Intrinsa

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Intrinsa 300 micrograms/24 hours transdermal patch 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each patch of 28 cm2 contains 8.4 mg testosterone and provides 300 micrograms of testosterone per 
24 hours. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Transdermal patch. 
 
Thin, clear, oval matrix-type transdermal patch consisting of three layers: a translucent backing film, 
an adhesive matrix drug layer, and a protective release liner that is removed prior to application. Each 
patch surface is stamped with T001. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Intrinsa is indicated for the treatment of hypoactive sexual desire disorder (HSDD) in bilaterally 
oophorectomised and hysterectomised (surgically induced menopause) women receiving concomitant 
estrogen therapy. 
 
4.2 Posology and method of administration 
 
Posology 
 
The recommended daily dose of testosterone is 300 micrograms. This is achieved by applying the 
patch twice weekly on a continuous basis. The patch should be replaced with a fresh patch every 3 to 
4 days. Only one patch is to be worn at a time. 
 
Concomitant estrogen treatment 
The appropriate use and restrictions associated with estrogen therapy should be considered before 
Intrinsa therapy is initiated and during routine re-evaluation of treatment. Continued use of Intrinsa is 
only recommended while concomitant use of estrogen is considered appropriate (i.e. the lowest 
effective dose for the shortest possible duration).  
 
Patients treated with conjugated equine estrogen (CEE) are not recommended to use Intrinsa, as 
efficacy has not been demonstrated (see sections 4.4 and 5.1). 
 
Duration of treatment 
Intrinsa treatment response should be evaluated within 3-6 months of initiation, to determine if 
continued therapy is appropriate. Patients who do not experience a meaningful benefit should be re-
evaluated and discontinuation of therapy be considered.  
 
As the efficacy and safety of Intrinsa have not been evaluated in studies of longer duration than 1 year, 
it is recommended that an appraisal of the treatment is undertaken every 6 months. 
 

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Special populations 
 
Renal impairment 
No studies have been conducted in patients with renal insufficiency. 
 
Hepatic impairment 
No studies have been conducted in patients with hepatic impairment. 
 
Elderly 
Intrinsa is recommended for use in surgically menopausal women up to the age of 60. Consistent with 
the prevalence of HSDD, there are limited data above the age of 60.  
 
Paediatric population 
There is no relevant use of Intrinsa in the paediatric population. 
 
Method of administration  
 
The adhesive side of the patch should be applied to a clean, dry area of skin on the lower abdomen 
below the waist. A particular application site should be rotated with an interval of at least 7 days 
between applications. Patches should not be applied to the breasts or other body regions. A skin site 
with minimal wrinkling and not covered by tight clothing is recommended. The site should not be oily, 
damaged, or irritated. To prevent interference with the adhesive properties of Intrinsa, no creams, 
lotions or powder should be applied to the skin where the patch is to be applied. 
 
The patch should be applied immediately after opening the sachet and removing both parts of the 
protective release liner. The patch should be pressed firmly in place for about 10 seconds, making sure 
there is good contact with the skin, especially around the edges. If an area of the patch lifts, pressure 
should be applied to that area. If the patch detaches prematurely, it may be reapplied. If the same patch 
cannot be reapplied, a new patch should be applied to another location. In either case, the original 
treatment regimen should be maintained. The patch is designed to remain in place during a shower, 
bath, swimming or exercising. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients. 
Known, suspected or past history of cancer of the breast or known or suspected estrogen-dependent 
neoplasia, or any other condition consistent with the contraindications for the use of estrogen. 
 
4.4 Special warnings and precautions for use 
Special warnings 
 
Androgenic reactions 
At regular intervals during treatment, physicians should monitor patients for potential androgenic 
undesirable reactions (e.g. acne, changes in hair growth or hair loss). Patients should be advised to self 
assess for androgenic undesirable effects. Signs of virilisation, such as voice deepening, hirsutism or 
clitoromegaly, may be irreversible and discontinuation of treatment should be considered. In clinical 
trials these reactions were reversible in the majority of patients (see section 4.8). 
 
Hypersensitivity 
Severe skin erythema, local oedema and blistering may occur due to hypersensitivity to the patch at 
the site of application. Use of the patch should be discontinued if this occurs. 
 
Long-term safety, including breast cancer 
The safety of Intrinsa has not been evaluated in double blind placebo controlled studies of longer than 
1 year duration. There is little information on long-term safety, including effects on breast tissue, the 
cardiovascular system and increase in insulin resistance. 

