Trepulmix

HOS-287859 · has-adverse-reaction-information · PDF-Seite 10

Summary of safety profile In addition to local effects resulting from the administration of treprostinil by subcutaneous infusion such as infusion site pain and infusion site reaction, adverse reactions with treprostinil are related to the pharmacological properties of prostacyclins. Tabulated summary of adverse reactions The adverse reactions are presented as MedDRA preferred terms under the MedDRA system organ class. The incidence of the adverse reactions below are expressed according to the following categories: 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). System organ class Adverse reaction Incidence Nervous system disorders Headache Very common Dizziness Common Eye disorders Eyelid oedema Uncommon Cardiac disorders Vasodilatation Very common Hypotension Common Gastrointestinal disorders Diarrhoea Very common Nausea Very common Dyspepsia Uncommon Vomiting Uncommon Skin and subcutaneous tissue Rash Common disorders Pruritus Uncommon Exanthema Uncommon Musculoskeletal, connective Jaw pain Very common tissue disorders Myalgia, arthralgia Common Pain in extremities Common Back pain Uncommon General disorders and Infusion site pain, infusion site Very common administration site conditions reaction, bleeding or haematoma Infusion site abscess Common Infusion site infection Common

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HOS-287855 · has-contraindication-information · PDF-Seite 7

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Pulmonary veno-occlusive disease. • Severe decompensated left heart failure. • Severe hepatic impairment (Child-Pugh Class C). • Active gastrointestinal ulcer, intracranial haemorrhage, gastrointestinal injury or other gastrointestinal bleeding. • Congenital or acquired valvular defects with clinically relevant myocardial dysfunction not related to pulmonary hypertension. • Severe coronary heart disease or unstable angina • Myocardial infarction within the last six months • Severe arrhythmias • Cerebrovascular events (e.g. transient ischaemic attack, stroke) within the last three months. • Co-administration with other prostanoids

HOS-287854 · has-indication-information · PDF-Seite 3

Trepulmix is indicated for the treatment of adult patients with WHO Functional Class (FC) III or IV and: - inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or - persistent or recurrent CTEPH after surgical treatment to improve exercise capacity.

HOS-287857 · has-interaction-information · PDF-Seite 8

Concomitant administration with diuretics, antihypertensive agents, or other vasodilators 8 Concomitant administration of treprostinil with diuretics, antihypertensive agents or other vasodilators increases the risk of systemic hypotension. Concomitant administration with platelet aggregation inhibitors, including NSAIDs and anticoagulants Treprostinil may inhibit platelet function. Concomitant administration of treprostinil with platelet aggregation inhibitors, including NSAIDs, nitric oxide donors or anticoagulants may increase the risk of bleeding. Surveillance of patients taking anticoagulants should be closely maintained. The concomitant use of other platelet inhibitors should be avoided in patients taking anticoagulants. Concomitant administration with cytochrome P450 (CYP2C8) enzyme inducers/inhibitors Gemfibrozil and other CYP2C8 inhibitors Pharmacokinetic studies in humans with oral treprostinil diolamine indicated that the concomitant administration of cytochrome P450 (CYP2C8) enzyme inhibitor gemfibrozil doubles the exposure (both Cmax and AUC) to treprostinil. In case a CYP2C8 inhibitor (e.g. gemfibrozil, trimethoprim and deferasirox) is added to or omitted from the patient’s treatment after the titration phase, a dose adjustment of treprostinil has to be considered. Rifampicin and other CYP2C8 inducers Pharmacokinetic studies in humans with oral treprostinil diolamine indicated that the concomitant administration of CYP2C8 enzyme inducer rifampicin resulted in a reduced (by about 20%) exposure to treprostinil. In case rifampicin is added to or omitted from the patient’s treatment after the titration phase, a dose adjustment of treprostinil has to be considered. Also other CYP2C8 inducers (e.g. phenytoin, carbamazepine, phenobarbital and St. John's Wort) may lead to reduced exposure to treprostinil. In case a CYP2C8 inhibitor is added to or omitted from the patient’s treatment after the titration phase, a dose adjustment of treprostinil has to be considered. Concomitant administration with bosentan In a pharmacokinetic study in humans, in which bosentan (250 mg/day) and treprostinil diolamine (oral dose of 2 mg/day) were administered concomitantly, no pharmacokinetic interaction between treprostinil and bosentan was observed. Concomitant administration with sildenafil In a pharmacokinetic study in humans, in which sildenafil (60mg/day) and treprostinil diolamine (oral dose of 2 m

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HOS-287858 · has-pregnancy-information · PDF-Seite 9

Pregnancy There are no or limited amount of data from the use of treprostinil in pregnant women. Animal studies are insufficient with respect to effects on pregnancy (see section 5.3). Treprostinil should only be used during pregnancy if the potential benefit to the mother justifies the potential risk to the foetus. Women of child-bearing potential Contraception is recommended during treprostinil treatment. Breast-feeding It is not known whether treprostinil is excreted in human milk. Breastfeeding women taking treprostinil should be advised to discontinue breastfeeding. 9

HOS-287856 · has-warning-information · PDF-Seite 7

General therapy The decision to initiate therapy with treprostinil should take into consideration the high probability that continuous infusion will have to be continued for a prolonged period. Thus the patient's ability to accept and to be responsible for an indwelling catheter and infusion device should be carefully considered. The clinical team responsible for the therapy must ensure that the patient is fully trained and competent to use the chosen infusion device (see section 4.2). Treprostinil is a potent pulmonary and systemic vasodilator. In subjects presenting with low systemic arterial pressure, treprostinil treatment may increase the risk of systemic hypotension. Treatment is not recommended for patients with systolic arterial pressure of less than 85 mmHg. It is recommended to monitor systemic blood pressure and heart rate during any change in dose with instructions to stop the infusion if symptoms of hypotension develop, or a systolic blood pressure of 85 mmHg or lower is detected. 7 If a patient develops pulmonary oedema while on treprostinil, the possibility of a concomitant pulmonary veno-occlusive disease should be considered. The treatment should be stopped as pulmonary veno-occlusive disease is a contraindication for therapy with treprostinil (see section 4.3). Caution is advised in situations where treprostinil may increase the risk of bleeding by inhibiting platelet aggregation (see section 4.5 and 4.8). Withdrawal Abrupt withdrawal or sudden marked reductions in the dose of treprostinil may cause a rebound in pulmonary hypertension (see section 4.2). Special populations Patients with hepatic and renal impairment should be dosed cautiously (see section 4.2). As treprostinil and its metabolites are excreted mainly through the urinary route, caution is recommended when treating patients with renal impairment in order to prevent deleterious consequences related to the possible increase of systemic exposure (see section 4.2). Concomitant medicinal products Concomitant administration of cytochrome P450 (CYP2C8) enzyme inhibitors (as gemfibrozil) may lead to increased exposure (both Cmax and AUC) to treprostinil. With an increased exposure there is a likelihood of a higher incidence of adverse events associated with the administration of treprostinil. Therefore, a dose reduction should be considered (see section 4.5). Concomitant administration of CYP2C8 enzyme ind

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