SOMAVERT® WITH PREFILLED DILUENT SYRINGE (pegvisomant with PREFILLED DILUENT SYRINGE) 6 ADVERSE REACTIONS

(pegvisomant with PREFILLED DILUENT SYRINGE)

Prescribing Information

6 ADVERSE REACTIONS

Clinically significant adverse reactions that appear in other section of the labeling include:

•: Hypoglycemia Associated with GH Lowering in Patients with Diabetes Mellitus [see Warnings and Precautions (5.1)]
•: Liver Toxicity [see Warnings and Precautions (5.2)]
•: Cross-Reactivity with GH Assays [see Warnings and Precautions (5.3)]
•: Lipohypertrophy [see Warnings and Precautions (5.4)]
•: Systemic Hypersensitivity [see Warnings and Precautions (5.5)]

Elevations of serum concentrations of ALT and AST greater than ten times the ULN were reported in two patients (0.8%) exposed to SOMAVERT in pre-approval clinical studies. One patient was rechallenged with SOMAVERT, and the recurrence of elevated transaminase levels suggested a probable causal relationship between administration of the drug and the elevation in liver enzymes. A liver biopsy performed on the second patient was consistent with chronic hepatitis of unknown etiology. In both patients, the transaminase elevations normalized after discontinuation of the drug.

Elevations in ALT and AST levels were not associated with increased levels of TBIL and ALP, with the exception of two patients with minimal associated increases in ALP levels (i.e., less than 3 times ULN). The transaminase elevations did not appear to be related to the dose of SOMAVERT administered, generally occurred within 4 to 12 weeks of initiation of therapy, and were not associated with any identifiable biochemical, phenotypic, or genetic predictors.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a 12-week randomized, placebo-controlled, double-blind, fixed-dose study of SOMAVERT in subjects with acromegaly, 32 subjects received placebo and 80 subjects received SOMAVERT once daily [see Clinical Studies (14)]. A total of 108 subjects (30 placebo, 78 SOMAVERT) completed 12 weeks of study treatment.

Overall, eight patients with acromegaly (5.3%) withdrew from pre-marketing clinical studies because of adverse events, including two patients with marked transaminase elevations, one patient with lipohypertrophy at the injection sites, and one patient with substantial weight gain. Most adverse events did not appear to be dose-dependent. Table 3 shows the incidence of adverse events that were reported in at least two patients treated with SOMAVERT and at frequencies greater than placebo during the 12-week, placebo-controlled study.

Table 3. Adverse Reactions in a 12-week Placebo-Controlled Study in Patients with Acromegaly*
	Placebo n=32	SOMAVERT
	Placebo n=32	10 mg/day n=26	15 mg/day n=26	20 mg/day N=28
* Table includes only those events that were reported in at least 2 patients and at a higher incidence in patients treated with SOMAVERT than in patients treated with placebo. † The 6 events coded as "infection" in the group treated with SOMAVERT 10 mg were reported as cold symptoms (3), upper respiratory infection (1), blister (1), and ear infection (1). The 2 events in the placebo group were reported as cold symptoms (1) and chest infection (1).
Infection†	2 (6%)	6 (23%)	0	0
Pain	2 (6%)	2 (8%)	1 (4%)	4 (14%)
Nausea	1 (3%)	0	2 (8%)	4 (14%)
Diarrhea	1 (3%)	1 (4%)	0	4 (14%)
Abnormal liver function tests	1 (3%)	3 (12%)	1 (4%)	1 (4%)
Flu syndrome	0	1 (4%)	3 (12%)	2 (7%)
Injection site reaction	0	2 (8%)	1 (4%)	3 (11%)
Dizziness	2 (6%)	2 (8%)	1 (4%)	1 (4%)
Accidental injury	1 (3%)	2 (8%)	1 (4%)	0
Back pain	1 (3%)	2 (8%)	0	1 (4%)
Sinusitis	1 (3%)	2 (8%)	0	1 (4%)
Chest pain	0	1 (4%)	2 (8%)	0
Peripheral edema	0	2 (8%)	0	1 (4%)
Hypertension	0	0	2 (8%)	0
Paresthesia	2 (6%)	0	0	2 (7%)

6.2 Postmarketing Experience

Adverse Reactions from Postmarketing Spontaneous Reports

The following adverse reactions have been identified during post-approval use of SOMAVERT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Systemic hypersensitivity reactions including anaphylactic reactions, laryngospasm, angioedema, generalized skin reactions (rash, erythema, pruritus, urticaria) have been reported in post-marketing use. Some patients required hospitalization. Symptoms did not re-occur in all patients after re-challenge [see Warnings and Precautions (5.5)].

Adverse Reactions from an Observational Study

ACROSTUDY was an international observational registry that captured long term safety data in 2221 patients with acromegaly treated with SOMAVERT for a mean treatment duration of 8.5 years. Patients could also receive other therapy for acromegaly during the registry period. Treatment dose and schedule were at the discretion of each treating healthcare provider. Although safety monitoring as per the recommended schedule was mandatory, not all assessments were performed at all time points for every patient. Because of this, comparison of rates of adverse events to those in the original clinical trial is not appropriate. Of the 1327 patients who had a normal AST and ALT at baseline, 20 (1.5%) patients had elevated tests >3-5 times ULN, and 22 (1.7%) patients had elevated tests >5 times ULN. Lipohypertrophy was reported in 35 (1.6%) patients. Of the 1795 patients who had a MRI reported at baseline and at least once during follow up in the study, MRI results showed that 128 (7.1%) were reported to have an increase, 310 (17.3%) were reported to have a decrease, 81 (4.5%) had both increase and decrease, and 1276 (71.1%) had no change.

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: • 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. • have diabetes. • have or have had liver problems. • 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. • 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: • insulin or other medicines used to treat diabetes. • 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? • Read the Instructions for Use at the end of this Patient Information for information about the right way to use SOMAVERT. • 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. • 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. • Your first injection of SOMAVERT should be given by your healthcare provider. • Your healthcare provider will teach you or your caregiver how to use SOMAVERT. • 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: • changes in your blood sugar level. Your healthcare provider may change your dose of diabetes medicine while you take SOMAVERT. • 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 o feeling very tired (fatigue or exhaustion) o nausea and vomiting	o pain in your stomach (abdomen) o generalized swelling o bruising easily
• skin thickening at your injection site that could lead to lumps (lipohypertrophy) • allergic reactions. Call your healthcare provider right away if you have any of the following symptoms of a serious allergic reaction:
	o swelling of your face, tongue, lips, or throat o wheezing or trouble breathing o skin rash, redness, or swelling	o severe itching o dizziness or fainting
The most common side effects of SOMAVERT include:
	• pain • infection • nausea • flu syndrome	• injection site reaction • diarrhea • 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? • Before you mix the SOMAVERT powder and the liquid: o Store SOMAVERT in a refrigerator at 36°F to 46°F (2°C to 8°C). o 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. o 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). o 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. • Throw away the SOMAVERT vials after the expiration date printed on the carton or the discard date, whichever is sooner. • 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. • Do not freeze SOMAVERT. • Read the Instructions for Use for the right way to mix SOMAVERT. • After you mix the SOMAVERT powder and liquid: o Keep the mixed SOMAVERT at room temperature between 59°F to 77°F (15°C to 25°C). o Keep SOMAVERT inside the vial or the syringe until you are ready to inject it. o You must use the mixed SOMAVERT immediately after you mix it. o 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. 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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