Mounjaro

HOS-099857 · has-adverse-reaction-information · PDF-Seite 8

Summary of safety profile In 14 completed phase 3 studies, 15 169 adult patients were exposed to tirzepatide alone or in combination with other glucose lowering medicinal products. The most frequently reported adverse reactions were gastrointestinal disorders and these were mostly mild or moderate in severity. The incidence of nausea, diarrhoea and vomiting was higher during the dose escalation period and decreased over time (see sections 4.2, and 4.4). Tabulated list of adverse reactions The following related adverse reactions from clinical studies are listed below by system organ class and in order of decreasing incidence (very common: ≥ 1/10; common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1 000 to < 1/100; rare: ≥ 1/10 000 to < 1/1 000; very rare: < 1/10 000). Within each incidence grouping, adverse reactions are presented in order of decreasing frequency. Table 1. Adverse reactions System organ Very common Common Uncommon Rare class Immune Hypersensitivity Anaphylactic system reactions reaction#, disorders Angioedema# Metabolism Hypoglycaemia1* Hypoglycaemia1* when Hypoglycaemia1* and nutrition when used with used with metformin when used with disorders sulphonylurea or and SGLT2i- metformin6, insulin, Weight decreased1 Decreased appetite1,7 8  Nervous system Dizziness2 Dysgeusia, disorders Dysaesthesia## Vascular Hypotension2 disorders Gastrointestina Nausea, Diarrhoea, Dyspepsia, Cholelithiasis, l disorders Vomiting3, Abdominal distention, Cholecystitis, Abdominal pain3, Eructation, Flatulence, Acute pancreatitis, Constipation4 Gastroesophageal Delayed gastric reflux disease emptying Skin and Hair l

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HOS-099853 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-099852 · has-indication-information · PDF-Seite 4

Type 2 diabetes mellitus Mounjaro is indicated for the treatment of adults, adolescents and children aged 10 years and above with 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 • in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control, the populations studied, and cardiovascular events see sections 4.4, 4.5 and 5.1. Weight management Mounjaro is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with an initial Body Mass Index (BMI) of • ≥ 30 kg/m2 (obesity) or • ≥ 27 kg/m2 to < 30 kg/m2 (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, prediabetes, or type 2 diabetes mellitus). For trial results with respect to obstructive sleep apnoea (OSA) and heart failure with preserved ejection fraction (HFpEF), see section 5.1.

HOS-099855 · has-interaction-information · PDF-Seite 7

Tirzepatide delays gastric emptying and thereby has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. This effect, resulting in decreased Cmax and a delayed tmax, is most pronounced at the time of tirzepatide treatment initiation. Based on the results from a study with paracetamol, which was used as a model medicinal product to evaluate the effect of tirzepatide on gastric emptying, no dose adjustments are expected to be required for most concomitantly administered oral medicinal products. However, it is recommended to monitor patients on oral medicinal products with a narrow therapeutic index (e.g., warfarin, digoxin), especially at initiation of tirzepatide treatment and following dose increase. The risk of delayed effect should also be considered for oral medicinal products for which a rapid onset of effect is of importance. Paracetamol Following a 5 mg single dose of tirzepatide, the maximum plasma concentration (Cmax) of paracetamol was reduced by 50 %, and the median (tmax) was delayed by 1 hour. The effect of tirzepatide on the oral absorption of paracetamol is dose and time dependent. At low doses (0.5 and 1.5 mg), there was only a minor change in paracetamol exposure. After four consecutive weekly doses of tirzepatide (5/5/8/10 mg), no effect on the paracetamol Cmax and tmax was observed. The overall exposure (AUC) was not influenced. No dose adjustment of paracetamol is necessary when administered with tirzepatide. Oral contraceptives Administration of a combination oral contraceptive (0.035 mg ethinyl estradiol plus 0.25 mg norgestimate, a prodrug of norelgestromin) in the presence of a single dose of tirzepatide (5 mg) resulted in a reduction of oral contraceptive Cmax and area under the curve (AUC). Ethinyl estradiol Cmax was reduced by 59 % and AUC by 20 % with a delay in tmax of 4 hours. Norelgestromin Cmax was reduced by 55 % and AUC by 23 % with a delay in tmax of 4.5 hours. Norgestimate Cmax was reduced by 66 %, and AUC by 20 % with a delay in tmax of 2.5 hours. This reduction in exposure after a single dose of tirzepatide is not considered clinically relevant. No dose adjustment of oral contraceptives is required.

HOS-099856 · has-pregnancy-information · PDF-Seite 7

Women of childbearing potential Women of childbearing potential are recommended to use contraception when treated with tirzepatide. Pregnancy There are no or a limited amount of data from the use of tirzepatide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Tirzepatide is not recommended during 7 pregnancy and in women of childbearing potential not using contraception. If a patient wishes to become pregnant, or pregnancy occurs, tirzepatide should be discontinued. Tirzepatide should be discontinued at least 1 month before a planned pregnancy due to the long half-life (see section 5.2). Breast-feeding Following a single 5 mg dose, the concentration of tirzepatide in breast milk was found to be undetectable to very low compared to plasma concentrations. As tirzepatide is an amino acid sequence, any low amount present in breast milk is expected to be degraded and not orally absorbed as intact drug by the breastfed infant. It is not known whether the reduced maternal food intake caused by tirzepatide affects composition or nutrient content of the breast milk. Overall, tirzepatide could be considered for use during breast-feeding. Fertility The effect of tirzepatide on fertility in humans is unknown. Animal studies with tirzepatide did not indicate direct harmful effects with respect to fertility (see section 5.3).

HOS-099854 · has-warning-information · PDF-Seite 6

Acute pancreatitis Tirzepatide has not been studied in patients with a history of pancreatitis, and should be used with caution in these patients. Acute pancreatitis has been reported in patients treated with tirzepatide. Patients should be informed of the symptoms of acute pancreatitis. If pancreatitis is suspected, tirzepatide should be discontinued. If the diagnosis of pancreatitis is confirmed, tirzepatide should not be restarted. In the absence of other signs and symptoms of acute pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis (see section 4.8). Hypoglycaemia Patients receiving tirzepatide in combination with an insulin secretagogue (for example, a sulphonylurea) or insulin may have an increased risk of hypoglycaemia. The risk of hypoglycaemia may be lowered by a reduction in the dose of the insulin secretagogue or insulin (see sections 4.2 and 4.8). Gastrointestinal effects Tirzepatide has been associated with gastrointestinal adverse reactions, which include nausea, vomiting, and diarrhoea (see section 4.8). These adverse reactions may lead to dehydration, which could lead to a deterioration in renal function including acute renal failure. Patients treated with tirzepatide should be advised of the potential risk of dehydration, due to the gastrointestinal adverse reactions and take precautions to avoid fluid depletion and electrolyte disturbances. This should particularly be considered in the elderly, who may be more susceptible to such complications. Severe gastrointestinal disease Tirzepatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and should be used with caution in these patients. Diabetic retinopathy Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with diabetic retinopathy should be monitored closely and treated according to clinical guidelines. Aspiration in association with general anaesthesia or deep sedation Cases of pulmonary aspiration have been reported in patients receiving GLP-1 receptor agonists undergoing general anaesthesia or deep sedation. Therefore, the increased risk of residual gastric 6 content due to delayed gastric emptying (see section 4.8) should be considered prior to performing procedures with general anaesthesia or deep sedation. Sodium content This medicinal product contains

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