Avonex

AVONEX is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

• For intramuscular use only (
  2.1 Dosing Information

  AVONEX is administered intramuscularly.

  The recommended dose is 30 micrograms once a week. To reduce the incidence and severity of flu-like symptoms that may occur when initiating AVONEX therapy at a dose of 30 micrograms, AVONEX may be started at a dose of 7.5 micrograms and the dose may be increased by 7.5 micrograms each week for the next three weeks until the recommended dose of 30 micrograms is achieved (see Table 1). An AVOSTARTGRIP™ kit containing 3 titration devices can be used for titration and is to be used only with AVONEX Prefilled Syringes.

  Table 1: Schedule for Dose Titration

  1Dosed once a week, intramuscularly
  	AVONEX Dose1	Recommended Dose
  Week 1	7.5 micrograms	1/4 dose
  Week 2	15 micrograms	1/2 dose
  Week 3	22.5 micrograms	3/4 dose
  Week 4+	30 micrograms	full dose
  )
• Recommended dose: 30 micrograms once a week (
  2.1 Dosing Information

  AVONEX is administered intramuscularly.

  The recommended dose is 30 micrograms once a week. To reduce the incidence and severity of flu-like symptoms that may occur when initiating AVONEX therapy at a dose of 30 micrograms, AVONEX may be started at a dose of 7.5 micrograms and the dose may be increased by 7.5 micrograms each week for the next three weeks until the recommended dose of 30 micrograms is achieved (see Table 1). An AVOSTARTGRIP™ kit containing 3 titration devices can be used for titration and is to be used only with AVONEX Prefilled Syringes.

  Table 1: Schedule for Dose Titration

  1Dosed once a week, intramuscularly
  	AVONEX Dose1	Recommended Dose
  Week 1	7.5 micrograms	1/4 dose
  Week 2	15 micrograms	1/2 dose
  Week 3	22.5 micrograms	3/4 dose
  Week 4+	30 micrograms	full dose
  )
• AVONEX may be titrated, starting with 7.5 micrograms for first week, to reduce flu-like symptoms (
  2.1 Dosing Information

  AVONEX is administered intramuscularly.

  The recommended dose is 30 micrograms once a week. To reduce the incidence and severity of flu-like symptoms that may occur when initiating AVONEX therapy at a dose of 30 micrograms, AVONEX may be started at a dose of 7.5 micrograms and the dose may be increased by 7.5 micrograms each week for the next three weeks until the recommended dose of 30 micrograms is achieved (see Table 1). An AVOSTARTGRIP™ kit containing 3 titration devices can be used for titration and is to be used only with AVONEX Prefilled Syringes.

  Table 1: Schedule for Dose Titration

  1Dosed once a week, intramuscularly
  	AVONEX Dose1	Recommended Dose
  Week 1	7.5 micrograms	1/4 dose
  Week 2	15 micrograms	1/2 dose
  Week 3	22.5 micrograms	3/4 dose
  Week 4+	30 micrograms	full dose
  )
• Increase dose by 7.5 micrograms each week for next 3 weeks until recommended dose of 30 micrograms (
  2.1 Dosing Information

  AVONEX is administered intramuscularly.

  The recommended dose is 30 micrograms once a week. To reduce the incidence and severity of flu-like symptoms that may occur when initiating AVONEX therapy at a dose of 30 micrograms, AVONEX may be started at a dose of 7.5 micrograms and the dose may be increased by 7.5 micrograms each week for the next three weeks until the recommended dose of 30 micrograms is achieved (see Table 1). An AVOSTARTGRIP™ kit containing 3 titration devices can be used for titration and is to be used only with AVONEX Prefilled Syringes.

  Table 1: Schedule for Dose Titration

  1Dosed once a week, intramuscularly
  	AVONEX Dose1	Recommended Dose
  Week 1	7.5 micrograms	1/4 dose
  Week 2	15 micrograms	1/2 dose
  Week 3	22.5 micrograms	3/4 dose
  Week 4+	30 micrograms	full dose
  )
• See patient instructions for use for complete administration instructions (
  2.2 Important Administration Instructions (All Dosage Forms)

  AVONEX dosage forms (prefilled syringe and prefilled autoinjector) are single-dose. See Patient's Instructions for Use for complete administration instructions.

  The first AVONEX injection should be performed under the supervision of an appropriately qualified healthcare professional. If patients or caregivers are to administer AVONEX, train them in the proper intramuscular injection technique and assess their ability to inject intramuscularly to ensure the proper administration of AVONEX.

