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references

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  1. Victoza® (liraglutide [rDNA origin] injection) Indications and Usage

    Victoza® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

    Because of the uncertain relevance of the rodent thyroid C-cell tumor findings to humans, prescribe Victoza® only to patients for whom the potential benefits are considered to outweigh the potential risk. Victoza® is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise.

    In clinical trials of Victoza®, there were more cases of pancreatitis with Victoza® than with comparators. Victoza® has not been studied sufficiently in patients with a history of pancreatitis to determine whether these patients are at increased risk for pancreatitis while using Victoza®. Use with caution in patients with a history of pancreatitis.

    Victoza® is not a substitute for insulin. Victoza® should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

    The concurrent use of Victoza® and insulin has not been studied.

    Victoza® Important Safety Information

    Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be ruled out by clinical or nonclinical studies. Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Based on the findings in rodents, monitoring with serum calcitonin or thyroid ultrasound was performed during clinical trials, but this may have increased the number of unnecessary thyroid surgeries. It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients should be counseled regarding the risk and symptoms of thyroid tumors.

    If pancreatitis is suspected, Victoza® should be discontinued. Victoza® should not be re-initiated if pancreatitis is confirmed.

    When Victoza® is used with an insulin secretagogue (e.g. a sulfonylurea) serious hypoglycemia can occur. Consider lowering the dose of the insulin secretagogue to reduce the risk of hypoglycemia.

    There have been no studies establishing conclusive evidence of macrovascular risk reduction with Victoza® or any other antidiabetic drug.

    The most common adverse reactions, reported in ≥5% of patients treated with Victoza® and more commonly than in patients treated with placebo, are headache, nausea, diarrhea, and anti-liraglutide antibody formation. Immunogenicity-related events, including urticaria, were more common among Victoza®-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.

    Victoza® has not been studied in type 2 diabetes patients below 18 years of age and is not recommended for use in pediatric patients.

    Victoza® should be used with caution in patients with renal impairment and in patients with hepatic impairment.

    Please see Prescribing InformationPrescribing Information and Medication GuideMedication Guide.

  2. Levemir® (insulin detemir [rDNA origin] injection) Indications and Usage

    Levemir® is indicated for once- or twice-daily subcutaneous administration for the treatment of adult and pediatric patients with type 1 diabetes mellitus or adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia.

    Levemir® Important Safety Information

    Levemir® is contraindicated in patients hypersensitive to insulin detemir or one of its excipients.

    Levemir® should not be diluted or mixed with any other insulin preparations.

    Hypoglycemia is the most common adverse effect of all insulin therapies, including Levemir®. As with other insulins, the timing of hypoglycemic events may differ among various insulin preparations. Glucose monitoring is recommended for all patients with diabetes. Levemir® is not to be used in insulin infusion pumps. Any change of insulin dose should be made cautiously and only under medical supervision. Concomitant oral antidiabetes treatment may require adjustment.

    Needles and Levemir® FlexPen® must not be shared.

    Inadequate dosing or discontinuation of treatment may lead to hyperglycemia and, in patients with type 1 diabetes, diabetic ketoacidosis. Insulin may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Dose and timing of administration may need to be adjusted to reduce the risk of hypoglycemia in patients being switched to Levemir® from other intermediate or long-acting insulin preparations. The dose of Levemir® may need to be adjusted in patients with renal or hepatic impairment.

    Other adverse events commonly associated with insulin therapy may include injection site reactions (on average, 3% to 4% of patients in clinical trials) such as lipodystrophy, redness, pain, itching, hives, swelling, and inflammation. Less common but more serious are severe cases of generalized allergy, including anaphylactic reaction, which may be life threatening.

    *Whether these observed differences represent true differences in the effects of Levemir®, NPH insulin, and insulin glargine is not known since these trials were not blinded and the protocols (e.g., diet and exercise instructions and monitoring) were not specifically directed at exploring hypotheses related to weight effects of the treatments compared. The clinical significance of the observed differences in weight has not been established.

    Please see Prescribing InformationPrescribing Information.

