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Novoseven

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Novoseven

Warnings
Precautions

WARNINGS

The extent of the risk of thrombotic adverse events after treatment with NovoSeven (coagulation factor viia (recombinant)) in patients with hemophilia and inhibitors is not known, but is considered to be low. Patients with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with aPCCs/PCCs (activated or nonactivated prothrombin complex concentrates) may have an increased risk of developing thrombotic events due to circulating TF or predisposing coagulopathy. (See ADVERSE REACTIONS and DRUG INTERACTIONS)

The extent of the risk of arterial and venous thromboembolic adverse events after treatment with NovoSeven (coagulation factor viia (recombinant)) in patients without hemophilia is also not known. A clinical study in elderly non-hemophilia intracerebral hemorrhage patients indicated a potential increased risk of arterial thromboembolic adverse events with use of NovoSeven (coagulation factor viia (recombinant)) , including myocardial ischemia, myocardial infarction, cerebral ischemia and/or infarction. 11

PRECAUTIONS

General

Patients who receive NovoSeven (coagulation factor viia (recombinant)) should be monitored if they develop signs or symptoms of activation of the coagulation system or thrombosis. When there is laboratory confirmation of intravascular coagulation or presence of clinical thrombosis, the rFVIIa dosage should be reduced or the treatment stopped, depending on the patient's symptoms.

Due to limited clinical studies which clearly address the effect of post-hemostatic dosing, precautions should be exercised when NovoSeven is used for prolonged dosing. (See DOSAGE AND ADMINISTRATION) Factor VII deficient patients should be monitored for prothrombin time and factor VII coagulant activity before and after administration of NovoSeven (coagulation factor viia (recombinant)) . If the factor VIIa activity fails to reach the expected level, or prothrombin time is not corrected, or bleeding is not controlled after treatment with the recommended doses, antibody formation may be suspected and analysis for antibodies should be performed.

Laboratory Tests

Laboratory coagulation parameters may be used as an adjunct to the clinical evaluation of hemostasis in monitoring the effectiveness and treatment schedule of NovoSeven (coagulation factor viia (recombinant)) although these parameters have shown no direct correlation to achieving hemostasis. Assays of prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma FVII clotting activity (FVII: C), may give different results with different reagents. Treatment with NovoSeven (coagulation factor viia (recombinant)) has been shown to produce the following characteristics:

PT: As shown below, in patients with hemophilia A/B with inhibitors, the PT shortened to about a 7-second plateau at a FVII: C level of approximately 5 U/mL. For FVII: C levels > 5 U/mL, there is no further change in PT.

NovoSeven® (recombinant)  PT versus FVII : C Illustration

aPTT: While administration of NovoSeven (coagulation factor viia (recombinant)) shortens the prolonged aPTT in hemophilia A/B patients with inhibitors, normalization has usually not been observed in doses shown to induce clinical improvement. Data indicate that clinical improvement was associated with a shortening of aPTT of 15 to 20 seconds.

FVIIa: C: FVIIa:C levels were measured two hours after NovoSeven (coagulation factor viia (recombinant)) administration of 35 μg/kg and 90 μg/kg following two days of dosing at two hour intervals. Average steady state levels were 11 and 28 U/mL for the two dose levels, respectively.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Two mutagenicity studies have given no indication of carcinogenic potential for NovoSeven (coagulation factor viia (recombinant)) . The clastogenic activity of NovoSeven (coagulation factor viia (recombinant)) was evaluated in both in vitro studies (i. e. , cultured human lymphocytes) and in vivo studies (i.e., mouse micronucleus test). Neither of these studies indicated clastogenic activity of NovoSeven (coagulation factor viia (recombinant)) . Other gene mutation studies have not been performed with NovoSeven (coagulation factor viia (recombinant)) (e. g., Ames test). No chronic carcinogenicity studies have been performed with NovoSeven (coagulation factor viia (recombinant)) .

A reproductive study in male and female rats at dose levels up to 3. 0 mg/kg/day had no effect on mating performance, fertility, or litter characteristics.

Pregnancy

Pregnancy Category C. Treatment of rats and rabbits with NovoSeven (coagulation factor viia (recombinant)) in reproduction studies has been associated with mortality at doses up to 6 mg/kg and 5 mg/kg. At 6mg/kg in rats, the abortion rate was 0 out of 25 litters; in rabbits at 5 mg/kg, the abortion rate was 2 out of 25 litters. Twenty-three out of 25 female rats given 6 mg/kg of NovoSeven (coagulation factor viia (recombinant)) gave birth successfully, however, two of the 23 litters died during the early period of lactation. No evidence of teratogenicity was observed after dosing with NovoSeven (coagulation factor viia (recombinant)) . There are no adequate and well-controlled studies in pregnant women. NovoSeven (coagulation factor viia (recombinant)) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

NovoSeven (coagulation factor viia (recombinant)) was administered to a FVII deficient patient (25 years of age, 66 kg) during a vaginal delivery (36 μg/kg) and during a tubal ligation (90 μg/kg). No adverse reactions were reported during labor, vaginal delivery, or the tubal ligation.

Nursing Mothers

It is not known whether NovoSeven (coagulation factor viia (recombinant)) is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of NovoSeven (coagulation factor viia (recombinant)) was not determined to be different in various age groups, from infants to adolescents (0 to 16 years of age). Clinical trials were conducted with dosing determined according to body weight and not according to age.

Geriatric Use

Clinical studies in hemophilia did not enroll geriatric patients.

REFERENCES

11. Mayer, S. A. , et al. : Recombinant Activated Factor VII for Acute Intracerebral Hemorrhage, New England Journal of Medicine2005; 352:777-785.

12. Parameswaran, R. , et al. :Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Hemophilia and Thrombosis Research Society Registry, Haemophilia 2005; 11: 100-106.

Last reviewed on RxList: 1/12/2009
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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