sanofi-aventis

4.1 Therapeutic indications

Removal of the word ‘inoperable’

Head and neck cancer

TAXOTERE in combination with cisplatin and 5‑fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.

4.2 Posology and method of administration

Addition of reference to TAX323 and TAX324.

Dosage adjustments during treatment

Removal of the word ‘inoperable’, and slight change to wording

4.8 Undesirable effects

Slight format change to adverse event information for head and neck cancer patients

5.1     Pharmacodynamic properties

Slightly different wording to include data from TAX323 and the addition of data from TAX324

 Addition of

 Head and neck cancer

 TAXOTERE (docetaxel) in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with inoperable locally advanced squamous cell carcinoma of the head and neck.

 4.2 Posology and method of administration

 Expansion of premedication recommendations in includes head and neck cancer

 Recommended dosage:

 For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can be used (see section 4.4). Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.

 4.2 Posology and method of administration

 Addition of

 Head and neck cancer

 For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head neck (SCCHN), the recommended dose of TAXOTERE is 75 mg/m2 as a 1 hour infusion followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. Patients must receive premedication with antiemetics and appropriate hydration (prior to and after cisplatin administration). Prophylactic GCSF may be used to mitigate the risk of hematological toxicities. For cisplatin and 5-fluorouracil dose modifications, see manufacturer’s summary of product characteristic.

 Dosage adjustments during treatment:

 In the pivotal trial in patients who received an induction treatment with docetaxel for inoperable locally advanced squamous SCCHN and who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 6-15) in all subsequent cycles.

 4.8 Undesirable effects

 Addition of adverse event information for head and neck cancer patients who received TAXOTERE in combination with cisplatin and 5-fluorouracil (please refer to SPC).

Section 4.4

In women receiving TAXOTERE, doxorubicin and cyclophosphamide (TAC), the risk of acute myeloid leukemia is comparable to the risk observed for other anthracycline/cyclophosphamide containing regimens.

Is now

In the TAXOTERE, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed myelodysplasia or myeloid leukaemia requires haematological follow-up.

Section 4.8

(TAC SE section)

Cardiac disorders:

Congestive Heart Failure (CHF) (1.6%) has also been reported. One patient in each treatment arm died due to cardiac failure.

Is now

Cardiac disorders:

Congestive Heart Failure (CHF) (2.3% at 70 months median follow-up) has also been reported. One patient in each treatment arm died due to cardiac failure.

(Post-Marketing Experience)

Addition of

Disseminated intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been reported.

Update to section 4.8 of the SPC to be in line with the MeDRA terminology

4.2       Posology and method of administration

Information on use in children changed from:-

Children: The safety and effectiveness of docetaxel in children have not been established.

To: - 

Children and adolescents:  The experience in children and adolescents is limited.

4.8.            Undesirable Effects

There has been revision to the text in the following areas: -

Neoplasms benign and malignant (including cysts and polyps)

Two patients were diagnosed with leukemia at a median follow-up time of 55 months and one case of leukemia was reported after the follow-up period. No cases of myelodysplastic syndrome occurred

Now reads as

Very rare cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in association with docetaxel when used in combination with other chemotherapy agents and/or radiotherapy

Blood and the lymphatic system disorders

TAXOTERE 100mg/m² in combination with trastuzumab

The addition of – “Note that this is likely to be an underestimate since docetaxel alone at a dose of 100mg/m² is known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts.”

Immune system disorders

Hypersensitivity reactions……“resolved after discontinuing the infusion and appropriate therapy” has been removed.

Skin and subcutaneous tissue disorders

The addition of – “In some cases concomitant factors may have contributed to the development of these effects.”

6.2              Incompatabilities

Rewording of this section to bring the SPC in line with standard formatting.

6.4       Special precautions for storage

Change from protect from bright light to protect from light.

Addition of “for storage conditions of the diluted medicinal product, see section 6.3.”

6.6       Special precautions for disposal

Change in section heading to bring SPC in line with standard formatting

Change from

Disposal

All materials that have been utilised for dilution and administration should be disposed of according to standard procedures

To: -

Any unused product or waste material should be disposed of in accordance with local requirements.