Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

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.

Cytokine release syndrome (CRS)

Most patients experienced CRS following tebentafusp infusions. Diagnosis of CRS was most frequently based on pyrexia followed by hypotension and infrequently hypoxia. Other commonly observed symptoms with CRS included chills, nausea, vomiting, fatigue, and headache.

In the majority of cases, CRS started on the day of infusion with median time to resolution of 2 days.
Pyrexia was noted in nearly all cases of CRS, and in these patients, an increase in body temperature generally occurred within the first 8 hours after tebentafusp infusion. CRS rarely (1.2 %) led to treatment discontinuation.

Patients should be monitored for signs or symptoms of CRS for at least 16 hours following first three infusions of tebentafusp in a hospital setting with immediate access to medicinal products and resuscitative equipment to manage CRS. If CRS is observed, prompt treatment with supportive care including antipyretics, intravenous fluids, tocilizumab, or corticosteroids should be initiated to avoid escalation to severe or life-threatening events and monitoring should be continued until resolution.

At subsequent doses, patients should be closely monitored after treatment for early identification of signs and symptoms of CRS (see section 4.2, Method of administration). Patients with co-morbidities, including cardiovascular disorders, may be at increased risk for sequalae associated with CRS.

Treatment with tebentafusp has not been studied in patients with clinically significant cardiac disease (see section 5.1). Depending on persistence and severity of CRS tebentafusp treatment should be withheld or discontinued (see section 4.2, Table 1).

Acute skin reactions

Acute skin reactions have been reported with tebentafusp infusion, which may be based on its mechanism of action and gp100 expression in normal melanocytes in the skin. Acute skin reactions mainly included rash, pruritus, erythema and cutaneous oedema (see section 4.8).

Acute skin reactions typically occurred following each of the first three tebentafusp infusions and decreased in severity and frequency over time. Majority of symptoms resolved without any systemic corticosteroid or any long term sequalae.

Acute skin reactions can be managed with antihistamine and topical corticosteroids. For persistent or severe symptoms, systemic steroids should be considered. Management of signs and symptoms of skin reactions may require temporary delays of subsequent tebentafusp treatments (see section 4.2, Table 2).

Cardiac disease

Cardiac events such as sinus tachycardia and arrhythmia have been observed in patients who have received tebentafusp treatment (see section 4.8). Patients with pre-existing cardiovascular disorders may be at increased risk for sequalae associated with CRS and should be monitored carefully. Any patient with signs or symptoms consistent with cardiac events should be evaluated and promptly treated. In addition, appropriate treatment should be administered for any underlying CRS as a precipitating factor.

Cases of QT interval prolongation were reported following tebentafusp treatment (see section 4.8).
Tebentafusp treatment should be administered with caution in patients with history of or predisposition to QT interval prolongation and in patients who are taking medicinal products that are known to prolong QT interval.
An electrocardiogram (ECG) should be performed in all patients before and after tebentafusp treatment during the first 3 weeks of treatment and subsequently as clinically indicated. If QTcF exceeds 500 msec or increases by ≥ 60 msec from baseline value tebentafusp treatment should be withheld and patients should be treated for any underlying precipitating factors including electrolyte abnormalities.
Tebentafusp treatment should be resumed once QTcF interval improves to <500 msec or is < 60 msec from baseline value. Depending on persistence and severity of the cardiac event and any associated CRS tebentafusp treatment should be withheld or discontinued (see section 4.2, Table 1).

Contraception

Women of childbearing potential have to use effective contraception during and for at least 1 week after last dose of tebentafusp treatment (see section 4.6)

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially ‘sodium-free’

Effects on Driving

4.7    Effects on ability to drive and use machines
Tebentafusp has no or negligible influence on the ability to drive and use machines.