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®
ANGELIQ
Estradiol and Drospirenone
The First HRT with Drospirenone
Prescribing information can be found at the end of this presentation
®
ANGELIQ : The Product
Estradiol and Drospirenone
3
ANGELIQ®
The Product
• Low dose continuous combined HRT containing 2 mg
drospirenone and 1 mg estradiol1
• Angeliq relieves oestrogen deficiency symptoms 1
• Drospirenone's antimineralocorticoid activity counters
water and sodium retention helping to reduce the
likelihood of fluid retention that some women may
experience with HRT1-4
1. Schürmann R et al. Climacteric 2004;7:189-196. 2. Fuhrmann U et al. Contraception 1996;54:
243-251. 3. Strothmann A and Schneider HPG. Climacteric 2003:6: 337-346. 4. Sitruk-Ware R.
Drugs Aging 2004;21 (13):865-883.
4
ANGELIQ®
ANGELIQ®
O
H3C
H3C
O
H H
H
OH
H
H
H
H
CH3
O
H
H
HO
H
Drospirenone
Estradiol
Angeliq: continuous combined hormone therapy
with 2 mg of drospirenone plus 1 mg of estradiol
1. Angeliq SmPC, 2004.
5
ANGELIQ®
Therapeutic Indications
• Hormone replacement therapy for oestrogen deficiency
symptoms in postmenopausal women more than 1 year
post menopause1
• Prevention of osteoporosis in postmenopausal women at
high risk of future fractures who cannot take other
medication for the prevention of osteoporosis1
1. Angeliq SmPC, 2004.
Pharmacological profile
of drospirenone (DRSP)
7
ANGELIQ®
Comparison of Drospirenone With Other Progestogens
Progestogens
C-21
Pregnanes
• Medroxyprogesterone
acetate
• Dydrogesterone
• Megestrol acetate
• Cyproterone acetate
C-19
Estranes
• Norethindrone
• Noreth. acetate
• Ethynodiol diacetate
• Lynestrenol
• Norethynodrel
Spirolactone
Gonanes
• Norgestrel
• Levonorgestrel
• Norgestimate
• Desogestrel
• Gestodene
Drospirenone
8
ANGELIQ®
Comparison of Drospirenone With Other Progestogens
(cont.)
Estrogenic
Androgenic
Anti-androgenic
Glucocorticoid
Antimineralocort
-icoid
Progesterone
-
-
(+)
(+)
+
Drospirenone
-
-
+
-
+
Norethisterone
(+)
+
-
-
-
Dydrogesterone
-
-
-
-
(+)
Medroxyprogesterone
-
(+)
-
+
-
Key: + relevant activity; (+) activity not clinically relevant; – no activity
Adapted from Climacteric 2004; 7(Supp 1): 11-35.
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ANGELIQ®
Comparison of Drospirenone With Other Progestogens
(cont.)
Progestogenic activity
Progestogen
Progesterone
Dose required to produce secretory
activity in endometrium (mg/cycle)
4200
Drospirenone
50
Norethisterone
125
Dydrogesterone
140
Medroxyprogesterone
80
1. Schindler et al. Maturitas. 2003; 46(suppl 1): S7–S16.
®
ANGELIQ : Principal Clinical
Studies
11
ANGELIQ®
Principal Clinical Studies
ANGELIQ® (Drospirenone/Estradiol)
Vasomotor symptoms
(4 months; n=225)
Osteoporosis prevention
(2 years; n=240)
Endometrial protection
(Study I: 1 year; n=1142)
Special studies
(women with systolic hypertension;
concomitant use of ACEIs/AIIRAs)
ACEIs, angiotensin-converting enzyme inhibitors; AIIRAs, angiotensin II receptor
antagonists.
