Pegvisomant

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Subcutaneous [preservative free]:

Somavert: 10 mg (1 ea); 15 mg (1 ea); 20 mg (1 ea); 25 mg (1 ea); 30 mg (1 ea)

Pharmacology

Mechanism of Action

An analogue of human growth hormone, pegvisomant selectively binds to growth hormone (GH) receptors, blocking the binding of endogenous GH, leading to decreased serum concentrations of insulin-like growth factor-1 (IGF-I) and other GH-responsive proteins.

Pharmacokinetics/Pharmacodynamics

Absorption

SubQ: 57%

Distribution

7 L

Excretion

Urine (<1%)

Time to Peak

Serum: 33 to 77 hours

Half-Life Elimination

~60 to 138 hours (~2.5 to 6 days)

Use: Labeled Indications

Acromegaly: 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 Endocrine Society suggests use of pegvisomant as an initial option for adjuvant therapy in patients with persistent, significant disease (ie, moderate to severe signs/symptoms of growth hormone excess and without local mass effects) postoperatively. Alternative agents are suggested for patients with mild disease postoperatively (Endocrine Society [Katznelson 2014]).

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to pegvisomant and any component of the formulation.

Dosage and Administration

Dosing: Adult

Acromegaly: SubQ: Initial loading dose: 40 mg; maintenance dose: 10 mg once daily beginning the day after the initial loading dose; doses may be adjusted by 5 mg increments or decrements in 4- to 6-week intervals based on IGF-I concentrations (recommended dosing range: 10 to 30 mg/day; maximum dose: 30 mg/day). Note: If clinical and/or biochemical response is inadequate at maximum dosage consider combination therapy with a somatostatin analog or a dopamine agonist (Endocrine Society [Katznelson 2014]).

Dosing: Geriatric

Refer to adult dosing; use with caution.

Reconstitution

Remove vial and diluent from refrigerator approximately 10 minutes prior to administration. Reconstitute each vial with 1 mL diluent. Aim diluent along glass wall of vial, do not inject diluent directly on powder. Gently swirl solution in order to dissolve powder; do not invert the vial or shake the solution. After reconstitution, each vial will contain 10, 15, 20, 25, or 30 mg/mL of pegvisomant. Use only 1 dose per vial.

Administration

SubQ: For SubQ administration only; to minimize the risk for lipohypertrophy, rotate injection site daily; if 2 injections are required, select a different injection site for second injection; may administer in upper arm, upper thigh, abdomen, or buttocks; do not rub injection site. Do not use on area of skin with rash, lumps, bruising or on broken skin. The manufacturer recommends the initial dose be administered under the supervision of prescribing healthcare provider.

Storage

Store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F); protect from freezing. Following reconstitution, use within 6 hours. Do not use reconstituted solution if cloudy or foaming.

Drug Interactions

Blood Glucose Lowering Agents: Pegvisomant may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Macimorelin: Growth Hormone Products may diminish the diagnostic effect of Macimorelin. Avoid combination

Opioid Agonists: May diminish the therapeutic effect of Pegvisomant. Monitor therapy

Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Monitor therapy

Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Monitor therapy

Somatostatin Analogs: May enhance the adverse/toxic effect of Pegvisomant. Specifically, this combination may increase the risk for significant elevations of liver enzymes. Monitor therapy

Test Interactions

Interferes with measurement of serum GH concentrations by available GH assays; commercially available GH assays will overestimate true GH levels

Adverse Reactions

>10%:

Central nervous system: Pain (8% to 14%)

Gastrointestinal: Diarrhea (≤14%), nausea (≤14%)

Hepatic: Abnormal hepatic function tests (4% to 12%; >10 x ULN: ≤1%; ≤15 times ULN: <2%)

Immunologic: Antibody development (17%; non-neutralizing anti-GH antibodies; relevance unknown)

Infection: Infection (≤23%)

Local: Injection site reaction (4% to 11%)

Respiratory: Flu-like symptoms (4% to 12%)

1% to 10%:

Cardiovascular: Chest pain (≤8%), hypertension (≤8%), peripheral edema (≤8%)

Central nervous system: Dizziness (≤8%), paresthesia (≤7%)

Endocrine & metabolic: Lipohypertrophy (1%)

Neuromuscular & skeletal: Back pain (≤8%)

Respiratory: Sinusitis (≤8%)

Miscellaneous: Accidental injury (≤8%)

