(pegvisomant with PREFILLED DILUENT SYRINGE)

Prescribing Information
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12 CLINICAL PHARMACOLOGY

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Pegvisomant selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH, and thus interferes with GH signal transduction.

Inhibition of GH action results in decreased serum concentrations of IGF-1, as well as other GH-responsive serum proteins such as free IGF-1, the acid-labile subunit of IGF-1 (ALS), and insulin-like growth factor binding protein-3 (IGFBP-3).

12.2 Pharmacodynamics

Pegvisomant binds selectively to the GH receptor, and does not cross-react with 19 other cytokine receptors tested, including prolactin. Pegvisomant leads to decreased serum concentrations of IGF-1, free IGF-1, ALS, and IGFBP-3 [see Clinical Studies (14, Figure 1)].

12.3 Pharmacokinetics

Absorption: Following subcutaneous administration, peak serum pegvisomant concentrations are not generally attained until 33 to 77 hours after administration. The mean extent of absorption of a 20-mg subcutaneous dose was 57%, relative to a 10-mg intravenous dose.

Distribution: The mean apparent volume of distribution of pegvisomant is 7 L (12% coefficient of variation), suggesting that pegvisomant does not distribute extensively into tissues. After a single subcutaneous administration, exposure (Cmax, AUC) to pegvisomant increases disproportionately with increasing dose. Mean ± SEM serum pegvisomant concentrations after 12 weeks of therapy with daily doses of 10, 15, and 20 mg were 6600 ± 1330; 16,000 ± 2200; and 27,000 ± 3100 ng/mL, respectively.

The relative bioavailability of 1 × 30 mg pegvisomant was compared to 2 × 15 mg pegvisomant in a single-dose study. The AUCinf and Cmax of pegvisomant when administered as one injection of 30 mg strength was approximately 6% and 4% greater, respectively, as compared to when administered as two injections of 15 mg strengths.

Metabolism and Elimination: The pegvisomant molecule contains covalently bound polyethylene glycol polymers in order to reduce the clearance rate. Clearance of pegvisomant following multiple doses is lower than seen following a single-dose. The mean total body systemic clearance of pegvisomant following multiple doses is estimated to range between 36 to 28 mL/h for subcutaneous doses ranging from 10 to 20 mg/day, respectively. Clearance of pegvisomant was found to increase with body weight. Pegvisomant is eliminated from serum with a mean half-life estimates ranging from 60 to 138 hours following either single or multiple doses. Less than 1% of administered drug is recovered in the urine over 96 hours. The elimination route of pegvisomant has not been studied in humans.

Drug Interaction Studies

In clinical studies, patients on opioids often needed higher serum pegvisomant concentrations to achieve appropriate IGF-1 suppression compared with patients not receiving opioids. The mechanism of this interaction is not known [see Drug Interactions (7.2)].

Specific Populations

No pharmacokinetic studies have been conducted in patients with renal impairment, patients with hepatic impairment, geriatric patients, or pediatric patients and the effects of race on the pharmacokinetics of pegvisomant has not been studied. No gender effect on the pharmacokinetics of pegvisomant was found in a population pharmacokinetic analysis.

12.6 Immunogenicity

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of SOMAVERT or other growth hormone analogs.

In pre-marketing clinical studies, approximately 17% of the SOMAVERT-treated patients developed low titer, non‑neutralizing anti-GH antibodies. Although the presence of these antibodies did not appear to impact the efficacy of SOMAVERT, the long term clinical significance of these antibodies is not known. No assay for anti-pegvisomant antibodies is commercially available for patients receiving SOMAVERT.

The data above reflect the percentage of patients whose test results were considered positive for antibodies to SOMAVERT. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to SOMAVERT with the incidence of antibodies to other products may be misleading.

Medication Guide

MEDICATION GUIDE

This Patient Information has been approved by the U.S. Food and Drug Administration.

Revised: 7/2023

PATIENT INFORMATION
SOMAVERT (SOM-ah-vert)
(pegvisomant)
for injection, for subcutaneous use

What is SOMAVERT?
SOMAVERT is a prescription medicine used to treat people who have too much growth hormone (acromegaly). SOMAVERT is used to treat people who are not able to be treated or have not already been helped by surgery or radiation.
It is not known if SOMAVERT is safe and effective in children.

Before you use SOMAVERT, tell your healthcare provider about all of your medical conditions, including if you:

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are allergic to pegvisomant or any of the ingredients in SOMAVERT. Do not take SOMAVERT if you are allergic to pegvisomant or any of the ingredients in SOMAVERT. See the end of this Patient Information leaflet for a complete list of ingredients in SOMAVERT.
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have diabetes.
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have or have had liver problems.
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are pregnant or plan to become pregnant. It is not known if SOMAVERT will harm your unborn baby. Tell your healthcare provider if you become pregnant while using SOMAVERT.
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are breastfeeding or plan to breastfeed. It is not known if SOMAVERT passes into your breast milk. You and your healthcare provider should decide how you will feed your baby if you take SOMAVERT.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
SOMAVERT may affect the way other medicines work, and other medicines may affect how SOMAVERT works.
Especially tell your healthcare provider if you take:

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insulin or other medicines used to treat diabetes.
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narcotics (opioid medicines). Your healthcare provider may change your dose of SOMAVERT if you take opioids.

