onasemnogene abeparvovec (Rx)

Brand and Other Names:Zolgensma, onasemnogene abeparvovec-xioi

Dosing & Uses

AdultPediatric

See Pediatric Dosing

Dosage Forms & Strengths

suspension for IV infusion

  • Provided in a kit containing 2 to 9 vials, as a combination of 2 vial fill volumes (either 5.5 mL or 8.3 mL)
  • All vials have a nominal concentration of 2 x 10^13 vector genomes (vg) per mL
  • Each vial contains an extractable volume of not less than either 5.5 mL or 8.3 mL

Spinal Muscular Atrophy Type 1

Indicated for gene replacement therapy in children aged <2 years with spinal muscular atrophy (SMA) type 1 (also called Werdnig-Hoffman disease) who have biallelic mutation in the survival motor neuron 1 (SNM1) gene

≥2 years: Safety and efficacy not established

<2 years

  • Administered as a one-time, single IV infusion through a venous catheter
  • 1.1 x 1014 vector genomes per kilogram (vg/kg) of body weight

Dose calculation

  • See prescribing information for weight-range dosing chart
  • Age <2 yr weighing 2.6-13.5 kg: Dose volume calculated using upper limit of patient weight range
  • Age <2 yr weighing ≥13.6 kg: Dose volume will require a combination of onasemnogene abeparvovec kits

Dosage Modifications

Hepatic impairment

  • Carefully considered use in patients with hepatic impairment
  • Cases of acute serious liver injury and acute liver failure reported in patients with preexisting liver abnormalities

Dosing Considerations

Prior to infusion

  • Administer to patients who are clinically stable in their overall baseline health status (eg, hydration and nutritional status, absence of infection)
  • Due to the increased risk of serious systemic immune response, postpone therapy in patients with concurrent infections until the infection has resolved; clinical signs or symptoms of infection should not be evident at time of administration
  • Assess liver function
  • Measure creatinine, complete blood count (CBC), including hemoglobin and platelet counts, and troponin-I
  • Perform baseline testing for presence of anti-AAV9 antibodies
  • 1 day before infusion: Begin systemic corticosteroids equivalent to oral prednisolone 1 mg/kg/day for a total of 30 days

Monitoring parameters

  • Liver function by clinical examination and by laboratory testing on a regular basis
  • Continue to monitor liver function for at least 3 months after infusion (weekly for the first month, and then every other week for the second and third months, until results are unremarkable)
  • At the end of the 30-day period of systemic corticosteroid treatment: Check liver status clinically and by assessing ALT, AST, total bilirubin [TB], prothrombin time, and INR
  • Promptly assess and closely monitor patients with worsening liver function test results and/or signs or symptoms of acute illness (eg, vomiting, deterioration in health)
  • Patients with normal clinical exam, TB, and prothrombin time, and ALT and AST levels <2x ULN: Taper corticosteroid dose gradually over the next 28 days: do not stop systemic corticosteroids abruptly
  • Persistent liver function abnormalities: Continue systemic corticosteroids (equivalent to oral prednisolone at 1 mg/kg/day) until AST/ALT <2x ULN and all other assessments return to normal range, and then taper corticosteroid dose gradually over the next ≥28 days if needed; do not stop systemic corticosteroids abruptly
  • Liver function abnormalities continue to persist >2x ULN after the 30-day period of systemic corticosteroids: Consult a pediatric gastroenterologist or hepatologist
  • If oral corticosteroid therapy is not tolerated, consider IV corticosteroids as clinically indicated

Limitations of use

  • Safety and effectiveness of repeat administration has not been evaluated
  • Use for advanced SMA (eg, complete paralysis of limbs, permanent ventilator-dependence) has not been evaluated
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Interactions

Interaction Checker

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      Serious - Use Alternative

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            Contraindicated (16)

