Drug information of Tinzaparin

Mechanism of effect

Tinzaparin binds to the plasma protein antithrombin III, forming a complex with then accelerates the inhibition of factor Xa. Its affinity for factor Xa is 2-4 times greater than that of unbound ATIII.

The inactivation of factor Xa in turn will exponentially generation of thrombin (factor IIa) molecules, which is needed to activate fibrinogen to fibrin. The coagulation cascade is inhibited because fibrin cannot be formed in the presence of tinzaparin. Like all LMWH, it cannot be given intramuscularly due to increased risk of hematoma.

Pharmacodynamic

Tinzaparin, like other LMWHs, have a higher anti-Xa activity than anti-IIa activity. The anti-Xa activity of tinzaparin is 2.0 +/- 0.5 times greater than its to anti-IIa activity. Heparin exhibits approximately equal inhibitory activity against Xa and IIa. Tinzaparin is an anticoagulant that blocks the formation of thrombi. Like all LMWHs, tinzaparin only causes activated partial thromboplastin time (aPTT) prolongation at higher doses and routine monitoring is not recommended. However, anti-factor Xa levels may be monitored in some conditions such as pregnancy and renal dysfunction.

Its use should be avoided in patients with a creatinine clearance less than 20 mL/min. In these patients, unfractionated heparin should be used. Tinzaparin can be used in patients who have a creatinine clearance between 20-30 mL/min, giving it the highest safety threshold for use in renal failure patients compared to all the LMWHs.Tinzaparin must be given either subcutaneously or parenterally. LMWHs are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.

Pharmacokinetics

Half-life: 3-4 hr

Peak plasma time: 4-5 hr

Peak plasma concentration: 0.87 IU/mL

Bioavailability: 87%

Vd: 3.1-5.0 L

Clearance: 1.7 L/hr

Excretion: urine

Dosage

Usual Adult Dose for Deep Vein Thrombosis

175 anti-Xaintl units/kg subcutaneously once daily for at least 6 days and until the patient is adequately anticoagulated with warfarin.

Pediatric

Safety and efficacy not established

Side effects

Pain , Nosebleeds , Headache , nausea , chest pain , vomiting , fever , hemorrhage , local irritation , shortness of breath , thrombocytopenia , pulmonary embolism

Interactions

Protamine sulfat , Vitamin E , Desirudin , Tirofiban , Dalteparin , Glucagon , Chitosan , Eptifibatide , Erythromycin , Steradiol , Estrogen cojugated , Enoxaparin , Prasugrel , Cefamandole , Secobarbital , Roxithromycin , tibolone , fondaparinux , Butalbital and Acetaminophen , Antithrombin III , Estropipate , Cefoxitin , Butabarbital , Antithrombin alfa , Argatroban , Lepirudin , Mifepristone , Quinine , Abciximab , Anagrelide , Clopidogrel , Liothyronine , Pentobarbital , Amobarbital , Phenindione , Bivalirudin , Cilostazol , Phenobarbital , Levonorgestrol , Heparin , Warfarin , Clarithromycin , Primidone , Ticlopidine , Dipyridamole , Cefazolin , Ceftriaxone , Sulfadiazine , Tositumomab , Ibritumomab tiuxetan , Cefotetan , icosapent , Betrixaban , Ramucirumab , Netonal , Oxaprozin , Urokinase , Ipilimumab , Dasatinib , cangrelor , defibrotide , Omadacycline

Alerts

May increase risk for death compared to UHF when used to treat elderly patients with renal insufficiency

Black Box Warnings

Epidural or spinal hematomas may occur in patientsanticoagulated with LMWH or heparinoids who receive neuraxial (epidural/spinal) anesthesia or spinal puncture

These hematomas may result in long-term or permanent paralysis

Patients should be frequently monitored for signs and symptoms of neurologic impairment

If neurological compromise is noted, urgent treatment is necessary

Physicians should consider the benefits versus risk before neuraxial intervention in patientsanticoagulated or to be anticoagulated for thromboprophylaxis

Factors increasing risk of epidural or spinal hematomas

• Indwelling epidural catheters
• Concomitant use of other drugs that affect hemostasis (eg, NSAIDs, platelet inhibitors, other anticoagulants)
• History of traumatic or repeated epidural or spinal punctures
• History of spinal deformity or spinal surgery

Points of recommendation

• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• If you fall or hurt yourself, or if you hit your head, call your doctor right away. Talk with your doctor even if you feel fine.
• People who have any type of spinal or epidural procedure are more likely to have bleeding problems around the spine when already on this drug. This bleeding rarely happens, but can lead to not being able to move body (paralysis) long-term or paralysis that will not go away. The risk is raised in people who have problems with their spine, a certain type of epidural catheter, or have had spinal surgery. The risk is also raised in people who take any other drugs that may affect how the blood clots like blood-thinner drugs (like warfarin), aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs). Talk with the doctor.
• Tell your doctor you use tinzaparin before you have a spinal or epidural procedure. Call your doctor right away if you have any signs of nerve problems like back pain, numbness or tingling, muscle weakness, paralysis, or loss of bladder or bowel control.
• Talk with your doctor if you have recently had or will be having a spinal or epidural procedure. Some time may need to pass between the use of tinzaparin and your procedure.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using tinzaparin while you are pregnant.

• It is given as a shot into the fatty part of the skin.
• Follow how to use as you have been told by the doctor or read the package insert.
• To gain the most benefit, do not miss doses.
• Keep using tinzaparin as you have been told by your doctor or other health care provider, even if you feel well.
• Wash your hands before and after use.
• Move the site where you give the shot with each shot.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Pregnancy level

B

Related drugs

Dalteparin , Enoxaparin , Heparin , Ardeparin , Danaparoid