2.1 Recommended Dosage in Adults and Pediatric Patients 12 Years of Age and Older

For subcutaneous use only.
The recommended dosage of HYMPAVZI for adults and pediatric patients 12 years of age and older is as follows:

Loading Dose
300 mg (two 150 mg subcutaneous injections)

If more than one injection is required to deliver a complete dose, administer each injection at a different injection site.

Maintenance Dose
One week after the loading dose, initiate maintenance dosing of 150 mg every week by subcutaneous injection on the same day each week, at any time of day.

Dose Adjustment During Treatment
In patients weighing greater than or equal to 50 kg, consider a dose adjustment to 300 mg subcutaneous injection weekly when control of bleeding events is judged to be inadequate by the healthcare provider. Safety and efficacy of HYMPAVZI at doses above 300 mg weekly have not been established.

If more than one injection is required to deliver a complete dose, administer each injection at a different injection site.

Missed Doses
For patients on a maintenance dose of 150 mg:
If a dose is missed, administer as soon as possible before the day of the next scheduled dose, and then resume usual 150 mg subcutaneous weekly dosing schedule (same schedule as prior to the missed dose or new schedule based on date of administration of missed dose).

If more than 13 days have passed since the last dose was administered, administer a loading dose of 300 mg by subcutaneous injection followed by a resumption of 150 mg by subcutaneous injection once weekly thereafter.

For patients on a maintenance dose of 300 mg:
If one or more doses are missed, administer a dose as soon as possible, and then resume 300 mg subcutaneous weekly dosing schedule (same schedule as prior to the missed dose or new schedule based on date of administration of missed dose).

2.2 Recommended Dosage in Pediatric Patients 6 to less than 12 Years of Age

For subcutaneous use only.
The recommended dosage of HYMPAVZI for pediatric patients 6 to less than 12 years of age is as follows:

Loading Dose
150 mg (one 150 mg subcutaneous injection or two 75 mg subcutaneous injections)

If more than one injection is required to deliver a complete dose, administer each injection at a different injection site.

Maintenance Dose
One week after the loading dose, initiate maintenance dosing of 75 mg every week by subcutaneous injection on the same day each week, at any time of day.

Dose Adjustment During Treatment
In patients weighing greater than or equal to 25 kg, consider a dose adjustment to 150 mg subcutaneous injection (one 150 mg subcutaneous injection or two 75 mg subcutaneous injections) weekly when control of bleeding events is judged to be inadequate by the healthcare provider. Safety and efficacy of HYMPAVZI at doses above 150 mg weekly have not been established in children 6 to less than 12 years of age.

If more than one injection is required to deliver a complete dose, administer each injection at a different injection site.

Missed Doses
For patients on a maintenance dose of 75 mg:
If a dose is missed, administer as soon as possible before the day of the next scheduled dose, and then resume usual 75 mg subcutaneous weekly dosing schedule (same schedule as prior to the missed dose or new schedule based on date of administration of missed dose).

If more than 13 days have passed since the last dose was administered, administer a loading dose of 150 mg by subcutaneous injection followed by a resumption of 75 mg by subcutaneous injection once weekly thereafter.

For patients on a maintenance dose of 150 mg:
If one or more doses are missed, administer a dose as soon as possible, and then resume 150 mg subcutaneous weekly dosing schedule (same schedule as prior to the missed dose or new schedule based on date of administration of missed dose).

2.3 Preparation and Administration

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HYMPAVZI is intended for use under the guidance of a healthcare provider. After proper instruction in subcutaneous injection technique, a patient 12 years and older may self-inject or the patient’s caregiver may administer HYMPAVZI, if a healthcare provider determines that it is appropriate.

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Refer to the Instructions for Use for complete preparation and administration instructions.

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Prior to subcutaneous administration, HYMPAVZI may be removed from the refrigerator and allowed to warm at room temperature [up to 86°F (30°C)] in the carton for 15 to 30 minutes protected from direct sunlight. Do not warm by using a heat source such as hot water or a microwave. After removal of HYMPAVZI from the refrigerator, use within 7 days or discard [see How Supplied/Storage and Handling (16)].

