What is Somavert and how is it used?

Somavert is a prescription medicine used to treat the symptoms of Acromegaly. Somavert may be used alone or with other medications.

Somavert belongs to a class of drugs called Metabolic & Endocrine, Other.

It is not known if Somavert is safe and effective in children.

What are the possible side effects of Somavert?

Somavert may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• wheezing,
• thickening of the skin or a hard lump where you injected the medicine,
• easy bruising,
• nausea,
• upper stomach pain,
• itching,
• tired feeling,
• loss of appetite,
• dark urine,
• clay-colored stools, and
• yellowing of the skin or eyes (jaundice)

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Somavert include:

• pain,
• fever,
• chills,
• body aches,
• flu symptoms,
• nausea,
• diarrhea,
• abnormal liver function tests, and
• pain or irritation where the medicine was injected

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Somavert. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

DESCRIPTION

SOMAVERT contains pegvisomant, an analog of human growth hormone (GH) that has been structurally altered to act as a GH receptor antagonist.

Pegvisomant is a protein of recombinant DNA origin containing 191 amino acid residues to which several polyethylene glycol (PEG) polymers are covalently bound (predominantly 4 to 6 PEG/protein molecule). The molecular weight of the protein of pegvisomant is 21,998 Daltons. The molecular weight of the PEG portion of pegvisomant is approximately 5000 Daltons. The predominant molecular weights of pegvisomant are thus approximately 42,000, 47,000, and 52,000 Daltons. The schematic shows the amino acid sequence of the pegvisomant protein (PEG polymers are shown attached to the 5 most probable attachment sites). Pegvisomant is synthesized by a specific strain of Escherichia coli bacteria that has been genetically modified by the addition of a plasmid that carries a gene for GH receptor antagonist. Biological potency is determined using a cell proliferation bioassay. Binding of Somavert to the GH receptor results in disruption of the proper binding of the second GH receptor with inhibition of functional receptor dimerization and subsequent intracellular signaling.

INDICATIONS

SOMAVERT is indicated for the treatment of acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom these therapies are not appropriate. The goal of treatment is to normalize serum insulin-like growth factor-I (IGF-I) levels.

DOSAGE AND ADMINISTRATION

Dosage Information

The recommended loading dose of SOMAVERT is 40 mg given subcutaneously, under healthcare provider supervision. Provide proper training in subcutaneous injection technique to patients or their caregivers so they can receive once daily subcutaneous injections. On the next day following the loading dose, instruct patients or their caregivers to begin daily subcutaneous injections of 10 mg of SOMAVERT.

Titrate the dosage to normalize serum IGF-I concentrations (serum IGF-I concentrations should be measured every four to six weeks). The dosage should not be based on growth hormone (GH) concentrations or signs and symptoms of acromegaly. It is unknown whether patients who remain symptomatic while achieving normalized IGF-I concentrations would benefit from increased SOMAVERT dosage.

• Increase the dosage by 5 mg increments every 4–6 weeks if IGF-I concentrations are elevated.
• Decrease the dosage by 5 mg decrements every 4–6 weeks if IGF-I concentrations are below the normal range.
• IGF-I levels should also be monitored when a Somavert dose given in multiple injections is converted to a single daily injection [see CLINICAL PHARMACOLOGY].

The recommended dosage range is between 10 to 30 mg given subcutaneously once daily and the maximum daily dosage is 30 mg given subcutaneously once daily.

Assess Liver Tests Prior To Initiation Of SOMAVERT

Prior to the start of SOMAVERT, patients should have an assessment of baseline levels of liver tests [serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total bilirubin (TBIL), and alkaline phosphatase (ALP)]. For recommendations regarding initiation of SOMAVERT based on baseline liver tests and recommendations for monitoring of liver tests while on SOMAVERT, refer to Table 1 in Warning and Precautions.