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Data in the literature regarding the influence of testosterone on the risk of breast cancer in women are 
limited, inconclusive and conflicting. The long-term effect of testosterone treatment on the breast is 
currently unknown, therefore patients should be carefully monitored with regard to breast cancer in 
accordance with currently accepted screening practises and individual patient needs. 
 
Cardiovascular disease 
Patients with known cardiovascular disease have not been studied. Patients with cardiovascular risk 
factors, in particular hypertension, and patients with known cardiovascular disease should be carefully 
monitored, specifically regarding changes in blood pressure and weight. 
 
Diabetic patients 
In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore 
insulin requirements. Patients with diabetes mellitus have not been studied. 
 
Endometrial effects 
Little information is available on the effects of testosterone on the endometrium. The limited data 
evaluating the effect of testosterone on the endometrium neither allow conclusions nor reassurances on 
the incidence of endometrial cancer. 
 
Oedema 
Oedema (with or without congestive heart failure) may be a serious complication from high doses of 
testosterone or other anabolic steroids in patients with pre-existing cardiac, renal, or hepatic disease. 
However, this is not expected from the low dose of testosterone delivered by the Intrinsa patch. 
 
Precautions for use 
 
Intrinsa should not be used in naturally menopausal women 
Efficacy and safety of Intrinsa in naturally menopausal women with HSDD on concomitant estrogen, 
with or without progestogen, have not been evaluated. Intrinsa is not recommended in naturally 
menopausal women. 
 
Intrinsa should not be used in women on concomitant CEE 
Whereas Intrinsa is indicated with concomitant estrogen therapy, the subgroup of patients receiving 
oral conjugated equine estrogens (CEE) did not demonstrate a significant improvement in sexual 
function. Therefore, Intrinsa should not be used in women on concomitant CEE (see sections 4.2 and 
5.1). 
 
Thyroid hormone levels 
Androgens may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum 
levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, 
however, and there is no clinical evidence of thyroid dysfunction. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. When testosterone is given concomitantly with 
anticoagulants, the anticoagulant effect may increase. Patients receiving oral anticoagulants require 
close monitoring, especially when testosterone therapy is started or stopped. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Intrinsa must not be used in women who are or may become pregnant.  
 
Testosterone may induce virilising effects on the female foetus when administered to a pregnant 
woman. Studies in animals have shown reproductive toxicity (see section 5.3). 
 
In case of inadvertent exposure during pregnancy, use of Intrinsa must be discontinued. 

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Breastfeeding 
Intrinsa must not be used by breast-feeding women. 
 
Fertility 
No data is available of the effect of Intrinsa on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Intrinsa has no influence on the ability to drive and use machines. However, patients should be 
informed that migraine, insomnia, disturbance in attention and diplopia have been reported during 
treatment with Intrinsa. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The adverse reaction most often reported (30.4 %) was application site reactions. The majority of these 
adverse reactions consisted of mild erythema and itching and did not result in patient withdrawal. 
 
Hirsutism was also very commonly reported. Most reports concerned the chin and upper lip, were mild 
(≥ 90 %), and less than 1 % of all patients withdrew from the studies due to hirsutism. Hirsutism was 
reversible in the majority of patients. 
 
Other androgenic reactions commonly reported were acne, voice deepening and alopecia. More than 
90 % of these reports were considered mild. These reactions were reversible in the majority of 
patients. Less than 1 % of patients withdrew from the studies because of any of these reactions. All 
other common adverse reactions resolved in the majority of patients. 
 
Tabulated list of adverse reactions 
During 6-month double blind exposure the following adverse reactions occurred in the treatment group 
(n=549) at a greater incidence than placebo (n=545) and were assessed by the investigators as possibly 
or probably related to Intrinsa treatment. If an adverse reaction occurred at a higher frequency in the 
integrated phase III studies (Intrinsa patients n=1,498, placebo patients n=1,297), this frequency is 
reported in the table. Frequencies are defined as 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), or very rare (< 1/10,000), not known 
(cannot be estimated from the available data). 
 
