TEPEZZA

TEPEZZA must be administered as an intravenous infusion via an infusion pump. TEPEZZA must be administered by a healthcare professional and under the supervision of a physician experienced in the diagnosis and treatment of TED with access to appropriate medical support to manage potential severe reactions such as serious infusion-related reactions.

Posology TEPEZZA dosing is based on the patient’s actual body weight. The recommended dose of TEPEZZA is 10 mg/kg of body weight for the initial dose followed by 20 mg/kg of body weight for 7 additional doses given once every three weeks as an intravenous infusion.

For the first 2 infusions, the diluted solution is administered as an intravenous infusion over at least 90 minutes. If well tolerated, infusions 3 to 8 can be administered over 60 minutes every three weeks. Available data suggest that clinical response is usually achieved within 8 doses of treatment.

4). 2). There is no data in those over 80 years of age. 2). No dose adjustment is considered necessary in patients with mild to moderate renal impairment. Hepatic impairment The effect of hepatic impairment on the pharmacokinetics of TEPEZZA is unknown.

2). Paediatric population The safety and efficacy of TEPEZZA in children < 18 years of age has not been established. 1). Method of administration • TEPEZZA must be administered as an intravenous infusion via an infusion pump. 9%) solution for infusion, prior to infusion • TEPEZZA must not be co-administered with other medicinal products through the same infusion line.

• TEPEZZA must not be administered as an intravenous push or bolus. • For the first 2 infusions, administer the diluted solution intravenously over at least 90 minutes. If well tolerated, the minimum time for subsequent infusions can be reduced to 60 minutes.

• If not well tolerated, the minimum time for subsequent infusions should remain at 90 minutes, the rate of infusion should be reduced and pre-medication is recommended for subsequent infusions. 6.

9%). The most common serious adverse reactions are; diarrhoea, inflammatory bowel disease, infusion -related reaction. Tabulated list of adverse reactions The adverse reaction frequencies from clinical trials are based on all-cause adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes than the medicinal product, such as the disease, other medicines or unrelated causes.

Adverse reactions reported in clinical trials and derived from spontaneous reporting are listed below in table 1. The adverse reactions are listed by MedDRA System Organ Class and by frequency. The frequencies of adverse reactions is based on 4 placebo-controlled studies with 285 patients.

Patients were exposed to teprotumumab for a median of 148 days. Frequencies are defined according to the following convention: 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); not known (cannot be estimated from the available data).

Table 1. Adverse reactions MedDRA system organ class Very common (> 1/10) Common (> 1/100 to < 1/10) Uncommon (> 1/1 000 to < 1/100) Rare (> 1/1 0 000 to < 1/1 0 00) Not known/cannot be estimated from available data Infections and infestations COVID-19 Metabolism and nutrition disorders Hyperglycaemia1 Diabetic ketoacidosis Hyperosmolar hyperglycaemic state2 Nervous system disorders Headache Dysgeusia Ear and labyrinth disorders Ear discomfort, Autophony, Deafness, Eustachian tube dysfunction, Eustachian tube patulous, Hypoacusis, Neurosensory hypoacusis, Tinnitus Conductive deafness, Deafness unilateral, Hyperacusis, Tympanic membrane disorder Gastrointestinal disorders Diarrhoea Nausea Inflammatory bowel disease1 Skin and subcutaneous tissue disorders Alopecia Dry skin Nail bed disorder, Nail discoloration, Onychoclasis Ingrowing nail Musculoskeletal and connective tissue disorders Muscle spasms Reproductive system and breast disorders Amenorrhea, Hypomenorrhea, Dysmenorrhea, Irregular menstruation, Heavy menstrual bleeding General disorders and administration site conditions Fatigue Investigations Weight decreased Injury, poisoning and procedural complications Infusion -related reaction 1 1 See below description of selected adverse reactions 2 Observed in the post-marketing setting – frequency cannot be estimated from the available data.

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. Infusion-related reactions TEPEZZA may cause infusion reactions.

8). Patients should be advised to contact their healthcare professionals if they experience signs and symptoms of infusion-related reactions including but not limited to transient increases in blood pressure, feeling hot, tachycardia, dyspnoea, headache and muscular pain.

Patients should be monitored closely throughout the infusion and for 90 minutes after completion of the infusion. Based on the severity of the infusion- related reaction, TEPEZZA infusion should be interrupted or discontinued, and appropriate medical management should be instituted.

In patients who experience an infusion reaction, consideration should be given to pre-medicating with an antihistamine, antipyretic, corticosteroid and/or administering all subsequent infusions at a slower infusion rate. For patients who experience an anaphylactic reaction, discontinue TEPEZZA immediately and permanently.

Hyperglycaemia Hyperglycaemia or increased blood glucose may occur in patients treated with TEPEZZA. 2% of patients (80% of whom had pre-existing diabetes or impaired glucose tolerance) experienced hyperglycaemia. Adverse events associated with hyperglycaemia may include diabetes mellitus, diabetic ketoacidosis, glucose tolerance impaired, glycosylated haemoglobin increased and a hyperosmolar hyperglycaemic state.

Hyperglycaemic events should be managed with medications for glycaemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycaemia prior to infusion and continue to monitor while on treatment with TEPEZZA.

8). Blood glucose monitoring is recommended for 6 months after completion of treatment with teprotumumab. Hearing impairment TEPEZZA may cause severe hearing impairment including hearing loss, which in some cases may be permanent. 8).

1. 6).