Roctavian (valoctocogene roxaparvovec-rvox)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

For one-time single-dose IV use only. Administer as an IV infusion through a peripheral venous catheter; do not administer as an IV push or bolus.

*Treatment with valoctocogene roxaparvovec-rvox should be under the supervision of a physician experienced in the treatment of hemophilia and/or bleeding disorders.

*Administer valoctocogene roxaparvovec-rvox in a setting where personnel and equipment are immediately available to treat infusion-related reactions.

*Perform baseline testing to select patients, including testing for pre-existing antibodies to adeno-associated virus serotype 5 (AAV5), factor VIII inhibitor presence, and liver health assessments. Information on FDA-approved tests for the detection of antibodies to AAV5 is available at: http://www.fda.gov/CompanionDiagnostics.

*The recommended dose of valoctocogene roxaparvovec-rvox is 6 x 1013 vector genomes (vg) per kg of body weight administered as a single IV infusion using a flow rate-controlled syringe pump. See Full Prescribing Information for instructions on calculating dose and number of vials required.

*Start the infusion at 1 mL/minute. If tolerated, the rate may be increased every 30 minutes by 1 mL/minute up to a maximum rate of 4 mL/minute. 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.

*If an infusion-related reaction occurs during administration, 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/minute 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.

*See Full Prescribing Information for additional instructions on preparation and administration of valoctocogene roxaparvovec-rvox, and for monitoring recommendations.

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No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Valoctocogene Roxaparvovec/Efavirenz

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The mechanism of this interaction has not been established.(1)

CLINICAL EFFECTS: Co-administration of valoctocogene roxaparvovec with efavirenz was poorly tolerated and resulted in elevations of liver enzymes with subsequent decreased factor VIII levels and increased risk of bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of valoctocogene roxaparvovec states that co-administration with efavirenz is not recommended.(1)

DISCUSSION: In an HIV positive patient who had been stable on his antiretroviral regimen for over 10 years, treatment with valoctocogene roxaparvovec and the antiretroviral regimen of efavirenz, lamivudine, and tenofovir resulted in elevations of liver enzymes. The patient developed asymptomatic elevations in ALT, AST, and GGT (> 5 x ULN (upper limit of normal)) and serum bilirubin (> ULN and up to 1.5 x ULN). The liver enzyme elevations resolved after efavirenz was stopped, worsened with rechallenge of efavirenz, and resolved again after replacing efavirenz with raltegravir. In addition, the patient did not maintain detectable FVIII levels after gene therapy, experiencing 21 bleeding events and eventually reverting to prophylactic FVIII therapy.(1,2) In vitro studies indicate efavirenz suppresses factor VIII transcription independent of hepatotoxicity, and expression was not restored upon discontinuation.(1) In efavirenz HIV trials, 20% of hepatitis B or C coinfected patients who received efavirenz had ALT elevations > 5 times the upper limit of normal versus 7% of patients in the control arm.(3)

Valoctocogene Roxaparvovec/Isotretinoin

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The mechanism of this interaction has not been established.(1)

CLINICAL EFFECTS: Co-administration of valoctocogene roxaparvovec with isotretinoin resulted in decreased factor VIII activity, which may result in increased risk of bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of valoctocogene roxaparvovec states that co-administration with isotretinoin is not recommended in patients who are benefiting from valoctocogene roxaparvovec.(1)

DISCUSSION: In a patient treated with valoctocogene roxaparvovec and isotretinoin, decreased factor VIII activity without ALT elevation was noted after starting isotretinoin. The factor VIII activity recovered after isotretinoin was stopped.(1) In vitro studies indicate isotretinoin suppresses factor VIII transcription independent of hepatotoxicity, without impact of ALT, and expression was partially restored upon discontinuation.(1)

There are no moderate interactions for this drug.

*Active infections, either acute or uncontrolled chronic.

*Known significant hepatic fibrosis (stage 3 or 4), or cirrhosis.

*Known hypersensitivity to mannitol.

There are no contraindication contraindications for this drug.

• Infection

There are no moderate contraindications for this drug.

*Most common adverse reactions (incidence >= 5%) were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain.

*Most common laboratory abnormalities (incidence >= 10%) were increased ALT, increased AST, increased lactate dehydrogenase (LDH), increased creatine phosphokinase (CPK), increased factor VIII activity levels, increased gamma-glutamyl transferase (GGT) and increased bilirubin concentrations > ULN.

Less Frequent

• Hypersensitivity drug reaction

Rare or Very Rare

• Anaphylaxis

More Frequent

• Acute abdominal pain
• Fatigue
• Headache disorder
• Hyperbilirubinemia
• Increased alanine transaminase
• Increased aspartate transaminase
• Increased creatine kinase level
• Nausea
• Vomiting

No enhanced messaging available.

The safety and effectiveness of valoctocogene roxaparvovec in pediatric patients have not been established.

Valoctocogene roxaparvovec is not intended for administration in women. There are no data on the use of valoctocogene roxaparvovec-rvox in pregnant women to inform a drug-associated risk of adverse developmental outcome. Animal reproduction and developmental toxicity studies have not been conducted with valoctocogene roxaparvovec-rvox. It is not known whether valoctocogene roxaparvovec can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects occurs in 2 to 4% of the general population and miscarriage occurs in 15 to 20% of clinically recognized pregnancies.

Valoctocogene roxaparvovec is not intended for administration in women. There is no information regarding the presence of valoctocogene roxaparvovec-rvox in human milk, the effects on the breastfed infant, or the effects on milk production.

A single patient >= 65 years of age was treated with valoctocogene roxaparvovec-rvox in clinical studies. Clinical studies did not include sufficient numbers of patients 65 years of age and over to determine whether efficacy or safety differs compared to younger patients.