  3. NovoLog® (insulin aspart [rDNA origin] injection) Indications and Usage

    NovoLog® is an insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus.

    NovoLog® Important Safety Information

    NovoLog® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® or one of its excipients.

    NovoLog® has a more rapid onset and shorter duration of action than regular human insulin. An injection of NovoLog® should be immediately followed by a meal within 5 to 10 minutes. Because of the short duration of action of NovoLog®, a longer-acting insulin also should be used in patients with type 1 diabetes and may be needed in patients with type 2 diabetes. When used in an external subcutaneous insulin infusion pump, NovoLog® should not be mixed with any other insulin or diluent. Hypoglycemia is the most common adverse effect of all insulin therapies, including NovoLog®. The timing of hypoglycemia usually reflects the time-action profile of the administered insulins.

    Any change of insulin dose should be made cautiously and only under medical supervision. Glucose monitoring is recommended for all patients with diabetes and is particularly important for patients using external pump infusion therapy. As with all insulin preparations, the time course of action of NovoLog® may vary in different individuals or at different times in the same individual and is dependent on many conditions, including injection site, local blood supply, temperature, and level of physical activity.

    Needles and NovoLog® FlexPen® must not be shared.

    NovoLog® has not been studied in children with type 2 diabetes or in children with type 1 diabetes under the age of two.

    Severe, life-threatening generalized allergy, including anaphylactic reaction, may occur with any insulin product, including NovoLog®. Adverse reactions observed with NovoLog® include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus. Insulin, particularly when given intravenously or in settings of poor glycemic control, may cause hypokalemia. Like all insulins, NovoLog® requirements may be reduced in patients with renal impairment or hepatic impairment.

    All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy.

    Please see Prescribing InformationPrescribing Information.

  4. NovoLog® Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection, [rDNA origin]) Indications and Usage

    NovoLog® Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection, [rDNA origin]) is an insulin analog indicated to improve glycemic control in patients with diabetes mellitus.

    Important Limitations of Use:
    In premix insulins, such as NovoLog® Mix 70/30, the proportions of rapid acting and long acting insulins are fixed and do not allow for basal versus prandial dose adjustments.

    NovoLog® Mix 70/30 Important Safety Information

    NovoLog® Mix 70/30 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® Mix 70/30 or one of its excipients.

    NovoLog® Mix 70/30 has a faster onset of action than human insulin premix 70/30 and should be dosed within 15 minutes before meal initiation for patients with type 1 diabetes. For patients with type 2 diabetes, dosing should occur within 15 minutes before or after meal initiation.

    NovoLog® Mix 70/30 should not be administered intravenously or used in insulin infusion pumps. NovoLog® Mix 70/30 should not be mixed with any other insulin product.

    Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog® Mix 70/30. The timing of hypoglycemia may reflect the time-action profile of the insulin formulation. Glucose monitoring is recommended for all patients with diabetes. Any change of insulin should be made cautiously and only under medical supervision.

    Needles and NovoLog® Mix 70/30 FlexPen® must not be shared.

    Severe, life-threatening generalized allergy, including anaphylaxis, may occur with insulin products, including NovoLog® Mix 70/30. Adverse reactions observed with NovoLog® Mix 70/30 include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus. Insulin, particularly when given in settings of poor glycemic control, may cause hypokalemia. Like all insulins, NovoLog® Mix 70/30 requirements may be reduced in patients with renal impairment or hepatic impairment.

    The safety and effectiveness of NovoLog® Mix 70/30 has not been established in pediatric patients. Clinical studies of NovoLog® Mix 70/30 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.

    Please see Prescribing InformationPrescribing Information.

  5. Norditropin® (somatropin [rDNA origin] injection) Indications and Usage

    Norditropin® is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone, the treatment of children with short stature associated with Noonan syndrome or Turner syndrome, the treatment of children with short stature born small for gestational age (SGA) with no catch-up growth by age 2-4 years, and for the replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD) who meet either of the following two criteria: 1. Adult Onset: Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or 2. Childhood Onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

    Norditropin® Important Safety Information

    Somatropin should not be used to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure as increased mortality may occur.

    Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Norditropin® is not indicated for the treatment of patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

    Somatropin should not be used or should be discontinued with any evidence of active malignancy. Any preexisiting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Patients with preexisting tumors or GHD secondary to an intracranial lesion should be monitored routinely for progression or recurrence. In childhood cancer survivors, an increased risk of a second neoplasm, particularly meningiomas in patients treated with radiation to the head for their first neoplasm, has been reported in patients treated with somatropin.

    Somatropin should not be used in patients with active proliferative or severe non-proliferative diabetic retinopathy, for growth promotion in pediatric patients with closed epiphyses, or in patients with known hypersensitivity to somatropin or any of its excipients.

    Somatropin may decrease insulin sensitivity particularly at higher doses in susceptible patients. Glucose levels should be monitored periodically, including close monitoring of patients with preexisting diabetes or glucose intolerance. Doses of anti-hyperglycemic drugs (insulin or oral agents) may require adjustment for patients with diabetes on somatropin therapy.

    Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting, usually occurring within the first eight (8) weeks after initiation of somatropin therapy, has been reported in a small number of patients. In all reported cases, rapid resolution has occurred after therapy cessation or a reduction of dose. Funduscopic examination should be performed routinely before and during somatropin therapy. If papilledema is observed, somatropin treatment should be discontinued.

    Fluid retention during somatropin replacement therapy in adults may frequently occur. Clinical manifestations of fluid retention are usually transient and dose dependent.

    In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Periodic thyroid function tests are recommended and thyroid hormone replacement therapy should be initiated or adjusted as needed.

    Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders (including GHD and Turner syndrome) or with rapid growth. Onset of a limp or complaints of hip or knee pain in somatropin patients should be carefully evaluated. Rapid growth may also result in progression of preexisting scoliosis. Patients with a history of scoliosis or skeletal abnormalities, which may be present in untreated Noonan, Turner or Prader-Willi syndrome, should be monitored.

    Patients with Turner Syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. Somatropin may also increase the risk of IH in Turner patients. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.

    Congenital heart disease is an inherent component of Noonan syndrome. Though a clinical study in Noonan syndrome reported no evidence of somatropin-induced ventricular hypertrophy or exacerbation of preexisting ventricular hypertrophy (as judged by echocardiography), the safety of Norditropin® in children with Noonan syndrome and significant cardiac disease is not known.

    Other somatropin-related adverse reactions include injection site reactions/rashes, lipoatrophy and headaches. Subcutaneous injection of somatropin at the same site repeatedly may result in tissue atrophy and can be avoided by rotating the injection site.

    Somatropin inhibits 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) in adipose/hepatic tissue, and may significantly impact the metabolism of cortisol and cortisone. In patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked requiring glucocorticoid replacement therapy. In addition, patients treated with glucocorticoid replacement therapy, especially with cortisone acetate and prednisone, for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses.

    Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine) as limited published data suggest somatropin may alter clearance of these compounds.

    In adult women on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal.

    The safety and effectiveness of Norditropin® in patients age 65 years and older has not been evaluated in clinical studies. Elderly patients may be more sensitive to the actions of somatropin and may be more prone to develop adverse reactions.

    Please see Prescribing Information

  6. Activella® ([estradiol/norethindrone acetate] tablets) Indications and Usage

    Activella® 0.5 mg/0.1 mg (estradiol/norethindrone acetate) tablets is indicated in women who have a uterus for the treatment of moderate to severe vasomotor symptoms associated with menopause and the prevention of postmenopausal osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.

    Activella® 1.0 mg/0.5 mg (estradiol/norethindrone acetate) tablets is also indicated in women who have a uterus for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause. When used solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.

    Activella® Important Safety Information

    Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Dementia in the Prescribing Information.)

    The estrogen plus progestin substudy of the Women’s Health Initiative (WHI) reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) per day, relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Malignant neoplasms, Breast cancer in the Prescribing Information.)

    The estrogen-alone substudy of the WHI reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8 years and 7.1 years, respectively, of treatment with oral conjugated estrogens (CE 0.625 mg) per day, relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders in the Prescribing Information.)

