%), vomiting (1%)
Genitourinary: Hematuria (1%), urinary tract infection (4%)
Hematologic & oncologic: Anemia, hematoma, hemorrhage (2%; major hemorrhage ≤3%, including intracranial hemorrhage, retroperitoneal hemorrhage)
Local: Injection site reaction (including hematoma at injection site [prophylaxis dosing: <5%, treatment dosing: 10%], irritation at injection site, pain at injection site)
Nervous system: Headache (2%), pain (2%)
Neuromuscular & skeletal: Back pain (2%)
Respiratory: Dyspnea (1%), epistaxis (2%)
Miscellaneous: Fever (2%)
<1%:
Gastrointestinal: Abdominal pain, diarrhea
Hematologic & oncologic: Heparin-induced thrombocytopenia (type I, type II), thrombocythemia
Postmarketing:
Dermatologic: Allergic dermatitis, alopecia (Sarris 2003), bullous dermatitis (including hemorrhagic [Roy 2020]), ecchymoses, erythematous rash, maculopapular rash, pruritus, skin necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Increased gamma-glutamyl transferase
Genitourinary: Priapism (Purnell 2018)
Hematologic & oncologic: Bruise, purpuric disease
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Hypersensitivity: Hypersensitivity reaction
Neuromuscular & skeletal: Osteopenia, osteoporosis
Hypersensitivity to tinzaparin, heparin, or other low molecular weight heparins (LMWH), or any component of the formulation; active bleeding from a local lesion such as an acute ulcer (eg, gastric, duodenal) or ulcerating carcinoma; 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 septic endocarditis; active major hemorrhage or conditions/diseases involving increased risk 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 multi-dose vials containing benzyl alcohol in children <3 years of age, premature infants, and neonates.
Concerns related to adverse effects:
• Bleeding: Monitor patient closely for signs or symptoms of bleeding, which may occur at any site. 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, diabetes, renal dysfunction, preexisting metabolic acidosis, concomitant use of potassium-sparing diuretics or potassium supplements, long-term use of tinzaparin, and 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/GGT which typically resolve within 2 to 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 severe renal impairment; clearance is decreased in patients with CrCl ≤50 mL/minute; consider dosage reduction in patients with CrCl <30 mL/minute.
Special populations:
• Older adult: Use with caution due to increased bleeding risks. Avoid use 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 (except in hemodialysis patients); 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. Optimal timing between neuraxial procedures and tinzaparin administration is not known. Delay placement or removal of catheter for at least 12 hours after administration of the last prophylactic dose and at least 24 hours after the last treatment dose of tinzaparin; consider doubling these times in patients with creatinine clearance <30 mL/minute. Risk of neuraxial hematoma may still exist since antifactor Xa levels are still detectable at these time points. Consider holding the next tinzaparin dose for 24 hours if the spinal puncture caused trauma. 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. If neurological compromise is noted, urgent treatment is necessary. If spinal hematoma is suspected, diagnose and treat immediately; spinal cord decompression may be considered although it may not prevent or reverse neurological sequelae.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Aliskiren: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Aliskiren. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Antithrombin: May enhance the anticoagulant effect of Heparins (Low Molecular Weight). Risk C: 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. Risk X: Avoid combination
Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
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. Risk C: 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. Risk X: Avoid combination
Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: 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. Risk C: 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. Risk C: Monitor therapy
Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: 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. Risk X: Avoid combination
Eplerenone: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Risk C: Monitor therapy
Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination
Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: 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. Risk X: Avoid combination
Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Palifermin: Heparins (Low Molecular Weight) may increase the serum concentration of Palifermin. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Pentoxifylline: May enhance the anticoagulant effect of Heparins (Low Molecular Weight). Risk C: Monitor therapy
Potassium Salts: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Heparins (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. Risk C: Monitor therapy
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. Risk C: 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. Risk X: Avoid combination
Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance with anticoagulants is often recommended, see full Lexicomp or drug interaction monograph for details. Risk C: Monitor therapy
Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Urokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid combination
Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Patients undergoing assisted reproduction therapy (ART) may be at increased risk for thrombosis. Venous thromboembolism prophylaxis is not routinely recommended for patients undergoing ART; however, prophylactic doses of low-molecular-weight heparin (LMWH) are recommended for patients who develop severe ovarian hyperstimulation syndrome (ACCP [Bates 2012]; ASH [Bates 2018]; SOGC [Shmorgun 2017]). In addition, prophylactic doses of LMWH are recommended in patients undergoing ART who have a positive antiphospholipid antibody test but are not diagnosed with antiphospholipid syndrome (APS), as well as patients diagnosed with obstetric APS. Therapeutic doses of LMWH are recommended in patients undergoing ART diagnosed with thrombotic APS (ACR [Sammaritano 2020]).
