Macrilen

MACRILEN is indicated for the diagnosis of adult growth hormone deficiency (AGHD).

• • Recommended dose is 0.5 mg/kg as a single oral dose, after fasting for at least 8 hours (
  2.1 Recommended Dose

  The recommended dose is a single oral dose of 0.5 mg/kg of macimorelin. The dose is administered as a reconstituted solution

  [see Dosage and Administration ]

  in patients fasted for at least 8 hours.
  ).
• • See Full Prescribing Information for important preparation and administration instructions (
  2.3 Directions for Preparation and Administration

  Prepare and administer by a healthcare professional exactly as follows.

  Prepare the MACRILEN solution:

  • a.Weigh the patient in
    kilograms (i.e., kg)
    .
  • b.Determine the number of MACRILEN pouches needed to prepare the dose:
  • i. For a patient weighing up to 120 kg, use 1 pouch.
  • ii. For a patient weighing more than 120 kg, use 2 pouches.
  • c.Use a glass or transparent plastic container with graduation in
    milliliters (i.e., mL)
    to dissolve the entire contents of the pouch(es) in the appropriate volume of water.
  • i. For 1 pouch dissolve in 120 mL of water (corresponds to 60 mg/120 mL).
  • ii. For 2 pouches dissolve in 240 mL of water (corresponds to 120 mg/240 mL).
  • d.Stir the MACRILEN solution gently for about 2 to 3 minutes (a small amount of un-dissolved particles will remain).
    The solution will have a final concentration of 0.5 mg/mL
    .
  • e.Use the MACRILEN solution within 30 minutes after preparation.
  • f.Discard any unused MACRILEN solution.

  Determine the volume of MACRILEN solution needed for the test:

  • g.Determine the recommended dose to be administered
    by multiplying
    the patient weight in kilogram by 0.5 mg/kg.

    For example, a 70 kg patient will need a 35 mg dose.

  • h.Determine the volume of prepared MACRILEN solution to be administered
    by dividing
    the recommended dose by 0.5 mg/mL.

    For example, a patient requiring a dose of 35 mg will need 70 mL of reconstituted MACRILEN solution.

  • i.Use a syringe (without a needle) with graduations in mL to measure the exact volume of MACRILEN solution to be administered and transfer the required volume of MACRILEN solution into a drinking glass.

  Administer the MACRILEN solution and perform the test:

  • j.Have the patient being tested drink the entire volume of MACRILEN solution in the drinking glass (i.e., the dose) within
    30 seconds
    .
  • k.Observe the patient being tested per routine for the duration of the test.
  • l.Draw venous blood samples for GH determination at
    30 minutes, 45 minutes, 60 minutes and 90 minutes
    after administration of MACRILEN.
  • m.Prepare serum samples and send to a laboratory for growth hormone determinations.
  • n.
  • o.
  • p.
  • q.
  • r.
  • s.
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  ).
• • Discontinue therapy with strong CYP3A4 inducers, growth hormones and drugs that affect GH release for an adequate length of time before administering MACRILEN (
  2.2 Important Recommendations Before MACRILEN Use

  • •Discontinue strong CYP3A4 inducers prior to MACRILEN use
    [see Warning and Precautions and Drug Interactions ].
  • •Discontinue growth hormone (GH) therapy at least one week before administering MACRILEN
    [see Drug Interactions ]
    .
  • •Avoid the use of MACRILEN with drugs known to affect pituitary GH secretion
    [see Drug Interactions ]
    .
  • •For patients with deficiencies in sex hormones, thyroid hormone and/or glucocorticoid, adequately replace each of the missing hormones before administering MACRILEN.
  • •Ensure that the patient has fasted for at least 8 hours before MACRILEN use.
  ).
• • Adequately replace other hormone deficiencies before administering MACRILEN (
  2.2 Important Recommendations Before MACRILEN Use

  • •Discontinue strong CYP3A4 inducers prior to MACRILEN use
    [see Warning and Precautions and Drug Interactions ].
  • •Discontinue growth hormone (GH) therapy at least one week before administering MACRILEN
    [see Drug Interactions ]
    .
  • •Avoid the use of MACRILEN with drugs known to affect pituitary GH secretion
    [see Drug Interactions ]
    .
  • •For patients with deficiencies in sex hormones, thyroid hormone and/or glucocorticoid, adequately replace each of the missing hormones before administering MACRILEN.
  • •Ensure that the patient has fasted for at least 8 hours before MACRILEN use.
  ).