            • adenovirus types 4 and 7 live, oral

              onasemnogene abeparvovec decreases effects of adenovirus types 4 and 7 live, oral by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • BCG vaccine live

              onasemnogene abeparvovec decreases effects of BCG vaccine live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • cholera vaccine

              onasemnogene abeparvovec decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • dengue vaccine

              onasemnogene abeparvovec decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • influenza virus vaccine quadrivalent, intranasal

              onasemnogene abeparvovec decreases effects of influenza virus vaccine quadrivalent, intranasal by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • measles (rubeola) vaccine

              onasemnogene abeparvovec decreases effects of measles (rubeola) vaccine by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • measles mumps and rubella vaccine, live

              onasemnogene abeparvovec decreases effects of measles mumps and rubella vaccine, live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • measles, mumps, rubella and varicella vaccine, live

              onasemnogene abeparvovec decreases effects of measles, mumps, rubella and varicella vaccine, live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • rotavirus oral vaccine, live

              onasemnogene abeparvovec decreases effects of rotavirus oral vaccine, live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • rubella vaccine

              onasemnogene abeparvovec decreases effects of rubella vaccine by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • smallpox (vaccinia) vaccine, live

              onasemnogene abeparvovec decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • typhoid polysaccharide vaccine

              onasemnogene abeparvovec decreases effects of typhoid polysaccharide vaccine by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • typhoid vaccine live

              onasemnogene abeparvovec decreases effects of typhoid vaccine live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • varicella virus vaccine live

              onasemnogene abeparvovec decreases effects of varicella virus vaccine live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • yellow fever vaccine

              onasemnogene abeparvovec decreases effects of yellow fever vaccine by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            • zoster vaccine live

              onasemnogene abeparvovec decreases effects of zoster vaccine live by immunosuppressive effects; risk of infection. Contraindicated. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. Avoid live vaccines for at least 1 month when initiating or after high-dose systemic corticosteroid therapy administered for =2 weeks.

            Serious - Use Alternative (0)

              Monitor Closely (31)

              • anthrax vaccine adsorbed

                onasemnogene abeparvovec decreases effects of anthrax vaccine adsorbed by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • haemophilus influenzae type b vaccine

                onasemnogene abeparvovec decreases effects of haemophilus influenzae type b vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • hepatitis A vaccine inactivated

                onasemnogene abeparvovec decreases effects of hepatitis A vaccine inactivated by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • hepatitis a/b vaccine

                onasemnogene abeparvovec decreases effects of hepatitis a/b vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • hepatitis b vaccine

                onasemnogene abeparvovec decreases effects of hepatitis b vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • HIV vaccine

                onasemnogene abeparvovec decreases effects of HIV vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • human papillomavirus vaccine, nonavalent

                onasemnogene abeparvovec decreases effects of human papillomavirus vaccine, nonavalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • human papillomavirus vaccine, quadrivalent

                onasemnogene abeparvovec decreases effects of human papillomavirus vaccine, quadrivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza A (H5N1) vaccine

                onasemnogene abeparvovec decreases effects of influenza A (H5N1) vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine (H5N1), adjuvanted

                onasemnogene abeparvovec decreases effects of influenza virus vaccine (H5N1), adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine quadrivalent

                onasemnogene abeparvovec decreases effects of influenza virus vaccine quadrivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine quadrivalent, adjuvanted

                onasemnogene abeparvovec decreases effects of influenza virus vaccine quadrivalent, adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine quadrivalent, cell-cultured

                onasemnogene abeparvovec decreases effects of influenza virus vaccine quadrivalent, cell-cultured by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine quadrivalent, recombinant

                onasemnogene abeparvovec decreases effects of influenza virus vaccine quadrivalent, recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine trivalent

                onasemnogene abeparvovec decreases effects of influenza virus vaccine trivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine trivalent, adjuvanted

                onasemnogene abeparvovec decreases effects of influenza virus vaccine trivalent, adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • influenza virus vaccine trivalent, recombinant

                onasemnogene abeparvovec decreases effects of influenza virus vaccine trivalent, recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • Japanese encephalitis virus vaccine

                onasemnogene abeparvovec decreases effects of Japanese encephalitis virus vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • meningococcal A C Y and W-135 diphtheria conjugate vaccine

                onasemnogene abeparvovec decreases effects of meningococcal A C Y and W-135 diphtheria conjugate vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • meningococcal A C Y and W-135 polysaccharide vaccine combined