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Administer HYMPAVZI by subcutaneous injection, once weekly, at any time of the day in the abdomen or front of thigh. Other injection sites are acceptable if required. Administration of HYMPAVZI in the back of upper arm (prefilled syringe only) or buttocks (prefilled pen only) should be performed by a caregiver or healthcare professional only. HYMPAVZI should not be administered into bony areas or areas where the skin is bruised, red, tender or hard, or areas where there are scars or stretch marks. HYMPAVZI should not be injected into a vein. Rotate the injection site with each new injection.

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During treatment with HYMPAVZI, other medicinal products for subcutaneous administration should, preferably, be injected at different anatomical sites.

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Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. HYMPAVZI is a clear and colorless to light yellow solution. Do not use if the solution is cloudy, dark yellow, or contains flakes or particles.

2.4 Changing to HYMPAVZI

Changing from prophylactic factor replacement therapy or bypassing agents to HYMPAVZI: Prior to initiation of HYMPAVZI, discontinue treatment with clotting factor concentrates (factor VIII or factor IX concentrates) or bypassing agents (e.g., recombinant FVIIa [rFVIIa] or activated prothrombin complex concentrate [aPCC]). HYMPAVZI can be initiated at any time after discontinuing clotting factor concentrates or bypassing agents.

No data are available in patients changing from other non-factor-based hemophilia medicinal products to HYMPAVZI.

2.5 Guidance on Use with Breakthrough Bleed Treatments

Factor VIII and factor IX products or bypassing agents (e.g., rFVIIa or aPCC) can be administered for the treatment of breakthrough bleeds in patients receiving HYMPAVZI. Do not use additional doses of HYMPAVZI to treat breakthrough bleeds. Healthcare providers should discuss with all patients and/or caregivers the dose and schedule of the clotting factor concentrates or bypassing agents to use, if required, while receiving HYMPAVZI prophylaxis.

When treating breakthrough bleeds with factor VIII or factor IX products or with bypassing agents, the lowest effective dose according to the product prescribing information is recommended [see Warnings and Precautions (5.1)]. Please refer to the Full Prescribing Information for the clotting factor concentrate or bypassing agent being used. For rFVIIa, a maximum dose of 90 mcg/kg body weight per dose and a maximum dosing frequency of every 2 hours is recommended. For aPCC, a maximum dose of 100 units/kg body weight within 24 hours is recommended.

2.6 Temporary Interruption for Surgery and Other Interventions

Management in the Perioperative Setting
HYMPAVZI has not been evaluated in the setting of major surgery. Patients have had minor surgical procedures without discontinuing HYMPAVZI prophylaxis in clinical studies.

For major surgery, pause HYMPAVZI at least 7 days prior and initiate management per local standard of care with clotting factor concentrate or bypassing agent and measures to manage the risk of venous thrombosis which can be elevated in the perioperative period. Consult the product information for the clotting factor concentrate or bypassing agent for dosage guidelines in patients with hemophilia undergoing major surgery. Resumption of HYMPAVZI therapy should consider the overall clinical status of the patient, including the presence of post-surgical thromboembolic risk factors, use of other hemostatic products and other concomitant medications [see Dosage and Administration (2.1)].

Management in Patients with Acute Severe Illness
There is limited experience with the use of HYMPAVZI in patients with acute severe illness. Reasons to consider temporary dose interruption of HYMPAVZI include occurrence of acute severe illness (e.g., serious infection, sepsis, trauma) in which there may be increased activation of coagulation and which the healthcare provider considers could increase the risks associated with HYMPAVZI administration. Treatment of acute severe illness should be managed per local standard of care, and continued treatment with HYMPAVZI in this situation should be weighed against the potential risks involved. Resume HYMPAVZI therapy once patient has clinically recovered [see Dosage and Administration (2.1)].

2.7 Pregnancy Testing

Verify that females of reproductive potential are not pregnant prior to initiating HYMPAVZI [see Warnings and Precautions (5.3), Use in Specific Populations (8.1, 8.3)].

2.8 Immune Tolerance Induction

The safety and efficacy of HYMPAVZI in patients receiving ongoing Immune Tolerance Induction (ITI), a desensitization strategy for the eradication of inhibitors, have not been established, and no data are available. Careful assessment of the potential benefits and risks should be performed if continuation or initiation of HYMPAVZI during ITI is considered.