If you are not sure, ask your healthcare provider or pharmacist whether you take these medicines.

How should I use SOMAVERT?

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Read the Instructions for Use at the end of this Patient Information for information about the right way to use SOMAVERT.
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Your healthcare provider should do blood tests to check your liver and insulin-like growth factor-1 (IGF-1) levels before you start and while you use SOMAVERT. Your healthcare provider may need to change your dose of SOMAVERT.
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SOMAVERT is given 1 time each day as an injection under your skin (subcutaneous). Some people may need to give 2 injections for their dose each day. Your healthcare provider will tell you if you need to give 2 injections for your dose.
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Your first injection of SOMAVERT should be given by your healthcare provider.
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Your healthcare provider will teach you or your caregiver how to use SOMAVERT.
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If you use too much SOMAVERT, call your healthcare provider right away.
•
If you miss a dose of SOMAVERT, just take the next dose at the regular time. Do not take 2 doses at the same time. If you are not sure about your dosing, ask your healthcare provider.

What are the possible side effects of SOMAVERT?
SOMAVERT may cause serious side effects, including:

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changes in your blood sugar level. Your healthcare provider may change your dose of diabetes medicine while you take SOMAVERT.
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liver problems. Stop injecting SOMAVERT right away and call your healthcare provider if you have any of the following symptoms of liver problems:
o
yellowing of your eyes (jaundice)
o
dark, amber-colored urine
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feeling very tired (fatigue or exhaustion)
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nausea and vomiting
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pain in your stomach (abdomen)
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generalized swelling
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bruising easily
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skin thickening at your injection site that could lead to lumps (lipohypertrophy)
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allergic reactions. Call your healthcare provider right away if you have any of the following symptoms of a serious allergic reaction:
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swelling of your face, tongue, lips, or throat
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wheezing or trouble breathing
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skin rash, redness, or swelling
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severe itching
o
dizziness or fainting

The most common side effects of SOMAVERT include:

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pain
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infection
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nausea
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flu syndrome
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injection site reaction
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diarrhea
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abnormal liver tests. If your liver test results are too high, you may have to have more frequent liver tests

These are not all of the possible side effects of SOMAVERT. For more information, ask your healthcare provider or pharmacist.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store SOMAVERT?

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Before you mix the SOMAVERT powder and the liquid:
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Store SOMAVERT in a refrigerator at 36°F to 46°F (2°C to 8°C).
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The One Day Package and intermediate cartons in the 30-Day Package containing the SOMAVERT vials, may be stored at room temperature up to 77°F (25°C) for a single period of up to 30 days.
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In the space provided on the carton, record the date when the carton was removed from the refrigerator and the discard date (30 days after removal from the refrigerator).
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After the carton has been stored at room temperature, it should not be placed back into the refrigerator. If not used within 30 days at room temperature, the vials should be thrown away.
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Throw away the SOMAVERT vials after the expiration date printed on the carton or the discard date, whichever is sooner.
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The prefilled syringes maybe stored at a temperature up to 86°F (30°C) until the expiration date printed on the carton. After that time, they should be thrown away.
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Do not freeze SOMAVERT.
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Read the Instructions for Use for the right way to mix SOMAVERT.
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After you mix the SOMAVERT powder and liquid:
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Keep the mixed SOMAVERT at room temperature between 59°F to 77°F (15°C to 25°C).
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Keep SOMAVERT inside the vial or the syringe until you are ready to inject it.
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You must use the mixed SOMAVERT immediately after you mix it.
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If you have not used the mixed SOMAVERT immediately, throw it away.

Keep SOMAVERT and all medicines out of the reach of children.

General information about the safe and effective use of SOMAVERT.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use SOMAVERT for a condition for which it was not prescribed. Do not give SOMAVERT to other people, even if they have the same symptoms that you have. It may harm them.
This Patient Information summarizes the most important information about SOMAVERT. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about SOMAVERT that is written for health professionals.

What are the ingredients in SOMAVERT?
Active ingredient: pegvisomant, including polyethylene glycol
Inactive ingredients: glycine, mannitol, sodium dihydrogen phosphate monohydrate, and sodium phosphate dibasic anhydrous.

Logo

U.S. License No. 1216


LAB-0783-4.0

For more information, go to www.SOMAVERT.com or call 1-800-645-1280.

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