MedDRA  
System organ class 

Very common 
 

Common 
 

Uncommon 
 

Infections and infestations   Sinusitis 
Blood and lymphatic system 
disorders 

  Abnormal clotting factor 

Immune system disorders   Hypersensitivity 
Metabolism and nutrition 
disorders 

  Increased appetite 

Psychiatric disorders  Insomnia Agitation, anxiety 
Nervous system disorders  Migraine Disturbance in attention, 

dysgeusia, impaired balance, 
hyperaesthesia, oral 
paraesthesia, transient 
ischemic attack 

Eye disorders   Diplopia, eye redness  
Cardiac disorders   Palpitations 
Respiratory, thoracic and 
mediastinal disorders 

 Voice 
deepening 

Nasal congestion, throat 
tightness 

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MedDRA  
System organ class 

Very common 
 

Common 
 

Uncommon 
 

Gastrointestinal disorders  Abdominal 
pain 

Diarrhoea, dry mouth, 
nausea  

Skin and subcutaneous tissue 
disorders 

Hirsutism Acne, alopecia Eczema, increased sweating, 
rosacea 

Musculoskeletal and connective 
tissue disorders 

  Arthritis 

Reproductive system and breast 
disorders 

 Breast pain  Breast cyst, clitoral 
engorgement, enlarged 
clitoris, genital pruritus, 
vaginal burning sensation 

General disorders and 
administration site conditions 

Application site 
reaction 
(erythema, 
itching) 

 Anasarca, asthenia, chest 
tightness, chest discomfort 

Investigations  Increased 
weight  

Abnormal blood fibrinogen, 
increased heart rate, 
increased alanine 
aminotransferase, increased 
aspartate aminotransferase, 
increased blood bilirubin, 
abnormal liver function test, 
increased blood triglycerides 

 
 
4.9 Overdose 
 
The mode of administration of Intrinsa makes overdose unlikely. Removal of the patch results in a 
rapid decrease in serum testosterone levels (see section 5.2). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Sex hormones and modulators of the genital system, androgens, ATC 
code: G03BA03 
 
Mechanism of action 
Testosterone, the primary circulating androgen in women, is a naturally occurring steroid, secreted by 
the ovaries and adrenal glands. In premenopausal women, the rate of production of testosterone is 100 
to 400 micrograms/24 hours, of which half is contributed by the ovary as either testosterone or a 
precursor. Serum levels of androgens fall as women age. In women, who have undergone bilateral 
oophorectomy, serum levels of testosterone decline by approximately 50 % within days after surgery. 
 
Intrinsa is a transdermal therapy for HSDD, which improves sexual desire while achieving 
testosterone concentrations compatible with premenopausal levels. 
 
Clinical efficacy and safety 
Two multi-centre, double-blind, placebo-controlled six month studies in 562 (INTIMATE SM1) and 
533 (INTIMATE SM2) oophorectomised and hysterectomised women (surgically induced 
menopause), aged 20 to 70 years, with HSDD on concomitant estrogen were used to evaluate the 
efficacy and safety of Intrinsa. Total satisfying sexual activity (primary endpoint), sexual desire, and 
distress associated with low sexual desire (secondary endpoints) were evaluated with validated 
instruments. 

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In the combined study analysis at 24 weeks, the difference in the mean frequency of total satisfying 
episodes between Intrinsa and placebo was 1.07 per 4 weeks. 
 
A significantly higher percentage of women who received Intrinsa reported a benefit in the three 
endpoints, that they considered clinically meaningful compared to women who received placebo. In 
the combined phase III data, excluding patients taking oral CEE, in whom there was no significant 
improvement in sexual function, 50.7 % of women (n=274) treated with Intrinsa and 29.4 % of those 
treated with placebo (n=269) were responders with regard to total satisfying sexual activity (primary 
endpoint), when a responder was predefined as having an increase in the 4-week frequency of 
satisfying activities of > 1. 
 
Effects of Intrinsa were observed at 4 weeks after initiation of therapy (the first measured time point) 
and at all monthly efficacy time points thereafter. 
 
Efficacy versus placebo was significant across a range of subgroups which included patients separated 
by the following baseline characteristics: age (all subgroups up to age 65 years); body weight (up to 
80 kg) and oophorectomy (up to 15 years ago). 
 
