Drugs List

Therapeutic Indications

Uses

Acromegaly: other treatments unsuitable/ineffective

Administration

For subcutaneous injection immediately after reconstitution.

Contraindications

Children under 18 years
Serum transaminases above 3 times upper limit of normal at baseline
Breastfeeding
Pregnancy

Precautions and Warnings

Diabetes mellitus
Hepatic impairment
Renal impairment
Serum transaminases above 3 times upper limit of normal

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Treatment to be initiated and supervised by a specialist
For single use only
Rotate injection sites within a given area to avoid lipodystrophy
Perform liver function tests before commencing therapy and during therapy
Monitor for signs of pituitary tumour expansion
Monitor levels of IGF-1
Monitor LFTs weekly, monthly or 4-6 weekly dependent on previous result
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
If evidence of tumour expansion appears, consider alternative procedures
Interrupt treatment if ALT or AST > 5 x ULN
Suspend treatment if transaminases > 3 X ULN and serum bilirubin elevated
Female: Ensure adequate contraception during treatment

Patients with elevated ALT or AST levels or a history of somatostatin analogue treatment should have obstructive biliary disease ruled out.

Recommendation for initiation of treatment based on baseline liver function tests (LFTs)
LFTs normal: Patient can be treated. ALT and AST should be monitored every 4 to 6 weeks for the first 6 months of treatment. Monitor LFTs if signs/symptoms suggestive of hepatitis occur.
LFTs elevated but less than or equal to 3 X ULN: Patient can be treated. Monitor LFTs every month for at least 1 year after initiation and then every 6 months for the next year.
LFTs greater than 3 X ULN: Patient cannot be treated until a comprehensive hepatic workup establishes the cause of liver dysfunction. If then the decision is to treat, the patient should be monitored very closely.

Recommendation based on abnormal LFTs during treatment
LFTs elevated but less than or equal to 3 X ULN: Patient can continue treatment. Monitor LFTs every month.
LFTs greater than or equal to 3 X ULN but less than 5 X ULN (without signs/symptoms of liver injury or increased TBIL): Patient can continue treatment. Monitor LFTs every week and perform a comprehensive hepatic workup.
LFTs greater than or equal to 5 x ULN or greater than 3 X ULN with increase in serum TBIL (with or without signs symptoms of liver injury): Discontinue treatment. Perform a comprehensive hepatic workup. If LFTs normalize, consider cautious reinitiation with frequent LFT monitoring.
Signs/symptoms of liver injury: Perform a comprehensive hepatic workup. If liver injury is confirmed, treatment must be discontinued.

Combination therapy involving pegvisomant and other medicinal products for acromegaly treatment has not been adequately studied.

16.9% of patients treated with pegvisomant developed low-titre anti-growth hormone antibodies but the clinical significance of this is unknown.

Pregnancy and Lactation

Pregnancy

Pegvisomant is contraindicated in pregnancy.

At the time of writing there is very limited data concerning exposed pregnancies and their outcomes and no adequate well-controlled studies have been performed. Animal studies are also very limited and there is insufficient information is available to determine the potential effects on pregnancy, embryonal/foetal development, parturition or postnatal development. Therefore the use of pegvisomant is not recommended during pregnancy. If pegvisomant is used during pregnancy, pegvisomant dose adjustments may be required and IGF-I levels should be monitored closely especially during the first trimester.

Schaefer concludes that inadvertent use during pregnancy is not grounds for either termination or invasive diagnostic procedures (Schaefer 2007).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pegvisomant is contraindicated in breastfeeding.

The excretion of pegvisomant into breast milk has not been studied in animals. Clinical data are too limited to draw any conclusion on the excretion of pegvisomant into human breast milk. Pegvisomant should therefore not be used in a breastfeeding woman unless the benefits outweigh the risks.

Schaefer, LactMed (via ToxNet) and the UK Drugs in Lactation Advisory Service all conclude based on limited clinical data that pegvisomant is poorly excreted into breast milk and is unlikely to adversely affect the breastfed infant since it is not orally absorbed (Schaefer 2007).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Altered liver function tests
Anger
Apathy
Arthralgia
Arthritis
Asthenia
Asthenopia
Bruising
Bruising at injection site
Confusion
Constipation
Contusion
Diarrhoea
Dizziness
Dream abnormalities
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Dyspnoea
Eye pain
Facial oedema
Fatigue
Feeling abnormal
Flatulence
Haematuria
Haemorrhoids
Headache
Hunger
Hypercholesterolaemia
Hyperglycaemia
Hypersalivation
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypertrophy (injection site)
Hypoesthesia
Hypoglycaemia
Impaired healing
Increased bleeding tendency
Increased libido
Influenza-like syndrome
Injection site reactions
Leukocytosis
Leukopenia
Meniere's disease
Migraine
Minor bleeding (injection site)
Myalgia
Narcolepsy
Nausea
Night sweats
Panic attack
Peripheral oedema
Polyuria
Proteinuria
Pruritus
Pyrexia
Rash
Renal impairment
Short term memory loss
Sleep disturbances
Somnolence
Sweating
Thrombocytopenia
Tooth disorder
Tremor
Vomiting
Weight gain

Presentation

Powder for solution for injection containing pegvisomant.

These products have been produced by recombinant technology using E.coli.

Drugs List

Therapeutic Indications

Uses

Acromegaly: other treatments unsuitable/ineffective

Dosage

Adults

Administration

For subcutaneous injection immediately after reconstitution.

