SPC Changes, Zoladex 10.8

Section 4.8
Text update in first paragraph, now reads, “The following frequency categories for adverse drug reactions (ADRs) were calculated based on reports from Zoladex clinical trials and post-marketing sources. The most commonly observed adverse reactions include hot flushes, sweating and injection site reactions.”

Text update in Table, now reads,

Table: Zoladex LA adverse drug reactions presented by MedDRA System Organ Class

a          A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes mellitus.

b              These are pharmacological effects which seldom require withdrawal of therapy.

c              These may manifest as hypotension or hypertension, have been occasionally observed in patients administered Zoladex. The changes are usually transient, resolving either during continued therapy or after cessation of therapy with Zoladex. Rarely, such changes have been sufficient to require medical intervention, including withdrawal of treatment from Zoladex.

d              These are generally mild, often regressing without discontinuation of therapy.

e              Initially, prostate cancer patients may experience a temporary increase in bone pain, which can be managed symptomatically.

f               Observed in a pharmaco-epidemiology study of LHRH agonists used in the treatment of prostate cancer. The risk appears to be increased when used in combination with anti-androgens.

Section 10
15th July 2010

SmPC changes to Zoladex 10.8 Implant

Section 4.3

Deletion and additional text to this section,

“Known severe hypersensitivity to the active substance or to any of the excipients of this product.”

Section 4.4

Deletion and additional text to 2^nd paragraph,

“Zoladex LA is not indicated for use in children, as safety and efficacy have not been established in this patient group.”

Additional 3^rd paragraph,

“There is no data on removal or dissolution of the implant.”

Additional text to 4^th paragraph,

“The use of Zoladex LA in patients at particular risk of developing ureteric obstruction or spinal cord compression should be considered carefully and the patients monitored closely during the first month of therapy. If spinal cord compression or renal impairment due to ureteric obstruction are present or develop, specific standard treatment of these complications should be instituted. “

Deletion and additional text to 6^th paragraph,

“The use of LHRH agonists may cause reduction in bone mineral density. In men, preliminary data suggest that the use of a bisphosphonate in combination with an LHRH agonist may reduce bone mineral loss. Particular caution is necessary in patients with additional risk factors for osteoporosis (e.g. chronic alcohol abusers, smokers, long-term therapy with anticonvulsants or corticosteroids, family history of osteoporosis).”

Additional 7^th paragraph,

“Mood changes, including depression have been reported. Patients with known depression and patients with hypertension should be monitored carefully.”

Deletion and additional text to 8^th paragraph,

“Reduction in glucose tolerance has been observed in men receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in patients with pre-existing diabetes mellitus. Thus, monitoring of blood glucose levels should be considered.”

New final paragraph,

“Treatment with Zoladex may lead to positive reactions in anti-doping tests.”

Section 4.5

Minor Changed text,

“Not known.”

Section 4.7

Minor changed text,

“There is no evidence that Zoladex LA would result in impairment of ability to drive or operate machinery.”

Section 4.8

Deletion of text and additional text and table,

“The following frequency categories were based on all adverse reactions from clinical trials, post-marketing studies and spontaneous reports. The most commonly observed adverse reactions include hot flushes, sweating and injection site reactions.

The following convention has been used for classification of frequency: 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 the available data).

Table: Zoladex LA adverse drug reactions presented by MedDRA System Organ Class

a           A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes mellitus.

b          These are pharmacological effects which seldom require withdrawal of therapy.

c          These may manifest as hypotension or hypertension, have been occasionally observed in patients administered Zoladex. The changes are usually transient, resolving either during continued therapy or after cessation of therapy with Zoladex. Rarely, such changes have been sufficient to require medical intervention, including withdrawal of treatment from Zoladex.

d          These are generally mild, often regressing without discontinuation of therapy.

e          Initially, prostate cancer patients may experience a temporary increase in bone pain, which can be managed symptomatically.

Post-marketing experience

A small number of cases of changes in blood count, hepatic dysfunction, pulmonary embolism and interstitial pneumonia have been reported in connection with Zoladex.”

The following frequency categories were based on all adverse reactions from clinical trials, post-marketing studies and spontaneous reports. The most commonly observed adverse reactions include hot flushes, sweating and injection site reactions.

