avert. 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. 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. table 1. recommendations of initiating somavert based on baseline lts and periodic monitoring of lts during somavert treatment baseline lt levels recommendations normal may treat with somavert. monitor lts at monthly intervals during the first 6 months of treatment, quarterly for the next 6 months and then bi-annually for the next year. 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 do not treat with somavert until a comprehensive workup establishes the cause of the patient's liver dysfunction. determine if cholelithiasis or choledocholithiasis is present, particularly in patients with a history of prior therapy with somatostatin analogs. based on the workup, consider initiation of therapy with somavert. if the decision is to treat, lts and clinical symptoms should be monitored very closely. 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) may continue therapy with somavert. however, monitor lts weekly to determine if further increases occur (see below). perform a comprehensive hepatic workup to discern if an alternative cause of liver dysfunction is present. 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) discontinue somavert immediately. perform a comprehensive hepatic workup, including serial lts, to determine if and when serum levels return to normal. if lts normalize (regardless of whether an alternative cause of the liver dysfunction is discovered), consider cautious re-initiation of therapy with somavert, with frequent lt monitoring. 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) immediately perform a comprehensive hepatic workup. if liver injury is confirmed, the drug should be discontinued. 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. 5.4 lipohypertrophy 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 patients with systemic hypersensitivity reactions, caution and close monitoring should be exercised when re-initiating somavert therapy [see adverse reactions (6.3) ] .

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 (12) ] . the recommended dosage range is between 10 mg to 30 mg given subcutaneously once daily and the maximum daily dosage is 30 mg given subcutaneously once daily. 2.2 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 (5.2) . 2.3 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 2 vials of lyophilized powder of somavert each containing 20 mg of pegvisomant with supplied diluent [two vials of lyophilized powder and two syringes containing 1 ml of diluent (sterile water for injection, usp) 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). (a) before administering the loading dose, remove 1 vial of lyophilized powder of somavert containing 20 mg of pegvisomant and one syringe containing 1 ml of diluent from the refrigerator, if refrigerated, about 10 minutes prior to the planned injection time. (b) reconstitute the first 20 mg vial of lyophilized powder of somavert containing 20 mg of pegvisomant with diluent. when using the diluent in the syringe, inject the contents of the syringe slowly onto the sides of the vial containing lyophilized powder of somavert. do not inject the diluent directly on the powder. (c) 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. (d) 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. (e) withdraw the 1 ml reconstituted somavert solution. the solution must be administered immediately after reconstitution. (f) 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. (g) repeat steps (a) to (e) to reconstitute the second somavert dose of 20mg. (h) 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). 2.4 maintenance dose injection procedure for patient or caregiver instructions for reconstitution and administration of daily doses (10 mg to 30 mg), see the patient's instructions for use . a) before administering the dose, remove 1 vial of lyophilized powder of somavert containing 10 mg, 15 mg, 20 mg, 25 mg or 30 mg of pegvisomant and one syringe containing 1 ml of diluent from the refrigerator, if refrigerated, about 10 minutes prior to the planned injection time. b) reconstitute the lyophilized powder of somavert with diluent. when using the diluent in the 2.25 ml syringe, inject the contents of the syringe slowly onto the sides of the vial containing lyophilized powder of somavert. do not inject the diluent directly on the powder. c) 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. d) 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 mg, 15 mg, 20 mg, 25 mg or 30 mg of pegvisomant in 1 ml of solution. e) withdraw the 1 ml reconstituted somavert solution. the solution must be administered immediately after reconstitution. f) inject the reconstituted somavert solution subcutaneously into the upper arm, upper thigh, abdomen, or buttocks using a 90-degree angle.

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. most common reported adverse reactions (>6%) are infection, pain, nausea, diarrhea, abnormal liver tests, flu syndrome, injection site reaction. ( 6 ) to report suspected adverse reactions, contact pfizer inc. at 1-800-438-1985 or fda at 1-800-fda-1088 or www.fda.gov/medwatch. 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 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. placebo n=32 somavert 10 mg/day n=26 15 mg/day n=26 20 mg/day n=28 infection 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). 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 immunogenicity 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. 6.3 postmarketing experience 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) ] . registry of patients with acromegaly treated with somavert acrostudy is an international observational registry that captures long term safety data in patients with acromegaly treated with somavert, as used in clinical practice. treatment dose and schedule were at the discretion of each treating physician. 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. in an interim report, there were 1288 patients enrolled (mean duration of treatment 3.7 years). at the start of somavert treatment 648 patients were on somavert monotherapy for acromegaly. of the 454 patients who had a normal ast and alt at baseline, 4 patients had elevated tests >3 times uln, two of whom had elevated tests >5 times uln. lipohypertrophy was reported in 6 (0.5%) patients. mris were compared to any previous ones, and a change in tumor volume was reported as significant locally only if the diameter increased by more than 3 mm for microadenomas or volume increased by more than 20% for macroadenomas. all mri changes considered significant at the local reading were reanalyzed centrally. of the 747 patients who had a mri reported at baseline and at least once during follow up in the study, 51 (7%) were reported to have an increase by local mri. of these, 16 patients (2%) had confirmation of this increase, 6 patients had a decrease, 12 had "no change"; there was 1 with insufficient data and 16 patients did not have a central mri reading.

