Tiglutik

TIGLUTIK is indicated for the treatment of amyotrophic lateral sclerosis (ALS).

• Recommended dosage: 50 mg (10 mL), twice daily, taken orally or via percutaneous endoscopic gastrostomy tubes (PEG-tubes), every 12 hours (
  
  
  2.1 Dosage Information

  The recommended dosage for TIGLUTIK is 50 mg (10 mL) taken orally or via Percutaneous Endoscopic Gastrostomy tubes (PEG-tubes) twice daily, every 12 hours. TIGLUTIK should be taken at least 1 hour before or 2 hours after a meal

  [see Clinical Pharmacology (12.3)].
  )
  
• Measure serum aminotransferases before and during treatment (
  
  
  2.2 Monitoring to Assess Safety

  Measure serum aminotransferases before and during treatment with TIGLUTIK

  [see Warnings and Precautions (5.1)].
  ,
  
  
  5.1 Hepatic Injury

  TIGLUTIK can cause liver injury. Cases of drug-induced liver injury, some of which were fatal, have been reported in patients taking riluzole. Asymptomatic elevations of hepatic transaminases have also been reported, and in some patients have recurred upon re-challenge with riluzole.

  In clinical studies, the incidence of elevations in hepatic transaminases was greater in riluzole-treated patients than placebo-treated patients. The incidence of elevations of ALT above 5 times the upper limit of normal (ULN) was 2% in riluzole-treated patients. Maximum increases in ALT occurred within 3 months after starting riluzole. About 50% and 8% of riluzole-treated patients in pooled controlled efficacy studies (Studies 1 and 2) had at least one elevated ALT level above ULN and above 3 times ULN, respectively

  [see Clinical Studies (14)].

  Monitor patients for signs and symptoms of hepatic injury, every month for the first 3 months of treatment, and periodically thereafter. The use of TIGLUTIK is not recommended if patients develop hepatic transaminases levels greater than 5 times the ULN. Discontinue TIGLUTIK if there is evidence of liver dysfunction (e.g., elevated bilirubin). Concomitant use with other hepatotoxic drugs may increase the risk for hepatotoxicity

  [see Drug Interactions (7.3)]

  .
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• Take at least 1 hour before or 2 hours after a meal (
  
  
  2.3 Important Administration Instructions

  Gently shake the TIGLUTIK bottle for at least 30 seconds before administration.

  TIGLUTIK can be administered by mouth or via percutaneous endoscopic gastrostomy tubes (PEG-tubes). Both silicone and polyurethane PEG tubes can be used.

  See the Instructions for Use for further administration details.
  )
  

Oral suspension: 50 mg/10 mL (5 mg/mL) slightly brown, opaque, homogeneous suspension in a 300-mL multiple-dose amber bottle.

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

  Risk Summary

  There are no studies of riluzole in pregnant women, and case reports have been inadequate to inform the drug-associated risk. The background risk for major birth defects and miscarriage in patients with amyotrophic lateral sclerosis is unknown. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

  In studies in which riluzole was administered orally to pregnant animals, developmental toxicity (decreased embryofetal/offspring viability, growth, and functional development) was observed at clinically relevant doses

  [see Data]

  . Based on these results, women should be advised of a possible risk to the fetus associated with use of TIGLUTIK during pregnancy.

  Data

  Animal Data

  Oral administration of riluzole (3, 9, or 27 mg/kg/day) to pregnant rats during the period of organogenesis resulted in decreases in fetal growth (body weight and length) at the high dose. The mid dose, a no-effect dose for embryofetal developmental toxicity, is approximately equal to the recommended human daily dose (RHDD, 100 mg) on a mg/m2 basis. When riluzole was administered orally (3, 10, or 60 mg/kg/day) to pregnant rabbits during the period of organogenesis, embryofetal mortality was increased at the high dose and fetal body weight was decreased and morphological variations increased at all but the lowest dose tested. The no-effect dose (3 mg/kg/day) for embryofetal developmental toxicity is less than the RHDD on a mg/m2 basis. Maternal toxicity was observed at the highest dose tested in rat and rabbit.

  When riluzole was orally administered (3, 8, or 15 mg/kg/day) to male and female rats prior to and during mating and to female rats throughout gestation and lactation, increased embryofetal mortality and decreased postnatal offspring viability, growth, and functional development were observed at the high dose. The mid dose, a no-effect dose for pre- and postnatal developmental toxicity, is approximately equal to the RHDD on a mg/m2 basis.
  )