  Advise patients and caregivers to:

  • Rotate injection sites with each administration to minimize the likelihood of injection site reactions, including necrosis or localized infection
    [see Warnings and Precautions ]
  • NOT inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way
  • Check the injection site after 2 hours for redness, swelling, or tenderness
  • Contact their healthcare provider if they have a skin reaction and it does not clear up in a few days

  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

  A 25 gauge, 1” needle for intramuscular injection with AVONEX prefilled syringe may be substituted for the 23 gauge, 1 ¼” needle by the healthcare provider, if deemed appropriate. A 25 gauge, 5/8” needle specific to the prefilled autoinjector is supplied with the AVONEX PEN^®Administration Dose Pack.

  DO NOT

  use any other needle with the autoinjector.

  Use safe disposal procedures for needles and syringes.

  DO NOT

  re-use needles, prefilled syringes, or autoinjectors. Following the administration of each titrated dose, discard any remaining product.
  )
• Perform first injection under the supervision of an appropriately qualified health care professional (
  2.2 Important Administration Instructions (All Dosage Forms)

  AVONEX dosage forms (prefilled syringe and prefilled autoinjector) are single-dose. See Patient's Instructions for Use for complete administration instructions.

  The first AVONEX injection should be performed under the supervision of an appropriately qualified healthcare professional. If patients or caregivers are to administer AVONEX, train them in the proper intramuscular injection technique and assess their ability to inject intramuscularly to ensure the proper administration of AVONEX.

  Advise patients and caregivers to:

  • Rotate injection sites with each administration to minimize the likelihood of injection site reactions, including necrosis or localized infection
    [see Warnings and Precautions ]
  • NOT inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way
  • Check the injection site after 2 hours for redness, swelling, or tenderness
  • Contact their healthcare provider if they have a skin reaction and it does not clear up in a few days

  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

  A 25 gauge, 1” needle for intramuscular injection with AVONEX prefilled syringe may be substituted for the 23 gauge, 1 ¼” needle by the healthcare provider, if deemed appropriate. A 25 gauge, 5/8” needle specific to the prefilled autoinjector is supplied with the AVONEX PEN^®Administration Dose Pack.

  DO NOT

  use any other needle with the autoinjector.

  Use safe disposal procedures for needles and syringes.

  DO NOT

  re-use needles, prefilled syringes, or autoinjectors. Following the administration of each titrated dose, discard any remaining product.
  )
• Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms (
  2.3 Premedication for Flu-like Symptoms

  Concurrent use of analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with AVONEX use.
  )

• Injection: 30 micrograms per 0.5 mL clear, colorless solution in a single-dose prefilled syringe
• Injection: 30 micrograms per 0.5 mL clear, colorless solution in a single-dose prefilled autoinjector

• Pregnancy: Epidemiological data do not suggest a clear relationship between interferon beta use and major congenital malformations, but interferon beta may cause fetal harm based on animal data. (
  8.1 Pregnancy

  Risk Summary

  Data from a large population-based cohort study, as well as other published studies over several decades, have not identified a drug-associated risk of major birth defects with the use of interferon beta products during early pregnancy. Findings regarding a potential risk for low birth weight or miscarriage with the use of interferon beta products in pregnancy have been inconsistent

  (see Data).

  In a study in pregnant monkeys, administration of interferon beta during pregnancy resulted in an increased rate of abortion at doses greater than those used clinically (

  see Data

  ).

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

  Data

  Human Data

  The majority of observational studies reporting on pregnancies exposed to interferon beta products did not identify an association between the use of interferon beta products during early pregnancy and an increased risk of major birth defects.

  In a population-based cohort study conducted in Finland and Sweden, data were collected from 1996--2014 in Finland and 2005--2014 in Sweden on 2,831 pregnancy outcomes from women with MS. 797 pregnancies were in women exposed to interferon beta only. No evidence was found of an increased risk of major birth defects among women with MS exposed to interferon beta products compared to women with MS that were unexposed to any non-steroid therapy for MS (n=1,647) within the study. No increased risks were observed for miscarriages and ectopic pregnancies, though there were limitations in obtaining complete data capture for these outcomes, making the interpretation of the findings more difficult.

  Two small cohort studies that examined pregnancies exposed to interferon beta products (without differentiating between subtypes of interferon beta products) suggested that a decrease in mean birth weight may be associated with interferon beta exposure during pregnancy, but this finding was not confirmed in larger observational studies. Two small studies observed an increased prevalence of miscarriage, although the finding was only statistically significant in one study. Most studies enrolled patients later in pregnancy which made it difficult to ascertain the true percentage of miscarriages. In one small cohort study, a significantly increased risk of preterm birth following interferon beta exposure during pregnancy was observed.

  Animal Data

  In pregnant monkeys given interferon beta at 100 times the recommended weekly human dose (based upon a body surface area [mg/m²] comparison), no adverse effects on embryofetal development were observed. Abortifacient activity was evident following 3 to 5 doses at this level. No abortifacient effects were observed in monkeys treated at 2 times the recommended weekly human dose (based upon mg/m²).
  )