                onasemnogene abeparvovec decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • meningococcal group B vaccine

                onasemnogene abeparvovec decreases effects of meningococcal group B vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • pneumococcal vaccine 13-valent

                onasemnogene abeparvovec decreases effects of pneumococcal vaccine 13-valent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • pneumococcal vaccine heptavalent

                onasemnogene abeparvovec decreases effects of pneumococcal vaccine heptavalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • pneumococcal vaccine polyvalent

                onasemnogene abeparvovec decreases effects of pneumococcal vaccine polyvalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • poliovirus vaccine inactivated

                onasemnogene abeparvovec decreases effects of poliovirus vaccine inactivated by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • rabies vaccine

                onasemnogene abeparvovec decreases effects of rabies vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • rabies vaccine chick embryo cell derived

                onasemnogene abeparvovec decreases effects of rabies vaccine chick embryo cell derived by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • smallpox (vaccinia) and monkeypox vaccine, live, nonreplicating

                onasemnogene abeparvovec decreases effects of smallpox (vaccinia) vaccine, attenuated by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • smallpox (vaccinia) vaccine, attenuated

                onasemnogene abeparvovec decreases effects of smallpox (vaccinia) vaccine, attenuated by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • tetanus toxoid adsorbed or fluid

                onasemnogene abeparvovec decreases effects of tetanus toxoid adsorbed or fluid by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              • zoster vaccine recombinant

                onasemnogene abeparvovec decreases effects of zoster vaccine recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Adjust vaccinations to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion. When initiating systemic corticosteriod therapy, wait 2 weeks after an inactivated vaccine.

              Minor (0)

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                Adverse Effects

                >10%

                Elevated aminotransferases (>ULN) (27.3%)

                1-10%

                Vomiting (6.8%)

                Postmarketing Reports

                Blood and lymphatic system disorders: Thrombotic microangiopathy

                Hepatobiliary Disorders: Acute liver failure, acute liver injury

                General disorders and administration site conditions: Pyrexia

                Investigations: Troponin increased

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                Warnings

                Black Box Warnings

                Acute serious liver injury and acute liver failure

                • Cases of serious acute liver failure with fatal outcomes reported
                • Acute liver injury and elevated ALT/AST can also occur
                • Patients with preexisting liver impairment may be at higher risk
                • Before infusion, assess liver function of all patients by clinical examination and laboratory testing (eg, AST/ALT, total bilirubin, prothrombin time)
                • Administer systemic corticosteroid to all patients before and after infusion
                • Continue to monitor liver function for at least 3 months after infusion, and as clinically indicated

                Contraindications

                None

                Cautions

                Acute serious liver injury, acute liver failure, or elevated AST/ALT

                • Acute serious liver injury, acute liver failure and elevated aminotransferases can occur
                • Hepatotoxicity (which may be immune-mediated), generally manifested as elevated ALT/AST levels and at times as acute serious liver injury or acute liver failure, has been reported
                • Immune-mediated hepatotoxicity may require adjustment of the corticosteroid treatment regimen, including longer duration, increased dose, or prolongation of the corticosteroid taper
                • Patients with preexisting liver impairment or acute hepatic viral infection may be at higher risk of acute serious liver injury/acute liver failure
                • Patients with ALT/AST, or TB levels (except due to neonatal jaundice) >2x ULN have not been studied in clinical trials
                • If acute serious liver injury or acute liver failure is suspected, consult a pediatric gastroenterologist or hepatologist

                Systemic immune response

                • Due to activation of humoral and cellular immunity following infusion, patients with underlying active infection, either acute (eg, respiratory, gastrointestinal) or chronic uncontrolled (eg, chronic active hepatitis B), could be at increased risk of serious systemic immune response, potentially resulting in more severe clinical courses of the infection
                • Serious systemic immune response can present with various findings (eg, high fever, hypotension)
                • Patients with infection were excluded from participation in clinical trials
                • Recommend increased vigilance in the prevention, monitoring, and management of infection before and after infusion
                • Mitigate risk of serious and life-threatening systemic immune response by administering to patients who are clinically stable in their overall baseline health status (eg, hydration and nutritional status, absence of infection) before infusion
                • Postpone In patients with infections until resolved and patient is clinically stable
                • Recommend seasonal prophylaxis against influenza, RSV, COVID-19; vaccination status should be current before administration

