Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050, Bruxelles, Belgium
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Growth hormone-secreting pituitary tumours may sometimes expand, causing serious complications (for example, visual field defects). Treatment by pegvisomant does not reduce tumour size. All patients with these tumours should be carefully monitored in order to avoid any eventual progression in tumour size under treatment.
Pegvisomant is a potent antagonist of growth hormone action. A growth hormone deficient state may result from administration of this medicinal product, despite the presence of elevated serum growth hormone levels. Serum IGF-I concentrations should be monitored and maintained within the age-adjusted normal range by adjustment of the pegvisomant dose.
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)].
Evidence of obstructive biliary tract disease should be ruled out in patients with elevations of ALT and AST or in patients with a prior history of treatment with any somatostatin analogue. Administration of pegvisomant should be discontinued if signs of liver disease persist. For recommendations regarding initiation of SOMAVERT, based on baseline liver tests (LTs) and recommendations for monitoring of liver tests while on SOMAVERT, refer to Table A.
Table A. Recommendations for initiation of SOMAVERT treatment based on baseline LTs and for periodic monitoring of LTs during SOMAVERT treatment:
| Baseline LT Levels | Recommendations |
|---|---|
| Normal | May treat with SOMAVERT. |
| • Serum concentrations of ALT and AST should be monitored at 4- to 6-week intervals for the first 6 months of treatment with SOMAVERT, or at any time in patients exhibiting symptoms suggestive of hepatitis. | |
| Elevated, but less than or equal to 3 times ULN | May treat with SOMAVERT; however, monitor LTs monthly for at least 1 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. |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate transaminase; LT = liver test; ULN = upper limit of normal.
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 B).
Table B. Clinical recommendations based on abnormal liver test results while on SOMAVERT:
| LT Levels and Clinical Signs/Symptoms | Recommendations |
|---|---|
| Elevated, but less than or equal to 3 times ULN | May continue therapy with SOMAVERT. However, monitor LTs monthly to determine if further increases occur |
| Greater than 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 reinitiation 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. |
The study conducted with pegvisomant in diabetic patients treated either by insulin or by oral hypoglycaemic medicinal products revealed the risk of hypoglycaemia in this population. Therefore, in acromegalic patients with diabetes mellitus, doses of insulin or hypoglycaemic medicinal products may need to be decreased (see section 4.5).
The therapeutic benefits of a reduction in IGF-I concentration which results in improvement of the patient’s clinical condition could potentially increase fertility in female patients. Patients should be advised to use adequate contraception if necessary. Pegvisomant is not recommended during pregnancy (see section 4.6).
No interaction studies have been performed. It should be considered whether to continue treatment with somatostatin analogues. The use of this medicine in combination with other medicinal products for the treatment of acromegaly has not been extensively investigated.
Patients receiving insulin or oral hypoglycaemic medicinal products may require dose reduction of these active substances due to the effect of pegvisomant on insulin sensitivity (see section 4.4).
Pegvisomant has significant structural similarity to growth hormone which causes it to cross-react in commercially available growth hormone assays. Since serum concentrations of therapeutically-effective doses of this medicine are generally 100 to 1000 times higher than the actual serum growth hormone concentrations seen in acromegalics, measurements of serum growth hormone concentrations will be spuriously reported in commercially available growth hormone assays. Pegvisomant treatment should therefore not be monitored or adjusted based on serum growth hormone concentrations reported from these assays.
See section 4.4.
For pegvisomant no clinical data on exposed pregnancies are available. Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The potential risk for humans is unknown. SOMAVERT should not be used during pregnancy unless clearly necessary (see section 4.4).
The excretion of pegvisomant in breast milk has not been studied in animals. Clinical data are too limited (one reported case) to draw any conclusion on the excretion of pegvisomant in human breast milk. Therefore, pegvisomant should not be used in breast-feeding women. However, breast-feeding may be continued if this medicine is discontinued: this decision should take into account the benefit of pegvisomant therapy to the mother and the benefit of breast-feeding to the child.
For pegvisomant no data on fertility are available.
No studies on the effects on the ability to drive and use machines have been performed.
The list below contains adverse reactions seen in clinical trials with SOMAVERT.
In clinical studies, for patients treated with pegvisomant (n=550), the majority of adverse reactions to pegvisomant were of mild to moderate intensity, of limited duration and did not require discontinuation of treatment.
The most commonly reported adverse reactions occurring in 10% of patients with acromegaly treated with pegvisomant during the clinical trials were headache 25%, arthralgia 16% and diarrhoea 13%.
The list below contains adverse reactions seen in clinical trials or that were spontaneously reported, classified by system organ class and frequency.
Adverse reactions are listed according to the following categories: Very common: ≥1/10, Common: ≥1/100 to <1/10, Uncommon: ≥1/1,000 to <1/100, Not known (cannot be estimated from the available data).
Uncommon: thrombocytopenia, leukopenia, leukocytosis, haemorrhagic diathesis
Uncommon: hypersensitivity reactionsb
Not known: anaphylactic reactionb, anaphylactoid reactionb
Common: hypercholesterol aemia, hyperglycaemia, hypoglycaemia, weight increased
Uncommon: hypertriglyceridemia
Common: abnormal dreams
Uncommon: panic attack, short term memory loss, apathy, confusion, sleep disorder, libido increased
Not known: anger
Very common: headache
Common: somnolence, tremor, dizziness, hypoaesthesia
Uncommon: narcolepsy, migraine, dysgeusia
Common: eye pain
Uncommon: asthenopia
Uncommon: Meniere’s disease
Common: oedema peripheral
Common: hypertension
Common: dyspnoea
Not known: laryngospasmb
Very common: diarrhoea
Common: vomiting, constipation, nausea, abdominal distension, dyspepsia, flatulence
Uncommon: haemorrhoids, salivary hypersecretion, dry mouth, tooth disorder
Common: abnormal liver function tests (e.g. transaminase elevation) (see section 4.4)
Common: hyperhidrosis, contusion, pruritusb, rashb
Uncommon: face oedema, dry skin, increased tendency to bruise, night sweats, erythemab, urticariab
Not known: angioedemab
Very common: arthralgia
Common: myalgia, arthritis
Common: haematuria
Uncommon: proteinuria, polyuria, renal impairment
Common: injection site reaction (including injection site hypersensitivity), injection site bruising or bleeding, injection site hypertrophy (e.g. lipohypertro phy)a, influenza-like illness, fatigue, asthenia, pyrexia
Uncommon: feeling abnormal, impaired healing, hunger
a see Description of selected adverse reactions below
b ADR related to hypersensitivity reaction
Most injection site reactions characterised as localised erythemas and soreness, spontaneously resolved with local symptomatic treatment, while pegvisomant therapy continued. Occurrence of injection site hypertrophy has been observed, including lipohypertrophy.
The development of isolated low-titre anti-growth hormone antibodies was observed in 16.9% of patients treated with pegvisomant. The clinical significance of these antibodies is unknown.
Systemic hypersensitivity reactions including anaphylactic/anaphylactoid reactions, laryngospasm, angioedema, generalized skin reactions (rash, erythema, pruritus, urticaria).have been reported in post marketing use. Some patients required hospitalization. Upon re-administration, symptoms did not re-occur in all patients.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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