Safety Information About Nexavar and Treatment for Advanced Renal Cell Carcinoma (RCC)*

Generally well tolerated with a predictable side effect profile demonstrated in the largest placebo-controlled phase III clinical trial in advanced RCC*

Discontinuations due to adverse reactions were comparable: Nexavar 10% vs placebo 8%.

Chart — Adverse events occuring in at least 5% of patients in any treatment group

^aHand-foot skin reaction corresponds to palmar plantar erythodysaesthesia syndrome in MeDRA.

Incidence of fatigue as compared to placebo

Overall incidence of fatigue was 15% with Nexavar vs 11% with placebo. The incidence of Grade 3/4 fatigue was comparable to placebo (2% Nexavar vs 1% placebo).

Incidence of Grade 3/4 haematological and biochemical abnormalities as compared to placebo

The incidence of Grade 3/4 lymphopenia and neutropenia occurred in > 5% Nexavar-treated patients.

Incidence of Grade 3/4 haematological and biochemical abnormalities as compared to placebo

Managing skin toxicities

The most common skin irritations were rash and hand-foot skin reaction, which generally appeared during the first 6 weeks of treatment. Management of dermatologic toxicities may include topical therapies for symptomatic relief, temporary treatment interruption, and/or dose modification of Nexavar, or in severe or persistent cases, permanent discontinuation of Nexavar.

NCI-CTCAE v3.0 descriptions of rash/desquamation and hand-foot skin reaction, Grades 1-4

Hypertension

An increased incidence of arterial hypertension was observed in Nexavar-treated patients. Hypertension was usually mild to moderate, occurred early in the course of treatment, and was amenable to management with standard antihypertensive therapy. Blood pressure should be monitored regularly and treated, if required, in accordance with standard medical practice. In cases of severe or persistent hypertension or hypertensive crisis despite institution of antihypertensive therapy, permanent discontinuation of Nexavar should be considered.

Haemorrhage

An increased risk of bleeding may occur following Nexavar administration. If any bleeding event necessitates medical intervention, permanent discontinuation of Nexavar should be considered.

Cardiac ischaemia and/or infarction

In the phase III trial, the incidence of treatment-emergent cardiac ischaemia/infarction events was higher in the Nexavar group (2.9%) compared with the placebo group (0.4%). Patients with unstable coronary artery disease or recent myocardial infarction were excluded from this study. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischaemia and/or infarction.

Gastrointestinal perforation

Gastrointestinal perforation is an uncommon event and has been reported in less than 1% of patients taking Nexavar. In some cases this was not associated with apparent intraabdominal tumour. In the event of gastrointestinal perforation Nexavar therapy should be discontinued.

Patients on warfarin

Infrequent bleeding events or elevations of the International Normalised Ratio (INR) have been reported in some patients taking warfarin while on Nexavar therapy. Patients taking concomitant warfarin or phenprocoumon should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes.

Wound healing complications

No formal studies of the effect of Nexavar on wound healing have been conducted. Temporary interruption of Nexavar therapy is recommended for precautionary reasons in patients undergoing major surgical procedures. There is limited clinical experience regarding the timing of reinitiation of Nexavar therapy following major surgical intervention. Therefore, the decision to resume Nexavar therapy following a major surgical intervention should be based on clinical judgment of adequate wound healing.

Contraindications

Nexavar is contraindicated in patients with known hypersensitivity to sorafenib or any other component of Nexavar.

Information for patients

Inform patients about the possibility of hand-foot skin reaction and rash during Nexavar treatment
Inform patients that hypertension may develop during Nexavar treatment, especially during the first 6 weeks of therapy, and that blood pressure should be monitored regularly during treatment
Inform patients that Nexavar may increase the risk of bleeding and that they should report any episodes of bleeding
Inform patients that taking Nexavar with warfarin or phenprocoumon should be monitored regularly to check for bleeding
Inform patients that myocardial infarction has been reported during Nexavar treatment, and that they should immediately report any symptoms of cardiac ischaemia
Inform patients that Nexavar treatment might affect wound healing and should report if they have recently had major surgery or are planning to do so
Remind patients to disclose if they are taking irinotecan or docetaxel, as Nexavar may increase the effects and, in particular, side effects of these medications
Inform patients with severe hepatic impairment that they may experience more severe side effects when taking Nexavar
Counsel all patients to use effective birth control during treatment as Nexavar may reduce fertility
Inform female patients that they should not become pregnant during treatment with Nexavar

*Nexavar is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha- or interleukin-2-based therapy or are considered unsuitable for such therapy.

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Term

Explanation for term.