Roctavian Dosage

Generic name: VALOCTOCOGENE ROXAPARVOVEC 20000000000000{GC} in 1mL
Dosage form: injection, solution
Drug class: Miscellaneous coagulation modifiers

Medically reviewed by Drugs.com. Last updated on Mar 4, 2024.

For one-time single-dose intravenous use only.

Treatment with ROCTAVIAN should be under the supervision of a physician experienced in the treatment of hemophilia and/or bleeding disorders.

For Patient Selection

Perform testing for pre-existing antibodies to AAV5 using the FDA approved companion diagnostic.
DO NOT administer ROCTAVIAN to patients with a positive test for antibodies to AAV5. Information on FDA-approved tests for the detection of antibodies to AAV5 is available at: http://www.fda.gov/CompanionDiagnostics.
Perform factor VIII inhibitor titer testing [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.6)].
DO NOT administer ROCTAVIAN to a patient with a positive test for factor VIII inhibitor.
Perform liver health assessments, which include:
- Liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin and international normalized ration (INR)]
- Ultrasound and elastography or laboratory assessments for liver fibrosis
In case of radiological liver abnormalities and/or liver function test abnormalities (ALT, AST, GGT, ALP or total bilirubin > 1.25 × ULN or INR ≥ 1.4), consider a consultation with a hepatologist to assess eligibility for ROCTAVIAN.
Assess patient's ability to receive corticosteroids and/or other immunosuppressive therapy that may be required for an extended period [see Dosage and Administration (2.3)]. Ensure that the risks associated with immunosuppression are acceptable for the individual patient.
DO NOT administer ROCTAVIAN to patients with active acute or uncontrolled chronic infections, known significant hepatic fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent) or cirrhosis, or mannitol hypersensitivity [see Contraindications (4) and Use in Specific Populations (8.8)].

Dose

The recommended dose of ROCTAVIAN is 6 × 1013 vector genomes per kilogram (vg/kg) body weight, administered as a single intravenous infusion. ROCTAVIAN is administered using an infusion pump at a rate of 1 mL/min, which can be increased every 30 minutes by 1 mL/min up to a maximum rate of 4 mL/min.

Calculating Dose in Milliliters (mL) and Number of Vials Required

Patient dose volume in mL:

Body weight in kg multiplied by 3 = dose in mL.

The multiplication factor 3 represents the per kilogram dose (6 × 1013 vg/kg) divided by the amount of vector genomes per mL of the ROCTAVIAN suspension (2 × 1013 vg/mL).
Number of ROCTAVIAN vials to be thawed:

Patient dose volume (mL) divided by 8 = number of vials to be thawed (round up to next whole number of vials).

The division factor 8 represents the minimum volume of ROCTAVIAN extractable from a vial (8 mL).

Table 1: Example of Dose Volume and Number of Vials to be Thawed
Patient Weight	Patient Dose by Volume (mL) (body weight multiplied by 3)	Number of Vials to be Thawed (dose volume divided by 8, then rounded up)
70 kg	210 mL	27 vials (rounded up from 26.25)

ROCTAVIAN can be administered only once.

Preparation for Administration

Required Equipment and Materials

Flow rate-controlled syringe pump
Syringes for ROCTAVIAN administration (the number of syringes will depend on the patient's dose volume and the syringe pump used and should be prepared prior to administration of ROCTAVIAN)
18- to 21-gauge sharp needles
High-volume, in-line, low protein binding infusion filter with a pore size of 0.22 microns and maximum operating pressure adequate for the syringe pump or pump settings. Ensure availability of a sufficient number of replacement filters, according to the specifications for maximum filtered fluid volume.
Syringe of 0.9% Sodium Chloride Injection, USP sodium chloride 9 mg/mL (0.9%) solution for priming and flushing the infusion line
When assembling the infusion system, refer to the compatible materials with ROCTAVIAN suspension listed in Table 2.

Table 2: Compatible Infusion System Component Materials
Component	Compatible Materials
* Tubing extensions should not exceed 40 inches in length. † Do not use filter needles to extract ROCTAVIAN from vials.
Syringes	Polypropylene barrel with a synthetic rubber plunger tip
Syringe cap	Polypropylene
Infusion tubing*	Polyethylene
0.22 micron in-line filter	Polyvinylidene fluoride filter with polyvinyl chloride body
Infusion catheter	Polyurethane based polymer
Stopcocks	Polycarbonate
18 to 21-gauge sharp needles for extraction from vials†	Stainless steel

General Precautions

Do not expose ROCTAVIAN to the light of an ultraviolet radiation disinfection lamp.
Prepare ROCTAVIAN using aseptic technique. Wear gloves and safety glasses during preparation and administration.
Treat spills of ROCTAVIAN with a virucidal agent with proven activity against non-enveloped viruses and blot using absorbent materials.
Dispose unused medicinal product and materials that may have come in contact with ROCTAVIAN in accordance with the local biosafety guidelines.