Tinzaparin does not cross the placenta.
An increased risk of fetal bleeding or teratogenic effects has not been reported (ACCP [Bates 2012]).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of low-molecular-weight heparin (LMWH) may be altered; dosing adjustment may be required. Prophylactic doses of LMWH may also need modified in pregnant patients at extremes of body weight (ACOG 2018).
Use is contraindicated in conditions involving increased risks of hemorrhage, including patients with imminent abortion.
The risk of venous thromboembolism (VTE) is increased in pregnant patients, especially during the third trimester and first week postpartum. LMWH is recommended over unfractionated heparin for the treatment of acute VTE in pregnant patients. LMWH is also recommended over unfractionated heparin for VTE prophylaxis in pregnant patients with certain risk factors (eg, homozygous factor V Leiden, antiphospholipid antibody syndrome with ≥3 previous pregnancy losses) (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]; ESC [Regitz-Zagrosek 2018]). Consult current recommendations for appropriate use in pregnancy.
LMWH may be used prior to cesarean delivery in patients with additional risk factors for developing VTE. Risk factors may include a personal history of deep vein thrombosis or pulmonary embolism, inherited thrombophilia, or patients with class III obesity (Pacheco 2020).
LMWH may also be used in pregnant patients with mechanical heart valves. When choosing therapy, fetal outcomes (ie, pregnancy loss, malformations), maternal outcomes (ie, VTE, hemorrhage), burden of therapy, and maternal preference should be considered. Patients with mechanical heart valves have an increased risk of adverse fetal and maternal outcomes (including valve thrombosis), and these risks are greater without appropriate anticoagulation. Increased monitoring of anti-factor Xa levels is required; frequent dose titration may be needed to maintain adequate therapeutic anti-factor Xa concentrations during pregnancy (consult current recommendations for details) (ACC/AHA [Otto 2021]; ESC [Regitz-Zagrosek 2018]).
LMWH is the recommended class of anticoagulants for pregnant patients hospitalized for manifestations of COVID-19, taking into consideration risk factors for bleeding, including threatened delivery. Prophylactic doses are recommended during hospitalization if there are no contraindications to use. Recommendations for or against the use of therapeutic doses are not available due to insufficient data in pregnant patients with COVID-19 without VTE. Patients prescribed antithrombotic therapy prior to a COVID-19 diagnosis should continue their therapy (NIH 2022).
Multiple-dose vials contain benzyl alcohol (avoid use in pregnant patients due to association with gasping syndrome in premature infants); use of preservative-free formulation is recommended.
It is not known if tinzaparin is present in breast milk.
Small amounts of another low-molecular-weight heparin (LMWH) have been detected in breast milk; however, because they have a low oral bioavailability, LMWHs are unlikely to cause adverse events in a breastfeeding infant. According to the manufacturer, caution should be used if administered to a breastfeeding patient. LMWH is considered compatible with breastfeeding (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]).
CBC with platelet count (at baseline then periodically throughout therapy); renal function (use Cockcroft-Gault formula); hepatic function; potassium (baseline and regularly thereafter in patients at risk for hyperkalemia); 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) (ACCP [Guyatt 2012]). Peak anti-Xa levels are measured 4 to 6 hours after administration. Monitoring of PT and/or aPTT is not recommended.
Anti-Xa level (measured 4 hours after administration): Fixed-dose (3,500 units): 0.15 anti-Xa units/mL; weight-based (75 to 175 units/kg): 0.34 to 0.70 anti-Xa units/mL; in treatment of venous thromboembolism, a target of 0.85 anti-Xa units/mL has been recommended (Garcia 2012)
Children: Target anti-Xa level: 0.5 to 1 anti-Xa units/mL 4 to 6 hours after administration or 0.5 to 0.8 anti-Xa units/mL 2 to 6 hours after administration (Monagle 2012)
Tinzaparin is a low molecular weight heparin (average molecular weight ranges between 5,500 and 7,500 daltons, distributed as <2,000 daltons [<10%], 2,000 to 8,000 daltons [60% to 72%], and >8,000 daltons [22% to 36%]) that binds antithrombin III, enhancing the inhibition of several clotting factors, particularly factor Xa. Tinzaparin anti-Xa activity (70 to 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.
Note: Values reflective of anti-Xa activity.
Duration: Detectable anti-Xa activity persists for 24 hours
Absorption: Slow; absorption half-life ~3 hours after subcutaneous administration
Distribution: 4 L
Metabolism: Does not undergo hepatic metabolism
Bioavailability: SubQ: ~90%
Half-life elimination: 82 minutes; prolonged in renal impairment
Time to peak: 4 to 6 hours
Excretion: Urine
