Nymalize

NYMALIZE is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V).

• Administer only enterally (e.g., oral, nasogastric tube, or gastric tube route). Do not administer intravenously or by other parenteral routes. (
  
  
  2.1 Administration Instructions

  Administer only enterally (e.g., oral, nasogastric tube, or gastric tube route). Do not administer intravenously or by other parenteral routes. For all routes of administration, begin NYMALIZE within 96 hours of the onset of SAH. Administer one hour before a meal or two hours after a meal for all routes of administration

  [see Clinical Pharmacology (12.3)]

  .
  )
  
• Give one hour before a meal
  
  
  or
  two hours after a meal. (
  
  
  2.1 Administration Instructions

  Administer only enterally (e.g., oral, nasogastric tube, or gastric tube route). Do not administer intravenously or by other parenteral routes. For all routes of administration, begin NYMALIZE within 96 hours of the onset of SAH. Administer one hour before a meal or two hours after a meal for all routes of administration

  [see Clinical Pharmacology (12.3)]

  .
  )
  
• Start dosing within 96 hours of the SAH. (
  
  
  2.1 Administration Instructions

  Administer only enterally (e.g., oral, nasogastric tube, or gastric tube route). Do not administer intravenously or by other parenteral routes. For all routes of administration, begin NYMALIZE within 96 hours of the onset of SAH. Administer one hour before a meal or two hours after a meal for all routes of administration

  [see Clinical Pharmacology (12.3)]

  .
  )
  
• Recommended dose is 10 mL (60 mg) every 4 hours for 21 consecutive days. (
  
  
  2.2 Administration by Oral Route

  The recommended oral dosage is 10 mL (60 mg) every 4 hours for 21 consecutive days.
  )
  
• Nasogastric or Gastric Tube Administration:
  Administer 10 mL (60 mg) every 4 hours with supplied prefilled oral syringe. Refill syringe with 10 mL of 0.9% saline water solution; flush remaining contents from nasogastric or gastric tube into stomach. (
  
  
  2.3 Administration Via Nasogastric or Gastric Tube

  Using the supplied prefilled oral syringe labeled "For Oral Use Only", administer 10 mL (60 mg) every 4 hours into a nasogastric or gastric tube for 21 consecutive days. For each dose, refill the syringe with 10 mL of 0.9% saline solution and then flush any remaining contents from nasogastric or gastric tube into the stomach.
  )
  
• Patients with Cirrhosis:
  Reduce dosage to 5 mL (30 mg) every 4 hours. (
  
  
  2.4 Dosage Adjustments in Patients with Cirrhosis

  In patients with cirrhosis, reduce the dosage to 5 mL (30 mg) every 4 hours

  [

  s

  ee Warnings and Precautions (5.2)

  ,

  Clinical Pharmacology (12.3)]

  .
  )
  

Oral Solution (6 mg per mL):

• 60 mg per 10 mL, pale yellow solution in unit-dose prefilled syringe
• 30 mg per 5 mL, pale yellow solution in unit-dose prefilled syringe
• 30 mg per 5 mL, pale yellow solution in unit-dose prefilled ENFit
  
  ^® syringe
  
• 60 mg per 10 mL (6 mg/mL), pale yellow solution in 8 oz bottle

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

  Risk Summary

  There are no adequate data on the developmental risk associated with the use of NYMALIZE in pregnant women. In animal studies, oral administration of nimodipine during pregnancy resulted in adverse effects on development (increased embryofetal mortality, increased incidences of fetal structural abnormalities, decreased fetal growth) at doses equivalent to (rat) or less than (rabbit) 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 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

  Data

  Animal Data

  Nimodipine has been shown to have a teratogenic effect in two studies in rabbit. In one study, incidences of malformations and stunted fetuses were increased at oral doses of 1 mg/kg/day and 10 mg/kg/day administered throughout organogenesis but not at 3 mg/kg/day. In the second study, an increased incidence of stunted fetuses was seen at 1 mg/kg/day but not at higher doses (3 mg/kg/day and 10 mg/kg/day). The lowest effect dose in rabbits (1 mg/kg/day) is less than the recommended human dose (RHD) of 360 mg/day on a body surface area (mg/m²) basis.

  Nimodipine was embryotoxic, causing resorption and stunted growth of fetuses in rats at 100 mg/kg/day administered orally throughout organogenesis; this dose is approximately 3 times the RHD on a mg/m²basis. In two other studies in rats, nimodipine administered orally at 30 mg/kg/day throughout organogenesis and continued until sacrifice (day 20 of pregnancy or day 21 postpartum) was associated with higher incidences of skeletal variation, stunted fetuses, and stillbirths but no malformations; this dose is similar to the RHD on a mg/m²basis.
  )
  

• Hypotension:
  Monitor blood pressure. (
  
  
  5.1 Hypotension

  Blood pressure should be carefully monitored during treatment with NYMALIZE. In clinical studies of patients with subarachnoid hemorrhage, about 5% of nimodipine-treated patients compared to 1% of placebo-treated patients had hypotension and about 1% of nimodipine-treated patients left the study because of this

  [see Adverse Reactions (6)].
  )
  
• Patients with Cirrhosis:
  Higher risk of adverse reactions. Monitor blood pressure and pulse. (
  
  
  5.2 Possible Increased Risk of Adverse Reactions in Patients with Cirrhosis

  Given that the plasma levels of nimodipine are increased in patients with cirrhosis, these patients are at higher risk of adverse reactions. Therefore, monitor blood pressure and pulse rate closely and administer a lower dosage

  [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)]

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  )
  
• CYP3A4 Strong Inhibitors:
  May significantly increase risk of hypotension. Concomitant use with NYMALIZE should generally be avoided. (
  
  
  5.3 Possible Increased Risk of Hypotension with Strong CYP3A4 Inhibitors

  Concomitant use of strong inhibitors of CYP3A4, such as some macrolide antibiotics (e.g., clarithromycin, telithromycin), some HIV protease inhibitors (e.g., indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (e.g., boceprevir, telaprevir), some azole antimycotics (e.g., ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan, delavirdine, and nefazodone with nimodipine should generally be avoided because of a risk of significant hypotension

  [see Drug Interactions (7.2)]

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  )
  
• CYP3A4 Strong Inducers:
  May significantly reduce efficacy of nimodipine. Concomitant use with NYMALIZE should generally be avoided. (
  
  
  5.4 Possible Reduced Efficacy with Strong CYP3A4 Inducers

  Concomitant use of strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort) and nimodipine should generally be avoided, as nimodipine plasma concentration and efficacy may be significantly reduced

  [see Drug Interactions (7.3)].
  )