Thaw and Inspect

1.: Keep each vial in its carton until ready to thaw. ROCTAVIAN is sensitive to light.
2.: Thaw ROCTAVIAN at room temperature. Do not thaw or warm vials any other way. Thawing time is approximately 2 hours.
3.: Remove the required number of vials from their cartons.
4.: Inspect the vials for damage to the vial or cap. Do not use if damaged.
5.: Set the vials upright. To achieve optimal thawing, spread them out evenly or place them in racks that have been kept at room temperature.
6.: Visually confirm that all vials have been thawed. There should be no visible ice.
7.: Very gently invert each vial 5 times to mix. It is important to minimize foaming.
8.: Let the suspension settle for approximately 5 minutes before continuing.
9.: Visually inspect the fully thawed vials. Do not use a vial if the suspension is not clear, not colorless to pale yellow, or contains visible particles.

ROCTAVIAN contains no preservative. For microbiological safety, keep the thawed suspension in the vials until it is time for infusion.

If necessary, an intact vial (stopper not yet punctured) that has been thawed at room temperature can be stored refrigerated between 2 to 8°C (36 to 46°F) for up to 3 days, upright and protected from light (e.g., in the original carton).

Thawed ROCTAVIAN (in vials or syringes) can be held at room temperature, up to 25°C (77°F), for a maximum of 10 hours including hold time in intact vial, preparation time into the syringes, and duration of infusion.

Extraction into Syringes

10.: Using 18 to 21-gauge sharp needles, slowly extract ROCTAVIAN from the vials into the infusion-pump syringes. All infusion-pump syringes should be prepared prior to administering ROCTAVIAN. The contents of multiple vials may be combined into a single syringe.

Addition of In-line Filter and Priming of the Infusion System

11.: Insert the in-line filter close to the infusion site.
12.: Prime tubing and filter with ROCTAVIAN.
13.: When replacing filters during the infusion, use 0.9% Sodium Chloride Injection, USP, for priming and flushing.

Incompatibilities

Do not use infusion system components other than those described in Table 2. ROCTAVIAN must not be mixed or diluted with infusion solutions; 0.9% Sodium Chloride Injection, USP is used to prime and flush the infusion line.

Administration

Administer ROCTAVIAN in a setting where personnel and equipment are immediately available to treat infusion-related reactions [see Warnings and Precautions (5.1)].
Infuse the suspension through a suitable peripheral vein, using an infusion catheter with in-line filter and a programmable syringe pump.
Start the infusion at a rate of 1 mL/min. If tolerated, the rate may be increased every 30 minutes by 1 mL/min up to a maximum rate of 4 mL/min. The infusion time depends on infusion volume, rate and patient response and can be, for example, 2 to 5 hours or longer for a patient weighing 100 kg.
In the event of an infusion-related reaction during administration [see Warnings and Precautions (5.1)],
- Decrease the infusion rate or stop the infusion.
- Administer treatment as needed to manage infusion reaction.
- If the infusion is stopped, restart the infusion at a rate of 1 mL/min and consider maintaining it at a previously tolerated level for the remainder of the infusion. If the infusion needs to be restarted, the infusion should be completed within 10 hours of initial drug product thaw.
- Discontinue infusion for anaphylaxis.
DO NOT administer ROCTAVIAN as an intravenous push or bolus.
DO NOT infuse ROCTAVIAN in the same intravenous line with any other products.
DO NOT use a central line or port.
To ensure the patient receives the complete dose, after the content of the last ROCTAVIAN-containing syringe is infused, flush the infusion line with a sufficient volume of 0.9% Sodium Chloride Injection, USP, through the same tubing and filter, and at the same infusion rate.
Maintain venous access during the subsequent observation period [see Warnings and Precautions (5.1)].

Monitoring Post-Administration

Conduct the following tests after ROCTAVIAN administration [see Warnings and Precautions (5.2, 5.4, 5.5)].