    The Women’s Health Initiative Memory Study (WHIMS), a substudy of the WHI study, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with CE 0.625 mg combined with MPA 2.5 mg and during 5.2 years of treatment with CE 0.625 mg alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL STUDIES, WARNINGS, Dementia and PRECAUTIONS, Geriatric Use in the Prescribing Information.)

    Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these trials, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

    Activella® should not be used in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or history of cancer of the breast; known or suspected estrogen-dependent neoplasia; active deep vein thrombosis, pulmonary embolism, or history of these conditions; active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction); liver dysfunction or disease; known hypersensitivity to the ingredients of Activella® 0.5 mg/0.1 mg; known or suspected pregnancy.

    Other warnings include: gallbladder disease, hypercalcemia and visual abnormalities.

    In a clinical trial, the most commonly reported adverse events (reported at a frequency of ≥5%) were back pain, headache, pain in extremity, nausea, diarrhea, nasopharyngitis, endometrial thickening and vaginal hemorrhage.

    For additional information about Activella® please refer to Prescribing Information, including boxed warning.

  7. Vagifem® (estradiol vaginal tablets) Indications and Usage

    Vagifem® is an estrogen (estradiol) indicated for the treatment of atrophic vaginitis due to menopause.

    Vagifem® Important Safety Information

    WARNING: CARDIOVASCULAR DISORDERS, ENDOMETRIAL CANCER, BREAST CANCER and PROBABLE DEMENTIA

    Estrogen-Alone Therapy

    Endometrial Cancer
    There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

    Cardiovascular Disorders and Probable Dementia
    Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.

    The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg], relative to placebo.

    The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

    In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

    Estrogen Plus Progestin Therapy

    Cardiovascular Disorders and Probable Dementia
    Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.

    The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.

    The WHIMS estrogen plus progestin ancillary study of the WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

    Breast Cancer
    The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer.

    In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins.

    Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.


    The use of Vagifem® is contraindicated in women who exhibit one or more of the following: undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; active deep vein thrombosis, pulmonary embolism or history of these conditions; active arterial thromboembolic disease or a history of these conditions; known liver dysfunction or disease, or known or suspected pregnancy.

    Other warnings include: gallbladder disease, severe hypercalcemia, loss of vision, severe hypertriglyceridemia, cholestatic jaundice, and vaginal abrasion caused by the Vagifem® applicator. Women on thyroid replacement therapy should have their thyroid function monitored.

    In prospective, randomized, placebo-controlled, double-blind studies the most common adverse reactions (incidence ≥5 percent) were upper respiratory tract infection, headache, abdominal pain, back pain, genital pruritus, moniliasis, vulvovaginal mycotic infection, and diarrhea.

    For additional information about Vagifem® please refer to Prescribing Information, including boxed warning.

  8. GlucaGen® (glucagon [rDNA Origin] for injection) Indications and Usage

    GlucaGen® is used to treat severe hypoglycemic (low blood sugar) reactions which may occur in patients with diabetes treated with insulin.

    Glucagen® Important Safety Information

    GlucaGen® should be used with caution in patients with conditions such as prolonged fasting, starvation, adrenal insufficiency, or chronic hypoglycemia because these conditions result in low levels of releasable glucose in the liver and an inadequate reversal of hypoglycemia by GlucaGen® treatment. Nausea and vomiting may occur, especially with doses above 1 mg. Allergic reactions may occur and include generalized rash. Do not use GlucaGen® if you are allergic to glucagon or to one of the inactive ingredients in GlucaGen®. Hypoglycemia may occur again following treatment.

    Please see Prescribing Information.

  9. NovoSeven® Coagulation Factor VIIa (Recombinant) Indications and Usage

    For the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to FVIII or FIX and in patients with acquired hemophilia; prevention of bleeding in surgical interventions or invasive procedures in hemophilia A or B patients with inhibitors to FVIII or FIX and in patients with acquired hemophilia; treatment of bleeding episodes in patients with congenital Factor VII deficiency and prevention of bleeding in surgical interventions or invasive procedures in patients with congenital FVII deficiency.