                Thrombocytopenia

                • Transient decreases in platelet counts, some meeting criteria for thrombocytopenia, observed after infusion
                • Monitor platelet counts before infusion and regularly afterwards (weekly for first month; q2wk for next 2 months)

                Thrombotic microangiopathy

                • Thrombotic microangiopathy (TMA) reported within first 2 weeks after infusion, characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury; concurrent immune system activation (eg, infections, vaccinations) were identified in some cases
                • Prompt attention to signs and symptoms of TMA advised, as TMA can result in life-threatening or fatal outcomes
                • Monitor platelet counts and signs/symptoms of TMA (eg, hypertension, bruising, seizures, decreased urine output)
                • If these signs and symptoms occur in the presence of thrombocytopenia, further diagnostic evaluation for hemolytic anemia and renal dysfunction is recommended
                • If clinical signs, symptoms and/or laboratory findings consistent with TMA occur, consult a pediatric hematologist and/or pediatric nephrologist immediately to manage TMA as clinically indicated

                Elevated troponin-I

                • Elevated cardiac troponin-I levels observed after infusion
                • Clinical importance of these findings is unknown
                • Cardiac toxicity observed in animal studies; monitor troponin-I before infusion and then for at least 3 months afterwards (weekly for first month; q2wk for next 2 months)
                • Consider cardiology consult if troponin elevations is accompanied by clinical signs or symptoms (eg, heart rate changes, cyanosis, tachypnea, respiratory distress)

                Drug interaction overview

                • Where feasible, adjust vaccination schedule to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion
                • Certain vaccines (eg, MMR, varicella) are contraindicated for patients on a substantially immunosuppressive steroid dose (ie, ≥2 weeks of prednisone 2 mg/kg/day or 20 mg/day or equivalent)
                • Seasonal RSV prophylaxis is not precluded
                • Refer to CDC vaccination guidelines for immunosuppressed patients
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                Pregnancy

                Pregnancy

                There are no data regarding use in pregnant women

                No animal reproductive studies conducted

                Lactation

                Unknown if secreted in human milk

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Recombinant AAV9-based gene therapy designed to deliver a copy of the gene encoding the human survival motor neuron (SMN) protein

                Spinal muscular atrophy is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression

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                Administration

                IV Preparation

                Thaw before use; contents of kit will thaw in ~16 hr if refrigerator or ~6 hr if at room temperature

                If thawed in refrigerator, remove from refrigerator on day of dosing

                Do not refreeze

                When thawed, should appear clear to slightly opaque, colorless to faint white liquid, free of particles

                Visually inspect vials for particulate matter and discoloration before infusion

                Do not use vials if particulates or discoloration are present

                Do NOT shake

                Draw the appropriate dose volume from all vials into a syringe, remove air from the syringe, cap the syringe, and deliver the syringe at room temperature to the patient infusion location

                Use within 8 hr of drawing into syringe

                Discard the vector-containing syringe if the drug is not infused within the 8-hr time frame

                IV Administration

                Administer as a slow IV infusion over 60 minutes

                For single-dose slow IV infusion only; do NOT infuse as an IV push or bolus

                Place primary catheter into vein (generally a peripheral vein in the arm or leg)

                Insertion of a back-up catheter is recommended

                Program syringe pump for saline priming, or prime tubing manually with saline

                Flush line with saline following completion of infusion

                Storage

                Product is shipped and delivered frozen (≤ -60°C [-76°F]) in clear vials

                Upon receipt, immediately place the kit in refrigerator at 2-8°C (36-46F)

                Stable for 14 days from receipt when stored refrigerated as directed

                Do NOT refreeze

                Must use within 14 days of receipt

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                Images

                No images available for this drug.
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                Patient Handout

                A Patient Handout is not currently available for this monograph.
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                Formulary

                FormularyPatient Discounts

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                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.