Tinzaparin dosing

The following table provides tinzaparin doses for the treatment of DVT with or without PE. It is necessary to calculate the appropriate tinzaparin dose for patient weights not displayed in the table. 

Dose may depend on the lapsed time after LMWH administration (e.g., 0.5 mg protamine per 100 units dalteparin or tinzaparin to a maximum of 50 mg if >8 h has passed since the last administered dose)... 

Adults - The recommended dose for the treatment of DVT with or without PE is 175 anti-Xa units/kg of body weight, administered subcutaneously once daily for at least 6 days and until the patient is adequately anticoagulated with warfarin (INR at least 2 for 2 consecutive days). Initiate warfarin sodium therapy when appropriate (usually within 1 to 3 days of tinzaparin initiation). 

As tinzaparin may theoretically affect the prothrombin time (PT)/INR, draw blood for PT/INR determination just prior to the next scheduled dose of tinzaparin for patients receiving tinzaparin and warfarin. 

Tinzaparin Weight-Based Dosing for Treatment of DVT With or Without Symptomatic PE... 

Use the following equation to calculate the volume (mL) of tinzaparin 175 anti-Xa units/kg subcutaneous dose for treatment of DVT ... 

Benzyl alcohol The multiple-dose vials of dalteparin, enoxaparin, and tinzaparin contain benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal gasping syndrome in premature infants. Because benzyl alcohol may cross the placenta, do not use LMWHs preserved with benzyl alcohol in pregnant women. Thromboembolic events If thromboembolic events occur despite LMWH prophylaxis, discontinue and initiate appropriate therapy. 

The mean plasma anti-factor Xa and anti-factor Ha activities following single 175 IU/kg subcutaneous administration of test and reference formulations is shown graphically in Fig. 8.2 A and B, respectively. The mean maximum plasma anti-Xa activity (Amax) was approximately 0.818 IU/mL at 4 h after tinzaparin injection. Anti-Xa activity fell to undetectable levels by 24—30 h in all subjects. The mean maximum plasma anti-IIa activity was 0.308 IU/mL at 5 h post-dose, and anti-IIa activity fell to undetectable levels by 24 h in all subjects. Inter-subject var-... 

Table8.4 Formulation characteristics of test and reference LMWH (tinzaparin) formulations evaluated in a single-dose crossover (bioequivalence) design.

Table 8.6 Pharmacokinetic and bioequivalence metrics from a single-dose, two-way crossover study of LMWH (tinzaparin) formulations administered to healthy volunteers.

Low-molecular-weight heparins, such as enoxaparin, dal-teparin, and tinzaparin, were introduced in 1982. These are parenteral agents that have fixed or weight-adjusted dosing, involve less monitoring, and are easier to administer. The half-lives of LMWHs are longer than that of UFH. Because LMWHs are metabolized renally and due to a 90% cross-reactivity to HIT antibodies, they are contraindicated in patients with poor renal function and patients with HIT. In rare instances, antifactor Xa levels are measured. This peak level is drawn 4 hours after the third dose (prophylaxis 0.2-0.4 units/mL treatment 0.5-1.0 units/mL). 

If major bleeding occurs in a patient receiving an LMWH, it is recommended that protamine sulfate be administered intravenously. However, because of its limited binding to the shorter LMWH chains, protamine sulfate cannot neutralize their anticoagulant effects completely. When given in equimolar concentrations, protamine sulfate neutralizes an estimated 60% to 75% of the antithrombotic activity. The recommended dose of protamine sulfate is 1 mg/1 mg of enoxaparin or 1 mg/100 anti-factor Xa units of dalteparin or tinzaparin administered in the previous 8 hours. If the LMWH dose was given in the previous 8 to 12 hours, a 0.5-mg dose of protamine should be given for every 100 anti-factor Xa units. The use of protamine sulfate is not recommended if the LMWH was administered more than 12 hours earlier. 

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