ively. clinical considerations disease-associated maternal and/or embryofetal risk published data from case reports, case series, and a small interventional study in pregnant women with acromegaly have demonstrated that acromegaly may improve or stabilize without treatment during pregnancy, particularly if acromegaly is treated before pregnancy. in rare cases, acromegaly may worsen during pregnancy. since igf-1 levels may change physiologically during pregnancy and interpreting igf-1 and growth hormone levels in pregnant women with acromegaly may be unreliable, clinical monitoring is recommended. data animal data the effects of pegvisomant on early embryonic development and embryo-fetal development were evaluated in two separate studies, which 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 administration during organogenesis. at the 10-mg/kg/day dose (6 times the maximum human therapeutic dose based on body surface area), a reproducible, slight increase in post-implantation loss was observed in both studies. 8.2 lactation risk summary limited information from a case report in published literature reported that the level of pegvisomant in human milk was below the level of detection. there is no information available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for somavert and any potential adverse effects on the breastfed child from somavert or from the underlying maternal condition. 8.3 females and males of reproductive potential discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction in growth hormone (gh) levels and normalization of insulin-like growth factor 1 (igf-1) concentration in acromegalic females treated with pegvisomant may lead to improved fertility. 8.4 pediatric use the safety and effectiveness of somavert in pediatric patients have not been established. 8.5 geriatric use 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. 8.6 renal impairment somavert was not studied in patients with renal impairment and the safety and efficacy in these patients is not known.

tudy in pregnant women with acromegaly have demonstrated that acromegaly may improve or stabilize without treatment during pregnancy, particularly if acromegaly is treated before pregnancy. in rare cases, acromegaly may worsen during pregnancy. since igf-1 levels may change physiologically during pregnancy and interpreting igf-1 and growth hormone levels in pregnant women with acromegaly may be unreliable, clinical monitoring is recommended. data animal data the effects of pegvisomant on early embryonic development and embryo-fetal development were evaluated in two separate studies, which 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 administration during organogenesis. at the 10-mg/kg/day dose (6 times the maximum human therapeutic dose based on body surface area), a reproducible, slight increase in post-implantation loss was observed in both studies.

as 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 (c max , 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 auc inf and c max 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-i 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.

rength 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-i 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.