12
ANGELIQ®
Efficacy Data
• Double-blind, randomised, placebo-controlled study of safety &
efficacy of 3 dose regimens
• 225 healthy postmenopausal women aged 45-65
• Reporting at least 5 moderate to severe hot flushes per day
• Randomised to 1 of 4 groups: either placebo or 1 mg estradiol plus
1, 2, or 3 mg drospirenone taken orally, daily for 16 weeks
• Primary endpoint: change from baseline in the frequency and
intensity of hot flushes
1. Schürmann R et al. Climacteric. 2004;7: 189-196. Estradiol & drospirenone for climacteric
symptoms in postmenopausal women
13
ANGELIQ®
Safety and efficacy data
• Double-blind, placebo-controlled, randomised 2-year study
performed at one centre
• 180 women at least 1 year postmenopausal – 45-65 years of age
• Patients were randomised to 4 groups: either placebo or 1 mg
estradiol combined with 1, 2 or 3 mg drospirenone orally daily
• Bone mineral density (BMD) at lumbar spine, hip and total body;
markers of bone turnover; endometrial thickness; serum lipids and
bleeding profile were measured
1. Warming L et al. Climacteric, 2004;7: 103-111. Safety & efficacy of drospirenone used in a
continuous combination with 17-ß estradiol for prevention of postmenopausal osteoporosis
14
ANGELIQ®
Safety and efficacy data
• 1142 postmenopausal women
• 1 mg estradiol with either 0.5 mg,1 mg, 2 mg or 3 mg DRSP as
opposed to 1 mg estradiol alone. 1 tablet taken daily over 13 cycles
• Objectives: To determine the effect of drospirenone - estradiol
compared with estradiol alone on the endometrium of postmenopausal
women
• Primary outcome variable: endometrial hyperplasia
• Secondary outcome variables: bleeding patterns; hot flush frequency
& severity and urogenital symptoms
1. Archer D et al. Accepted, Menopause 2005. Multicenter trial of efficacy & safety of
drospirenone-estradiol when used for hormone therapy.
®
ANGELIQ : Efficacy Data
Oestrogen deficiency symptoms
Bleeding patterns
Effect on bone
16
ANGELIQ®
Hot Flushes
• Number of hot flushes significantly decreased from week
3 in all treatment groups (reduction of 85-88%), compared
to placebo (reduction of 47%) (p<0.001)
• Angeliq reduced the number of hot flushes by 88%
• Remained suppressed at 16 weeks
1. Schürmann R et al. Climacteric 2004;7: 189-196.
17
ANGELIQ®
Number of Hot Flushes
Frequency of hot flushes significantly reduced from week 3 (p<0.001) in comparison
with placebo
Adapted from Schürmann et al. Climacteric.2004; 7: 189-196. A 16-week, randomised,
placebo-controlled study of 225 post-menopausal women with  5 hot flushes per day.
18
ANGELIQ®
Bleeding Profile
• 94% of patients on Angeliq were bleed free by cycle 13
• This effect persisted in the majority of patients from then
on
• Spotting was the most recorded bleeding intensity
followed by mild bleeding
1. Warming L et al. Climacteric. 2004; 7: 103-111.
ANGELIQ®
Amenorrhoea
94% of patients were bleed free by cycle 13 – this effect persisted in the majority of
patients from then on
Patients without spotting or bleeding (%)
19
Adapted from Warming L et al. Climacteric 2004;7: 103-111. Two-year prospective study of 180
post-menopausal women aged 45-65. Figures are shown as mean values.
20
ANGELIQ®
Effects on Bone
• After 2 years of treatment, bone mineral density at
lumbar spine, hip & total body increased by 7, 4 & 3%
respectively for Angeliq versus placebo (all p<0.05)
1. Warming L et al. Climacteric. 2004;7: 103-111.
21
ANGELIQ®
Angeliq Significantly Increased Lumbar Spine BMD By
7% Compared With Placebo
(P <0.05)
Adapted from Warming et al. Climacteric 2004;7: 103-111. Two-year prospective study of 180 postmenopausal women aged 45-65.
