Saxenda: composition and pharmaceutical form
Saxenda is a solution for subcutaneous injection in a pre-filled pen. One millilitre of solution contains 6 mg of liraglutide, and one pen contains 18 mg of liraglutide in 3 ml. Liraglutide is an analogue of human glucagon-like peptide-1 (GLP-1) obtained by DNA recombination in Saccharomyces cerevisiae cells.
The medicine is given only subcutaneously — intravenous and intramuscular administration is not permissible. One dose contains less than 1 mmol of sodium (23 mg), so the medicine is regarded as essentially sodium-free.
How Saxenda works
Liraglutide is an acylated analogue of human GLP-1 whose amino acid sequence is 97% identical to that of the endogenous hormone. It binds to the GLP-1 receptor and activates it. Under physiological conditions GLP-1 controls the appetite and the amount of food eaten, although its mechanism of action is not fully understood.
In animal studies liraglutide given peripherally was detected in specific areas of the brain responsible for appetite control: there the activation of the GLP-1 receptors strengthened the main satiety signals and weakened the main hunger signals, which led to a reduction in body weight. GLP-1 receptors are also present in the heart, the vessels, the immune system and the kidneys. In experiments on mice with atherosclerosis liraglutide prevented the development of plaque and reduced the inflammation within it, and it also had a favourable influence on plasma lipids, but it did not reduce the size of an already formed plaque in stable atherosclerosis.
Indications
In adults the medicine is prescribed together with a low-calorie diet and increased physical activity for weight management with an initial body mass index of 30 kg/m² or above — that is, in obesity — or from 27 to 30 kg/m² in overweight combined with at least one weight-related illness: a disturbance of carbohydrate metabolism (prediabetes or type 2 diabetes), arterial hypertension, dyslipidaemia or obstructive sleep apnoea syndrome.
In adolescents from 12 years the medicine may be used as an addition to healthy eating and physical activity in obesity corresponding to a body mass index of 30 kg/m² or above by the international cut-off points for age and sex, and with a body weight above 60 kg. Treatment is not open-ended: in adults it is stopped if after 12 weeks on 3 mg a day the body weight has not fallen by at least 5% from the initial value; in adolescents the result is assessed by the body mass index, and with a fall of less than 4% in 12 weeks the therapy is reviewed.
Method of use and dosage
The injections are given once a day at any time, independently of food — into the front abdominal wall, the thigh or the upper arm. The injection site and the time can be changed without adjusting the dose, but it is more convenient to choose roughly the same time of day. One starts with 0.6 mg a day and raises the dose by 0.6 mg at intervals of no less than a week until 3.0 mg a day is reached: the gradual build-up is needed so that the digestive tract has time to adapt. If within two weeks of a given increase the medicine is poorly tolerated, the doctor considers stopping treatment. Daily doses above 3.0 mg are not recommended.
| Situation | What to do |
|---|---|
| A dose has been missed and less than 12 hours have passed | Give it as soon as possible |
| Less than 12 hours remain until the next dose | Do not give the missed dose, continue the usual schedule; a double dose is not given |
| Age 65 and over | No dose adjustment for age is needed; from 75 years the medicine is not recommended |
| Mild and moderate impairment of kidney function (creatinine clearance of 30 ml/min and above) | No dose adjustment is required |
| Severe impairment of kidney function, including the terminal stage | The medicine is not recommended |
| Impairment of liver function | In mild and moderate impairment, caution; in severe impairment the medicine is not recommended |
Patients with type 2 diabetes are not prescribed the medicine together with another GLP-1 receptor agonist. At the start of treatment the doctor considers reducing the dose of insulin or of agents that enhance insulin secretion, for example sulfonylurea derivatives, in order to lower the risk of hypoglycaemia; self-monitoring of the glucose level is necessary for this.
Contraindications
The only direct contraindication is hypersensitivity to liraglutide or to any excipient of the medicine.
Separately, a number of situations are singled out in which the medicine is not recommended: severe impairment of kidney and liver function, congestive heart failure of NYHA class IV, age 75 and over, pregnancy and breastfeeding, and the concomitant use of other products for weight management.
Special warnings and precautions
The most frequent undesirable effects concern digestion, and most of the precautions relate to them. The patient is warned of the risk of dehydration against a background of nausea, vomiting and diarrhoea and of the need to replace fluid: in people receiving GLP-1 receptor agonists, signs of dehydration, impaired kidney function and acute renal failure have been described. In inflammatory bowel disease and diabetic gastroparesis experience of use is limited and the medicine is not recommended.
