Vumerity

VUMERITY 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.

• Blood tests are required prior to initiation of VUMERITY (
  2.1 Blood Tests Prior to Initiation of VUMERITY

  Obtain the following prior to treatment with VUMERITY:

  • A complete blood cell count (CBC), including lymphocyte count
    [see Warnings and Precautions ]
    .
  • Serum aminotransferase, alkaline phosphatase, and total bilirubin levels
    [see Warnings and Precautions ]
    .
  )
• Starting dose: 231 mg twice a day, orally, for 7 days (
  2.2 Dosing Information

  The starting dosage for VUMERITY is 231 mg twice a day orally. After 7 days, the dosage should be increased to the maintenance dosage of 462 mg (administered as two 231 mg capsules) twice a day orally. Temporary dosage reductions to 231 mg twice a day may be considered for individuals who do not tolerate the maintenance dosage. Within 4 weeks, the recommended dosage of 462 mg twice a day should be resumed. Discontinuation of VUMERITY should be considered for patients unable to tolerate return to the maintenance dosage. Administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to VUMERITY dosing may reduce the incidence or severity of flushing

  [see Clinical Pharmacology

  ].
  )
• Maintenance dose after 7 days: 462 mg (administered as two 231 mg capsules) twice a day, orally (
  2.2 Dosing Information

  The starting dosage for VUMERITY is 231 mg twice a day orally. After 7 days, the dosage should be increased to the maintenance dosage of 462 mg (administered as two 231 mg capsules) twice a day orally. Temporary dosage reductions to 231 mg twice a day may be considered for individuals who do not tolerate the maintenance dosage. Within 4 weeks, the recommended dosage of 462 mg twice a day should be resumed. Discontinuation of VUMERITY should be considered for patients unable to tolerate return to the maintenance dosage. Administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to VUMERITY dosing may reduce the incidence or severity of flushing

  [see Clinical Pharmacology

  ].
  )
• Swallow VUMERITY capsules whole and intact. Do not crush, chew, or sprinkle capsule contents on food (
  2.3 Administration Instructions

  Swallow VUMERITY capsules whole and intact. Do not crush or chew, or sprinkle the capsule contents on food.

  If taken with food, avoid a high-fat, high-calorie meal/snack; the meal/snack should contain no more than 700 calories and no more than 30 g fat

  [see Warnings and Precautions

  and Clinical Pharmacology ]

  .

  Avoid co-administration of VUMERITY with alcohol

  [see Clinical Pharmacology ]

  .
  )
• Avoid administration of VUMERITY with a high-fat, high-calorie meal/snack (
  2.3 Administration Instructions

  Swallow VUMERITY capsules whole and intact. Do not crush or chew, or sprinkle the capsule contents on food.

  If taken with food, avoid a high-fat, high-calorie meal/snack; the meal/snack should contain no more than 700 calories and no more than 30 g fat

  [see Warnings and Precautions

  and Clinical Pharmacology ]

  .

  Avoid co-administration of VUMERITY with alcohol

  [see Clinical Pharmacology ]

  .
  )
• Avoid co-administration of VUMERITY with alcohol (
  2.3 Administration Instructions

  Swallow VUMERITY capsules whole and intact. Do not crush or chew, or sprinkle the capsule contents on food.

  If taken with food, avoid a high-fat, high-calorie meal/snack; the meal/snack should contain no more than 700 calories and no more than 30 g fat

  [see Warnings and Precautions

  and Clinical Pharmacology ]

  .

  Avoid co-administration of VUMERITY with alcohol

  [see Clinical Pharmacology ]

  .
  )

VUMERITY is available as hard, delayed-release capsules containing 231 mg of diroximel fumarate. The capsules have a white cap and a white body, printed with “DRF 231 mg” in black ink on the body.

• Pregnancy: Based on animal data, may cause fetal harm. (
  8.1 Pregnancy

  Pregnancy Exposure Registry

  There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VUMERITY during pregnancy. Encourage patients to enroll by calling 1-833-569-2635 or visiting www.vumeritypregnancyregistry.com.

  Risk Summary

  There are no adequate data on the developmental risk associated with the use of VUMERITY in pregnant women. Available data from a pregnancy registry for dimethyl fumarate (which has the same active metabolite as VUMERITY), observational studies, and pharmacovigilance pertaining to dimethyl fumarate use in pregnant women have not indicated an increased risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Most of the reported exposures to dimethyl fumarate occurred during the first trimester of pregnancy (see Data). In animal studies, administration of diroximel fumarate during pregnancy or throughout pregnancy and lactation resulted in adverse effects on embryofetal and offspring development (increased incidences of skeletal abnormalities, increased mortality, decreased body weights, neurobehavioral impairment) at clinically relevant drug exposures [

  see Data

  ].

  The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

  Data

  Human Data

  In a prospective observational pregnancy registry for dimethyl fumarate (2013-2022), the rate of major birth defects among 362 live births and stillbirths from women who were exposed to dimethyl fumarate during pregnancy was 3.6% (95% CI: 1.9-6.1). No specific pattern of major birth defects was identified. Important potential study limitations include exposure misclassification, no adjustment for confounders, and lack of an internal comparator cohort.

  Animal Data

  Oral administration of diroximel fumarate (0, 40, 100, or 400 mg/kg/day) to pregnant rats throughout organogenesis resulted in a decrease in fetal body weight and an increase in fetal skeletal variations at the highest dose tested, which was associated with maternal toxicity. Plasma exposures (AUC) for MMF and HES (the major circulating drug-related compound in humans) at the no-effect dose (100 mg/kg/day) for adverse effects on embryofetal development were approximately 2 times those in humans at the recommended human dose (RHD) of 924 mg/day.

  Oral administration of diroximel fumarate (0, 50, 150, or 350 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in an increase in fetal skeletal malformations at the mid and high doses and reduced fetal body weight and increases in embryofetal death and fetal skeletal variations at the highest dose tested. The high dose was associated with maternal toxicity. Plasma exposures (AUC) for MMF and HES at the no-effect dose (50 mg/kg/day) for adverse effects on embryofetal development were similar to (MMF) or less than (HES) those in humans at the RHD.

  Oral administration of diroximel fumarate (0, 40, 100, or 400 mg/kg/day) to rats throughout gestation and lactation resulted in reduced weight, which persisted into adulthood, and adverse effects on neurobehavioral function in offspring at the highest dose tested. Plasma exposures (AUC) for MMF and HES at the no-effect dose for adverse effects on postnatal development (100 mg/kg/day) were approximately 3 times (MMF) or similar to (HES) those in humans at the RHD.
  )
• VUMERITY is not recommended in patients with moderate or severe renal impairment. (
  8.6 Renal Impairment

  No dosage adjustment is necessary in patients with mild renal impairment. Because of an increase in the exposure of a major metabolite [2-hydroxyethyl succinimide (HES)], use of VUMERITY is not recommended in patients with moderate or severe renal impairment

  [see Clinical Pharmacology ]

  .
  )