Humate-P

antihemophilic factor/von willebrand factor complex (human)

Dosage Form: injection
FULL PRESCRIBING INFORMATION

Indications and Usage for Humate-P

Hemophilia A

Humate-P, Antihemophilic Factor/von Willebrand Factor Complex (Human), is indicated for treatment and prevention of bleeding in adults with hemophilia A (classical hemophilia).

Von Willebrand Disease (VWD)

Humate-P is also indicated in adult and pediatric patients with von Willebrand disease (VWD) for:

(1)

treatment of spontaneous and trauma-induced bleeding episodes, and

(2)

prevention of excessive bleeding during and after surgery. This applies to patients with severe VWD as well as patients with mild to moderate VWD where use of desmopressin (DDAVP) is known or suspected to be inadequate.


Controlled clinical trials to evaluate the safety and efficacy of prophylactic dosing with Humate-P to prevent spontaneous bleeding have not been conducted in VWD subjects (see Clinical Studies [14]).

Humate-P Dosage and Administration

Therapy for Hemophilia A

One IU of Factor VIII (FVIII) activity per kg body weight will increase the circulating FVIII level by approximately 2.0 International Units (IU)/dL. Dosage must be individualized based on the patient's weight, type and severity of hemorrhage, FVIII level, and presence of inhibitors. Judge the adequacy of treatment by clinical effects and, in all cases, adjust doses as needed based on clinical judgment and on frequent monitoring of the patient's FVIII level. Table 1 provides dosing recommendations for the treatment of hemophilia A in adults.

Table 1: Dosing Recommendations for the Treatment of Hemophilia A in Adults1

Hemorrhagic Event	Dosage (IU FVIII:C/kg Body Weight)
IU = International Units.
Minor hemorrhage: Early joint or muscle bleed Severe epistaxis	Loading dose 15 IU FVIII:C/kg to achieve a FVIII:C plasma level of approximately 30% of normal; one infusion may be sufficient. If needed, half of the loading dose may be given once or twice daily for 1-2 days.
Moderate hemorrhage: Advanced joint or muscle bleed Neck, tongue, or pharyngeal hematoma (without airway compromise) Tooth extraction Severe abdominal pain	Loading dose 25 IU FVIII:C/kg to achieve a FVIII:C plasma level of approximately 50% of normal, followed by 15 IU FVIII:C/kg every 8-12 hours for the first 1-2 days to maintain the FVIII:C plasma level at 30% of normal. Continue the same dose once or twice daily for up to 7 days or until adequate wound healing is achieved.
Life-threatening hemorrhage: Major surgery Gastrointestinal bleeding Neck, tongue, or pharyngeal hematoma (with potential for airway compromise) Intracranial, intraabdominal, or intrathoracic bleeding Fractures	Initially 40-50 IU FVIII:C/kg, followed by 20-25 IU FVIII:C/kg every 8 hours to maintain the FVIII:C plasma level at 80-100% of normal for 7 days. Continue the same dose once or twice daily for another 7 days to maintain the FVIII:C level at 30-50% of normal.

Treatment of Bleeding Episodes in VWD

Administer 40 to 80 International Units (IU) VWF:RCo (corresponding to 17 to 33 International Units (IU) FVIII in Humate-P) per kg body weight every 8 to 12 hours. Adjust the dosage based on the extent and location of bleeding. Administer repeat doses as long as needed based on monitoring of appropriate clinical and laboratory measures (see Warnings and Precautions [5.2 and 5.3]). Expected levels of VWF:RCo are based on an expected in vivo recovery (IVR) of 2.0 International Units (IU)/dL rise per International Unit (IU)/kg VWF:RCo administered. The administration of 1 International Unit (IU) of FVIII per kg body weight can be expected to lead to a rise in circulating VWF:RCo of approximately 5 International Units (IU)/dL. Table 2 provides dosing recommendations for adult and pediatric patients (see also Pediatric Use [8.4]).2

Table 2: VWF:RCo Dosing Recommendations for the Treatment of Bleeding Episodes by VWD Type