Subgroup analyses suggested that the route and type of concomitant estrogen (transdermal oestradiol, 
oral conjugated equine estrogen (CEE), oral non-CEE) can influence patient response. A responder 
analysis of the pivotal phase II and III studies showed significant improvements in all three major 
clinical endpoints versus placebo in patients on concomitant transdermal and oral non-CEE estrogens. 
However, the subgroup of patients receiving oral CEE did not demonstrate a significant improvement 
in sexual activity compared to placebo (see sections 4.2 and 4.4). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Testosterone from Intrinsa is transported across intact skin by a passive diffusion process that is 
primarily controlled by permeation across the stratum corneum. Intrinsa is designed to systemically 
deliver 300 micrograms/day. Following application of the patch on abdominal skin, maximum serum 
concentrations of testosterone are reached within 24-36 hours, with a wide inter-individual variability. 
Serum concentrations of testosterone attain steady-state by the application of the second patch when 
applied in a twice-a-week regimen. Intrinsa did not influence serum concentrations of sex hormone 
binding globulin (SHBG), estrogens or adrenal hormones. 
 
Serum concentrations of testosterone and SHBG in patients receiving Intrinsa in clinical safety and 
efficacy studies 
Hormone Baseline Week 24 Week 52 
 N Mean (SEM) N Mean (SEM) N Mean (SEM) 
Free testosterone 
(pg/ml) 

544 0.92 (0.03) 412 4.36 (0.16) 287 4.44 (0.31) 

Total testosterone 
(ng/dl) 

547 17.6 (0.4) 413 79.7 (2.7) 288 74.8 (3.6) 

DHT (ng/dl) 271 7.65 (0.34) 143 20.98 (0.98) 169 21.04 (0.97) 
SHBG (nmol/l) 547  91.7 (2.5) 415 93.9 (2.8) 290 90.0 (3.6) 
DHT = dihydrotestosterone, SHBG = sex hormone binding globulin 
SEM = Standard Error of the Mean 
 
Distribution 
In women, circulating testosterone is primarily bound in the serum to SHBG (65-80 %) and to albumin 
(20-30 %) leaving only about 0.5-2 % as the free fraction. The affinity of binding to serum SHBG is 
relatively high and the SHBG bound fraction is regarded as not contributing to biological activity. 
Binding to albumin is of relatively low affinity and is reversible. The albumin-bound fraction and the 
unbound fraction are collectively termed ‘bioavailable’ testosterone. The amount of SHBG and 
albumin in serum and the total testosterone concentration determine the distribution of free and 

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bioavailable testosterone. Serum concentration of SHBG is influenced by the route of administration 
of concomitant estrogen therapy. 
 
Biotransformation 
Testosterone is metabolised primarily in the liver. Testosterone is metabolised to various 
17-ketosteroids and further metabolism results in inactive glucuronides and other conjugates. The 
active metabolites of testosterone are estradiol and dihydrotestosterone (DHT). DHT has a greater 
affinity to SHBG than does testosterone. DHT concentrations increased in parallel with testosterone 
concentrations during Intrinsa treatment. There were no significant differences in serum estradiol and 
estrone levels in patients treated with Intrinsa for up to 52 weeks compared to baseline. 
 
On removal of an Intrinsa patch, testosterone serum concentrations return to near baseline values 
within 12 hours due to its short terminal exponential half-life (approximately 2 hours). There was no 
evidence of accumulation of testosterone over 52 weeks of treatment. 
 
Elimination 
Testosterone is mainly excreted in the urine as glucuronic and sulphuric acid conjugates of 
testosterone and its metabolites. 
 
5.3 Preclinical safety data 
 
Toxicological studies of testosterone have only revealed effects which can be explained based on the 
hormone profile. 
 
Testosterone has been found to be nongenotoxic. Non-clinical studies on a relationship between 
testosterone treatment and cancer suggest that high doses may promote tumour growth in sex organs, 
mammary glands and liver in laboratory animals. The significance of these data for the use of Intrinsa 
in patients is not known. 
 
Testosterone has a masculinising effect on female rat foetuses when dosed subcutaneously at 0.5 or 
1 mg/day (as the propionate ester) to pregnant rats during organogenesis.   
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Backing layer 
Translucent polyethylene backing film  
Printing ink  
sunset yellow FCF (E110) 
latolrubine BK (E180) 
copper phthalocyanine blue pigment.  
 
Self adhesive matrix drug layer 
Sorbitan oleate  
Acrylic co-polymer adhesive containing 2-Ethylhexylacrylate – 1-Vinyl-2-pyrrolidone co-polymer. 
 
Protective release liner 
Siliconised polyester film 
 
6.2 Incompatibilities 
 
Not applicable. 
 

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6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
Do not refrigerate or freeze. 
 
