Tinzaparin Sodium

Pronunciation: tin-ZAP-a-rin SOE-dee-um
Class: Low molecular weight heparin

Trade Names

Innohep
- Injection, solution 20,000 units/mL

Pharmacology

Inhibits reactions that lead to the clotting of blood, including the formation of fibrin clots.

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Pharmacokinetics

Absorption

T _max is approximately 4 to 5 h and C _max is approximately 0.25 to 0.87 units/mL. Bioavailability is 86.7%.

Distribution

Vd is 3.1 to 5 L.

Metabolism

Partially metabolized by desulphation and depolymerization.

Elimination

Half-life is approximately 3 to 4 h. Cl is approximately 1.7 L/h and the primary route of elimination is renal.

Special Populations

A reduction in Cl in moderate (30 to 50 mL/min) and severe (less than 30 mL/min) renal impairment was observed. Patients with severe renal impairment exhibited a 24% reduction in tinzaparin Cl. Administer to patients with severe renal impairment with caution.

No prospective studies have assessed tinzaparin pharmacokinetics patients with hepatic impairment. However, the hepatic route is not a major route of elimination.

Because renal function is known to decline with age, elderly patients may show reduced elimination of tinzaparin.

Weight is an important factor for the prediction of tinzaparin Cl.

Indications and Usage

Treatment of acute symptomatic deep vein thrombosis (DVT) with or without pulmonary embolism when administered with warfarin.

Unlabeled Uses

Venous thromboembolism prophylaxis in general or gynecologic surgery; prophylaxis of DVT, which may lead to pulmonary embolism, in patients undergoing orthopedic surgery, hip fracture surgery, or neurosurgery who are at risk for thromboembolic complications.

Contraindications

Active major bleeding; patients with or history of heparin-induced thrombocytopenia; hypersensitivity to tinzaparin, heparin, sulfites, benzyl alcohol, or pork products.

Dosage and Administration

Subcutaneous 175 anti-Xa units/kg once daily for more than 6 days and until patient is adequately anticoagulated with warfarin (INR of at least 2 for two consecutive days). Initiate warfarin therapy when appropriate (usually within 1 to 3 days of tinzaparin initiation).

General Advice

• Administer by subcutaneous injection. Do not administer by IM or IV injection.
• Place the patient in the supine or sitting position before administration.
• Alternate injection sites between the left and right anterolateral and left and right posterolateral abdominal wall.
• Hold skinfold between the thumb and forefinger until the injection is completed.
• Introduce the full length of the needle into the skinfold and inject without aspiration.
• To minimize bruising, do not rub the injection site after completion of the injection.
• Do not mix with other injections or infusions.
• Inspect visually for particulate matter and discoloration prior to administration.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

The risk of severe bleeding may be increased. Close clinical and laboratory monitoring (aPTT and/or anti-Xa) is indicated during coadministration of tinzaparin and antithrombin. Adjust the dose of tinzaparin accordingly. Reduced doses of tinzaparin are recommended when coadministered with antithrombin III.

Use with caution because of increased risk of bleeding.

The risk of severe bleeding may be increased. Carefully monitor the coagulation status of the patient and observe the patient for bleeding. Adjust therapy as needed.

Laboratory Test Interactions

Asymptomatic reversible increases in AST and ALT concentrations.

Adverse Reactions

Cardiovascular

Angina pectoris, deep leg thrombophlebitis, deep thrombophlebitis, hypertension, hypotension, tachycardia (1% or more); peripheral ischemia (postmarketing).

CNS

Headache (2%); confusion, dizziness, insomnia (1% or more).

Dermatologic

Bullous eruption, erythematous rash, pruritus, skin disorder (1% or more); rash (1%); cutis aplasia of the scalp, epidermal necrolysis, ischemic necrosis, Steven-Johnson syndrome, urticaria (postmarketing).

GI

Nausea (2%); flatulence, GI disorder (1% or more); abdominal pain, constipation, diarrhea, vomiting (1%); rectal bleeding (postmarketing).

Genitourinary

UTI (4%); dysuria, urinary retention (1% or more); hematuria (1%); priapism (postmarketing).

Hematologic

Epistaxis, hemorrhage (2%); anemia, bleeding, hematoma, thrombocytopenia (1% or more); agranulocytosis, pancytopenia, thrombocythemia (postmarketing).

Hepatic

Elevated ALT (13%); elevated AST (9%); cholestatic hepatitis, increase in hepatic enzymes (postmarketing).

Local

Hematoma (16%); mild local irritation, pain, and ecchymosis.

Respiratory

Pulmonary embolism (2%); dyspnea (1%); pneumonia; respiratory disorder (1% or more).

Miscellaneous

Back pain, chest pain, fever, pain (2%); healing impaired, infection, reaction unclassified (1% or more); anaphylactoid reactions; abscess, acute febrile reaction, allergic purpura, angioedema, hemoptysis, necrosis, neonatal hypotonia, ocular hemorrhage (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

May increase the risk of death, compared with unfractionated heparin, when administered to elderly patients with renal insufficiency.

Hypersensitivity

Allergic-type reactions may occur.

Renal Function

Effect of tinzaparin may be prolonged. Use with caution. May increase the risk of death compared with unfractionated heparin when administered to elderly patients with renal insufficiency.

Special Risk Patients

Use drug with caution in patients with diabetic retinopathy, bleeding diathesis, uncontrolled arterial hypertension, or history of recent GI ulceration and hemorrhage.

Fatal gasping syndrome

Fatal gasping syndrome in premature infants has been associated with the benzyl alcohol preservative present in tinzaparin.

Hemorrhage

Use with caution in conditions with increased risk of hemorrhage (eg, bacterial endocarditis, severe uncontrolled hypertension, active ulcerative GI disease).

Interchangeability

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

Priapism

Has been reported as a rare occurrence.

Sulfite sensitivity

Tinzaparin contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening asthmatic episodes, in certain susceptible people.

Thrombocytopenia

May occur.

Overdosage

Symptoms

Bleeding complications, blood in urine, bruising, frank bleeding, nosebleeds, petechial hemorrhage, tarry stools.

Patient Information

• Instruct patient to take safety precautions to avoid cuts and bruises (eg, soft toothbrush, electric razor, handrails).
• Caution patient to avoid aspirin or other OTC anticoagulants.
• Instruct patients to report any current or future prescription, OTC, or herbal medication use to primary care provider.
• Advise patient to report bruises; bleeding; nosebleeds; bleeding gums; coffee-ground emesis; red-flecked sputum; or tarry, black, or red stools.

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