<1%, postmarketing, and/or case reports: Anaphylactoid reaction, anaphylaxis, angioedema, erythema, hypersensitivity reaction, increased serum alkaline phosphatase, laryngospasm, pruritus, skin rash, tumor growth, urticaria, weight gain

Warnings/Precautions

Concerns related to adverse effects:

• Hepatic effects: May increase liver function tests; transient but marked elevations (≤15 × ULN) in transaminase levels, usually without accompanying hyperbilirubinemia, have been reported with use; transaminase levels often normalized following interruption of therapy. Additionally, elevated transaminase (>20 × ULN) and total bilirubin (>2 × ULN) have been reported in postmarketing studies; discontinuation of therapy resulted in improvement or resolution in most cases. Use with caution in patients with hepatic impairment; monitor hepatic function periodically during therapy; discontinue use immediately with confirmed liver injury.
• Hypersensitivity: Systemic hypersensitivity reactions (eg, anaphylactic reactions, angioedema, laryngospasm, rash, erythema, pruritus, urticaria) have been reported; re-challenge with pegvisomant has been successful in some patients. Monitor closely for signs/symptoms of hypersensitivity if attempting re-initiation of therapy.
• Lipohypertrophy: May occur following administration; daily rotation of injection site may prevent or reduce incidence.

Disease-related concerns:

• Diabetes: May improve glucose tolerance in some patients. Monitor closely to prevent hypoglycemia; dosage adjustments of antidiabetic therapy may be necessary.

Other warnings/precautions:

• Administration: The manufacturer recommends the initial dose be administered under the supervision of prescribing health care provider.
• Monitoring: Interferes with commercially available GH assays; do not make dose adjustments based on serum GH concentrations reported from assays; use insulin-like growth factor I (IGF-I) levels to adjust therapy.

Monitoring Parameters

Magnetic resonance imaging (MRI) to assess GH-secreting tumor size 6 and 12 months after initiation of therapy then yearly based on tumor size (Endocrine Society [Katznelson 2014]), serum glucose in diabetic patients, serum IGF-I (every 4 to 6 weeks after initial dose and dosage change, every 6 months when normalized, and when multiple injections are converted to single daily injections); signs/symptoms of hepatic dysfunction

Liver function tests (ALT, AST, total bilirubin, and alkaline phosphatase levels):

Baseline:

Normal: Monthly for first 6 months, quarterly for next 6 months, biannually for the next year

Elevated, but ≤3 x ULN: Monitor monthly for at least 1 year, then biannually for the next year

>3 x ULN: Withhold treatment; perform comprehensive liver function evaluation (rule out cholelithiasis or choledocholithiasis); if appropriate for treatment, closely monitor hepatic function and clinical status.

During therapy:

≥3 x but <5 x ULN without signs/symptoms of hepatitis, hepatic injury or increase in total bilirubin: Monitor weekly for further increases; perform comprehensive hepatic work-up to rule out alternative cause of dysfunction

≥5 x ULN or transaminase ≥3 x ULN associated with any increase in total bilirubin (with or without signs/symptoms of hepatitis or other liver injury): Discontinue treatment immediately; perform comprehensive hepatic work-up. If hepatic function normalizes (regardless of source of dysfunction) may consider resuming therapy with frequent monitoring of hepatic function

Pregnancy

Pregnancy Considerations

Pregnancy outcome data concerning use of pegvisomant in pregnancy is limited (Brian 2007; Cheng 2012; Qureshi 2006; van der Lely 2015).

Use of pegvisomant during pregnancy is not recommended. If treatment for acromegaly is required during pregnancy for worsening symptoms (eg, headaches or evidence of tumor growth), alternative agents are recommended. Monitoring of insulin-like growth factor 1 (IGF-1) and/or growth hormone (GH) is not recommended during pregnancy, as an active placental GH variant present in maternal blood limits the usefulness of the results (Endocrine Society [Katznelson 2014]).

Because normalization of IGF-1 and GH may restore fertility in women with acromegaly, women of childbearing potential should use adequate contraception during treatment. The Endocrine Society suggests discontinuing pegvisomant approximately 2 months before attempts to conceive; short-acting octreotide may be used until conception if needed (Endocrine Society [Katznelson 2014]).

Patient Education

What is this drug used for?

• It is used to treat acromegaly.

Frequently reported side effects of this drug

• Diarrhea
• Common cold symptoms
• Injection site irritation
• Flu-like symptoms
• Back pain
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes
• Dizziness
• Passing out
• Vision changes
• Chest pain
• Severe headache
• Bruising
• Bleeding
• Swelling of arms or legs
• Skin changes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.