4.Possible side effects

....

Reporting of side effects

....

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

Malta

ADR Reporting Website:

Website: www.medicinesauthority.gov.mt/adrportal

...

6.Contents of the pack and other information

...

Marketing Authorisation Holder and Manufacturer

....

Zoladex 3.6 mg Implant is manufactured by AstraZeneca AB, Gärtunavägen, SE-151 85 152 57Södertälje, Sweden.

This leaflet was last revised in February 2019October 2023.

© AstraZeneca 20192023

Zoladex is a trade mark of the AstraZeneca group of companies.

ONC 19 0005 23 0040

4.Possible side effects

.....

Reporting of side effects

....

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

email: medsafety@hpra.ie

Malta

ADR Reporting Website:

Website:www.medicinesauthority.gov.mt/adrportal

6.Contents of the pack and other information

....

Marketing Authorisation Holder and Manufacturer

...

This leaflet was revised in February 2019October 2023.

© AstraZeneca 20192023

Zoladex is a trade mark of the AstraZeneca group of companies.

ONC 19 000423 0040

Section 4.2 – change of wording from ‘older’ to ‘elderly’

Section 6.5 – addition of text that syringe can also be moulded from styrene-butadiene copolymer

Section 10 – updated date of revision

Section 4.2 – addition of information on how to administer Zoladex and extra care to be taken when administering to patients with low BMI and/or who are receiving full anticoagulation medication

Section 4.4 – infomration on injection site injury added

Section 10 – updated date of revision

SmPC changes:

Section 2 – Editorial update in line with latest QRD template

Section 4.2 – Editorial update in line with latest QRD template

Section 4.3 – Editorial update in line with latest QRD template

Section 4.4 – Addition of warnings and precautions around Androgen Deprivation Therapy and effect on the QT interval. Editorial update in line with latest QRD template

Section 4.5 – Addition of information on interactions following addition of information around Androgen Deprivation Therapy and effect on the QT interval.

Section 4.6 – Editorial update in line with latest QRD template

Section 4.7 – Editorial update in line with latest QRD template

Section 4.8 – amendment of ADR wording details from IMB to HPRA

Section 4.8 – Addition of QT interval as side effect

Section 5.1 – Editorial update in line with latest QRD template

Section 6.3 - Editorial update in line with latest QRD template

Section 6.6 – Editorial update in line with latest QRD template

Section 9 – Editorial update in line with latest QRD template

Section 10 – Update to "Date of Revision"

Section 4.8 – Addition of PRAC recommended wording “Hyperhidrosis and hot flushes may continue after stopping Zoladex.” after footnote (b) of the table.

Section 4.8 – Addition of ADR statement.

Section 10 – Update to "Date of Revision"

Addition of wording on depression following PhVWP recommendation.

Update following PSUR WS completion.

Section 4.4

Addition of wording on depression and Myocardial infarction and cardiac failure

Section 4.8

Psychiatric disorders updated re depression.

Section 10

Date of revision amended to 18^th October 2012.

Section 4.8

Text added to table - Skin and subcutaneous tissue disorders

Column 4         In Common section - alopecia^g  added  

Column 2         Not Known added

Column 3         Alopecia^h   added

Column 4         (see Common) added

Text added to table – Investigations

Column 2 - weight increased added

Column 3- weight increased added

Additional footnotes added to table

 
g        Loss of head hair has been reported in females, including younger patients treated for benign conditions.  This is usually mild but occasionally can be severe.

h        Particularly loss of body hair, an expected effect of lowered androgen levels.

Section 10

Date of Revision of Text changed to 27th June 2011

Section 4.8

Update to Table under cardiac disorders, now row reads as,

Section 10

10^th December 2010

Section 4.8

Text changes to 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 changes to 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

IR Zoladex 10.8mg updates

Section 4.3

First paragraph, addition of the word ‘severe’ after the first word Known, section now reads,

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

Pregnancy and lactation (see section 4.6).”

Section 4.4

Re-wording in first paragraph, now reads,

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

Re-wording in sub paragraph ‘Males’, now reads,

“Males

The use of Zoladex LA in men 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. Consideration should be given to the initial use of an anti-androgen (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.

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).

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

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.”

Re-wording in sub paragraph ‘Females’, now reads,

“Females

In women, Zoladex LA is indicated only for the treatment of endometriosis and fibroids. For female patients who need goserelin treatment for other indications, see the prescribing information for Zoladex 3.6 mg.