22
ANGELIQ®
Angeliq Significantly Increased Hip BMD By 4%
Compared With Placebo (P<0.05)
Adapted from Warming et al. Climacteric 2004;7:103-111. Two-year prospective study of 180
post-menopausal women aged 45-65.
23
ANGELIQ®
Angeliq Significantly Increased Overall Body BMD By
3% Compared With Placebo
(P<0.05)
Adapted from Warming et al. Climacteric 2004;7:103-111. Two-year prospective study of
180 post-menopausal women aged 45-65.
24
ANGELIQ®
Bone Formation Markers
• Serum N-mid osteocalcin (sOC) had decreased by 52%
compared to baseline (p<0.001) in E2/DRSP treated
groups
• Serum bone-specific alkaline phosphatase (sBSAP)
showed a decrease of 46% compared to baseline
(p<0.001) in E2/DRSP treated groups
1. Warming L et al. Climacteric. 2004;7:103-111.
ANGELIQ®
25
Effect on Bone-Formation Markers
Placebo (n=60)
Angeliq (n=60)
20
15
*
10
5
Serum BSAP (U/L)
Serum osteocalcin (ng/mL)
20
15
10
5
Baseline
1 year
2 years
Serum N-mid osteocalcin
Baseline
1 year
2 years
Bone-specific alkaline phosphatase
1. Adapted from Warming L et al. Climacteric. 2004;7: 103–111.
26
ANGELIQ®
Bone Resorption Markers
• Bone resorption markers decreased significantly in the
E2/DRSP treated groups
• Urinary CTX had decreased by 75% compared to
baseline (p<0.001)
• Serum CTX decreased by 64% compared to baseline
(p<0.001)
1. Warming L et al. Climacteric. 2004;7: 103–111.
ANGELIQ®
27
Effect on Bone-Resorption Markers
Placebo (n=60)
Angeliq (n=60)
300
sCTX (ng/mL)
0.4
0.3
0.2
*
0.1
uCTX (µg/mmol creatinine)
0.5
250
200
150
100
50
0
0
Baseline
1 year
2 years
Serum CTX
Baseline
1. Adapted from Warming L et al. Climacteric. 2004;7: 103-111.
1 year
2 years
Urinary CTX
28
ANGELIQ®
Conclusion
Angeliq leads to:
• Prevention of post menopausal bone loss
• Decreased bone turnover
• Increased bone mass
1. Warming L et al. Climacteric. 2004;7: 103-111.
®
ANGELIQ : Safety Data
30
ANGELIQ®
Effects on Endometrium
1. Archer D et al. Accepted, Menopause 2005.
31
ANGELIQ®
Endometrial Hyperplasia
1. Archer et al. Accepted, Menopause 2005.
32
Tolerability
• Angeliq was well tolerated in clinical trials1,2
• The majority of adverse events were mild or moderate and in line with
those commonly experienced with HRT such as: breast pain, headaches,
irregular vaginal bleeding1
Adverse event
Placebo
DRSP 1mg
DRSP 2mg
DRSP 3mg
(n=61)
(n=54)
(n=52)
(n=56)
Any
10 (16.4%)
23 (42.6%)
14 (26.9%)
15 (26.8%)
Breast pain
0 (0.0%)
10 (18.5%)
4 (7.7%)
4 (7.1%)
Headache
2 (3.3%)
3 (5.6%)
2 (3.8%)
2 (3.6%)
Irregular bleeding
0 (0.0%)
2 (3.7%)
2 (3.8%)
0 (0.0%)
Abdominal pain
2 (3.3%)
2 (3.7%)
0 (0.0%)
0 (0.0%)
Nausea
1 (1.6%)
0 (0.0%)
1 (1.9%)
1 (1.8%)
