• Pegvisomant (Somavert) inhibits the binding of growth hormone to its receptors resulting in the reduction of IGF-1 levels.
• It is used to treat patients with acromegaly (excessive growth hormone production usually due to a pituitary adenoma) who respond poorly to surgery or radiation therapy, or when surgery and radiation therapy are inappropriate. The endocrine society recommends the use of pegvisomant postoperatively in patients with a persistent significant disease without mass effects. In mild disease, alternative agents may be preferred.

Pegvisomant dose in Adults

Pegvisomant dose in the treatment of Acromegaly:

• An initial loading dose of 40 mg subQ

• Maintenance dose:

  • 10 mg once a day beginning the day after the initial loading dose.
• The dose may be adjusted at 4 - 6 weeks intervals (based on IGF-1 levels) by increments of 5 mg.
• The recommended dosing range is 10 - 30 mg/day.
• The maximum dose is 30 mg/day.

Note: If the patient is not responding to the maximum dose (clinical or biochemical response based on IGF-1 levels), combination therapy should be considered. Combination therapy may include pegvisomant plus a somatostatin analog or pegvisomant plus a dopamine agonist.

Pegvisomant use in children:

It has not been studied in children

Pregnancy Risk Factor C

• Pegvisomant should not be used during pregnancy. However, there are limited data.
• Alternative therapies should be considered if the patient requires treatment for acromegaly, such as in cases where there is evidence of tumor growth or headaches from mass effects.
• It is not advised to monitor IGF-1 levels during pregnancy.
• Effective contraception should be recommended to women with reproductive potential, as it may restore fertility.
• The Endocrine Society recommends that you stop taking octreotide at least two months before a planned pregnancy. You can also use short-acting octreotide.

Pegvisomant use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• It is recommended that you use it with caution if you are breastfeeding.

Dose in kidney disease:

The manufacturer has not recommended any dose adjustment in patients with kidney disease.

Dose in liver disease:

• At initiation of therapy:

  • Patients with normal liver function test (LFT):

    • Adjustment in the dose is not necessary.
    • Liver function tests should be monitored monthly for the first 6 months, quarterly for the next 6 months, and then every 6 monthly.

  • Patients with baseline LFT less than 3 times the ULN elevated:

    • Adjustment in the dose is not necessary.
    • Liver function tests should be monitored monthly for one year and then every 6 monthly.

  • Patients with baseline LFTs greater than 3 times the ULN:

    • Treatment should not be initiated.
    • Gallstones or a history of gallstones should be ruled out especially in patients with a prior history of octreotide analog therapy.
    • LFTs should be monitored closely in these patients.

• With ongoing therapy:

  • Patients with LFTs 3 - 5 the ULN but without clinical features of hepatitis, hepatic injury or raised bilirubin:

    • Treatment may be continued, however, LFTs should be monitored weekly.
    • Alternative causes of hepatic injury should be ruled out.

  • LFTs more than 5 times the ULN or transaminase more than 3 times the ULN associated with any increase in total bilirubin (with or without clinical features of hepatitis):

    • Treatment should be discontinued promptly.
    • Treatment may be reinitiated after the LFTs return to baseline, however, frequent monitoring is required.

  • Features of hepatic injury or hepatitis:

    • Treatment should be permanently discontinued and immediate hepatic workup and treatment should be initiated.

Common Side Effects of Pegvisomant Include:

• Central Nervous System:

  • Pain

• Gastrointestinal:

  • Diarrhea
  • Nausea

• Hepatic:

  • Abnormal Hepatic Function Tests

• Immunologic:

  • Antibody Development

• Infection:

  • Infection

• Local:

  • Injection Site Reaction

• Respiratory:

  • Flu-Like Symptoms

Pegvisomant side effects (less common):

• Cardiovascular:

  • Chest Pain
  • Hypertension
  • Peripheral Edema

• Central Nervous System:

  • Dizziness
  • Paresthesia

• Endocrine & Metabolic:

  • Lipohypertrophy

• Neuromuscular & Skeletal:

  • Back Pain

• Respiratory:

  • Sinusitis

• Miscellaneous:

  • Accidental Injury

Contraindication to Pegvisomant Include:

You may have severe allergic reactions to any ingredient of the formulation or the drug.

