Lundbeck Inc.

Lundbeck Inc. Drugs

• Atryn
  

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  Atryn

  

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  For Intravenous Use Only after Reconstitution

  2.1 Preparation for Administration

  Bring vials to room temperature no more than 3 hours prior to reconstitution. Reconstitute with 10 mL Sterile Water for Injection [(WFI) not supplied with ATryn] immediately prior to use. Do not shake. Do not use solution containing visible particulates or if it is discolored or cloudy. Draw solution from one or more vials into a sterile disposable syringe for intravenous administration or add solution to an infusion bag containing 0.9% sterile sodium chloride for injection (e.g., dilute solution to obtain a concentration of 100 IU/mL). Administer using an infusion set with a 0.22 micron pore-size, in-line filter. Administer contents of infusion syringes or diluted solution within 8 to 12 hours of preparation when stored at room temperature (68-77°F (20-25°C)). Discard unused product in accordance with local requirements.

  2.2 Recommended Dose and Schedule

  The dosage of ATryn is to be individualized based on the patient's pre-treatment functional AT activity level (expressed in percent of normal) and body weight (expressed in kilograms) and using therapeutic drug monitoring (Table 1). The goal of treatment is to restore and maintain functional antithrombin (AT) activity levels between 80% - 120% of normal (0.8 - 1.2 IU/mL). Treatment should be initiated prior to delivery or approximately 24 hours prior to surgery to ensure that the plasma antithrombin level is in the target range at that time. Different dosing formulae are used for the treatment of surgical and pregnant patients. Pregnant women who need a surgical procedure other than Cesarean section should be treated according to the dosing formulae for pregnant patients. Administer loading dose as a 15-minute intravenous infusion, immediately followed by a continuous infusion of the maintenance dose. AT activity monitoring and dose adjustments should be made according to Table 2. Continue treatment until adequate follow-on anticoagulation is established. Table 1: Dosing Formula for Surgical Patients and Pregnant Women Loading Dose(IU) Maintenance Dose(IU/hour) Surgical Patients (100 - baseline AT activity level) x Body Weight (kg) / 2.3 (100 - baseline AT activity level) x Body Weight (kg) / 10.2 Pregnant Women (100 - baseline AT activity level) x Body Weight (kg) / 1.3 (100 - baseline AT activity level) Body Weight (kg) / 5.4

  AT Activity Monitoring and Dose Adjustment

  AT activity monitoring is required for proper treatment. Check AT activity once or twice per day with dose adjustments made according to Table 2.

  Table 2: AT Activity Monitoring and Dose Adjustment Initial Monitor Time AT Level Dose Adjustment Recheck AT Level 2 hours after initiation of treatment < 80% Increase 30% 2 hours after each dose adjustment 80% to 120% None 6 hours after initiation of treatment or dose adjustment > 120% Decrease 30% 2 hours after each dose adjustment

  As surgery or delivery may rapidly decrease the AT activity levels, check the AT level just after surgery or delivery. If AT activity level is below 80%, an additional bolus dose may be administered to rapidly restore decreased AT activity level. In such instances, the loading dose formulae in Table 1 should be used, utilizing in the calculation the last available AT activity result. Thereafter, restart the maintenance dose at the same rate of infusion as before the bolus.

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• Xenazine
  

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  Xenazine

  

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  2.1 General Dosing Considerations

  The chronic daily dose of XENAZINE used to treat chorea associated with Huntington's disease (HD) is determined individually for each patient. When first prescribed, XENAZINE therapy should be titrated slowly over several weeks to identify a dose of XENAZINE that reduces chorea and is tolerated. XENAZINE can be administered without regard to food [see Clinical Pharmacology (12.3)].

  2.2 Individualization of Dose

  The dose of XENAZINE should be individualized.

  Dosing Recommendations Up to 50 mg per day

  The starting dose should be 12.5 mg per day given once in the morning. After one week, the dose should be increased to 25 mg per day given as 12.5 mg twice a day. XENAZINE should be titrated up slowly at weekly intervals by 12.5 mg daily, to allow the identification of a tolerated dose that reduces chorea. If a dose of 37.5 to 50 mg per day is needed, it should be given in a three times a day regimen. The maximum recommended single dose is 25 mg. If adverse reactions such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety or sedation occur, titration should be stopped and the dose should be reduced. If the adverse reaction does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants) [see Adverse Reactions (6.1)].

  Dosing Recommendations Above 50 mg per day

  Patients who require doses of XENAZINE greater than 50 mg per day should be first tested and genotyped to determine if they are poor metabolizers (PMs) or extensive metabolizers (EMs) by their ability to express the drug metabolizing enzyme, CYP2D6. The dose of XENAZINE should then be individualized accordingly to their status as PMs or EMs [see Warnings and Precautions (5.3), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

  Extensive and Intermediate CYP2D6 Metabolizers

  Genotyped patients who are identified as extensive (EMs) or intermediate metabolizers (IMs) of CYP2D6, who need doses of XENAZINE above 50 mg per day, should be titrated up slowly at weekly intervals by 12.5 mg daily, to allow the identification of a tolerated dose that reduces chorea. Doses above 50 mg per day should be given in a three times a day regimen. The maximum recommended daily dose is 100 mg and the maximum recommended single dose is 37.5 mg. If adverse reactions such as akathisia, parkinsonism, depression, insomnia, anxiety or sedation occur, titration should be stopped and the dose should be reduced. If the adverse reaction does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants) [see Warnings and Precautions (5.3), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

  Poor CYP2D6 Metabolizers

  In PMs, the initial dose and titration is similar to EMs except that the recommended maximum single dose is 25 mg, and the recommended daily dose should not exceed a maximum of 50 mg [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

  2.3 Dosage Adjustments with CYP2D6 Inhibitors

  Strong CYP2D6 Inhibitors

  Medications that are strong CYP2D6 inhibitors such as quinidine or antidepressants (e.g., fluoxetine, paroxetine) significantly increase the exposure to α-HTBZ and β-HTBZ, therefore, the total dose of XENAZINE should not exceed a maximum of 50 mg and the maximum single dose should not exceed 25 mg [see Warnings and Precautions (5.3), Drug Interactions (7.1), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

  2.4 Discontinuation of Treatment

  Treatment with XENAZINE can be discontinued without tapering. Re-emergence of chorea may occur within 12 to 18 hours after the last dose of XENAZINE [see Drug Abuse and Dependence (9.2)].

  2.5 Resumption of Treatment

  Following treatment interruption of greater than five (5) days, XENAZINE therapy should be re-titrated when resumed. For short-term treatment interruption of less than five (5) days, treatment can be resumed at the previous maintenance dose without titration.

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