Perform regular ALT testing to monitor for elevations. Elevated liver enzymes, especially elevated ALT, may indicate immune-mediated hepatotoxicity and may be associated with decline in factor VIII activity.
The monitoring schedule for ALT, and recommendations for corticosteroid use (initiation and taper) are based on the clinical efficacy and safety experience of 112 patients in a clinical study with ROCTAVIAN.
- Monitor ALT weekly for at least 26 weeks following administration of ROCTAVIAN. See Table 3 for monitoring schedule. Monitor AST and creatine phosphokinase (CPK) as needed to help rule out alternative causes for ALT elevations (including potentially hepatotoxic medications or agents, alcohol consumption, or strenuous exercise). Consider repeating ALT testing within 24 to 48 hours to confirm ALT elevation prior to initiation of corticosteroid treatment and using the same laboratory to measure ALT activity at baseline and over time to minimize the impact of inter-laboratory variability on test results.
- If ALT ≥ 1.5 × baseline or above ULN consider corticosteroid treatment. For patients who need corticosteroid therapy, the recommended starting dose is 60 mg with a subsequent taper upon return of ALT levels to baseline (see Table 4 below for recommendation on corticosteroid treatment).
- Monitor ALT weekly, and as clinically indicated, during corticosteroid therapy. Continue to monitor ALT until its return to baseline.
- Monitor for and manage adverse reactions secondary to corticosteroid use. Refer to the corticosteroid prescribing information for risks and required precautions.

Table 3: ALT Monitoring Post-Administration*
Timeframe	Monitoring Frequency†
* Monitoring of ALT may be accompanied by monitoring of AST and CPK to rule out other causes of ALT elevation. † Weekly monitoring is recommended, and as clinically indicated, during corticosteroid tapering.
First 26 weeks	Weekly
Weeks 26 to 52 (Year 1)	Every 1 to 2 weeks
Year 2	Every 3 months
After Year 2	Every 6 months

Table 4: Recommended Corticosteroid Regimen in Response to ALT Elevations
	Corticosteroid Regimen (Prednisone or Equivalent Dose of Another Corticosteroid)
* If ALT continues to rise or has not improved after 2 weeks, increase the corticosteroid dose up to a maximum of 1.2 mg/kg, after ruling out alternative causes for ALT elevation. † Taper corticosteroids after ALT levels reach baseline. The taper may be individualized based on the trend of ALT decline, the patient's medical condition, corticosteroid tolerance, and adverse reactions to corticosteroid therapy.
Starting Dose*	60 mg daily for 2 weeks
Tapering†	40 mg daily for 3 weeks 30 mg daily for 1 week 20 mg daily for 1 week 10 mg daily for 1 week

There is limited information on the benefit of starting a corticosteroid course after the first year of ROCTAVIAN administration.

Other immunosuppressive therapies (e.g., tacrolimus, mycophenolate mofetil) may be considered if corticosteroids are contraindicated, ineffective or there are adverse reactions secondary to corticosteroid use necessitating discontinuation.

Monitor Factor VIII Activity
- Monitor factor VIII activity using the same schedule for ALT monitoring in Table 3 [see Warnings and Precautions (5.4)].
- Consider more frequent monitoring in patients with factor VIII activity levels ≤ 5 IU/dL and evidence of bleeding, taking into account the stability of factor VIII levels since the previous measurement.
- It may take several weeks after ROCTAVIAN infusion before ROCTAVIAN-derived factor VIII activity rises to a level sufficient for prevention of spontaneous bleeding episodes. Therefore, continued routine prophylaxis support with exogenous factor VIII or other hemostatic products used in the management of hemophilia A may be needed during the first few weeks after ROCTAVIAN infusion [see Clinical Pharmacology (12.3)]. Exogenous factor VIII or other hemostatic products may also be required in case of surgery, invasive procedures, trauma, or bleeds in the event that ROCTAVIAN-derived factor VIII activity is deemed insufficient for adequate hemostasis in such situations.
- The use of different assays may impact test results; therefore, use the same assay and reagents to monitor patients over time, if feasible [see Warnings and Precautions (5.4)].
- Use of exogenous factor VIII products before and after ROCTAVIAN administration may impede assessment of ROCTAVIAN-derived factor VIII activity.
Monitor patients for factor VIII inhibitors (neutralizing antibodies to factor VIII). Test for factor VIII inhibitors especially if bleeding is not controlled, or plasma factor VIII activity levels decrease [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.6)].
Perform regular liver ultrasound (e.g., annually) and alpha-fetoprotein (AFP) testing in patients with risk factors of hepatocellular carcinoma (e.g., hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age) [see Warnings and Precautions (5.5)].