Loading Dose Injection Procedure

The following instructions are for the healthcare provider to reconstitute and prepare the 40 mg loading dose. The healthcare provider will need to reconstitute 1 vial of lyophilized powder of SOMAVERT containing 20 mg of pegvisomant with supplied diluent (two vials of lyophilized powder and two vials of diluent will be needed for the 40 mg loading dose). The healthcare provider will also need to inject the reconstituted SOMAVERT solution twice into the patient's upper arm, upper thigh, abdomen, or buttocks (each injection in a different area).

1. Before administering the loading dose, remove the first package (1 vial of lyophilized powder of SOMAVERT containing 20 mg of pegvisomant and 1 vial containing the diluent) from the refrigerator about 10 minutes prior to the planned injection time.
2. Withdraw 1 mL of the supplied diluent (Sterile Water for Injection) and inject slowly onto the sides of the vial containing lyophilized powder of SOMAVERT. Do not inject the diluent directly on the powder.
3. Do not invert the vial or shake the solution as this may cause denaturation of the pegvisomant protein. Slowly swirl the solution to ensure that all of the lyophilized powder has gone into solution. If foaming of the reconstituted SOMAVERT solution is seen, the solution is likely damaged and therefore inappropriate to inject.
4. Visually inspect the reconstituted SOMAVERT solution for particulate matter and discoloration prior to administration. The reconstituted solution should be clear. If the solution is cloudy, do not use it. Once reconstituted, the solution will contain 20 mg of pegvisomant in 1 mL of solution.
5. Withdraw the 1 mL reconstituted SOMAVERT solution. The solution must be administered within 6 hours of reconstitution.
6. Inject the first reconstituted SOMAVERT solution (20 mg/mL) subcutaneously into the patient's upper arm, upper thigh, abdomen, or buttocks using a 90-degree angle.
7. Repeat steps (a) to (e) to reconstitute the second Somavert dose of 20mg.
8. Finally, inject the second reconstituted SOMAVERT solution (20 mg/mL) subcutaneously into the patient's upper arm, upper thigh, abdomen, or buttocks using a 90-degree angle (different area than the first injection).

Maintenance Dose Injection Procedure

1. For patient or caregiver instructions for reconstitution and administration of daily doses (10 to 30 mg), see the Patient's Instructions for Use.
2. Before administering the dose, remove one package (1 vial of lyophilized powder of SOMAVERT containing 10, 15, 20, 25 or 30 mg of pegvisomant and 1 vial containing the diluent) from the refrigerator about 10 minutes prior to the planned injection time.
3. Withdraw 1 mL of the supplied 5 ml diluent (Sterile Water for Injection) and inject slowly onto the sides of the vial containing lyophilized powder of SOMAVERT. Do not inject the diluent directly on the powder.
4. Do not invert the vial or shake the solution as this may cause denaturation of the pegvisomant protein. Slowly swirl the solution to ensure that all of the lyophilized powder has gone into solution. If foaming of the reconstituted SOMAVERT solution is seen, the solution is likely damaged and therefore inappropriate to inject.

1. Visually inspect the reconstituted SOMAVERT solution for particulate matter and discoloration prior to administration. The reconstituted solution should be clear. If the solution is cloudy, do not use it. Once reconstituted, the solution will contain 10, 15, 20, 25 or 30 mg of pegvisomant in 1 mL of solution.
2. Withdraw the 1 mL reconstituted SOMAVERT solution. The solution must be administered within 6 hours of reconstitution.
3. Inject the reconstituted SOMAVERT solution subcutaneously into the upper arm, upper thigh, abdomen, or buttocks using a 90-degree angle.a)

SIDE EFFECTS

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]
• Liver test elevations [see WARNINGS AND PRECAUTIONS]
• Cross-reactivity with GH assay [see WARNINGS AND PRECAUTIONS]
• Lipohypertrophy [see WARNINGS AND PRECAUTIONS]
• Systemic hypersensitivity [see WARNINGS AND PRECAUTIONS]

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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in clinical trials of a drug cannot be directly compared to rates in 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]. 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.