Macrilen

None

QT Prolongation

Macrilen causes an increase of about 11 msec in the corrected QT (QTc) interval [see Clinical Pharmacology (12.2)]. 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 (2.2) and Drug Interactions (7.1)].

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 (7.2)]. 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 (2.2)].

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.

In the event of an overdose, symptomatic and supportive measures should be employed.

Macrilen for oral solution is macimorelin acetate, a synthetic growth hormone secretagogue receptor agonist. Macimorelin acetate is described chemically as D-Tryptophanamide, 2-methylalanyl-N-[(1R)-1-(formylamino)-2-(1H-indol-3-yl)ethyl]-acetate.

The molecular formula for macimorelin acetate is C28H34N6O5 with a molecular weight of 534.6 g/mol.

Figure 1: Chemical structure of macimorelin acetate

Each aluminum pouch of Macrilen contains 60 mg of macimorelin, equivalent to 68 mg of macimorelin acetate, and the following inactive ingredients: lactose monohydrate, crospovidone, sodium stearyl fumarate, saccharin sodium and colloidal silicon dioxide.

Instruct patients to discontinue treatment with GH at least one week before administering Macrilen. Also, instruct patients to discontinue other medications that may interfere with the diagnostic test results prior to Macrilen administration [see Drug Interactions (7.2, 7.3)].

Instruct patients to fast for at least 8 hours before Macrilen administration [see Dosage and Administration (2.2)].

Manufactured by:
Allphamed Pharbil Arzneimittel GmbH, Goettingen, Germany

Distributed by: Strongbridge U.S. Inc., Trevose, PA 19053

Macrilen™ is a trademark of Aeterna Zentaris GmbH, licensed exclusively in the U.S. and Canada to Strongbridge Ireland Limited.

Macrilen is the subject of U.S. Patent Nos. 6,861,409 and 8,192,719.

STRONGBRIDGE BIOPHARMA® is a registered trademark of the Strongbridge Biopharma plc. companies, which include Strongbridge Ireland Limited and Strongbridge U.S. Inc.

Revised: January 2018

Principal Display Panel - Macrilen Pouch Label

Rx only

NDC 71090-002-02

Macrilen™

(macimorelin) for oral solution

60 mg

Must administer dose within
30 minutes after reconstitution.
Discard unused portion.

For oral use only.

193277/1

Principal Display Panel - Macrilen Carton Label

Rx only

NDC 71090-002-02

Macrilen™

(macimorelin) for oral solution

60 mg

One Pouch

Must administer dose within 30 minutes after
reconstitution. Discard unused portion.

For oral use only.

Strongbridge Biopharma

Applies to macimorelin: oral granule

Along with its needed effects, macimorelin (the active ingredient contained in Macrilen) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking macimorelin:

• Slow heartbeat

Some side effects of macimorelin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Body aches or pain
• change in taste
• chills
• cough
• diarrhea
• difficulty in breathing
• dizziness
• ear congestion
• feeling hot
• fever
• headache
• hunger
• increased sweating
• loss of taste
• loss of voice
• muscle aches
• nasal congestion
• nausea
• runny nose
• sneezing
• sore throat
• stuffy or runny nose
• unusual tiredness or weakness

For Healthcare Professionals

Applies to macimorelin: oral granule for reconstitution

Cardiovascular

Common (1% to 10%): Sinus bradycardia[Ref]

Gastrointestinal

Common (1% to 10%): Dysgeusia, nausea, diarrhea[Ref]

Nervous system

Common (1% to 10%): Dizziness, headache[Ref]

Immunologic

Common (1% to 10%): Upper respiratory tract infection, nasopharyngitis[Ref]

Other

Common (1% to 10%): Fatigue, feeling hot[Ref]

Metabolic

Common (1% to 10%): Hunger[Ref]

Dermatologic

Common (1% to 10%): Hyperhidrosis[Ref]

Some side effects of Macrilen may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

• It is used to test for growth hormone deficiency.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Macrilen (macimorelin), please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Tell your doctor about all medications you use. Using certain medications at the time of your GH test could cause false results.

You should not be treated with Macrilen if you are allergic to it.

Tell your doctor if you have ever had:

• a hormonal disorder;

• a thyroid disorder; or

• a hypothalamus disorder.

Tell your doctor if you are pregnant or breast-feeding.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• slow heartbeats;

• shortness of breath; or

• fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out).

Common side effects may include:

• headache, dizziness;

• hunger, nausea, diarrhea;

• increased sweating, feeling hot;

• feeling tired;

• changes in your sense of taste; or

• cold symptoms such as stuffy nose, sinus pain, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2018 Cerner Multum, Inc. Version: 1.01.

Medical Disclaimer

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Tell your doctor about all your other medicines. You could have false test results if you are using certain medications at the time of your GH test. You may need to stop using your other medications for a certain amount of time before you take macimorelin.

Macimorelin can cause a serious heart problem. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Many drugs can affect macimorelin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.