The following convention has been used for classification of frequency: 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 the available data).

Table: Zoladex LA adverse drug reactions presented by MedDRA System Organ Class

a           A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes mellitus.

b          These are pharmacological effects which seldom require withdrawal of therapy.

c          These may manifest as hypotension or hypertension, have been occasionally observed in patients administered Zoladex. The changes are usually transient, resolving either during continued therapy or after cessation of therapy with Zoladex. Rarely, such changes have been sufficient to require medical intervention, including withdrawal of treatment from Zoladex.

d          These are generally mild, often regressing without discontinuation of therapy.

e          Initially, prostate cancer patients may experience a temporary increase in bone pain, which can be managed symptomatically.

Post-marketing experience

A small number of cases of changes in blood count, hepatic dysfunction, pulmonary embolism and interstitial pneumonia have been reported in connection with Zoladex.”

Section 4.9

Deletion and additional text,

“There is not much experience of overdose in humans.  In cases where Zoladex has been given before the planned time of administration, or when a bigger dose of Zoladex than originally planned has been given, no clinically significant undesirable effects have been observed.  Animal tests suggest that no effect other than the intended therapeutic effects on sex hormone concentrations and on the reproductive tract will be evident with higher doses of Zoladex.  In case of overdosage, the condition should be managed symptomatically.”

Section 10

26^th October 2009

New and deleted text in red

4.4 Special warnings and special precautions for use

Zoladex LA is not indicated for use in females, since there is insufficient evidence of reliable suppression of serum estradiol.  For female patients requiring treatment with goserelin, refer to the prescribing information for Zoladex 3.6 mg.

Zoladex LA is not indicated for use in children, as safety and efficacy have not been established in this group of patients.

The use of Zoladex LA in patients at particular risk of developing ureteric obstruction or spinal cord compression should be considered carefully and the patients monitored closely during the first month of therapy.  Consideration should be given to the initial use of an antiandrogen (e.g. cyproterone acetate 300 mg daily for three days before, and three weeks after commencement of Zoladex) at the start of LHRH analogue therapy since this has been reported to prevent the possible sequelae of the initial rise in serum testosterone.

If spinal cord compression or renal impairment due to ureteric obstruction are present or develop, specific standard treatment of these complications should be instituted.

The use of LHRH agonists in men may cause a reduction in bone mineral density.

Section 4.1

Reworded to clarify the prostate cancer indication:

Zoladex is indicated (see also section 5.1):

§         In the treatment of metastatic prostate cancer

§         In the treatment of locally advanced prostate cancer, as an alternative to surgical castration

§         As adjuvant treatment to radiotherapy in patients with high-risk localised or locally advanced prostate cancer

§         As neo-adjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced prostate cancer

§         As adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at high risk of disease progression.

Section 5.1

Additional new 3^rd, 4^th and 5^th paragraphs

In the management of patients with metastatic prostate cancer, Zoladex has been shown in comparative clinical trials to give similar survival outcomes to those obtained with surgical castrations. 

In comparative trials, Zoladex has been shown to improve disease-free survival and overall survival when used as an adjuvant therapy to radiotherapy in patients with high‑risk localised (T₁-T₂ and PSA of at least 10 ng/mL or a Gleason score of at least 7), or locally advanced (T₃-T₄) prostate cancer.  The optimum duration of adjuvant therapy has not been established; a comparative trial has shown that 3 years of adjuvant Zoladex gives significant survival improvement compared with  radiotherapy alone.  Neo-adjuvant Zoladex prior to radiotherapy has been shown to improve disease-free survival in patients with high risk localised or locally advanced prostate cancer.

After prostatectomy, in patients found to have extra-prostatic tumour spread, adjuvant Zoladex may improve disease‑free survival periods, but there is no significant survival improvement unless patients have evidence of nodal involvement at time of surgery.  Patients with pathologically staged locally advanced disease should have additional risk factors such as PSA of at least 10 ng/mL or a Gleason score of at least 7 before adjuvant Zoladex should be considered.  There is no evidence of improved clinical outcomes with use of neo-adjuvant Zoladex before radical prostatectomy.

Section 10

New revision date of text: 28 January 2008