6.5 Nature and contents of container 
 
Each patch is packed in a sealed laminated sachet. The sachet material comprises of food grade 
paper/LDPE/aluminium foil/ethylene methacrylic acid copolymer (outer to inner layer). The ethylene 
methacrylic acid copolymer (Surlyn) is the heat seal layer which allows the two laminate sachet stocks 
to be heat-sealed together to form the sachet. 
Cartons of 2, 8 and 24 patches. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
The transdermal patch should not be flushed down the toilet. 
 
The used patch should be folded in half, sticking the patch to itself, and discarded in a safe way in 
order to keep it away from children (e.g in a rubbish bin). 
 
Any unused product or waste material should be disposed of in accordance with local requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Warner Chilcott UK Limited 
Old Belfast Road 
Millbrook, Larne 
County Antrim 
BT40 2SH 
United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/352/001-003 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28-July-2006 
Date of latest renewal: 28-July-2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

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 10 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR 

BATCH RELEASE 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 

 

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A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer(s) responsible for batch release 
 
Warner Chilcott Deutschland GmbH 
Dr.-Otto-Röhm-Strasse 2-4 
64331 Weiterstadt 
Germany 
 
Warner Chilcott France 
Parc d’activité de la Grande Brèche 
5 rue Désir Prévost 
91070 Bondoufle 
France 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to medical prescription. 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 
• OTHER CONDITIONS 
 
Pharmacovigilance system 
 
The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1 of the 
Marketing Authorisation, is in place and functioning before and whilst the product is on the market. 
The MAH will continue to submit 6 monthly PSURs unless otherwise specified by CHMP. 
 
Risk Management plan 
 
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in 
the Pharmacovigilance Plan, as agreed in the Risk Management Plan (RMP) dated 
19-September-2010, presented in Module 1.8.2. of the Marketing Authorisation and any subsequent 
updates of the RMP agreed by the CHMP. 
 
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, any 
updated RMP should be submitted at the same time as the following Periodic Safety Update Report 
(PSUR). 
 
In addition, an updated RMP should be submitted: 
• When new information is received that may impact on the current Safety Specification, 

Pharmacovigilance Plan or risk minimisation activities 
• Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 

reached 
• At the request of the European Medicines Agency 

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 12 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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 13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (Box of 2, 8 or 24 patches) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Intrinsa 300 micrograms/24 hours transdermal patch 
Testosterone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 patch of 28 cm2 contains 8.4 mg of testosterone and provides 300 micrograms per 24 hours. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: Sorbitan oleate, 2-Ethylhexylacrylate – 1-Vinyl-2-pyrrolidone copolymer, E110, E180, 
copper phthalocyanine blue pigment, polyethylene, siliconised polyester film. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
2 transdermal patches  
8 transdermal patches 
24 transdermal patches 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Apply immediately upon removal from the sachet. 
 
Read the package leaflet before use. 
 
Transdermal use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 

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9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
Do not refrigerate or freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Warner Chilcott UK Limited 
Old Belfast Road 
Millbrook, Larne 
County Antrim 
BT40 2SH 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/352/001-003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Intrinsa  
 
 

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--------------------------------------------------------------------------------------------------------------------------- 
 
Tuck flap here to close. 
 
Information to appear on the inside of the flap 
 
When to apply the patch: 
The patch needs to be changed twice weekly. Choose your two days and tick the box. Change the 
patch only on these two days. 
o Sunday + Wednesday 
o Monday + Thursday 
o Tuesday + Friday 
o Wednesday + Saturday 
o Thursday + Sunday  
o Friday + Monday 
o Saturday + Tuesday  
 
Continue to use for as long as your doctor prescribes. 
 
 

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 17 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SACHET 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Intrinsa 300 micrograms/24 hours transdermal patch 
Testosterone 
Transdermal use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 transdermal patch 
 
1 patch of 28 cm2 contains 8.4 mg of testosterone and provides 300 micrograms per 24 hours. 
 
 

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 18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Intrinsa 300 micrograms/24 hours transdermal patch 
Testosterone 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
 
In this leaflet: 
1. What Intrinsa is and what it is used for 
2. Before you use Intrinsa 
3. How to use Intrinsa 
4. Possible side effects 
5. How to store Intrinsa 
6. Further information 
 
 
1. WHAT INTRINSA IS AND WHAT IT IS USED FOR 
 
Intrinsa is a transdermal patch which constantly releases small amounts of testosterone that is absorbed 
through your skin into the bloodstream. The testosterone in Intrinsa is the same hormone as that 
produced naturally in men and women. 
 