VWD Type	Severity of Hemorrhage	Dosage (IU* VWF:RCo/kg Body Weight)
* IU = International Units. † For major bleeds in all types of VWD where repeated dosing is required, monitor and maintain the patient's FVIII level according to the guidelines for hemophilia A therapy.
Type 1 VWD – Mild (baseline VWF:RCo activity typically >30%)	Minor (e.g., epistaxis, oral bleeding, menorrhagia)	Typically treatable with desmopressin.
	Minor (when desmopressin is known or suspected to be inadequate)   Major† (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, traumatic hemorrhage)	Loading dose 40-60 IU/kg. Then 40-50 IU/kg every 8-12 hours for 3 days to keep the trough level of VWF:RCo >50%. Then 40-50 IU/kg daily for up to 7 days.
Type 1 VWD – Moderate or severe (baseline VWF:RCo typically <30%)	Minor (e.g., epistaxis, oral bleeding, menorrhagia)	40-50 IU/kg (1 or 2 doses).
	Major (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage)	Loading dose 50-75 IU/kg. Then 40-60 IU/kg every 8-12 hours for 3 days to keep the trough level of VWF:RCo >50%. Then 40-60 IU/kg daily for up to 7 days.
Type 2 VWD (all variants) and Type 3 VWD	Minor (clinical indications above)	40-50 IU/kg (1 or 2 doses).
	Major (clinical indications above)	Loading dose 60-80 IU/kg. Then 40-60 IU/kg every 8-12 hours for 3 days to keep the trough level of VWF:RCo >50%. Then 40-60 IU/kg daily for up to 7 days.

Prevention of Excessive Bleeding During and After Surgery in VWD

The following information provides guidelines for calculating loading and maintenance doses of Humate-P for patients undergoing surgery. However in the case of emergency surgery, administer a loading dose of 50 to 60 International Units (IU) VWF:RCo/kg body weight and, subsequently, closely monitor the patient's trough coagulation factor levels.

Measure incremental IVR and assess plasma VWF:RCo and FVIII:C levels in all patients prior to surgery when possible.

To determine IVR:

1. Measure the baseline plasma VWF:RCo level.


2. Infuse a calculated dose [International Units (IU)/kg] of VWF:RCo product intravenously at "time 0".


3. At "time+30 minutes", measure the plasma VWF:RCo level.

Use the following formula to calculate IVR:

IVR  =	(Plasma VWF:RCotime+30 min – Plasma VWF:RCobaseline International Units (IU)/dL)
	Calculated dose (International Units (IU)/kg)

For example, assuming a baseline VWF:RCo of 30 International Units (IU)/dL at "time 0", a calculated dose of 60 International Units (IU)/kg, and a VWF:RCo of 120 International Units (IU)/dL at "time+30 minutes", the IVR would be 1.5 International Units (IU)/dL per International Units (IU)/kg of VWF:RCo administered.

Loading Dose

Table 3 provides guidelines for calculating the loading dose for adult and pediatric patients based on the target peak plasma VWF:RCo level, the baseline VWF:RCo level, body weight in kilograms, and IVR. When individual recovery values are not available, a standardized loading dose can be used based on an assumed VWF:RCo IVR of 2.0 International Units (IU)/dL per International Unit (IU)/kg of VWF:RCo administered.

Table 3: VWF:RCo and FVIII:C Loading Dose Calculations for the Prevention of Excessive Bleeding During and After Surgery for All Types of VWD

Type of Surgery	VWF:RCo Target Peak Plasma Level	FVIII:C Target Peak Plasma Level	Calculation of Loading Dose (to be administered 1 to 2 hours before surgery)
IU = International Units. BW = body weight.
* Δ = Target peak plasma VWF:RCo level – baseline plasma VWF:RCo level. † IVR = in vivo recovery as measured in the patient. ‡ Oral surgery is defined as extraction of fewer than three teeth, if the teeth are non-molars and have no bony involvement. Extraction of more than one impacted wisdom tooth is considered major surgery due to the expected difficulty of the surgery and the expected blood loss, particularly in subjects with type 2A or type 3 VWD. Extraction of more than two teeth is considered major surgery in all patients.
Major	100 IU/dL	80-100 IU/dL	Δ* VWF:RCo × BW (kg) IVR†	= IU VWF:RCo required
			If the IVR is not available, assume an IVR of 2.0 IU/dL per IU/kg and calculate the loading dose as follows: (100 – baseline plasma VWF:RCo) × BW (kg) / 2.0
Minor/Oral‡	50-60 IU/dL	40-50 IU/dL	Δ* VWF:RCo × BW (kg) IVR	= IU VWF:RCo required
Emergency	100 IU/dL	80-100 IU/dL	Administer a dose of 50-60 IU VWF:RCo/kg body weight.