Warnings and precautions

• Hepatic effects
  • It can cause liver function tests to be elevated.
  • Despite the use of ALT, there have been cases of transient but marked elevations (up to 15x the normal upper limit) of ALT.
  • Patients with liver disease or pre-existing conditions should not use the therapy. Liver function should be closely monitored during treatment.
  • Patients with hepatic toxicities should stop taking the medication.
• Hypersensitivity
  • It has been associated with allergic reactions such as anaphylaxis and laryngeal swelling, angioedemas, rash, urticaria and pruritis.
  • It is possible to consider re-initiating treatment with caution.
• Lipohypertrophy
  • After repeated administration to a single site, lipohypertrophy can occur.
  • To reduce the risk of lipohypertrophy, rotate the injection site daily.
• Diabetes:
  • Diabetes patients should be closely monitored as this may lead to an increase in glucose tolerance.
  • It is possible that you will need to adjust your anti-diabetic medications.

Pegvisomant: Drug Interaction

Monitor:

• Assess the GH-secreting tumor size every 6 to 12 months after the initiation of therapy and then yearly (based on tumor size) with MRI.
• Monitor blood sugars in diabetic patients.
• Monitor serum IGF-1 levels 4 - 6 weeks after the start of therapy and after the dose is changed and every 6 months once normalized.
• Monitor liver injury or dysfunction.

Monitor:

• LFTs (Liver function tests) as:

  At the initiation of therapy:

  • Patients with normal liver function test (LFT):

    • Adjustment in the dose is not necessary.
    • Liver function tests should be monitored monthly for the first 6 months, quarterly for the next 6 months, and then every 6 monthly.

  • Patients with baseline LFT less than 3 times the ULN elevated:

    • Adjustment in the dose is not necessary.
    • Liver function tests should be monitored monthly for one year and then every 6 monthly.

  • Patients with baseline LFTs greater than 3 times the ULN:

    • Treatment should not be initiated.
    • Gallstones or a history of gallstones should be ruled out especially in patients with a prior history of octreotide analog therapy.
    • LFTs should be monitored closely in these patients.

• With ongoing therapy:

  • Patients with LFTs 3 - 5 the ULN but without clinical features of hepatitis, hepatic injury or raised bilirubin:

    • Treatment may be continued, however, LFTs should be monitored weekly.
    • Alternative causes of hepatic injury should be ruled out.

  • LFTs more than 5 times the ULN or transaminase more than 3 times the ULN associated with any increase in total bilirubin (with or without clinical features of hepatitis):

    • Treatment should be discontinued promptly.
    • Treatment may be reinitiated after the LFTs return to baseline, however, frequent monitoring is required.

  • Features of hepatic injury or hepatitis:

    • Treatment should be permanently discontinued and immediate hepatic workup and treatment should be initiated.

How to administer Pegvisomant?

• Its route of administration is subcutaneous only.
• The injection site should be rotated daily to avoid lipo-hypertrophy.
• Patients who require two injections, both should be injected at different sites.
• The injection may be administered in the upper arm, upper thigh, buttocks, or abdomen.
• Avoid rubbing the injection site. It should not be injected into a broken, infected, or bruised skin.
• Injection into a lump or a rash should also be avoided.
• The first injection should be administered under the supervision of a healthcare provider.

Pegvisomant mechanism of action:

• It acts as an antagonist of growth hormone receptors. 
• Pegvisomant binding inhibits growth hormone binding to its receptors, resulting in a decrease in insulin-like growth factor (IGF-1) release.
• This blocks excessive growth hormone production in the body, as seen in patients with growth hormone secreting pituitary tumors.

Nearly half(57%) of the drug is absorbedAfter subQ administration.

Distribution: 7 L

Half-life elimination: abiut 60 to 138 hours (~2.5 to 6 days)

Time to reach peak serum concentration: 33 - 77 hours

Excretion: Urine (<1%)

International Brands of Pegvisomant:

• Somavert

Pegvisomant Brands in Pakistan:

Pegvisomant is not available in Pakistan