(n=32), 10 mg/day (n=26), 15 mg/day (n= 26), or 20 mg/day (n=28) of somavert subcutaneously igf-i. the primary efficacy endpoint was igf-i percent change in igf-i concentrations from baseline to week 12. the three groups that received somavert showed statistically significant (p<0.01) reductions in serum levels of igf-i compared with the placebo group (table 4). table 4. mean percent change from baseline in igf-i at week 12 for intent-to-treat population placebo n=31 somavert 10 mg/day n=26 15 mg/day n=26 20 mg/day n=28 mean baseline igf-i (ng/ml) (sd) 670 (288) 627 (251) 649 (293) 732 (205) mean percent change from baseline in igf-i (sd) -4.0 (17) -27 (28) -48 (26) -63 (21) somavert minus placebo (95% ci for treatment difference) -23 p<0.01; n=number of patients; sd = standard deviation (-35, -11) -44 (-56, -33) -59 (-68, -49) there were also reductions in serum levels of free igf-i, igfbp-3, and als compared with placebo at all post-baseline visits (figure 1). figure 1. effects of somavert on serum markers (mean ± standard error) after 12 weeks of treatment, the following percentages of patients had normalized igf-1 (figure 2): figure 2. percent of patients whose igf-i levels normalized at week 12 table 5 shows the effect of treatment with somavert on ring size (standard jeweler's sizes converted to a numeric score ranging from 1 to 63), and on signs and symptoms of acromegaly. each individual score for a sign or symptom of acromegaly (for soft-tissue swelling, arthralgia, headache, perspiration and fatigue) was based on a nine-point ordinal rating scale (0 = absent and 8 = severe and incapacitating), and the total score for signs or symptoms of acromegaly was derived from the sum of the individual scores. mean baseline scores were as follows: ring size = 47.1; total signs and symptoms = 15.2; soft tissue swelling = 2.5; arthralgia = 3.2; headache = 2.4; perspiration = 3.3; and fatigue = 3.7. table 5. mean change from baseline (sd) at week 12 for ring size and signs and symptoms of acromegaly placebo n=30 somavert 10 mg/day n=26 15 mg/day n=24–25 20 mg/day n=26–27 ring size -0.1 (2.3) -0.8 (1.6) -1.9 (2.0) -2.5 (3.3) total score for signs and symptoms of acromegaly 1.3 (6.0) -2.5 (4.3) -4.4 (5.9) -4.7 (4.7) soft-tissue swelling 0.3 (2.3) -0.7 (1.6) -1.2 (2.3) -1.3 (1.3) arthralgia 0.1 (1.8) -0.3 (1.8) -0.5 (2.5) -0.4 (2.1) headache 0.1 (1.7) -0.4 (1.6) -0.3 (1.4) -0.3 (2.0) perspiration 0.1 (1.7) -0.6 (1.6) -1.1 (1.3) -1.7 (1.6) fatigue 0.7 (1.5) -0.5 (1.4) -1.3 (1.7) -1.0 (1.6) serum growth hormone (gh) concentrations, as measured by research assays using antibodies that do not cross-react with pegvisomant, rose within two weeks of beginning treatment with somavert. the largest increase in gh concentration was seen in patients treated with doses of somavert 20 mg/day. this effect is presumably the result of diminished inhibition of gh secretion as igf-i levels fall. as shown in figure 3, when patients with acromegaly were given a loading dose of somavert followed by a fixed daily dose, the rise in gh was inversely proportional to the fall in igf-i and generally stabilized by week 2. serum gh concentrations remained stable in patients treated with somavert for the average of 43 weeks (range, 0–82 weeks). figure 3. percent change in serum gh and igf-i concentrations in the open-label extension to the clinical study, 109 subjects (including 6 new patients) with mean treatment exposure of 42.6 weeks (range 1 day – 82 weeks), 93 (85.3%) subjects had an adverse event, 16 (14.7%) had an sae, and 4 (3.7%) discontinued due to an ae (headaches, elevated liver function tests, pancreatic cancer, and weight gain). a total of 100 (92.6%) of the 108 subjects with available igf-i data had a normal igf-i concentration at any visit during the study. figure 1 figure 2 figure 3

to reconstitution: the one day package of somavert should be stored in a refrigerator at 2°c to 8°c (36°f to 46°f). for the 30-day package, remove the three intermediate cartons containing the somavert vials and store in a refrigerator at 2°c to 8°c (36°f to 46°f). for convenience, the one day package and intermediate cartons in the 30-day package containing the somavert vial(s), may be stored at room temperature up to 25°c (77°f) for a single period of up to 30 days. 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). once 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 vial(s) should be discarded. discard the somavert vial(s) after the expiration date printed on the carton or the discard date, whichever is sooner. the prefilled syringe(s) may be stored at a temperature up to 30°c (86°f) until the expiration date printed on the carton, at which point they should be discarded. do not freeze.

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. inform patients (and/or their caregivers) about the storage options prior to reconstitution of the product [see how supplied/storage and handling (16) ] . advise patients to follow the directions for reconstitution provided in the instructions for use. include that spraying the diluent directly onto the powder may cause foaming and that shaking may induce denaturation (destruction) of the active ingredient (therefore do not shake ). this product's labeling may have been updated. for the most recent prescribing information, please visit www.pfizer.com. u.s. license no. 1216 lab-0782-3.0 logo

ur 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 health care 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-i (igf-i) 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 leve l. 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: yellowing of your eyes (jaundice) dark, amber-colored urine feeling very tired (fatigue or exhaustion) nausea and vomiting pain in your stomach (abdomen) generalized swelling 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: swelling of your face, tongue, lips, or throat wheezing or trouble breathing skin rash, redness, or swelling sever itching 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: store somavert in a refrigerator at 36°f to 46°f (2°c to 8°c). for convenience, the one day package and intermediate cartons in the 30-day package containing the somavert vial(s), may be stored at room temperature up to 77°f (25°c) for a single period of up to 30 days. 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). once 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 vial(s) should be thrown away. throw away the somavert vial(s) after the expiration date printed on the carton or the discard date, whichever is sooner. the prefilled syringe(s) maybe stored at 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: keep the mixed somavert at room temperature between 59°f to 77°f (15°c to 25°c). keep somavert inside the vial or the syringe until you are ready to inject it. you must use the mixed somavert immediately after you mix it . 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-0783-3.0 for more information, go to www.somavert.com or call 1-800-645-1280. logo