For example, the loading dose of Humate-P required assuming a target VWF:RCo level of 100 International Units (IU)/dL, a baseline VWF:RCo level of 20 International Units (IU)/dL, an IVR of 2.0 International Units (IU)/dL per International Units (IU)/kg, and a body weight of 70 kg would be 2,800 International Units (IU) VWF:RCo, calculated as follows:

IU = International Units.
(100 IU/dL – 20 IU/dL) × 70 kg	= 2,800 IU VWF:RCo required
2.0 (IU/dL)/(IU/kg)

Attaining a target peak FVIII:C plasma level of 80 to 100 International Units (IU) FVIII:C/dL for major surgery and 40 to 50 International Units (IU) FVIII:C/dL for minor surgery or oral surgery might require additional dosing with Humate-P. Because the ratio of VWF:RCo to FVIII:C activity in Humate-P is 2.4:1, any additional dosing will increase VWF:RCo proportionally more than FVIII:C. Assuming an incremental IVR of 2.0 International Units (IU) VWF:RCo/dL per International Units (IU)/kg infused, additional dosing to increase FVIII:C in plasma will also increase plasma VWF:RCo by approximately 5 International Units (IU)/dL for each International Unit (IU)/kg of FVIII administered.

Maintenance Doses

The initial maintenance dose of Humate-P for the prevention of excessive bleeding during and after surgery should be half of the loading dose, irrespective of additional dosing required to meet FVIII:C targets. Subsequent maintenance doses should be based on the patient's VWF:RCo and FVIII levels. Table 4 provides recommendations for target trough plasma levels (based on type of surgery and number of days following surgery) and minimum duration of treatment for subsequent maintenance doses. These recommendations apply to both adult and pediatric patients.

Table 4: VWF:RCo and FVIII:C Target Trough Plasma Level and Minimum Duration of Treatment Recommendations for Subsequent Maintenance Doses for the Prevention of Excessive Bleeding During and After Surgery

Type of Surgery	VWF:RCo Target Trough Plasma Level*		FVIII:C Target Trough Plasma Level*		Minimum Duration of Treatment
	Up to 3 days following surgery	After Day 3	Up to 3 days following surgery	After Day 3
IU = International Units.
* Trough levels for either coagulation factor should not exceed 100 IU/dL. † Oral surgery is defined as extraction of fewer than three teeth, if the teeth are non-molars and have no bony involvement. Extraction of more than one impacted wisdom tooth is considered major surgery due to the expected difficulty of the surgery and the expected blood loss, particularly in subjects with type 2A or type 3 VWD. Extraction of more than two teeth is considered major surgery in all patients. ‡ Administer at least one maintenance dose following oral surgery based on individual pharmacokinetic values. Subsequent therapy with an antifibrinolytic agent is usually administered until adequate healing is achieved.
Major	>50 IU/dL	>30 IU/dL	>50 IU/dL	>30 IU/dL	72 hours
Minor	≥30 IU/dL	–	–	>30 IU/dL	48 hours
Oral†	≥30 IU/dL	–	–	>30 IU/dL	8-12 hours‡

Based on individual pharmacokinetic-derived half-lives, the frequency of maintenance doses is generally every 8 or 12 hours; patients with shorter half-lives may require dosing every 6 hours. In the absence of pharmacokinetic data, it is recommended that Humate-P be administered initially every 8 hours with further adjustments determined by monitoring trough coagulation factor levels. When hemostatic levels are judged insufficient or trough levels are outside the recommended range, consider modifying the administration interval and/or the dose.

It is advisable to monitor trough VWF:RCo and FVIII:C levels at least once a day in order to adjust Humate-P dosing as needed to avoid excessive accumulation of coagulation factors. The duration of treatment generally depends on the type of surgery performed, but must be assessed for individual patients based on their hemostatic response (see Clinical Studies [14.2]).

Reconstitution and Administration

Humate-P is for intravenous (IV) use only.

Inspect visually for particulate matter and discoloration prior to administration.

Use either the Mix2Vial™ filter transfer set provided with Humate-P (see How Supplied/Storage and Handling [16]) or a commercially available double-ended needle and vented filter spike.

Plastic disposable syringes are recommended for use with Humate-P. Protein solutions of this type tend to adhere to the ground glass surface of all-glass syringes.