1. Schürmann R et al. Climacteric. 2004; 7:189-196. 2. Warming L et al. Climacteric 2004; 7:103-111.
33
Tolerability
• Adverse events with Angeliq were generally mild to
moderate1,2,3
• Those experienced with Angeliq are in common with those
expected in a postmenopausal population taking a hormone
preparation1,2,3
1. Schürmann R et al. Climacteric. 2004; 7:189-196. 2. Warming L et al. Climacteric 2004; 7:103-111.
3. Archer D et al. Accepted, Menopause 2005
34
ANGELIQ®
Change in Lipid Levels at 1 year
* P<0.001 compared
to baseline
1. Warming L et al. Climacteric 2004;7: 103-111.
35
ANGELIQ®
Angeliq and Serum Potassium Levels
• Due to the antimineralocorticoid activity of DRSP,
potassium levels were measured in all Phase II/III studies
• Data were not suggestive of any impact of Angeliq on
potassium levels in most cases.
– However, serum potassium should be checked during
the first prescription cycle in patients with renal
impairment or using potassium sparing medication
1. Preston RA et al. AJH 2005;18: 797-804.
ANGELIQ®
Effect on Serum Potassium Levels
Estradiol 1 mg (n=219)
40
ANGELIQ (n=215)
35
Percentage of patients
36
30
25
20
15
10
5
0
< -1.0
-1.0 to -0.5
-0.5 to -0.1
-0.1 to 0.1
0.1 to 0.5
0.5 to 1.0
1.0 to 1.5
Change in maximum postbaseline serum potassium (mEq/L)
1. Schering AG, data on file.
+1.5
37
ANGELIQ®
Summary
• Low-dose, continuous combined HRT – 2 mg
drospirenone, 1mg estradiol1
• Relieves oestrogen deficiency symptoms2
• Increases bone mineral density3
• Maintains amenorrhoea in the majority of women3
• Provides endometrial protection3,4
• Well tolerated2,3,4
1. Angeliq SmPC, 2004 2. Schürmann R et al. Climacteric. 2004;7:189-196 3. Warming
L et al. Climacteric 2004;7:103-111 4. Archer D et al. Accepted, Menopause 2005
Drospirenone – A Progestogen
with Antimineralocorticoid
Activity
39
Incidence of Chronic Diseases in Relation to a
Woman’s Age
300
Annual incidence per 1000 women
CHD
250
200
150
Stroke
Hip fracture
100
50
Breast cancer
0
30
40
50
60
Age (years)
1. Wenger. BMJ 1997;315: 1085–1090.
70
80
40
Relevance of Cardiovascular Disease UK
Leading causes of death for females in the UK (2002)
British Heart Foundation www.heartstats.org page 20
41
Women’s Perceptions of their Greatest Health
Problems
Cardiovascular Disease
Don’t Know/
No Answer
7%
16%
Other
Problems
Breast
Cancer
34%
16%
27%
Cancer
Adapted from Mosca L et al. Arch Fam Med. 2000;9: 506-15.
42
Prevalence of Hypertension in UK 2002
Women
Men
90
Percentage of population
80
70
60
50
40
30
20
10
0
16-24
25-34
35-44
45-54
55-64
65-74
>75
Age
British Heart Foundation Statistics database www.heartstats.org 2004 Page 157
Data derived from: Health survey for England 2002Department of Health, UK
Systolic BP>140; Diastolic BP>90mmHg
43
Definitions and Classification of Blood Pressure Levels
European Society of Hypertension – European Society
of Cardiology (2003)
Category
Systolic (mmHg)
Diastolic (mmHg)
Optimal
<120
<80
Normal
120–129
80–84
High normal
130–139
85–89
Grade 1 hypertension (mild)
140–159
90–99
Grade 2 hypertension (moderate)
160–179
100–109
Grade 3 hypertension (severe)
>180
>110
Isolated systolic hypertension
>140
90
When a patient’s SBP and DBP fall into different categories, the higher category should
apply. Isolated systolic hypertension can also be graded (1–3) according to SBP values in
the ranges indicated, provided DBP values are <90.