Contraindications

Children under 18 years
Serum transaminases above 3 times upper limit of normal at baseline
Breastfeeding
Pregnancy

Precautions and Warnings

Diabetes mellitus
Hepatic impairment
Renal impairment
Serum transaminases above 3 times upper limit of normal

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Treatment to be initiated and supervised by a specialist
For single use only
Rotate injection sites within a given area to avoid lipodystrophy
Perform liver function tests before commencing therapy and during therapy
Monitor for signs of pituitary tumour expansion
Monitor levels of IGF-1
Monitor LFTs weekly, monthly or 4-6 weekly dependent on previous result
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
If evidence of tumour expansion appears, consider alternative procedures
Interrupt treatment if ALT or AST > 5 x ULN
Suspend treatment if transaminases > 3 X ULN and serum bilirubin elevated
Female: Ensure adequate contraception during treatment

Patients with elevated ALT or AST levels or a history of somatostatin analogue treatment should have obstructive biliary disease ruled out.

Recommendation for initiation of treatment based on baseline liver function tests (LFTs)
LFTs normal: Patient can be treated. ALT and AST should be monitored every 4 to 6 weeks for the first 6 months of treatment. Monitor LFTs if signs/symptoms suggestive of hepatitis occur.
LFTs elevated but less than or equal to 3 X ULN: Patient can be treated. Monitor LFTs every month for at least 1 year after initiation and then every 6 months for the next year.
LFTs greater than 3 X ULN: Patient cannot be treated until a comprehensive hepatic workup establishes the cause of liver dysfunction. If then the decision is to treat, the patient should be monitored very closely.

Recommendation based on abnormal LFTs during treatment
LFTs elevated but less than or equal to 3 X ULN: Patient can continue treatment. Monitor LFTs every month.
LFTs greater than or equal to 3 X ULN but less than 5 X ULN (without signs/symptoms of liver injury or increased TBIL): Patient can continue treatment. Monitor LFTs every week and perform a comprehensive hepatic workup.
LFTs greater than or equal to 5 x ULN or greater than 3 X ULN with increase in serum TBIL (with or without signs symptoms of liver injury): Discontinue treatment. Perform a comprehensive hepatic workup. If LFTs normalize, consider cautious reinitiation with frequent LFT monitoring.
Signs/symptoms of liver injury: Perform a comprehensive hepatic workup. If liver injury is confirmed, treatment must be discontinued.

Combination therapy involving pegvisomant and other medicinal products for acromegaly treatment has not been adequately studied.

16.9% of patients treated with pegvisomant developed low-titre anti-growth hormone antibodies but the clinical significance of this is unknown.

Pregnancy and Lactation

Pregnancy

Pegvisomant is contraindicated in pregnancy.

At the time of writing there is very limited data concerning exposed pregnancies and their outcomes and no adequate well-controlled studies have been performed. Animal studies are also very limited and there is insufficient information is available to determine the potential effects on pregnancy, embryonal/foetal development, parturition or postnatal development. Therefore the use of pegvisomant is not recommended during pregnancy. If pegvisomant is used during pregnancy, pegvisomant dose adjustments may be required and IGF-I levels should be monitored closely especially during the first trimester.

Schaefer concludes that inadvertent use during pregnancy is not grounds for either termination or invasive diagnostic procedures (Schaefer 2007).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pegvisomant is contraindicated in breastfeeding.

The excretion of pegvisomant into breast milk has not been studied in animals. Clinical data are too limited to draw any conclusion on the excretion of pegvisomant into human breast milk. Pegvisomant should therefore not be used in a breastfeeding woman unless the benefits outweigh the risks.

Schaefer, LactMed (via ToxNet) and the UK Drugs in Lactation Advisory Service all conclude based on limited clinical data that pegvisomant is poorly excreted into breast milk and is unlikely to adversely affect the breastfed infant since it is not orally absorbed (Schaefer 2007).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Altered liver function tests
Anger
Apathy
Arthralgia
Arthritis
Asthenia
Asthenopia
Bruising
Bruising at injection site
Confusion
Constipation
Contusion
Diarrhoea
Dizziness
Dream abnormalities
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Dyspnoea
Eye pain
Facial oedema
Fatigue
Feeling abnormal
Flatulence
Haematuria
Haemorrhoids
Headache
Hunger
Hypercholesterolaemia
Hyperglycaemia
Hypersalivation
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypertrophy (injection site)
Hypoesthesia
Hypoglycaemia
Impaired healing
Increased bleeding tendency
Increased libido
Influenza-like syndrome
Injection site reactions
Leukocytosis
Leukopenia
Meniere's disease
Migraine
Minor bleeding (injection site)
Myalgia
Narcolepsy
Nausea
Night sweats
Panic attack
Peripheral oedema
Polyuria
Proteinuria
Pruritus
Pyrexia
Rash
Renal impairment
Short term memory loss
Sleep disturbances
Somnolence
Sweating
Thrombocytopenia
Tooth disorder
Tremor
Vomiting
Weight gain

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Joint Formulary Committee. British National Formulary. 70th ed. London: BMJ Group and Pharmaceutical Press; 2015.

Summary of Product Characteristics: Somavert 10 mg, 15 mg, 20 mg, 25 mg & 30 mg powder and solvent for solution for injection. Pfizer Ltd. Revised January 2021.

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Last accessed: 15 March 2016

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Pegvisomant. Last revised: 07 September 2013
Last accessed: 16 March 2016