Intuniv

Intuniv Manufacturers

• Shire Us Manufacturing Inc.
  

  ×

  Intuniv | Shire Us Manufacturing Inc.

  

  ---

  2.1 General Instruction for Use

  Swallow tablets whole. Do not crush, chew, or break tablets because this will increase the rate of guanfacine release. Do not administer with high fat meals, due to increased exposure.

  2.2 Dose Selection

  Take INTUNIV orally once daily, either in the morning or evening, at approximately the same time each day. Begin at a dose of 1 mg/day, and adjust in increments of no more than 1 mg/week.

  In monotherapy clinical trials, there was dose- and exposure-related clinical improvement as well as risks for several clinically significant adverse reactions (hypotension, bradycardia, sedative events). To balance the exposure-related potential benefits and risks, the recommended target dose range depending on clinical response and tolerability for INTUNIV® is 0.05-0.12 mg/kg/day (total daily dose between 1-7 mg) (See Table 1).

  Table 1: Recommended Target Dose Range for Therapy with INTUNIV® Weight Target dose range (0.05 - 0.12 mg/kg/day) Doses above 4 mg/day have not been evaluated in children (ages 6-12 years) and doses above 7 mg/day have not been evaluated in adolescents (ages 13-17 years) 25-33.9 kg 2-3 mg/day 34-41.4 kg 2-4 mg/day 41.5-49.4 kg 3-5 mg/day 49.5-58.4 kg 3-6 mg/day 58.5-91 kg 4-7 mg/day >91 kg 5-7 mg/day

  In the adjunctive trial which evaluated INTUNIV® treatment with psychostimulants, the majority of patients reached optimal doses in the 0.05-0.12 mg/kg/day range. Doses above 4 mg/day have not been studied in adjunctive trials.

  2.3 Switching from Immediate-Release Guanfacine to INTUNIV®

  If switching from immediate-release guanfacine, discontinue that treatment, and titrate with INTUNIV® following above recommended schedule.

  Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. INTUNIV® has significantly reduced Cmax (60% lower), bioavailability (43% lower), and a delayed Tmax (3 hours later) compared to those of the same dose of immediate-release guanfacine [see Clinical Pharmacology (12.3)].

  2.4 Maintenance Treatment

  Pharmacological treatment of ADHD may be needed for extended periods. Healthcare providers should periodically re-evaluate the long-term use of INTUNIV®, and adjust weight-based dosage as needed. The majority of children and adolescents reach optimal doses in the 0.05-0.12 mg/kg/day range. Doses above 4 mg/day have not been evaluated in children (ages 6-12 years) and above 7 mg/day have not been evaluated in adolescents (ages 13-17 years) [see Clinical Studies (14)].

  2.5 Discontinuation of Treatment

  Following discontinuation of INTUNIV®, patients may experience increases in blood pressure and heart rate [see Adverse Reaction (6.1)]. Patients/caregivers should be instructed not to discontinue INTUNIV® without consulting their health care provider. Monitor blood pressure and pulse when reducing the dose or discontinuing the drug. Taper the daily dose in decrements of no more than 1 mg every 3 to 7 days to avoid rebound hypertension.

  2.6 Missed Doses

  When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, consider titration based on patient tolerability.

  2.7 Dosage Adjustment with Concomitant Use of Strong CYP3A4 Inhibitors or Inducers

  Dosage adjustments for INTUNIV® are recommended with concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole), or CYP3A4 inducers (e.g., carbamazepine) (Table 2) [see Drug Interactions (7)].

  Table 2: INTUNIV® Dosage Adjustments for Patients Taking Concomitant CYP3A4 Inhibitors or Inducers Clinical Scenarios Starting INTUNIV® while currently on a CYP3A4 modulator Continuing INTUNIV® while adding a CYP3A4 modulator Continuing INTUNIV® while stopping a CYP3A4 modulator CYP3A4
    Strong Inhibitors Decrease INTUNIV® dosage to half the recommended level.
  (see Table 1) Decrease INTUNIV® dosage to half the recommended level.
  (see Table 1) Increase INTUNIV® dosage to recommended level.
  (see Table 1) CYP3A4
    Strong Inducers Consider increasing INTUNIV® dosage up to double the recommended level.
  (see Table 1)
  
