Table: Post Marketing Experience
MedDRA System
Preferred Term
Organ Class
Immune system
Hypersensitivity (including anaphylactic shock,
disorders
flushing, urticaria, rash, angioedema)
Vascular disorders
Thromboembolic events (including hepatic artery
thrombosis, myocardial infarction, cerebral infarction,
intestinal infarction, intracardiac thrombus, peripheral
ischemia, portal vein thrombosis, myocardial
ischemia, renal artery thrombosis)
DRUG INTERACTIONS: Avoid simultaneous use of activated prothrombin
complex concentrates or prothrombin complex concentrates. The risk of a potential
interaction between NovoSeven ® RT and coagulation factor concentrates has not
been adequately evaluated in preclinical or clinical studies. Do not mix NovoSeven ®
RT with infusion solutions. Thrombosis may occur if NovoSeven ® RT is administered
concomitantly with Coagulation Factor XIII.
USE IN SPECIFIC POPULATIONS: Pregnancy: Pregnancy Category C. There
are no adequate and well-controlled studies in pregnant women. NovoSeven ® RT
should be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus. Treatment of rats and rabbits with NovoSeven ® in reproduction
studies has been associated with mortality at doses up to 6 mg per kg body weight
and 5 mg per kg body weight respectively. At 6 mg per kg body weight in rats, the
abortion rate was 0 out of 25 litters; in rabbits at 5 mg per kg body weight, the abortion
rate was 2 out of 25 litters. Twenty-three out of 25 female rats given 6 mg per kg
body weight of NovoSeven® 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 ®. Labor and Delivery: There are no adequate and
well-controlled studies in labor, delivery, and postpartum periods. NovoSeven® RT
has caused thrombosis when used to control post-partum hemorrhage. Nursing
Mothers: It is not known whether NovoSeven ® RT 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: Clinical trials enrolling pediatric patients
were conducted with dosing determined according to body weight and not according
to age. Hemophilia A or B with Inhibitors: During the investigational phase of product
development NovoSeven ® was used in 16 children aged 0 to <2 years for 151
bleeding episodes, 27 children aged 2 to <6 years for 140 bleeding episodes, 43
children aged 6 to <12 for 375 bleeding episodes and 30 children aged 12 to 16 years
for 446 bleeding episodes. In a double-blind, randomized comparison trial of two
dose levels of NovoSeven ® in the treatment of joint, muscle and mucocutaneous
hemorrhages in hemophilia A and B patients with and without inhibitors 20 children
aged 0 to <12 and 8 children aged 12 to 16 were treated with NovoSeven ® in doses
of 35 or 70 micrograms per kg dose. Treatment was assessed as effective (definite
relief of pain/tenderness as reported by the patient and/or a measureable decrease
of the size of the hemorrhage and/or arrest of bleeding within 8 hours [rated as
excellent = 51%], within 8-14 hours [rated as effective = 18%] or after 14 hours
[rated as partially effective = 25%]) in 94% of the patients. NovoSeven® was used
in two trials in surgery. In a dose comparison 22 children aged 0 to 16 years were
treated with NovoSeven ®. Effective intraoperative hemostasis (defined as bleeding
that had stopped completely or had decreased substantially [rated as effective =
86%] or bleeding that was reduced but continued [rated as partially effective = 9%])
was achieved in 21/22 (95%) patients. Effective hemostasis was achieved in 10/10
(100%) patients in the 90 mcg/kg dose group and 10/12 (83%) in the 35 mcg/kg
dose group at 48 hours; effective hemostasis was achieved in 10/10 (100%) in the
90 mcg/kg dose group and 9/12 (75%) in the 35 mcg/kg dose group at 5 days. In the
surgery trial comparing bolus (BI) and continuous infusion (CI) 6 children aged 10 to
15 years participated, 3 in each group. Both regimens were 100% effective (defined
as bleeding has stopped completely, or decreased substantially) intra-operatively,
through the first 24 hours and at day 5. At the end of the study period (Postoperative
day 10 or discontinuation of therapy) hemostasis in two patients in the BI group
was rated effective and hemostasis in one patient was rated as ineffective (defined
as bleeding is the same or has worsened). Hemostasis in all three