General MedicationsINTRAVENOUSHigh Alert

AMONDYS 45

CASIMERSEN

Standard Dose

2 DOSAGE AND ADMINISTRATION Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45 ( 2.1 ) 30 milligrams per kilogram of body weight once weekly ( 2.2 ) Administer as an intravenous (IV) infusion over 35 to 60 minutes via an in-line 0.2 micron filter ( 2.2 , 2.4 ) Dilution required prior to administration ( 2.3 ) 2.1 Monitoring to Assess Safety Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio (UPCR) should be measured before starting AMONDYS 45. Consider measurement of glomerular filtration rate prior to initiation of AMONDYS 45. Monitoring for kidney toxicity during treatment is recommended. Obtain the urine sample prior to infusion of AMONDYS 45 or at least 48 hours after infusion [see Warnings and Precautions ( 5.2 )] . 2.2 Dosing Information The recommended dosage of AMONDYS 45 is 30 milligrams per kilogram administered once weekly as a 35 to 60-minute intravenous infusion via an in-line 0.2 micron filter. If a dose of AMONDYS 45 is missed, it may be administered as soon as possible after the scheduled dose. 2.3 Preparation Instructions AMONDYS 45 is supplied in single-dose vials as a preservative-free concentrated solution that requires dilution prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use aseptic technique. Calculate the total dose of AMONDYS 45 to be administered based on the patient's weight and the recommended dose of 30 milligrams per kilogram. Determine the volume of AMONDYS 45 needed and the correct number of vials to supply the full calculated dose. Allow the vials to warm to room temperature. Mix the contents of each vial by gently inverting 2 or 3 times. Do not shake. Visually inspect each vial of AMONDYS 45. The solution is a clear to slightly opalescent, colorless liquid, and may contain trace amounts of small, white to off-white amorphous particles. Do not use if the solution in the vials is cloudy, discolored or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles. With a syringe fitted with a 21-gauge or smaller bore non-coring needle, withdraw the calculated volume of AMONDYS 45 from the appropriate number of vials. To avoid dulling the needle and fragmenting the stoppers, replace the needle periodically during preparation. Dilute the withdrawn AMONDYS 45 in 0.9% Sodium Chloride Injection, USP, to make a total volume of 100 to 150 mL. Gently invert 2 to 3 times to mix. Do not shake. Visually inspect the diluted solution. Do not use if the solution is cloudy, discolored or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles. Administer the diluted solution via an in-line 0.2 micron filter. AMONDYS 45 contains no preservatives and should be administered immediately after dilution. Complete infusion of diluted AMONDYS 45 within 4 hours of dilution. If immediate use is not possible the diluted product may be stored for up to 24 hours at 2 °C to 8 °C (36 °F to 46 °F). Do not freeze. Discard unused AMONDYS 45. 2.4 Administration Instructions Application of a topical anesthetic cream to the infusion site prior to administration of AMONDYS 45 may be considered. AMONDYS 45 is administered via intravenous infusion. Flush the intravenous access line with 0.9% Sodium Chloride Injection, USP, prior to and after infusion. Infuse the diluted AMONDYS 45 over 35 to 60 minutes via an in-line 0.2 micron filter. Do not mix other medication with AMONDYS 45 or infuse other medications concomitantly via the same intravenous access with AMONDYS 45. If a hypersensitivity reaction occurs, consider slowing the infusion, interrupting or discontinuing the AMONDYS 45 therapy [see Contraindications ( 4 ), Warning and Precautions ( 5.1 ) and Adverse Reactions ( 6.2 )] .

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE AMONDYS 45 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.

Summary

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] .

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE AMONDYS 45 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. AMONDYS 45 is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45 ( 2.1 ) 30 milligrams per kilogram of body weight once weekly ( 2.2 ) Administer as an intravenous (IV) infusion over 35 to 60 minutes via an in-line 0.2 micron filter ( 2.2 , 2.4 ) Dilution required prior to administration ( 2.3 ) 2.1 Monitoring to Assess Safety Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio (UPCR) should be measured before starting AMONDYS 45. Consider measurement of glomerular filtration rate prior to initiation of AMONDYS 45. Monitoring for kidney toxicity during treatment is recommended. Obtain the urine sample prior to infusion of AMONDYS 45 or at least 48 hours after infusion [see Warnings and Precautions ( 5.2 )] . 2.2 Dosing Information The recommended dosage of AMONDYS 45 is 30 milligrams per kilogram administered once weekly as a 35 to 60-minute intravenous infusion via an in-line 0.2 micron filter. If a dose of AMONDYS 45 is missed, it may be administered as soon as possible after the scheduled dose. 2.3 Preparation Instructions AMONDYS 45 is supplied in single-dose vials as a preservative-free concentrated solution that requires dilution prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use aseptic technique. Calculate the total dose of AMONDYS 45 to be administered based on the patient's weight and the recommended dose of 30 milligrams per kilogram. Determine the volume of AMONDYS 45 needed and the correct number of vials to supply the full calculated dose. Allow the vials to warm to room temperature. Mix the contents of each vial by gently inverting 2 or 3 times. Do not shake. Visually inspect each vial of AMONDYS 45. The solution is a clear to slightly opalescent, colorless liquid, and may contain trace amounts of small, white to off-white amorphous particles. Do not use if the solution in the vials is cloudy, discolored or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles. With a syringe fitted with a 21-gauge or smaller bore non-coring needle, withdraw the calculated volume of AMONDYS 45 from the appropriate number of vials. To avoid dulling the needle and fragmenting the stoppers, replace the needle periodically during preparation. Dilute the withdrawn AMONDYS 45 in 0.9% Sodium Chloride Injection, USP, to make a total volume of 100 to 150 mL. Gently invert 2 to 3 times to mix. Do not shake. Visually inspect the diluted solution. Do not use if the solution is cloudy, discolored or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles. Administer the diluted solution via an in-line 0.2 micron filter. AMONDYS 45 contains no preservatives and should be administered immediately after dilution. Complete infusion of diluted AMONDYS 45 within 4 hours of dilution. If immediate use is not possible the diluted product may be stored for up to 24 hours at 2 °C to 8 °C (36 °F to 46 °F). Do not freeze. Discard unused AMONDYS 45. 2.4 Administration Instructions Application of a topical anesthetic cream to the infusion site prior to administration of AMONDYS 45 may be considered. AMONDYS 45 is administered via intravenous infusion. Flush the intravenous access line with 0.9% Sodium Chloride Injection, USP, prior to and after infusion. Infuse the diluted AMONDYS 45 over 35 to 60 minutes via an in-line 0.2 micron filter. Do not mix other medication with AMONDYS 45 or infuse other medications concomitantly via the same intravenous access with AMONDYS 45. If a hypersensitivity reaction occurs, consider slowing the infusion, interrupting or discontinuing the AMONDYS 45 therapy [see Contraindications (

Monitoring

• 5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with AMONDYS 45.
• If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion, interrupting or discontinuing the AMONDYS 45 infusion ( 2.4 , 5.1 ) Kidney Toxicity: Based on animal data, may cause kidney toxicity.
• Kidney function should be monitored; creatinine may not be a reliable measure of renal function in DMD patients.
• ( 5.2 , 13.2 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with AMONDYS 45.

Interaction Notes

• Review official label interaction section.