5 WARNINGS AND PRECAUTIONS
5.1 Hypoglycemia Associated with GH Lowering in Patients with Diabetes Mellitus
GH opposes the effects of insulin on carbohydrate metabolism by decreasing insulin sensitivity; thus, glucose tolerance may improve in some patients treated with SOMAVERT. Patients should be carefully monitored and doses of anti-diabetic drugs reduced as necessary to avoid hypoglycemia in patients with diabetes mellitus.
5.2 Liver Toxicity
Asymptomatic, transient elevations in transaminases up to 15 times ULN have been observed in < 2% of subjects among two open-label trials (with a total of 147 patients). These reports were not associated with an increase in bilirubin. Transaminase elevations normalized with time, most often after suspending treatment. Postmarketing reports have identified elevations in serum hepatic transaminases up to greater than 20 times ULN associated with elevation in total bilirubin greater than 2 times ULN. In many of these cases, discontinuation of SOMAVERT therapy resulted in improvement or resolution of hepatic laboratory abnormalities.
SOMAVERT should be used in accordance with the information presented in Table 2 with respect to liver test abnormalities while on SOMAVERT treatment.
|Baseline LT Levels||Recommendations|
|Elevated, but less than or equal to 3 times ULN||May treat with SOMAVERT; however, monitor LTs monthly for at least one year after initiation of therapy and then bi-annually for the next year.|
|Greater than 3 times ULN||
If a patient develops LT elevations, or any other signs or symptoms of liver dysfunction while receiving SOMAVERT, the following patient management is recommended (Table 2).
|LT Levels and Clinical Signs/Symptoms||Recommendations|
|Greater than or equal to 3 but less than 5 times ULN (without signs/symptoms of hepatitis or other liver injury, or increase in serum TBIL)||
|At least 5 times ULN, or transaminase elevations at least 3 times ULN associated with any increase in serum TBIL (with or without signs/symptoms of hepatitis or other liver injury)||
|Signs or symptoms suggestive of hepatitis or other liver injury (e.g., jaundice, bilirubinuria, fatigue, nausea, vomiting, right upper quadrant pain, ascites, unexplained edema, easy bruisability)||
5.3 Cross-Reactivity with GH Assays
SOMAVERT has significant structural similarity to growth hormone (GH) which causes it to cross-react in commercially available GH assays. Since serum concentrations of therapeutically effective doses of SOMAVERT are generally 100 to 1000 times higher than the actual serum GH concentrations seen in patients with acromegaly, measurements of serum GH concentrations will appear falsely elevated.
There have been cases of lipohypertrophy in patients treated with SOMAVERT. In a double-blind, 12-week, placebo-controlled study, there was one case (1.3%) of injection site lipohypertrophy reported in a subject receiving 10 mg/day. The subject recovered while on treatment. Among two open-label trials (with a total of 147 patients), there were two subjects, both receiving 10 mg/day, who developed lipohypertrophy. One case recovered while on treatment, and one case resulted in a discontinuation of treatment. Injection sites should be rotated daily to help prevent lipohypertrophy (different area than the last injection).
5.5 Systemic Hypersensitivity
In subjects with systemic hypersensitivity reactions, caution and close monitoring should be exercised when re-initiating SOMAVERT therapy [see Adverse Reactions (6.3)].