" Citing a lack of cardiovascular benefit, the FDA is taking the unusual step of withdrawing approvals it had previously given for use of niacin and fenofibric acid with statins to treat high cholesterol.
The decision affects niac"...
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.
Liver Test Elevations
Baseline serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total bilirubin (TBIL), and alkaline phosphatase (ALP) levels should be obtained prior to initiating therapy with SOMAVERT. Table 1 lists recommendations regarding initiation of treatment with SOMAVERT, based on the results of these liver tests (LTs).
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 (SOMAVERT should be used in accordance with the information presented in Table 2 with respect to liver test abnormalities while on Somavert treatment).
Table 1: Recommendations of Initiating SOMAVERT Based
on Baseline LTs and Periodic Monitoring of LTs During SOMAVERT Treatment
|Baseline LT Levels||Recommendations|
|Elevated, but less than or equal to 3 times ULN||May treat with SOMAVERT; however, monitor LT s 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).
Table 2: Clinical Recommendations Based on Liver Test
Results While on SOMAVERT
|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)||
Cross -Reactivity With GH Assays
SOMAVERT has significant structural similarity to growth hormone (GH) which causes it to crossreact 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).
In subjects with systemic hypersensitivity reactions, caution and close monitoring should be exercised when re-initiating Somavert therapy [see ADVERSE REACTIONS].
Patient Counseling Information
See FDA- approved patient labeling (Patient Information and Instructions for Use).
Inform patients (and/or their caregivers) of the following information to aid in the safe and effective use of SOMAVERT:
- Not to use SOMAVERT if they are allergic to SOMAVERT or anything in it.
- They will need blood testing to check IGF-I levels and liver tests before and during treatment with SOMAVERT and that the dose of SOMAVERT may be changed based on the results of these tests
- SOMAVERT has not been studied in pregnant women and instruct them to notify their healthcare provider as soon as they are aware that they are pregnant.
- It is not known whether SOMAVERT is excreted in human milk and instruct them to notify their healthcare provider if they plan to do so.
Advise patients (and/or their caregivers) of the following adverse reactions:
- The most common reported adverse reactions are injection site reaction, elevations of liver tests, pain, nausea, and diarrhea.
- If they have liver test elevations they may need to have more frequent liver tests and/or discontinue SOMAVERT. Instruct patients to immediately discontinue therapy and contact their physician if they become jaundiced.
- GH-secreting tumors may enlarge in people with acromegaly and that these tumors need to be watched carefully and monitored by MRI imaging.
- Thickening under the skin may occur at the injection site that could lead to lumps and that switching sites may prevent or lessen this.
- If they have diabetes mellitus, they may require careful monitoring and dose reductions of insulin and/or oral hypoglycemic agents while on SOMAVERT.
- If they take opioids, they may need higher SOMAVERT doses to achieve appropriate IGF-I suppression.
Advise patients that SOMAVERT is supplied as lyophilized powder in different strengths of 10 mg, 15 mg, 20 mg, 25 mg, and 30 mg in a sterile glass vial within a package also containing a single-dose flip top vial of sterile water (diluent) for injection. Advise patients that the stoppers on both vials are not made with natural rubber latex. Advise patients to follow the directions for reconstitution provided with each package including shaking may cause denaturation (destruction) of the active ingredient (therefore do not shake).
Advise patients that the package of SOMAVERT should be stored in a refrigerator 2 to 8°C (36 to 46°F) prior to use. It should NOT BE FROZEN.
Carcinogenesis Mutagenesis and Impairment of Fertility
Pegvisomant was administered subcutaneously to rats daily for 2 years at doses of 2, 8 and 20 mg/kg (about 2, 10 and 25-fold a single 20 mg dose in humans on an AUC basis). Long term treatment with pegvisomant at 8 and 20 mg/kg caused an increase in malignant fibrous histiocytoma at injection sites in males. Injection site tumors were not seen in female rats at the same doses. The increased incidence of injection site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections.
Pegvisomant did not cause genetic damage in standard in vitro assays (bacterial mutation, human lymphocyte chromosome aberration).
Impairment of Fertility
Pegvisomant was found to have no effect on fertility or reproductive performance of female rabbits at subcutaneous doses up to 10 mg/kg/day (10-fold the recommended human dose on a body surface area basis)
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Early embryonic development and teratology studies were conducted in pregnant rabbits with pegvisomant at subcutaneous doses of 1, 3, and 10 mg/kg/day. There was no evidence of teratogenic effects associated with pegvisomant treatment during organogenesis. At the 10-mg/kg/day dose (10 times the maximum human therapeutic dose based on body surface area), a reproducible, slight increase in post-implantation loss was observed in both studies. Because animal reproduction studies are not always predictive of human responses, SOMAVERT should be used during pregnancy only if clearly needed.
It is not known whether pegvisomant is excreted in human milk. Because many drugs are excreted in milk, caution should be exercised when SOMAVERT is administered to a nursing woman.
The safety and effectiveness of SOMAVERT in pediatric patients have not been established.
Clinical studies of SOMAVERT did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
SOMAVERT was not studied in patients with renal impairment and the safety and efficacy in these patients is not known.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/7/2016
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