Orgovyx · 4.4 Special warnings and precautions for use · 1

HOS-099541 · has-adverse-reaction-information · PDF-Seite 15

Summary of the safety profile The most commonly observed adverse reactions during relugolix therapy are physiological effects of testosterone suppression, including hot flushes (54%), musculoskeletal pain (30%), and fatigue (26%). Other very common adverse reactions include diarrhoea and constipation (12% each). Tabulated list of adverse reactions Adverse reactions listed in Table 3 are classified according to frequency and system organ class. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. Frequencies are defined as 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), and not known (cannot be estimated from available data). 15 Table 3. Adverse reactions reported in clinical trials and during post-marketing experience Blood and lymphatic system disorders Common Anaemia Endocrine disorders Common Gynaecomastia Psychiatric disorders Common Insomnia Depression Nervous system disorders Common Dizziness Headache Cardiac disorders Uncommon Myocardial infarction Unknown QT prolonged (see sections 4.4 and 4.5) Vascular disorders Very common Hot flush Common Hypertension Gastrointestinal disorders Very common Diarrhoeaa Constipation Common Nausea Skin and subcutaneous tissue disorders Common Hyperhidrosis Rash Uncommon Urticaria Angioedema Musculoskeletal and connective tissue disorders Very common Musculoskeletal painb Uncommon Osteoporosis/osteopenia Reproductive and breast disorders Common Libido decreased General disorder and administration site conditions Very common Fatiguec Investigations Common Weight increased Glucose increasedd

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HOS-099537 · has-contraindication-information · PDF-Seite 3

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

HOS-099536 · has-indication-information · PDF-Seite 2

Orgovyx is indicated for the treatment of adult patients with advanced hormone-sensitive prostate cancer.

HOS-099539 · has-interaction-information · PDF-Seite 4

Potential for other medicinal products to affect the exposure to relugolix Clinical interaction studies with P-gp inhibitors (erythromycin and azithromycin) and combined P-gp and strong CYP3A4 inducers (rifampicin) have shown to affect the exposure of relugolix to a clinically relevant extent. Effect of co-administration on the exposure to 4 relugolix and associated dosing recommendations are summarised in Table 1. This list also includes expected effect and recommendations with other potentially interacting medicinal products. P-gp inhibitors Co-administration of Orgovyx and oral P-gp inhibitors is not recommended. Relugolix is a P-gp substrate (see section 5.2). If co-administration with once or twice daily oral P-gp inhibitors is required, Orgovyx should be taken first, with the oral P-gp inhibitor taken 6 hours thereafter, and patients should be monitored more frequently for adverse reactions. Alternatively, treatment with Orgovyx may be interrupted for up to 2 weeks for a short course of treatment with a P-gp inhibitor (e.g. for certain macrolide antibiotics). If treatment with Orgovyx is interrupted for more than 7 days, resume administration of Orgovyx with a 360 mg loading dose on the first day followed by 120 mg once daily (see section 4.2). Combined P-gp and strong CYP3A inducers Co-administration of Orgovyx with combined P-gp and strong CYP3A inducers is not recommended. If co-administration is required, the Orgovyx dose should be increased (see section 4.2). After discontinuation of the combined P-gp and strong CYP3A inducer, the recommended dose of Orgovyx should be resumed once daily. Other medicinal products No clinically significant differences in the pharmacokinetics of relugolix were observed upon co-administration of relugolix with acid-reducing agents. Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4). 5 Table 1. Effect of co-administered medicinal products on relugolix exposure (Cmax, AUC0- inf) and recommendations Interacting drug d

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HOS-099540 · has-pregnancy-information · PDF-Seite 14

This medicinal product is not indicated in women of childbearing potential. It is not to be used in women who are, or may be, pregnant or breast-feeding (see section 4.1). Contraception It is not known whether relugolix or its metabolites are present in semen. Based on findings in animals and mechanism of action, if a patient engages in sexual intercourse with a woman of childbearing potential, effective contraception during treatment and for 2 weeks after the last dose of Orgovyx must be used. Pregnancy There is a limited amount of data from the use of relugolix in pregnant women. Studies in animals have shown that exposure to relugolix in early pregnancy may increase the risk of 14 early pregnancy loss (see section 5.3). Based on the pharmacological effects, an adverse effect on pregnancy cannot be excluded. Breast-feeding Results from nonclinical studies indicate that relugolix is excreted into the milk of lactating rats (see section 5.3). No data are available regarding the presence of relugolix or its metabolites in human milk or its effect on the breast-fed infant. An effect on breast-feeding newborns/infants cannot be excluded. Fertility Based on findings in animals and mechanism of action, Orgovyx may impair fertility in males of reproductive potential (see section 5.3).

HOS-099538 · has-warning-information · PDF-Seite 3

Effect on QT/QTc interval prolongation Androgen deprivation therapy may prolong the QT interval. In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see section 4.5), 3 physicians should assess the benefit-risk ratio including the potential for Torsade de pointes prior to initiating Orgovyx. A thorough QT/QTc study showed that there was no intrinsic effect of relugolix on prolongation of the QTc interval (see section 4.8). Cardiovascular disease Cardiovascular disease such as myocardial infarction and stroke has been reported in the medical literature in patients with androgen deprivation therapy. Therefore, all cardiovascular risk factors should be taken into account. Changes in bone density Long-term suppression of testosterone in men who have had orchiectomy or who have been treated with a GnRH receptor agonist or GnRH antagonist is associated with decreased bone density. Decreased bone density, in patients with additional risk factors, may lead to osteoporosis and increased risk of bone fracture. Hepatic impairment Patients with known or suspected hepatic disorder have not been included in long-term clinical trials with relugolix. Mild, transient increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been observed but were not accompanied by an increase in bilirubin or associated with clinical symptoms (see section 4.8). Monitoring of liver function in patients with known or suspected hepatic disorder is advised during treatment. The pharmacokinetics of relugolix in patients with severe hepatic impairment has not been evaluated (see section 5.2). Severe renal impairment The exposure to relugolix in patients with severe renal impairment may be increased by up to 2-fold (see section 5.2). Because a lower dose of relugolix is not available, caution in patients with severe renal impairment is warranted upon administration of a 120-mg dose of relugolix once daily. The amount of relugolix removed by haemodialysis is unknown. Prostate-specific antigen (PSA) monitoring The effect of Orgovyx should be monitored by clinical parameters and prostate-specific antigen (PSA) serum levels. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.