  Consider increasing INTUNIV® dosage up to double the recommended level over 1 to 2 weeks.
  (see Table 1)
  Decrease INTUNIV® dosage to recommended level over 1 to 2 weeks.
  (see Table 1)

  Close
  No Recall

  More Info
• Tya Pharmaceuticals
  

  ×

  Intuniv | Tya Pharmaceuticals

  

  ---

  2.1 General Instruction for Use

   Do not administer with high fat meals, due to increased exposure. Swallow tablets whole. Do not crush, chew, or break tablets because this will increase the rate of guanfacine release.

  2.2 Dose Selection

  INTUNIV should be taken once daily, either in the morning or evening, at approximately same time each day. Begin at a dose of 1 mg/day, and adjust in increments of no more than 1 mg/week. Maintain the dose within the range of 1 mg to 4 mg once daily, depending on clinical response and tolerability, for both monotherapy and adjunctive therapy to a psychostimulant. Doses above 4 mg/day have not been systematically studied in controlled clinical studies . [ ] see Clinical Studies (14.1)

  Clinically relevant improvements were observed beginning at doses in the range 0.05-0.08 mg/kg once daily in both mono- and adjunctive therapy. Efficacy increased with increasing weight-adjusted dose (mg/kg). If well tolerated, doses up to 0.12 mg/kg once daily may provide additional benefit.

  In clinical trials, there were dose-related and exposure-related risks for several clinically significant adverse reactions (hypotension, bradycardia, sedative events). Thus, consideration should be given to dosing INTUNIV on a mg/kg basis, in order to balance the exposure-related potential benefits and risks of treatment. ®

  2.3 Switching from Immediate-Release Guanfacine to INTUNIV

  If switching from immediate-release guanfacine, discontinue that treatment, and titrate with INTUNIV following above recommended schedule. ®

  Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. INTUNIV has a delayed T , reduced C and lower bioavailability compared to those of the same dose of immediate-release guanfacine . ®maxmax[ ] see Clinical Pharmacology (12.3)

  2.4 Maintenance Treatment

  It is generally agreed that pharmacological treatment of ADHD may be needed for an extended period. The effectiveness of INTUNIV for longer-term use (more than 9 weeks) has not been systematically evaluated in controlled trials. Therefore the physician electing to use INTUNIV for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. ®®

  2.5 Discontinuation

  Infrequent, transient elevations in blood pressure above original baseline (i.e., rebound) have been reported to occur upon abrupt discontinuation of guanfacine. To minimize these effects, the dose should generally be tapered in decrements of no more than 1 mg every 3 to 7 days.

  2.6 Missed Doses

  When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, physicians should consider titration based on patient tolerability.

  2.7 Dose Adjustment with Concomitant Use of Strong CYP3A4 Inhibitors or Inducers

  Dosage adjustments for INTUNIV are recommended with concomitant use of strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole), or CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and St.John’s wort) (Table 1) . ®[] see Drug Interactions (7)

  Table 1: Dose Adjustments in Patients Taking Concomitant CYP3A4 Inhibitors or Inducers

     Comedications     Scenarios

  Initiate INTUNIV when taking comedications ®
  
  

  Continue INTUNIV   when adding a comedication ®
  
  Stop a comedication    when continuing INTUNIV  
  
  ® Strong CYP3A4 Inhibitors
  
  INTUNIV dose should be limited to 2 mg/day ®
  
  INTUNIV dose should be decreased by half. ®
  
  INTUNIV dose should be doubled based on patient tolerability. The maximum dose should not exceed 4 mg/day ®
  
  
  
  
  
  Strong CYP3A4 Inducers
  
  INTUNIV dose may be titrated up to 8 mg/day. Consider faster titration (e.g. in increments of 2 mg/week) ®
  
  
  
  
  Consider increase INTUNIV dose gradually in 1-2 weeks to 2 fold of the original dose based on patient tolerability.
  ®
  
  
  
  
  INTUNIV dose should be decreased by half in 1-2 weeks based on patient tolerability. The maximum dose should not exceed 4 mg/day ®
  
  
  
  
  
  
  

  Close
  No Recall

  More Info