1. J Hypertens 2003; 21(6): 1011-1053
44
CHD mortality (floating absolute risk and 95% CI)
Usual Blood Pressure and CVD Risk
Age at risk:
256
80 – 89 years
128
70 – 79 years
64
60 – 69 years
32
50 – 59 years
16
40 – 49 years
8
4
2
1
120
140
160
180
Usual systolic blood pressure (mmHg)
Meta analysis one million adults 61studies.
1. Lewington S et al. Lancet 2002;360: 1903-13.
45
Blood Pressure in Women
• What is the impact of lowering BP on CVD-risk in a
postmenopausal woman?
• A blood pressure reduction of 10–12 mmHg systolic or 56 mmHg diastolic can lead to a 38% decline in stroke
incidence and a 19% of reduction of coronary heart
disease events (irrespective of starting blood pressure).
1. MacMahon. Blood pressure and the prevention of stroke. J Hypertens Suppl. 1996;14: S39-S46.
Aldosterone - Its Impact On
The CVS
47
Renin-Angiotensin-Aldosterone System (RAAS)
Angiotensin I
+
Oestrogen
Renin substrate
(angiotensinogen)
Renin
- Increased plasma volume
- Increased blood pressure in susceptibles
Angiotensin II
- Water retention-related symptoms
(oedema, bloating, weight gain, breast tenderness)
Na+/water retention
K+ elimination
Progesterone
Aldosterone
48
 Vascular injury and fibrosis
 Endothelial dysfunction
 Central-acting hypertension
 Thrombogenesis
 Baroreceptor dysfunction
ALDOSTERONE
 Cardiac necrosis and fibrosis
 Magnesium loss
 Left ventricular hypertrophy
 Potassium loss
 Congestive heart failure
 Sodium retention
Struthers AD and MacDonald TM, Cardiovascular Res 2004;61: 663-670.
49
Normal Right and Left Ventricle
Slides given by Dr Mary Sheppard at The Royal Brompton
50
Hypertrophy of Right Ventricle and Left Ventricle
Slides given by Dr Mary Sheppard at The Royal Brompton
51
LVH with Fibrosis
Slides given by Dr Mary Sheppard at The Royal Brompton
52
Medial Hypertrophy and Intimal Fibrosis of
Hypertensive Vessel
Slides given by Dr Mary Sheppard at The Royal Brompton
53
Hypertensive Vessel
Slides given by Dr Mary Sheppard at The Royal Brompton
54
Superficial Scarring in
Keeping with
Nephrosclerosis
Vascular Hyaline
Thickening of Renal
Artery
Slides given by Dr Mary Sheppard at The Royal Brompton
55
Rationale for additional benefits of aldosterone
inhibition in patients already on ACE inhibition
Angiotensin I
(-)
ACE inhibitors
Angiotensin II
(-)
(-)
ATII receptor
antagonists
Vascular injury
Adrenal gland
Aldosterone
(-)
Spironolactone
56
Spironolactone in Heart Failure – Randomised Aldactone
Evaluation Study (RALES)
Number at risk
841
775
723
378
628
592
565
483
379
280
179
92
36
Placebo
822
766
739
698
669
639
608
526
419
316
193
122
43
Spironolactone
1. Pitt. N Engl J Med. 1999;341: 709–717.
57
Antimineralocorticoid Activity
Relative efficiency in rats
1000
800
750
500
250
100
35
20
Progesterone
Gestodene
0
Spironolactone
1. Losert W et al. Drug Res 1985;35: 459–471.
Drospirenone
58
Blood Pressure in Hypertensive Subgroup of the
Endometrial Safety Study (post hoc analysis)
mmHg
0
Systolic blood
pressure
-1
Diastolic blood
pressure
-2
-3
-4
-2.7
-3.7
-5
-6
-5.7 p<0.001 vs
baseline
-7
-8
-9
-9
-10
Estradiol 1mg (n=15)
1. Archer et al. Accepted, Menopause 2005
p<0.05 vs
baseline
ANGELIQ (n=15)
59
ANGELIQ®
Fluid retention
• HRT benefits are often offset by unwanted effects, such as fluid
retention1
• In a European study, 13% of women discontinued HRT due to fluid
retention such as abdominal swelling and swelling of the ankles1
• Side effects such as oedema due to fluid retention and bloating, which
may occur when women first start taking HRT, are recognised to impair
compliance2
• The antimineralocorticoid activity of drospirenone counters water and
sodium retention and this may help avoid the fluid retention some
women can experience with HRT 1,3-5
1. Strothmann A, Schneider HPG. Climacteric 2003;6: 337-346. 2. Schurman R et al. Climacteric
2004; 7: 189-196. 3. Fuhrmann U et al. Contraception 1996; 54: 243-251. 4. Sitruk-Ware R.