For oral solution: 60 mg white to off-white granules in a pouch for reconstitution in 120 mL of water, resulting in a solution of 0.5 mg/mL of macimorelin.

There are no available data with MACRILEN use in pregnant women to inform a drug associated risk for adverse developmental outcomes. Animal reproduction studies have not been conducted with MACRILEN. MACRILEN is indicated as a single dose which limits the risk of adverse developmental outcomes from exposure to MACRILEN.

The estimated background risk of major birth defects and miscarriage for the indicated populations 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.

• •
  QT Prolongation:
  QT prolongation can lead to development of torsade de pointes-type ventricular tachycardia. Avoid the concomitant use of MACRILEN with drugs that are known to prolong QT interval (
  5.1 QT Prolongation

  MACRILEN causes an increase of about 11 msec in the corrected QT (QTc) interval

  [see Clinical Pharmacology ]

  . QT prolongation can lead to development of torsade de pointes-type ventricular tachycardia with the risk increasing as the degree of prolongation increases. The concomitant use of MACRILEN with drugs that are known to prolong the QT interval should be avoided

  [see Dosage and Administration and Drug Interactions ]

  .
  ,
  7.1 Drugs that Prolong QT Interval

  Co-administration of MACRILEN with drugs that prolong the QT interval (such as antipsychotic medications (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), Class 1A (e.g., quinidine, procainamide) and Class III (e.g., amiodarone, sotalol) antiarrhythmic medications or any other medications known to prolong the QT interval) may lead to development of torsade de pointes-type ventricular tachycardia. Avoid concomitant use of MACRILEN with drugs that prolong the QT interval. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of MACRILEN is recommended

  [see Dosage and Administration and Warnings and Precautions ]

  .
  ).
• •
  Potential for False Positive Test Results with Use of Strong CYP3A4 Inducers:
  Discontinue and washout strong CYP3A4 inducers before testing (
  5.2 Potential for False Positive Test Results with Use of Strong CYP3A4 Inducers

  Concomitant use of strong CYP3A4 inducers with MACRILEN can decrease macimorelin plasma levels significantly and thereby lead to a false positive result

  [see Drug Interactions ]

  . Strong CYP3A4 inducers should be discontinued and enough time should be given to allow washout of CYP3A4 inducers prior to test administration

  [see Dosage and Administration ].
  ,
  7.2 Cytochrome P450 (CYP) 3A4 Inducers

  Co-administration of a strong CYP3A4 inducer with MACRILEN (e.g., carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort, bosentan, efavirenz, etravirine, modafinil, armodafinil, rufinamide) may reduce the plasma macimorelin concentrations and may lead to false positive test results. Discontinue strong CYP3A4 inducers prior to MACRILEN use. Sufficient washout time of strong CYP3A4 inducers prior to administration of MACRILEN is recommended

  [see Dosage and Administration and Warnings and Precautions ]

  .
  ).
• •
  Potential for False Negative Test Results in Recent Onset Hypothalamic Disease:
  Consider repeat testing if indicated (
  5.3 Potential for False Negative Test Results in Recent Onset Hypothalamic Disease

  Adult growth hormone (GH) deficiency caused by a hypothalamic lesion may not be detected early in the disease process. Macimorelin acts downstream from the hypothalamus and macimorelin stimulated release of stored GH reserves from the anterior pituitary could produce a false negative result early when the lesion involves the hypothalamus. Repeat testing may be warranted in this situation.
  ).