RELUGOLIX

Treatment with relugolix should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. Posology Treatment with relugolix should be initiated with a loading dose of 360 mg (three tablets) on the first day, followed by a 120 mg (one tablet) dose taken once daily at approximately the same time each day.

Relugolix may be used as neo-adjuvant or adjuvant therapy prior to or in combination with radiotherapy in high-risk localised and locally advanced prostate cancer. Because relugolix does not induce an increase in testosterone concentrations, it is not necessary to add an anti-androgen as surge protection at initiation of therapy.

Dose modification for use with P-gp inhibitors Co-administration of relugolix with oral P-glycoprotein (P-gp) inhibitors is not recommended. 5). Treatment with this medicine may be interrupted for up to 2 weeks if a short course of treatment with a P- gp inhibitor is required.

Dose modification for use with combined P-gp and strong CYP3A inducers Co-administration of relugolix with combined P-gp and strong cytochrome P450 (CYP) 3A inducers is not recommended. If co-administration is required, the dose must be increased to 240 mg once daily.

5). Missed doses If a dose is missed, it must be taken as soon as the patient remembers. If the dose was missed by more than 12 hours, the missed dose must not be taken, and regular dosing schedule should be resumed the following day.

If treatment with relugolix is interrupted for greater than 7 days, it must be restarted with a loading dose of 360 mg on the first day, followed with a dose of 120 mg once daily. 2). Renal impairment No dose adjustment in patients with mild, or moderate renal impairment is required.

2). 2). Paediatric population There is no relevant use in children and adolescents under 18 years of age for the indication of treatment of advanced hormone sensitive prostate cancer. Method of administration Oral use. 2). Tablets should be taken with some liquid as needed and should be swallowed whole.

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 1 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). Within each frequency group, adverse reactions are presented in order of decreasing seriousness.

Table 3. 5) Vascular disorders Very common Hot flush Common Hypertension Gastrointestinal disorders Diarrhoeab Very common Constipation Common Nausea Skin and subcutaneous tissue disorders HyperhidrosisCommon Rash UrticariaUncommon Angioedema Musculoskeletal and connective tissue disorders Very common Musculoskeletal painc Uncommon Osteoporosis/osteopenia Reproductive and breast disorders Common Libido decreased General disorder and administration site conditions Very common Fatigued Investigations Weight increased Glucose increasede Triglyceride increasedd Common Blood cholesterol increasedf Aspartate aminotransferase increasedUncommon Alanine aminotransferase increasede a Includes libido decreased and loss of libido b Includes diarrhoea and colitis c Includes arthralgia, back pain, pain in extremity, musculoskeletal pain, myalgia, bone pain, neck pain, arthritis, musculoskeletal stiffness, non-cardiac chest pain, spinal pain, and musculoskeletal discomfort d Includes fatigue and asthenia e Grade 3/4 increases identified through clinical laboratory test monitoring (see below) f There were no reported cholesterol increases > grade 2 g Includes myocardial infarction and acute myocardial infarction Description of selected adverse reactions Changes in laboratory parameters Changes in laboratory values observed during up to 1 year of treatment in the phase 3 study (N = 622) were in the same range for relugolix and a GnRH agonist (leuprorelin) used as active comparator.

Effect on QT/QTc interval prolongation Androgen deprivation therapy may prolong the QT interval. 5), physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating this medicine. 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. 8). Monitoring of liver function in patients with known or suspected hepatic disorder is advised during treatment.

2). 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 relugolix 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’.

1.