1. Ensure that the Humate-P and diluent are at room temperature. Using aseptic technique, follow these steps to reconstitute Humate-P.
2. Place the product vial, diluent vial and Mix2Vial on a flat surface.
3. Remove product and diluent vial flip caps and treat the stoppers with the alcohol swab provided, and allow to dry prior to opening the Mix2Vial package.
4. Open the Mix2Vial package by peeling away the lid (Fig. 1). Leave the Mix2Vial in the clear package. Place the diluent vial on a flat surface and hold the vial tight. Grip the Mix2Vial together with the package and snap the blue end onto the diluent stopper (Fig. 2).	Fig. 1 Fig. 2
5. Carefully remove the clear package from the Mix2Vial set. Make sure that you only pull up the package and not the Mix2Vial set (Fig. 3).	Fig. 3
6. With the product vial placed firmly on a flat surface, invert the diluent vial with the set attached and snap the transparent adapter onto the product vial stopper (Fig. 4). The diluent will automatically transfer into the product vial.	Fig. 4
7. With the diluent and product vial still attached, gently swirl the product vial to ensure the product is fully dissolved (Fig. 5). Do not shake vial.	Fig. 5
8. With one hand grasp the product-side of the Mix2Vial set and with the other hand grasp the blue diluent-side of the Mix2Vial set and unscrew the set into two pieces (Fig. 6).	Fig. 6
9. Draw air into an empty, sterile syringe. While the product vial is upright, screw the syringe to the Mix2Vial set. Inject air into the product vial. While keeping the syringe plunger pressed, invert the system upside down and draw the concentrate into the syringe by pulling the plunger back slowly (Fig. 7).	Fig. 7
10. Now that the concentrate has been transferred into the syringe, firmly grasp the barrel of the syringe (keeping the syringe plunger facing down) and unscrew the syringe from the Mix2Vial set (Fig. 8). Attach the syringe to a suitable intravenous (IV) administration set.	Fig. 8
11. If the same patient is to receive more than one vial, you may pool the contents of multiple vials. Use a separate unused Mix2Vial for each product vial.

When the reconstitution procedure is followed precisely, it is not uncommon for a few small flakes or particles to remain. The Mix2Vial should remove those particles.

Do not refrigerate Humate-P after reconstitution. Administer within 3 hours after reconstitution.

Slowly infuse the solution (maximally 4 mL/minute) with a suitable IV administration set.

Discard the administration equipment and any unused Humate-P after use.

Dosage Forms and Strengths

Humate-P is a sterile, lyophilized powder for intravenous administration. Each vial of Humate-P contains the labeled amount of VWF:RCo and FVIII activity expressed in International Units (IU). The average ratio of VWF:RCo to FVIII is 2.4:1.

Approximate potencies are shown below; check each carton/vial for the actual potency prior to reconstitution:

VWF:RCo/vial	FVIII/vial	Diluent
* IU = International Units.
600 IU	250 IU	5 mL
1200 IU	500 IU	10 mL
2400 IU	1000 IU	15 mL

Contraindications

Humate-P is contraindicated in individuals who have had an anaphylactic or severe systemic reaction to antihemophilic factor or von Willebrand factor preparations.

Warnings and Precautions

Thromboembolic Events (VWD Patients)

Thromboembolic events have been reported in VWD patients receiving Antihemophilic Factor/von Willebrand Factor Complex replacement therapy, especially in the setting of known risk factors for thrombosis.3,4 Early reports indicate a higher incidence may occur in females. Endogenous high levels of FVIII have also been associated with thrombosis, but no causal relationship has been established. Exercise caution and consider antithrombotic measures in all at-risk VWD patients who are receiving coagulation factor replacement therapy.

Monitoring for Intravascular Hemolysis

Humate-P contains blood group isoagglutinins (anti-A and anti-B). When doses are very large or need to be repeated frequently (for example, when inhibitors are present or when pre- and post-surgical care is involved), monitor patients of blood groups A, B, and AB for signs of intravascular hemolysis and decreasing hematocrit values and treat appropriately.

Monitoring VWF:RCo and FVIII Levels

Monitor the VWF:RCo and FVIII levels of VWD patients receiving Humate-P using standard coagulation tests, especially in cases of surgery. It is advisable to monitor trough VWF:RCo and FVIII:C levels at least once a day in order to adjust the dosage of Humate-P as needed to avoid excessive accumulation of coagulation factors (see Dosage and Administration [2.2, 2.3]).

Transmission of Infectious Agents

Humate-P is made from human plasma. Products made from human plasma may contain infectious agents (e.g., viruses and theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that can cause disease (see Description [11] and Patient Counseling Information [17.1]). The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses during manufacturing (see Description [11.1] for virus reduction measures).

Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Thus the risk of transmission of infectious agents cannot be eliminated completely. Report all infections thought by a physician possibly to have been transmitted by this product to CSL Behring Pharmacovigilance at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Some viruses, such as Parvovirus B19 virus (B19V) or hepatitis A (HAV), are particularly difficult to remove or inactivate. B19V may most seriously affect pregnant women and immune-compromised individuals.

Although the overwhelming number of B19V and HAV cases are community acquired, reports of these infections have been associated with the use of some plasma-derived products. Therefore, physicians should be alert to the potential symptoms of B19V and HAV infections (see Patient Counseling Information [17.1]).

Symptoms of B19V may include low-grade fever, rash, arthralgias, and transient symmetric, nondestructive arthritis. Diagnosis is often established by measuring B19V-specific IgM and IgG antibodies. Symptoms of HAV include low-grade fever, anorexia, nausea, vomiting, fatigue, and jaundice. A diagnosis may be established by measuring specific IgM antibodies.

Physicians should strongly consider administration of hepatitis A and hepatitis B vaccines to individuals receiving plasma derivatives. Potential risks and benefits of vaccination should be weighed by the physician and discussed with the patient.

Adverse Reactions

The most serious adverse reaction observed in patients receiving Humate-P is anaphylaxis. Thromboembolic events have also been observed in patients receiving Humate-P for the treatment of VWD (see Warnings and Precautions [5.1]). Reports of thromboembolic events in VWD patients with other thrombotic risk factors receiving coagulation factor replacement therapy have been obtained from spontaneous reports, published literature, and a European clinical study. In some cases, inhibitors to coagulation factors may occur. However, no inhibitor formation was observed in any of the clinical studies.

In patients receiving Humate-P in clinical studies for treatment of VWD, the most commonly reported adverse reactions observed by >5% of subjects are allergic-anaphylactic reactions (including urticaria, chest tightness, rash, pruritus, and edema). For patients undergoing surgery, the most common adverse reactions are postoperative wound and injection-site bleeding, and epistaxis.

Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

Treatment of Bleeding Episodes in VWD

Allergic symptoms, including allergic reaction, urticaria, chest tightness, rash, pruritus, and edema, were reported in 6 of 97 (6%) subjects in a Canadian retrospective study (see Clinical Studies [14.1]). Four of 97 (4%) subjects experienced seven adverse events that were considered to have a possible or probable relationship to Humate-P. These included chills, phlebitis, vasodilation, paresthesia, pruritus, rash, and urticaria. All were mild in intensity with the exception of a moderate case of pruritus.

In a prospective, open-label safety and efficacy study of Humate-P in VWD subjects with serious life- or limb-threatening bleeding or undergoing emergency surgery, seven of 71 (10%) subjects experienced nine adverse reactions. These were one occurrence each of mild vasodilation and mild pruritis; two occurrences of mild paresthesia; and one occurrence each of moderate peripheral edema and extremity pain and severe pseudothrombocytopenia (platelet clumping with a false low reading). Humate-P was discontinued in the subject who experienced the peripheral edema and extremity pain.

Prevention of Excessive Bleeding During and After Surgery in VWD

Among the 63 VWD subjects who received Humate-P for prevention of excessive bleeding during and after surgery, including one subject who underwent colonoscopy without the planned polypectomy, the most common adverse events were postoperative hemorrhage (35 events in 19 subjects with five subjects experiencing bleeding at up to three different sites), postoperative nausea (15 subjects), and postoperative pain (11 subjects). Table 5 presents the postoperative hemorrhagic adverse events.

Table 5: Hemorrhagic Adverse Events in 63 Surgical Subjects

Adverse Event	Surgical Procedure Category	Number of Subjects/Events	Onset* (Number of Events)		Severity (Number of Events)
			On	Post	Mild	Mod	Severe
* On = on-therapy; onset while receiving Humate-P or within 1 day of completing Humate-P administration. Post = post-therapy; onset at least one day after completing Humate-P administration. † Reported as serious adverse events following intracranial surgery. ‡ Two of these events were reported as serious adverse events following gastrojejunal bypass. § Reported as a serious adverse event requiring hysterectomy following hysteroscopy and dilation and curettage.
Wound/injection site bleeding	Major	8/11	7	4	9	–	2
	Minor	2/2	2	–	1	1	–
	Oral	2/6	–	6	3	3	–
Epistaxis	Major	4/4	2	2	3	1	–
	Minor	1/1	1	–	1	–	–
Cerebral hemorrhage/ subdural hematoma	Major	1/2	2†	–	–	2	–
Gastrointestinal bleeding	Major	1/3	3‡	–	–	2	1
Menorrhagia	Major	1/1	1§	–	–	1	–
Groin bleed	Oral	1/1	–	1	1	–	–
Ear bleed	Major	1/1	1	–	1	–	–
Hemoptysis	Major	1/1	1	–	1	–	–
Hematuria	Major	1/1	1	–	1	–	–
Shoulder bleed	Major	1/1	1	–	1	–	–