Drugs Aging 2004; 21 (13): 865-883. 5. van Seumeren I. Maturitas 2000; 34: s3-s38.
ANGELIQ®
Change in Body Weight
In HRT users, fear of weight gain is a significant compliance issue, indeed it is
estimated that as many as 20% stop HRT because of weight gain1
Change from baseline in mean body weight, kg2
1
Estradiol 1 mg (n=226)
ANGELIQ (n=227)
0.5
Weight (Kg)
60
0
0
1
3
7
10
13
-0.5
-1
* **
-1.5
** * p<0.001 vs estradiol 1mg, p<0.001 vs baseline
1. van Seumeren I. Maturitas 2000; 34: s3-s38. 2. Archer D et al. Accepted, Menopause 2005
61
ANGELIQ®
Women’s Attitude to Hormone Therapy
• Recorded European women’s views on HRT
• Conducted 7 months after publication of WHI trial
• Over 8,000 women, aged 45-75,were interviewed
• Outcome measures were history of HRT use, opinions &
knowledge of HRT, reasons for use, reasons for refusing
and stopping treatment, and reasons for changing HRT
• Results demonstrated differences across Europe in
awareness of benefits & risks of HRT
1. Strothmann A, Schneider HPG, Climacteric 2003;6: 337-346.
62
ANGELIQ®
Main Reasons for Changing HRT Product
Inadequate symptom relief
36
Perceived weight gain
26
Bleeding problems
25
Breast problems
22
Fluid retention
14
12
Breast cancer concerns
9
Development of varicose veins
7
Heart disease concerns
27
Other reasons (e.g. advice from doctor 7.2%)
0
10
20
30
40
50
Percent
Base: n = 1146 Current & Former HRT users
1. Strothmann A, Schneider HPG, Climacteric 2003;6: 337-346.
63
ANGELIQ®
Main Reasons for Discontinuing HRT
Abolition of symnptoms
31
Breast cancer concerns
26
Weight gain
25
22
Development of clinical problem
16
Breast problems
14
To stop bleeding
Fluid retention
13
heart disease concerns
12
9
Development of varicose veins
21
Other reasons (e.g. advice from doctor 7.7%)
0
10
20
30
40
Percent
Base: n = 1279 Former HRT users
1. Strothmann A, Schneider HPG, Climacteric 2003;6:337-346.
50
64
Summary
• Angeliq:
– Provides relief from oestrogen deficiency symptoms1
– Helps prevent osteoporosis in post-menopausal
women2
– Provides endometrial protection2
– Drospirenone counters water and sodium retention
helping to reduce the likelihood of fluid retention that
some women may experience with HRT3,4
1. Schürmann R et al. Climacteric 2004;7; 189-196. 2. Warming L et al. Climacteric 2004;7:
103-111. 3. Fuhrmann U et al. Contraception1996;54: 243-251 4. Sitruk-Ware R. Drugs Aging
2004; 21(13) 865-883.
65
1
1. Angeliq Summary of Product Characteristics
66
Angeliq® Film coated tablets (estradiol/drospirenone) Prescribing Information. Presentation: 28 tablets each containing 1 mg estradiol (as
hemihydrate) and 2 mg drospirenone. Uses: Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in women at least 1 year
post menopause. Prevention of postmenopausal osteoporosis in women at high risk of future fractures and who cannot use other treatments.