After removal of the ovaries, testosterone drops to half of the levels compared to before the operation. 
Decrease in testosterone has been associated with low sexual desire, reduced sexual thoughts and 
reduced sexual arousal. All or any of these problems can cause personal distress or relationship 
difficulties. The medical term for this condition is Hypoactive Sexual Desire Disorder, also known as 
HSDD. 
 
Intrinsa is used to treat HSDD. 
Intrinsa is intended for use by women up to the age of 60 years who: 
- have a low sexual desire which is causing distress or concern, and 
-  have had both of their ovaries removed, and 
-  have had their womb removed (hysterectomy), and 
-  are receiving estrogen therapy. 
 
It may take longer than one month for you to notice an improvement. If you have not experienced a 
positive effect of Intrinsa within 3-6 months, you should inform your doctor, who will suggest that 
treatment be discontinued. 
 
 
2. BEFORE YOU USE INTRINSA 
 
Do not use Intrinsa 
-  if you are allergic (hypersensitive) to testosterone or any of the other ingredients of Intrinsa (see 

section ‘Further information’ at the end of this leaflet). 
-  if you know that you have had in the past, currently have, or think that you might have, breast 

cancer or any other cancer which your doctor has described as being caused or stimulated by the 
female hormone estrogen, also called ‘estrogen-dependent’ cancers. 

-  if you have other conditions that your doctor may consider not appropriate for the use of 
estrogen and/or testosterone. 

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Take special care with Intrinsa 
-  if you have a history of heart, liver or kidney disease. Oedema may be a serious complication 

from high doses of testosterone, however, this is not expected from low dose of testosterone 
delivered by the Intrinsa patch. 

-  if you have cancer of the lining of the womb (endometrial cancer), be aware that there is little 
information available on the effects of testosterone on the lining of the womb (endometrium). 

-  if you are diabetic, as testosterone may lower blood glucose levels. 
-  if you have a history of excessive adult acne, body or facial hair, hair loss, enlargement of the 

clitoris or voice deepening or hoarseness. 
 
If you have any of the above, tell your doctor before you start to use Intrinsa. Your doctor will advise 
you on what you should do. 
 
The efficacy of Intrinsa is reduced if your estrogen therapy is of a certain type (‘conjugated equine 
estrogens’). Therefore, you need to discuss your type of estrogen with your doctor, who could advise 
you which type of estrogen is suitable together with Intrinsa. 
 
If you stop estrogen therapy you must also stop using Intrinsa. Keep in mind that estrogens should be 
administered for the shortest possible duration.  
 
Use Intrinsa only as long as you experience a positive effect of the treatment. There is no information 
on the safety of Intrinsa beyond 12 months. 
 
There are limited data about the use in women above the age of 60. Intrinsa is intended for use by 
women up to the age of 60 years who have had both their ovaries and their womb removed.  
 
It is not known whether Intrinsa increases the risk of breast cancer and endometrium cancer. Your 
doctor will carefully monitor you with regard to breast cancer and endometrium cancer. 
 
Children and adolescents 
Intrinsa is not for use in children and adolescents. 
 
Taking other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without prescription. 
 
Tell your doctor if you are taking blood-thinning (anticoagulant) treatment. 
 
Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. 
Intrinsa is only indicated for women in their menopause after the ovaries and uterus have been 
removed. Do not use Intrinsa if you are, or suspect that you may be pregnant or are able to become 
pregnant, because it may cause harm to the unborn child. 
Do not use Intrinsa in case of breast-feeding because it may cause harm to the child. 
 
Driving and using machines 
You can drive and use machines while using Intrinsa. 
 
 
3. HOW TO USE INTRINSA 
 
Always use Intrinsa exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure of the instructions or if you want any more information. The usual dose 
is one patch twice weekly (each 3 to 4 days), see below ‘How and when to change your patch’. The 
active substance is released from the patch constantly over 3 to 4 days (corresponding to 300 
micrograms per 24 hours) and is absorbed through your skin. 

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 21 

 
Where to stick the patch 
-  Stick the patch onto your lower abdomen, below your waist. Do not stick the patch on the 

breasts or bottom. 
 

  
 

Make sure that your skin at the application site is: 
 clean and dry (free of lotions, moisturisers, and powders) 
 as smooth as possible (no major creases or skin folds) 
 not cut or irritated (free of rashes or other skin problems) 
 unlikely to be rubbed by clothing excessively 
 preferably free from hair. 

