Semaglutide

Registered South African indications:

• Insufficiently controlled type 2 diabetes mellitus (as an adjunct to diet and exercise)
• Risk reduction of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non fatal stroke) in patients with type 2 diabetes mellitus and established cardiovascular disease

Risk of thyroid C-cell tumours

• In rodents, semaglutide triggers dose-dependent and treatment-duration-dependent thyroid C-cell tumours at clinically relevant exposures
• It is unknown whether semaglutide causes thyroid C-cell tumours, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumours has not been determined
• Semaglutide is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2)
• Patients should be counselled regarding the potential risk for MTC with the use of semaglutide and informed of symptoms of thyroid tumours (e.g., a mass in the neck, dysphagia, dyspnoea, persistent hoarseness)
• The value of routine monitoring of serum calcitonin or using thyroid ultrasound for early detection of MTC in patients treated with semaglutide is uncertain

Contraindications

Registered South African contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• Personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Pregnancy
  - Women who may become pregnant should use effective contraception while taking semaglutide
• Breastfeeding

 Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or to any of its excipients

Cautions

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment
• Severe hepatic impairment
• Elderly (≥75 years)
• Type 1 diabetes mellitus
• Diabetic ketoacidosis
• Misuse: Use as a substitute for insulin
• Congestive heart failure NYHA class IV
• History of pancreatitis
• Diabetic retinopathy
• Coadministration with oral medicinal products that require rapid gastrointestinal absorption
• Coadministration with a sulfonylurea or insulin

Forms avail. In SA and covered in this monograph: pfp

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Insufficiently controlled type 2 diabetes mellitus (as an adjunct to diet and exercise)
- As monotherapy when metformin is considered inappropriate due to intolerance or contraindications
- As combination therapy with oral antidiabetic medicines (metformin, thiazolidinediones, sulphonylurea), basal insulin with or without metformin and pre-mix insulin
Risk reduction of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in patients with type 2 diabetes mellitus and established cardiovascular disease

• SC: Initial: 0.25mg, weekly; After 4 weeks: Titrate to 0.5mg, weekly and maintain for at least 4 weeks; If necessary to further improve glycaemic control: Titrate to 1mg, weekly

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A semaglutide dose of 0.25mg is not a therapeutic dose

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Semaglutide can be used as monotherapy or as combination therapy with one or more antidiabetic medicines

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When semaglutide is added to existing metformin and/or thiazolidinedione therapy, the current dose of metformin and/or thiazolidinedione can be continued unchanged. When semaglutide is added to existing sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy, the current dose of SGLT2 inhibitor can be continued unchanged

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When semaglutide is added to existing therapy of a sulfonylurea or insulin, a reduction in the dose of sulfonylurea or insulin should be considered to reduce the risk of hypoglycaemia

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The use of semaglutide does not require blood glucose self-monitoring. Self-monitoring should be performed when semaglutide is used together with metformin, sulfonylurea or insulin in order to allow adjustment of the dose of these medicines

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Missed dose: If a dose is missed, it should be administered as soon as possible and within 5 days after the missed dose. If more than 5 days have passed, the missed dose should be skipped, and the next dose should be administered on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule

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Semaglutide is to be administered once weekly at any time of the day, with or without meals. See additional prescribing points for administration instructions

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Contraindicated
• Studies in animals have shown reproductive toxicity
• Semaglutide should not be used during pregnancy
• The safety of semaglutide in pregnant women has not been established
• Semaglutide should be discontinued at least 2 months before a planned pregnancy due to the long half-life
• Women who may become pregnant should use effective contraception while taking semaglutide and for 2 months after stopping the medicine

Recommendations in other jurisdictions

• Caution; positive evidence of risk in animal studies
• Studies in animals have shown reproductive toxicity
• There are limited data from the use of semaglutide in pregnant women. Therefore, semaglutide should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, semaglutide should be discontinued
• Semaglutide should be discontinued at least 2 months before a planned pregnancy due to the long half-life
• Women of childbearing potential are recommended to use contraception when treated with semaglutide