- acute pancreatitis has been seen with GLP-1 receptor agonists: if it is suspected, liraglutide is withdrawn and, once the diagnosis is confirmed, treatment is not resumed;
- in the weight management studies gallstone disease and cholecystitis occurred more often than on placebo; they may require hospital admission and removal of the gallbladder, so their characteristic symptoms are explained to the patient;
- caution is needed in thyroid disease: in the studies, patients with pre-existing disease of the gland showed undesirable reactions, including enlargement of it;
- liraglutide increases the heart rate, so the pulse is monitored regularly; with a clinically significant persistent increase at rest, treatment is stopped;
- in patients with type 2 diabetes combined with insulin or sulfonylurea derivatives the risk of hypoglycaemia grows — it is reduced by lowering the dose of those medicines;
- the medicine does not replace insulin: in insulin-dependent patients diabetic ketoacidosis has been described with abrupt withdrawal or reduction of the insulin dose;
- efficacy and safety have not been established in obesity secondary to endocrine or eating disorders, or in people taking medicines that promote weight gain;
- for the traceability of biological medicines, the name and batch number of the product given are recorded in the medical notes.
On the ability to drive a car and to operate machinery the medicine has virtually no influence; however, in the first three months of treatment dizziness is possible — one should not get behind the wheel while it lasts.
Drug interactions
Under in vitro conditions liraglutide showed a very low potential for pharmacokinetic interactions with substances metabolised by the cytochrome P450 system and weak binding to plasma proteins. A small delay in gastric emptying could theoretically affect the absorption of medicines taken by mouth; however, no clinically significant delay in absorption was found in the studies, and dose adjustment is not required.
Caution is needed with substances that are poorly soluble or have a narrow therapeutic range — for example warfarin. Patients taking warfarin or other coumarin derivatives are advised to monitor the INR more frequently at the start of treatment with liraglutide. In addition, the acute diarrhoea noted in some patients is itself capable of altering the absorption of medicines taken by mouth. On the overall exposure to paracetamol at a dose of 1000 mg liraglutide had no influence.
Pregnancy and breastfeeding
Data on the use of liraglutide in pregnant women are scarce, and animal studies showed a harmful influence on reproduction; the risk to humans is unknown. During pregnancy the medicine must not be used. If a woman is planning a pregnancy or a pregnancy has already occurred, treatment is stopped.
Whether liraglutide passes into human breast milk is unknown; in animal studies small amounts of liraglutide and of structurally close metabolites reached the milk, and in rat pups a slowing of growth was noted during treatment. Because of the lack of experience of use, the medicine is not used during breastfeeding. On fertility, apart from a slight reduction in the number of implanted embryos in animals, no harmful influence was found.
Adverse effects
The safety of the medicine was studied in five double-blind placebo-controlled trials involving 5813 patients with obesity or overweight and at least one concomitant illness. Most often — in 67.9% of the participants — disturbances of the gastrointestinal tract were noted.
- very common — nausea, vomiting, diarrhoea, constipation;
- common — dry mouth, dyspepsia, gastritis, gastro-oesophageal reflux, pain in the upper abdomen, increased gas, belching, bloating;
- common — hypoglycaemia, insomnia, dizziness, disturbances of taste;
- common — gallstone disease, injection site reactions, asthenia, tiredness, a rise in the level of lipase and amylase;
- uncommon — pancreatitis, delayed gastric emptying, cholecystitis;
- uncommon — dehydration, tachycardia, urticaria, feeling unwell;
- rare — acute renal failure and impaired kidney function;
- rare — anaphylactic reaction.
In studies in people with overweight or obesity without type 2 diabetes no severe hypoglycaemia requiring the help of other people was recorded: symptoms of hypoglycaemia were noted by 1.6% of those receiving the medicine against 1.1% on placebo, and in most cases they were mild. In patients with type 2 diabetes who were also taking sulfonylurea derivatives, severe hypoglycaemia occurred in 0.7%.
Overdose
In clinical studies and after the medicine came onto the market, cases of doses of up to 72 mg being given have been described — 24 times more than the dose recommended for weight management. Marked nausea and vomiting were seen, that is, the expected manifestations of a liraglutide overdose. In no case was there severe hypoglycaemia, and all the patients recovered without complications.
In an overdose supportive treatment is given according to the symptoms. The patient is watched for signs of dehydration and the blood glucose level is monitored.
How to get a prescription for Saxenda online
Liraglutide for weight management is dispensed on prescription: prescribing it requires calculating the body mass index, assessing concomitant illnesses and teaching the technique of subcutaneous injections.
During the online consultation the doctor will discuss with you the indications, the scheme for the gradual increase of the dose and the criteria by which the effect is assessed after 12 weeks and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