 
-  When changing your patch, stick the new patch on to a different area of the skin of your 

abdomen, otherwise you are more likely to cause skin irritation. 
 
-  Only one patch is to be worn at a time. 
 
-  If you are also using estrogen patches, make sure that the Intrinsa patch and the estrogen patch 

do not overlap. 
 
-  For at least one week after removing a patch, do not place a new patch in the same area. 
 
How to stick on the patch 
Step 1 Tear open the sachet. Do not use scissors as you may accidentally damage the patch. Remove 

the patch. Apply the patch immediately after removing it from the sachet. 
 

 
 
Step 2 While holding the patch, remove half of the protective liner that covers the sticky part of the 

patch. Avoid touching the sticky side of the patch with your fingers. 
 

 
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Step 3 Apply the sticky side of the patch to the selected area onto your skin. Press the sticky side of 
the patch firmly into place for about 10 seconds. 

 

 
 
Step 4 Fold back the patch and carefully remove the other half of the liner. Press the entire patch 

firmly against your skin with the palm of your hand for about 10 seconds. Use your fingers to 
make sure the edges of the patch stick to the skin. If an area of the patch lifts, apply pressure to 
that area. 

 

 
 
 
How and when to change your patch 
- You will need to change your patch every 3 to 4 days, which means using two patches each 

week. This will mean that you wear one patch for 3 days and the other for 4 days. Decide which 
two days each week you are going to change your patch, and change the patch on the same two 
days each week.   

 
For example: If you decide to start treatment on a Monday, then you have to change your patch 
always on a Thursday and a Monday. 
 

o Sunday + Wednesday 
 Monday + Thursday 
o Tuesday + Friday 
o Wednesday + Saturday 
o Thursday + Sunday 
o Friday + Monday 
o Saturday + Tuesday 

 
 As a reminder, mark on the outer carton your chosen patch-change days. 
 
-  On the patch-change day, remove the used patch and immediately stick the new patch on to a 

different area of skin of your abdomen. Continue your treatment for as long as your doctor 
advises. 

 
-  Fold the used patch in half, sticking the patch to itself, and discard it in a safe way in order to 

keep it away from children (e.g. in a rubbish bin). Medicines should not be disposed of via 
wastewater (do not flush it down the toilet). Ask your pharmacist how to dispose of medicines 
no longer required. These measures will help to protect the environment. 

 
What about showering, bathing and exercising? 
You may shower, bath, swim and exercise as normal while wearing the patch. The patch is designed to 
remain in place during these times. However, do not scrub the area where the patch has been placed 
too hard. 
 
What about sunbathing? 
Always make sure your patch is covered by clothing. 

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 23 

 
What if your patch becomes loose, lifts at the edges or falls off? 
If a patch does begin to come off, you may be able to make it stick again by pressing on it firmly. If 
you cannot get the patch to stick successfully, remove the loose patch and use a new patch. Then 
continue with your regular schedule of patch-change days, even if this means discarding a patch after 
you have worn it for less than 3-4 days. 
 
If you use more patches than you should 
If you have applied more than one patch at a time 
Remove all the patches sticking on to your skin and consult your doctor or pharmacist for further 
information on how to continue treatment with Intrinsa. Overdosing with Intrinsa is unlikely when 
used as directed, because once the patch is taken off testosterone is quickly removed by the body. 
 
If you forget to use a patch 
If you forget to change your patch 
Change your patch as soon as you remember, and then continue with your regular schedule of patch-
change days, even if this means discarding a patch after you have worn it for less than 3-4 days. 
Returning to your regular schedule will help you remember when to change your patch. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Intrinsa can cause side effects, although not everybody gets them.  
 
Tell your doctor immediately: 
- if you experience hair loss (a common side effect which may affect up to 1 in 10 people), 

enlargement of the clitoris (an uncommon side effect which may affect up to 1 in 100 people), 
an increase in the amount of hair on the chin or upper lip (a very common side effect which may 
affect more than 1 in 10 people), voice deepening or hoarseness (a common side effect), 
although these side effects may be mild. They are usually reversible if Intrinsa treatment is 
discontinued. 

 
You should self assess for increased acne (a common side effect), increased hair growth on your 
face, loss of hair, deepening of your voice or enlargement of your clitoris, which all could be 
signs of side effects of testosterone, which is the active substance in Intrinsa. 