Breastfeeding

South African recommendations

• Contraindicated
• It is unknown whether semaglutide is excreted in human milk
• In lactating rats, semaglutide was excreted in milk
• Women on treatment with semaglutide should not breastfeed their infants

Recommendations in other jurisdictions

• Caution; not recommended
• In lactating rats, semaglutide was excreted in milk. As a risk to a breastfed child cannot be excluded, semaglutide should not be used during breastfeeding

Fertility

South African recommendations

• No information available

Recommendations in other jurisdictions

• The effect of semaglutide on fertility in humans is unknown. Semaglutide did not affect male fertility in rats. In female rats, an increase in oestrous length and a small reduction in number of ovulations were observed at doses associated with maternal body weight loss

Renal Impairment

• Caution; no dose adjustment recommended
  Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions. This should be considered when treating patients, with impaired renal function as nausea, vomiting, and diarrhoea may cause dehydration which could cause a deterioration of renal function
  Experience with the use of semaglutide in patients with severe renal impairment is limited 
• End-stage renal disease: Not recommended for use

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended
  Experience with the use of semaglutide in patients with severe hepatic impairment is limited 

Elderly

• No dose adjustment recommended
• ≥75 years: Caution; no dose adjustment recommended
  Therapeutic experience in patients ≥75 years of age is limited

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Dysgeusia
• Fatigue

Cardiovascular Disorders

• Increased heart rate

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Abdominal distension
• Constipation
• Dyspepsia
• Gastritis
• Gastro-oesophageal reflux disease
• Eructation
• Flatulence
• Acute pancreatitis

Hepatobiliary Disorders

• Cholelithiasis

Endocrine and Metabolic Disorders

• Hypoglycaemia (when used with insulin, sulfonylurea or when used with other oral anti-diabetic drugs)
• Increased lipase
• Increased amylase
• Weight decreased
• Decreased appetite

Skin and Subcutaneous Tissue Disorders

• Angioedema
• Injection site reactions
  - Injection site rash
  - Erythema

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
  - Rash
  - Urticaria
• Anaphylactic reaction
• Antibody development

Sensory Disorders

• Diabetic retinopathy complications
  - Retinal photocoagulation
  - Vitreous haemorrhage
  - Diabetes-related blindness

No significant interactions

• Plasma glucose
• HbA1c 
• Renal function
• Triglycerides

Additional observations

• Signs and symptoms of:
  - Pancreatitis
  - Gallbladder disease

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Method of administration

• Semaglutide is to be injected subcutaneously (SC) in the abdomen, in the thigh or in the upper arm. The injection site can be changed without dose adjustment
• Semaglutide should not be administered intravenously (IV) or intramuscularly (IM)
• The day of weekly administration can be changed if necessary as long as the time between two doses is at least 2 days (>48 hours) 

Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions in glucose and appetite regulation, and in the cardiovascular system. The glucose and appetite effects are specifically mediated via GLP-1 receptors in the pancreas and the brain. Thus, semaglutide reduces blood glucose in a glucose dependent manner by stimulating insulin secretion and lowering glucagon secretion when blood glucose is high. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase. During hypoglycaemia, semaglutide diminishes insulin secretion and does not impair glucagon secretion.

Semaglutide reduces body weight and body fat mass through lowered energy intake, involving an overall reduced appetite. In addition, semaglutide reduces the preference for high fat foods. Semaglutide had a beneficial effect on plasma lipids, lowered systolic blood pressure and reduced inflammation in clinical studies. In animal studies, semaglutide attenuates the development of atherosclerosis by preventing aortic plaque progression and reducing inflammation in the plaque.

Disposable pen 2mg/1.5ml (0,25mg & 0.5mg/dose pre-filled pen)

• Ozempic (Novo Nordisk) originator

Disposable pen 4mg/3ml (1mg/dose pre-filled pen)

• Ozempic (Novo Nordisk) originator