Loss of bone mineral density

The use of LHRH agonists is likely to cause reduction in bone mineral density averaging 1% per month during a six month treatment period. Every 10% reduction in bone mineral density is linked with about a two to three times increased fracture risk. In the majority of women, currently available data suggest that recovery of bone loss occurs after cessation of therapy.

In patients receiving Zoladex for the treatment of endometriosis, the addition of hormone replacement therapy (HRT) has been shown to reduce bone mineral density loss and vasomotor symptoms. There is no experience of the use of HRT in women receiving Zoladex LA.

No specific data is available for patients with established osteoporosis or with risk factors for osteoporosis (e.g. chronic alcohol abusers, smokers, long-term therapy with drugs that reduce bone mineral density, e.g. anticonvulsants or corticosteroids, family history of osteoporosis, malnutrition, e.g. anorexia nervosa). Since reduction in bone mineral density is likely to be more detrimental in these patients, treatment with Zoladex should be considered on an individual basis and only be initiated if the benefits of treatment outweigh the risks following a very careful appraisal. Consideration should be given to additional measures in order to counteract loss of bone mineral density.

Withdrawal bleeding

During early treatment with Zoladex some women may experience vaginal bleeding of variable duration and intensity. If vaginal bleeding occurs it is usually in the first month after starting treatment. Such bleeding probably represents oestrogen withdrawal bleeding and is expected to stop spontaneously. If bleeding continues, the reason should be investigated.

Time to return of menses after cessation of therapy with Zoladex LA may be prolonged in some patients (the mean duration of secondary amenorrhoea after cessation of use of Zoladex LA is 7‑8 months). If quick return of menses is important, Zoladex 3.6 mg is recommended.

The use of Zoladex may cause an increase in cervical resistance and care should be taken when dilating the cervix.

There are no clinical data on the effects of treating benign gynaecological conditions with Zoladex for periods in excess of six months.

Fertile women should use non-hormonal contraceptive methods during treatment with Zoladex and until reset of menstruation following discontinuation of treatment with Zoladex.

Patients with known depression and patients with hypertension should be monitored carefully.

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

Section 4.5

Small update to text, now reads,

” Not known.”

Section 4.6

Re-wording to first paragraph, section now reads,

“Pregnancy

Zoladex LA should not be used during pregnancy since concurrent use of LHRH agonists is associated with a theoretical risk of abortion or foetal abnormality. Prior to treatment, potentially fertile women should be examined carefully to exclude pregnancy. Non‑hormonal methods of contraception should be employed during therapy until menses resume. (see also warning concerning the time to return of menses in section 4.4).

Lactation

The use of Zoladex LA during breast‑feeding is not recommended.”

Section 4.7

Small update to text, now reads,

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

Section 4.8

Re-wording to section and table, now reads,

“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.

A small number of cases of hypercalcaemia have been reported in women being treated for endometriosis and/or fibroids. In the presence of symptoms of hypercalcaemia (e.g. thirst), hypercalcaemia should be excluded.

Rarely, some women may enter the menopause during treatment with LHRH analogues and not resume menses on cessation of therapy. Whether this is an effect of Zoladex treatment or a reflection of their gynaecological condition is not known.”

Section 4.9

Re-wording to section, now reads,

” 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 LA. In case of overdosage, the condition should be managed symptomatically.”

Section 10

Date updated,

“23 March 2010”

Zoladex 10.8mg Implant SPC changes

Section 1

â symbol removed

Secton 2

Text change to second paragraph,

“For a full list of excipients, see section 6.1.”

Section 6.1

Changed text,

“Lactide/glycolide 95/5 copolymer Low Molecular Weight

Lactide/glycolide 95/5 copolymer High Molecular Weight”

Section 6.2

Changed text, “Not applicable”.

Section 9

Changed text, “7^th September 2001 / 2^nd February 2009”

Section 10

Changed text, “13^th November 2009”

Section 4.4

Amendment to wording only re: Reduction of Bone Mineral Density

New text 5th paragraph re: Addition of wording on Diabetes Mellitus and Alterered Glucose Metabolism

Section 4.8

new text 6th paragraph:  Addition of wording on Diabetes Mellitus and Alterered Glucose Metabolism

and deletion of the words ‘in men’ in the 7th paragraph

Section 10

New revision date of text: 22 April 2008