 
-  if you notice any skin reactions at the site of application (a very common side effect) such as 

redness, oedema, or blistering. In case of severe application site reaction, the treatment should 
be discontinued. 

 
Other common side effects  
Most of them are mild in nature and reversible. 
-  migraine 
- insomnia/inability to sleep properly 
-  breast pain 
-  weight gain 
-  stomach pain 
 
Other uncommon side effects  
Most of them are mild in nature and reversible. 
- sinusitis (inflammation of nasal sinus) 
- abnormal clotting factor 
- hypersensitivity (allergic reactions) 
- increased appetite 
- agitation 

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- anxiety 
- disturbance in attention 
- dysgeusia (distorted sense of taste) 
- impaired balance 
- hyperaesthesia (abnormal increase in sensitivity to stimuli of the senses) 
- oral paraesthesia (tingling or numb sensation in the mouth) 
- transient ischemic attack (mini stroke) 
- diplopia (double vision) 
- eye redness 
- palpitations (rapid and irregular heart beat) 
- nasal congestion 
- throat tightness 
- diarrhoea 
- dry mouth 
- nausea 
- eczema 
- increased sweating 
- rosacea (redness of the face) 
- arthritis 
- breast cyst 
- clitoral engorgement 
- genital pruritus (genital itching sensation) 
- vaginal burning sensation 
- anasarca (widespread swelling of the skin) 
- asthenia (lack of energy and strength) 
- chest tightness 
- chest discomfort 
- abnormal blood fibrinogen (abnormal blood clotting) 
- increased heart rate 
- increased alanine aminotransferase, increased aspartate aminotransferase, increased blood 

bilirubin, abnormal liver function test, increased blood triglycerides (all measures of liver 
function). 

 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor. 
 
 
5. HOW TO STORE INTRINSA 
 
-  Keep out of the reach and sight of children 
-  Do not use Intrinsa after the expiry date which is stated on the carton and sachet after EXP. The 

expiry date refers to the last day of that month. 
-  Do not store above 30°C. 
-  Do not refrigerate or freeze. 
- Medicines should not be disposed of via wastewater (do not flush it down the toilet) or 

household waste. Ask your pharmacist how to dispose of medicines no longer required. These 
measures will help to protect the environment. 

 
 
6. FURTHER INFORMATION 
 
What Intrinsa contains 
The active substance is testosterone. Each patch contains 8.4 mg of testosterone, releasing 
300 micrograms of testosterone over 24 hours. 
 
The other ingredients are: Sorbitan oleate, 2-Ethylhexylacrylate – 1-Vinyl-2-pyrrolidone co-polymer. 
Backing layer 

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Translucent polyethylene backing film printed with ink containing sunset yellow FCF (E110), 
latolrubine BK (E180) and copper phthalocyanine blue pigment. 
Protective release liner 
Siliconised polyester film. 
 
What Intrinsa looks like and contents of the pack 
Intrinsa is a thin, clear, oval patch with T001 stamped on the back. 
Each patch is sealed in a sachet. 
The following pack sizes are available: 2, 8 and 24 patches. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Warner Chilcott UK Limited 
Old Belfast Road 
Millbrook, Larne 
County Antrim 
BT40 2SH 
United Kingdom 
 
Manufacturer 
Warner Chilcott Deutschland GmbH 
Dr.-Otto-Röhm-Strasse 2-4 
64331 Weiterstadt 
Germany 
 
Warner Chilcott France 
Parc d’activité de la Grande Brèche 
5 rue Désir Prévost 
91070 Bondoufle 
France 
 
 
This leaflet was last approved in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
 

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 26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

GROUNDS FOR ONE ADDITIONAL RENEWAL 
 

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Grounds for one additional renewal 
 
Based upon the data that have become available since the granting of the initial Marketing 
Authorisation, the CHMP considers that the benefit-risk balance of Intrinsa remains positive, but 
considers that its safety profile is to be closely monitored for the following reasons: 
 
The off-label use is a safety risk. It is a CHMP concern that the data from the THIN (The Health 
Improvement Database) study suggests that approx 70% of the users are outside indication. 
 
The CHMP decided that the MAH should continue to submit 6 monthly PSURs. 
 
Therefore, based on the safety profile in Intrinsa, which requires the submission of 6 monthly PSURs, 
the CHMP concluded that the MAH should submit one additional renewal application in 5 years time. 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET
	GROUNDS FOR ONE ADDITIONAL RENEWAL