Table 6 lists the non-hemorrhagic adverse events reported in at least two subjects, regardless of causality, and the adverse events that were possibly related to Humate-P. Pulmonary embolus considered possibly related to Humate-P occurred in one elderly subject who underwent bilateral knee replacement.

Table 6: Non-Hemorrhagic and Possibly Related Adverse Events in 63 Surgical Subjects

Body System	Adverse Event (AE)	Number of Subjects With an AE Possibly Related to Humate-P	Number of Subjects With an AE Regardless of Causality*
* Events occurring in two or more subjects. † Events occurring in separate subjects.
Body as a whole	Pain	–	11
	Fever	–	4
	Abdominal pain	–	3
	Infection	–	3
	Surgery	–	3
	Back pain	–	2
	Facial edema	–	2
Cardiovascular	Chest pain	–	3
	Pulmonary embolus†	1	1
	Thrombophlebitis†	1	1
Digestive	Nausea	1	15
	Constipation	–	7
	Vomiting	1	3
	Sore throat	–	2
Hemic and lymphatic system	Anemia / decreased hemoglobin	–	2
Metabolic/nutritional	Increased SGPT	1	1
Nervous	Dizziness	1	5
	Headache	1	4
	Increased sweating	–	3
	Insomnia	–	2
Skin and appendages	Pruritus	–	3
	Rash	1	1
Urogenital	Urinary retention	–	4
	Urinary tract infection	–	2

Eight subjects experienced 10 postoperative serious adverse events: one with subdural hematoma and intracerebral bleeding following intracranial surgery related to an underlying cerebrovascular abnormality; one with two occurrences of gastrointestinal bleeding following gastrojejunal bypass; and one each with sepsis, facial edema, infection, menorrhagia requiring hysterectomy following hysteroscopy and dilation and curettage, pyelonephritis, and pulmonary embolus.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Humate-P. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Humate-P exposure.

Adverse reactions reported in patients receiving Humate-P for treatment of VWD or hemophilia A are allergic-anaphylactic reactions (including urticaria, chest tightness, rash, pruritus, edema, and shock), development of inhibitors to FVIII, and hemolysis. Additional adverse reactions reported for VWD are thromboembolic complications, chills and fever, and hypervolemia.

Drug Interactions

None reported.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Humate-P. It is also not known whether Humate-P can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Humate-P should be given to a pregnant woman only if clearly needed.

Labor and Delivery

It is not known whether Humate-P can cause harm to the mother or the fetus when administered during labor and delivery. Humate-P should be given during labor and delivery only if clearly needed.

Nursing Mothers

It is not know whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Humate-P is administered to a nursing woman.

Pediatric Use

Hemophilia A

Adequate and well-controlled studies with long-term evaluation of joint damage have not been done in pediatric subjects. Joint damage may result from suboptimal treatment of hemarthroses.

VWD

The safety and effectiveness of Humate-P for the treatment of VWD was demonstrated in 26 pediatric subjects, including infants, children, and adolescents, but have not been evaluated in neonates. The safety of Humate-P for the prevention of excessive bleeding during and after surgery was demonstrated in eight pediatric subjects (ages 3 to 15) with VWD. Of the 34 pediatric subjects studied for either treatment of bleeding episodes in VWD or prevention of excessive bleeding during and after surgery, four were infants (1 month to under 2 years of age), 23 were children (2 through 12 years), and seven were adolescents (13 through 15 years).

As in adults, pediatric patients should be dosed based on body weight (kg) (see Dosage and Administration [2.2, 2.3]).

Geriatric Use

Clinical studies of Humate-P did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects. As for all patients, dosing for geriatric patients should be appropriate to their overall situation.

Humate-P Description

Humate-P, Antihemophilic Factor/von Willebrand Factor Complex (Human), is a purified, sterile, lyophilized concentrate of Factor VIII (FVIII) and von Willebrand Factor (VWF) (Human) to be admin