Innohep Information
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q)
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Description
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is a sterile solution, containing tinzaparin sodium, a low molecular weight heparin. It is available in a multiple dose 2 mL vial.
Each 2 mL vial contains 20,000 anti-Factor Xa IU (anti-Xa) of tinzaparin sodium per mL, for a total of 40,000 IU, and 3.1 mg/mL sodium metabisulfite as a stabilizer. The vial contains 10 mg/mL benzyl alcohol as a preservative. Sodium hydroxide may be added to achieve a pH range of 5.0 to 7.5.
Tinzaparin sodium is the sodium salt of a low molecular weight heparin obtained by controlled enzymatic depolymerization of heparin from porcine intestinal mucosa using heparinase from . The majority of the components have a 2-O-sulpho-4-enepyranosuronic acid structure at the non-reducing end and a 2-N,6-O-disulpho-D-glucosamine structure at the reducing end of the chain.
Potency is determined by means of a biological assay and interpreted by the first International Low Molecular Weight Heparin Standard as units of anti-factor Xa (anti-Xa) activity per milligram. The mean tinzaparin sodium anti-factor Xa activity is approximately 100 IU per milligram. The average molecular weight ranges between 5,500 and 7,500 daltons. The molecular weight distribution is:
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Clinical Pharmacology
Tinzaparin sodium is a low molecular weight heparin with antithrombotic properties. Tinzaparin sodium inhibits reactions that lead to the clotting of blood including the formation of fibrin clots, both and . It acts as a potent co-inhibitor of several activated coagulation factors, especially Factors Xa and IIa (thrombin). The primary inhibitory activity is mediated through the plasma protease inhibitor, antithrombin.
Bleeding time is usually unaffected by tinzaparin sodium. Activated partial thromboplastin time (aPTT) is prolonged by therapeutic doses of tinzaparin sodium used in the treatment of deep vein thrombosis (DVT). Prothrombin time (PT) may be slightly prolonged with tinzaparin sodium treatment but usually remains within the normal range. Neither aPTT nor PT can be used for therapeutic monitoring of tinzaparin sodium.
Neither unfractionated heparin nor tinzaparin sodium have intrinsic fibrinolytic activity; therefore, they do not lyse existing clots. Tinzaparin sodium induces release of tissue factor pathway inhibitor, which may contribute to the antithrombotic effect. Heparin is also known to have a variety of actions that are independent of its anticoagulant effects. These include interactions with endothelial cell growth factors, inhibition of smooth muscle cell proliferation, activation of lipoprotein lipase, suppression of aldosterone secretion, and induction of platelet aggregation.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Indications And Usage
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is indicated for the treatment of acute symptomatic deep vein thrombosis with or without pulmonary embolism when administered in conjunction with warfarin sodium. The safety and effectiveness of Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® were established in hospitalized patients.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Contraindications
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is contraindicated in patients with active major bleeding, in patients with (or history of) heparin-induced thrombocytopenia, or in patients with hypersensitivity to tinzaparin sodium.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is contraindicated in patients aged 90 years or older with creatinine clearance ≤ 60 mL/min.
Patients with known hypersensitivity to heparin, sulfites, benzyl alcohol, or pork products should not be treated with Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ®.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Warnings
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is not intended for intramuscular or intravenous administration.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® cannot be used interchangeably (unit for unit) with heparin or other low molecular weight heparins as they differ in manufacturing process, molecular weight distribution, anti-Xa and anti-IIa activities, units, and dosage. Each of these medications has its own instructions for use.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Precautions
General:
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent gastrointestinal ulceration, diabetic retinopathy, and hemorrhage.
Consistent with expected age-related changes in renal function, elderly patients and patients with renal insufficiency may show reduced elimination of tinzaparin sodium. Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® should be used with care in these patients (see ). Patients aged 90 years or older with creatinine clearance ≤ 60 mL/min should not be treated with Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® (see ).
Laboratory Tests:
Drug Interactions:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Tinzaparin sodium displayed no genotoxic potential in an bacterial cell mutation assay (AMES test), Chinese hamster ovary cell forward gene mutation test, human lymphocyte chromosomal aberration assay, and mouse micronucleus assay. Tinzaparin sodium at SC doses up to 1800 IU/kg/day in rats (about 2 times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance.
Nursing Mothers:
Pediatric Use:
Geriatric Use:
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Adverse Reactions
Bleeding
Table 4.
Fatal or nonfatal hemorrhage from any tissue or organ can occur. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. Hemorrhagic complications may present as, but are not limited to, paralysis; paresthesia; headache, chest, abdomen, joint, muscle or other pain; dizziness; shortness of breath, difficult breathing or swallowing; swelling; weakness; hypotension, shock, or coma. Therefore, the possibility of hemorrhage should be considered in evaluating the condition of any anticoagulated patient with complaints which do not indicate an obvious diagnosis (see ).
Thrombocytopenia
3
Elevations of Serum Aminotransferases
Local Reactions
Hypersensitivity
Adverse Events
Table 5.
Other Adverse Events in Completed or Ongoing Trials
Body as a Whole:
Cardiovascular Disorders, General:
Central and Peripheral Nervous System Disorders:
Gastrointestinal System Disorders:
Heart Rate and Rhythm Disorders:
Myo-, Endo-, Pericardial and Valve Disorders:
Platelet, Bleeding and Clotting Disorders:
Psychiatric Disorders:
Red Blood Cell Disorders:
Resistance Mechanism Disorders:
Respiratory System Disorders:
Skin and Appendages Disorders:
Urinary System Disorders:
Vascular (Extracardiac) Disorders:
Serious adverse events reported in clinical trials or from post-marketing experience are included in and , respectively:
Spinal epidural hematoma with Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® administered at a therapeutic dose has been reported in at least one patient who had not received neuraxial anesthesia or spinal puncture.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) Dosage And Administration
All patients should be evaluated for bleeding disorders before administration of Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ®. Since coagulation parameters are unsuitable for monitoring Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® activity, routine monitoring of coagulation parameters is not required (see ).
The recommended dose of Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® for the treatment of DVT with or without PE is 175 anti-Xa IU/kg of body weight, administered SC once daily for at least 6 days and until the patient is adequately anticoagulated with warfarin (INR at least 2.0 for two consecutive days). Warfarin sodium therapy should be initiated when appropriate (usually within 1-3 days of Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® initiation). Pregnancy has little or no influence on the pharmacokinetics of Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® and no dosing adjustment is needed for pregnancy.
As Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® may theoretically affect the PT/INR, patients receiving both Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® and warfarin should have blood for PT/INR determination drawn just prior to the next scheduled dose of Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ®.
An appropriately calibrated syringe should be used to assure withdrawal of the correct volume of drug from Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® vials.
To calculate the volume (mL) of an Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® 175 anti-Xa IU per kg SC dose for treatment of deep vein thrombosis:
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is a clear, colorless to slightly yellow solution, and as with other parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is administered by SC injection. It must not be administered by intramuscular or intravenous injection.
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) How Supplied
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is available in a multiple dose 2 mL vial in the following packages:
Store at 25° C (77° F); excursions permitted to 15°-30° C (59°-86° F) [See USP Controlled Room Temperature].
Keep out of the reach of children.
MANUFACTURED FOR:Boulder, CO 80301
MANUFACTURED BY:DK-2750 Ballerup, Denmark
Innohep (Tinzaparin sodium, porcine 4500iu,ml vial sub-q) ® is a registered trademark of LEO Pharmaceutical Products.
