Tinzaparin

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).

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).

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 3 and/or thrombosis develops.

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:

Use with caution in patients with history of GI ulcer.

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 valve thrombosis has been reported in patients receiving thromboprophylaxis therapy with LMWHs. Pregnant women may be at increased risk.

Use with caution in severe renal impairment; clearance is decreased in patients with CrCl ≤50 mL/minute; consider dosage reduction in patients with CrCl Concurrent drug therapy issues:

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. Special populations:

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).

Use with caution in patients 120 kg; limited experience in these patients. Individualized clinical and laboratory monitoring are recommended. Dosage form specific issues:

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.

This product is derived from porcine intestinal mucosa and should not be used in patients allergic to pork products.

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:

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.

Not to be used interchangeably (unit for unit) with heparin or any other low molecular weight heparins.

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