Innohep-3500

Each vial of Innohep-3500 also contains benzyl alcohol as preservative.

Each 20,000-anti-Xa IU/mL strength vial and the prefilled syringe are stabilized with sodium bisulfite.

Innohep-3500 is a low molecular weight heparin produced by enzymatic depolymerization of conventional heparin of porcine origin.

The molecular mass is between 1000 and 14,000 dalton, with a peak maximum molecular mass of approximately 4500 dalton.

Innohep-3500® (tinzaparin) 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-3500® (tinzaparin) were established in hospitalized patients.

Preventing blood clots in patients who will be having certain types of surgery. It is also used to treat certain types of blood clots (deep vein thrombosis, pulmonary embolism). It is also used to prevent blood from clotting in dialysis lines. It may also be used for other conditions as determined by your doctor.

Innohep-3500 is a low molecular weight heparin (LMWH). It works by blocking the formation of blood clots.

All patients should be evaluated for bleeding disorders before administration of Innohep-3500®. Since coagulation parameters are unsuitable for monitoring Innohep-3500® activity, routine monitoring of coagulation parameters is not required.

Adult Dosage

The recommended dose of Innohep-3500® 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-3500® initiation). Pregnancy has little or no influence on the pharmacokinetics of Innohep-3500® and no dosing adjustment is needed for pregnancy.

As Innohep-3500® may theoretically affect the PT/INR, patients receiving both Innohep-3500® and warfarin should have blood for PT/INR determination drawn just prior to the next scheduled dose of Innohep-3500®.

Table 8 provides Innohep-3500® doses for the treatment of DVT with or without PE. It is necessary to calculate the appropriate Innohep-3500® dose for patient weights not displayed in Table 8.

An appropriately calibrated syringe should be used to assure withdrawal of the correct volume of drug from Innohep-3500® vials.

To calculate the volume (mL) of an Innohep-3500® 175 anti-Xa IU per kg SC dose for treatment of deep vein thrombosis:

Administration

Innohep-3500® 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-3500® is administered by SC injection. It must not be administered by intramuscular or intravenous injection.

Subcutaneous Injection Technique: Patients should be lying down (supine) or sitting and Innohep-3500® administered by deep SC injection. Administration should be alternated between the left and right anterolateral and left and right posterolateral abdominal wall. The injection site should be varied daily. The whole length of the needle should be introduced into a skin fold held between the thumb and forefinger; the skin fold should be held throughout the injection. To minimize bruising, do not rub the injection site after completion of the injection.

See also:
What is the most important information I should know about Innohep-3500?

Innohep-3500® (tinzaparin) is contraindicated in patients with active major bleeding, in patients with (or history of) heparin-induced thrombocytopenia, or in patients with hypersensitivity to Innohep-3500.

Patients with known hypersensitivity to heparin, sulfites, benzyl alcohol, or pork products should not be treated with Innohep-3500® (tinzaparin).

Use Innohep-3500 as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Innohep-3500. Talk to your pharmacist if you have questions about this information.
• Innohep-3500 is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Innohep-3500 at home, carefully follow the injection procedures taught to you by your health care provider.
• Use the proper technique taught to you by your doctor. Inject deep under the skin, NOT into the muscle or a vein.
• Do not use Innohep-3500 if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Innohep-3500, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Innohep-3500.

See also:
What other drugs will affect Innohep-3500?

Because of increased risk of bleeding, Innohep-3500® (tinzaparin) should be used with caution in patients receiving oral anticoagulants, platelet inhibitors (e.g., salicylates, dipyridamole, sulfinpyrazone, dextran, NSAIDs including ketorolac tromethamine, ticlopidine, and clopidogrel), and thrombolytics. If coadministration is essential, close clinical and laboratory monitoring of these patients is advised.

Laboratory Test Interactions

Elevation of Serum Transaminases

Asymptomatic reversible increases in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels have occurred in patients during treatment with Innohep-3500® (tinzaparin). Similar increases in transaminase levels have also been observed in patients and volunteers treated with heparin and other low molecular weight heparins.

Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, elevations that might be caused by drugs like Innohep-3500® (tinzaparin) should be interpreted with caution.

See also:
What are the possible side effects of Innohep-3500?

Bleeding: Bleeding is the most common adverse event associated with Innohep-3500® (Innohep-3500 injection); however, the incidence of major bleeding is low. In clinical trials, the definition of major bleeding included bleeding accompanied by ≥2 gram/dL decrease in hemoglobin, requiring transfusion of 2 or more units of blood products, or bleeding which was intracranial, retroperitoneal, or into a major prosthetic joint. The data are provided in 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.

Thrombocytopenia: In clinical studies thrombocytopenia was identified in 1% of patients treated with Innohep-3500®. Severe thrombocytopenia (platelet count <50,000/mm3) occurred in 0.13%.

Elevations of Serum Aminotransferases: Asymptomatic increases in aspartate (AST [SGOT]) and/or alanine (ALT [SGPT]) aminotransferase levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported in up to 8.8% and 13% for AST and ALT, respectively, of patients receiving Innohep-3500 for the treatment of DVT. Similar increases in aminotransferase levels have also been observed in patients and healthy volunteers treated with heparin and other low molecular weight heparins. Such elevations are reversible and are rarely associated with increases in bilirubin.

Local Reactions: Mild local irritation, pain, hematoma, and ecchymosis may follow SC injection of Innohep-3500®. Injection site hematoma has been reported in approximately 16% of patients treated with Innohep-3500®.

Hypersensitivity: Anaphylactic/anaphylactoid reactions may occur in association with Innohep-3500® use.

Adverse Events: Adverse events with Innohep-3500® or heparin reported at a frequency of ≥1% in clinical trials with patients undergoing treatment for proximal DVT with or without PE, are provided in Table 5.

Other Adverse Events in Completed or Ongoing Trials: Other adverse events reported at a frequency of ≥1% in 4,000 patients who received Innohep-3500® in completed or ongoing clinical trials are listed by body system:

Body as a Whole: injection site hematoma, reaction unclassified.

Cardiovascular Disorders, General: hypotension, hypertension.

Central and Peripheral Nervous System Disorders: dizziness.

Gastrointestinal System Disorders: flatulence, gastrointestinal disorder (not otherwise specified), dyspepsia.

Heart Rate and Rhythm Disorders: tachycardia.

Myo-, Endo-, Pericardial and Valve Disorders: angina pectoris.

Platelet, Bleeding and Clotting Disorders: hematoma, thrombocytopenia.

Psychiatric Disorders: insomnia, confusion.

Red Blood Cell Disorders: anemia.

Resistance Mechanism Disorders: healing impaired, infection.

Respiratory System Disorders: pneumonia, respiratory disorder.

Skin and Appendages Disorders: rash erythematous, pruritus, bullous eruption, skin disorder.

Urinary System Disorders: urinary retention, dysuria.

Vascular (Extracardiac) Disorders: thrombophlebitis deep, thrombophlebitis leg deep.

Serious adverse events reported in clinical trials or from post-marketing experience are included in Tables 6 and 7, respectively:

Ongoing Safety Surveillance: When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis.

Spinal epidural hematoma in association with neuraxial anesthesia or spinal puncture with Innohep-3500® has been reported.

Spinal epidural hematoma with Innohep-3500® administered at a therapeutic dose has been reported in at least one patient who had not received neuraxial anesthesia or spinal puncture.