Dosage and administration: 1 tablet daily without a break. Contraindications: Pregnancy; lactation;undiagnosed genital bleeding; known,
past or suspected breast cancer; known or suspected oestrogen dependent malignant tumours; untreated endometrial hyperplasia; previous
idiopathic or current venous thromboembolism; active or recent arterial thromboembolic disease; acute liver disease, or history of liver disease if
liver function tests have not returned to normal; porphyria; severe renal insufficiency or acute renal failure; hypersensitivity to any of the
ingredients. Precautions and special information: Include personal and family history as part of assessment prior to treatment. Exclude
possible contraindications, including pregnancy. Perform physicalexaminations if clinically indicated. Instruct patients in selfbreast examination.
Perform periodic check-ups adapted to individual’s needs. Close supervision needed if past or present: uterine fibroids or endometriosis; history
of, or risk factors for, thromboembolic disorders; risk factors for oestrogen dependent tumours; hypertension; liver disorders; diabetes mellitus;
cholelithiasis; migraine or severe headache; systemic lupus erythematosus; history of endometrial hyperplasia; epilepsy; asthma; otosclerosis.
Stop treatment at once if: jaundice or deterioration of liver function; significant increase in blood pressure; new onset migraine-type headache;
pregnancy; symptoms that are possible prodromata of vascular occlusion; other contraindications occur. Remind patients of the need to inform
doctor if they are aware of any new symptoms. Endometrial hyperplasia and carcinoma with unopposed oestrogen use is reduced by adding a
progestogen for at least 12 days per cycle. Investigate irregular bleeding. Some studies have reported an increased risk of breast cancer in
women taking HRT for several years. HRT is associated with an increased relative risk of developing venous thromboembolism (greater in first
year of use). Risk factors include: personal or family history of thrombosis; severe obesity; systemic lupus erythematosus; immobilisation; major
trauma; major surgery. Consider stopping HRT 4-6 weeks before elective surgery requiring immobilisation. Possible increased risk of
cardiovascular morbidity in the first year of use of HRT. HRT is associated with an increased risk of stroke. Long term use of oestrogens in
hysterectomised women is associated with an increased risk of ovarian cancer. Oestrogens may cause fluid retention. Monitor patients with
cardiac or renal dysfunction. Monitor pre-existing hypertriglyceridaemia closely since large increases in triglycerides leading to pancreatitis have
been reported. Certain laboratory tests may be affected. Oestrogens may increase circulating thyroid hormone, other binding proteins
and some plasma proteins. Chloasma may occur. HRT is associated with an increased risk of developing dementia in women who start using
HRT after the age of 65. Drospirenoneis an aldosterone antagonist with potassium-sparing properties. In renally-impaired patients, if
concomitant potassium-sparing drugs used, test potassium levels in the first treatment cycle. Potential interaction with hepatic enzyme inducers
and St.John’s wort. Side effects: Breakthrough bleeding and spotting is very common but decreases during the first few months of treatment.
Breast pain is also very common. Common side effects: abdominal pain or bloating, asthenia, pain in extremity,nausea, headache, mood swings,
hot flushes, nervousness, enlarged uterine fibroids, cervix neoplasm, leucorrhoea, benign breast neoplasms, breast enlargement. Uncommon
side effects: migraine, hypertension, abnormal liver function tests, hyperlipidaemia. See SPC for other uncommon side effects. Other side effects
reported with HRT include: breast cancer – risk increases with increasing duration of HRT use; endometrial cancer; venous thromboembolism;
myocardial infarction and stroke; gall bladder disease; skin and subcutaneous disorders; dementia. Legal Classification: POM Basic NHS
Price: £25.80 per 3 x 28 tablets PL Number: 0053/0341 PL Holder: Schering Health Care Ltd., The Brow, Burgess Hill, West Sussex RH15
9NE ®Angeliq is a registered trademark of Schering AG. PI revised: 2 December 04. L0505013 Date of Preparation: Aug 05