    (Acquired only) For the treatment of bleeding episodes in patients with acquired hemophilia. For the prevention of bleeding in surgical interventions or invasive procedures in patients with acquired hemophilia.

    NovoSeven® Important Safety Information

    • Most common adverse events: pyrexia, hemorrhage, injection site reaction, arthralgia, headache, hypertension, hypotension, nausea, vomiting, pain, edema, and rash.
    • Patients with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with activated or nonactivated prothrombin complex concentrates (aPCCs/PCCs) may have a potential risk of developing thrombotic events in association with NovoSeven treatment.
    • Contraindicated in patients with known hypersensitivity to NovoSeven, its components, or mouse, hamster, or bovine proteins.
    • Serious adverse events that may or may not have been related to the use of NovoSeven in acquired hemophilia (10 of 139 patients in the compassionate use program, HTRS registry, and the published literature) may include thrombotic serious adverse events and death.
    • Serious adverse events that may or may not have been related to the use of NovoSeven occurred in 14 of 298 patients with hemophilia A or B with inhibitors in the initial clinical program.

    Please see Prescribing Information.

  10. NovoSeven® RT (Coagulation Factor VIIa [Recombinant] Room Temperature Stable) Indications and Usage

    NovoSeven® RT is indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to FVIII or FIX and in patients with acquired hemophilia; prevention of bleeding in surgical interventions or invasive procedures in hemophilia A or B patients with inhibitors to FVIII or FIX and in patients with acquired hemophilia; treatment of bleeding episodes in patients with congenital FVII deficiency and prevention of bleeding in surgical interventions or invasive procedures in patients with congenital FVII deficiency.

    NovoSeven® RT Important Safety Information

    Warning: Serious thrombotic adverse events are associated with the use of NovoSeven® RT outside labeled indications. Arterial and venous thrombotic and thromboembolic events following administration of NovoSeven® RT have been reported during postmarketing surveillance. Clinical studies have shown an increased risk of arterial thromboembolic adverse events with NovoSeven® RT when administered outside the current approved indications. Fatal and non-fatal thrombotic events have been reported. Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT. Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis. Safety and efficacy of NovoSeven® RT has not been established outside the approved indications.

    Thrombotic events following the administration of NovoSeven® RT occurred in 0.28% of bleeding episodes treated, with the incidence in acquired hemophilia of 4% and in hemophilia patients of 0.20% in clinical trials within the approved indications. Fatal and non-fatal thrombotic events have been identified through postmarketing surveillance following NovoSeven® RT use for each of the approved indications.

    Patients with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with activated or nonactivated prothrombin complex concentrates (aPCCs/PCCs) have an increased risk of developing thrombotic events in association with NovoSeven® RT treatment. Caution should be exercised when administering NovoSeven® RT to patients with an increased risk of thromboembolic complications. These include, but are not limited to, patients with a history of coronary heart disease, liver disease, post-operative immobilization, elderly patients, and neonates. In each of these situations, the potential benefit of treatment with NovoSeven® RT should be weighed against the risk of these complications.

    Development of antibodies against FVII has been reported in FVII-deficient patients after treatment with NovoSeven® RT. FVII-deficient patients should be monitored for prothrombin time (PT) and FVII coagulant activity before and after administration of NovoSeven® RT.

    Use with caution in patients with known hypersensitivity to NovoSeven® RT, its components, or mouse, hamster, or bovine proteins.

    Laboratory coagulation parameters (PT/INR, aPTT, FVII:C) have shown no direct correlation to achieving hemostasis.

    In clinical trials, the most common adverse events of NovoSeven® RT therapy are pyrexia, hemorrhage, injection site reaction, arthralgia, headache, hypertension, hypotension, nausea, vomiting, pain, edema, and rash.

    Please see Prescribing Information.

FlexPen®, GlucaGen®, HypoKit®, Levemir®, NovoFine®, and NovoLog® are registered trademarks and NovoMedLink™ is a trademark of Novo Nordisk A/S. Norditropin® and NovoSeven® are registered trademarks of Novo Nordisk Health Care AG. Activella® and Vagifem® are registered trademarks of Novo Nordisk FemCare AG.