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TESTIM 50MG TRANSDERMAL GEL

Active substance(s): TESTOSTERONE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
TESTIM 50 mg Transdermal Gel

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
One single dose container of 5g contains 50 mg testosterone.

Excipient with known effect: 5 g contains 0.25 g propylene glycol.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Transdermal Gel.
A clear to translucent gel.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Testosterone replacement therapy for male hypogonadism when testosterone
deficiency has been confirmed by clinical features and biochemical tests (see
section 4.4).

4.2

Posology and method of administration
Posology
Adults and the Elderly
The recommended starting dose of TESTIM is testosterone 50mg (1 tube)/per day.
Dose titration should be based on serum testosterone levels or the persistence of
clinical signs and symptoms related to testosterone deficiency. To ensure proper
serum testosterone levels are achieved, early morning serum testosterone should be
measured before applying the next dose, approximately 7-14 days after initiation of
therapy. Currently there is no consensus about age specific testosterone levels. The
normal serum testosterone level for young eugonadal men is generally accepted to be
approximately 300 - 1000ng/dL (10.4 - 34.6nmol/L). However, it should be taken into
account that physiologically testosterone levels are lower with increasing age. If
serum testosterone concentrations are below the normal range, the daily testosterone
dose may be increased from 50mg (one tube) to 100mg (two tubes) once a day. The
duration of treatment and frequency of subsequent testosterone measurements should
be determined by the physician. Non-virilised patients may require treatment with one
tube for a longer period of time before the dose is increased, as needed. At any time

during treatment, after initial titration, the dose may need to be reduced if serum
testosterone levels are raised above the upper limit of the normal range. If morning
serum testosterone levels are above the normal range while applying 50mg (1 tube) of
TESTIM, the use of TESTIM should be discontinued. If serum testosterone levels are
below the normal limit, the dose may be increased, not exceeding 100mg per day.
Because of the variability in analytical values amongst diagnostic laboratories, all
testosterone measurements should be performed at the same laboratory.
Female population
TESTIM is not indicated for use in women.
Paediatric population
TESTIM is not indicated in children and has not been clinically evaluated in males
under 18 years of age.
Method of administration
The gel should be applied once a day, at about the same time each day, to clean, dry,
intact, skin of the shoulders and/or upper arms. It is preferable that the gel is applied
in the morning. For patients who wash in the morning, TESTIM should be applied
after washing, bathing or showering.
To apply the gel, patients should open one tube and squeeze the entire contents into
the palm of one hand. They should then apply the gel immediately to their shoulders
and/or upper arms. The gel should be spread on the skin gently as a thin layer. The
gel should then be rubbed until no gel is left on the skin. This process should then be
repeated with a second tube of TESTIM by patients who have been prescribed a daily
dose of testosterone 100mg. It is suggested that patients who require two tubes of gel
each day use both shoulders (one tube per shoulder) and/or upper arms as application
sites. Patients should thoroughly wash their hands immediately with soap and water
after TESTIM has been applied. After application of the gel, patients should allow the
application sites to dry for a few minutes and then dress with clothing that covers the
application sites.
Patients should be advised not to apply TESTIM to the genitals.

4.3

Contraindications
Androgens are contraindicated in men with carcinoma of the breast or known
or suspected carcinoma of the prostate.
Hypersensitivity to the active substance, which is chemically synthesized from
soy, or to any of the excipients listed in section 6.1.

4.4

Special warnings and precautions for use
Prior to testosterone initiation, all patients must undergo a detailed examination in
order to exclude the risk of pre-existing prostate cancer. Careful and regular
monitoring of the breast and prostate gland must be performed in accordance with
recommended methods (digital rectal examination and estimation of serum PSA) in
patients receiving testosterone therapy at least once yearly and twice yearly in elderly
patients and at risk patients (those with clinical or familial factors).

Androgens may accelerate the progression of sub-clinical prostate cancer and benign
prostatic hyperplasia.
Care should be taken in patients with skeletal metastases due to the risk of
hypercalcaemia/hypercalciuria developing from androgen therapy. In these patients,
serum calcium levels should be determined regularly.
Testosterone may cause a rise in blood pressure and TESTIM should be used with
caution in men with hypertension.
In patients suffering from severe cardiac, hepatic or renal insufficiency or ischaemic
heart disease, treatment with testosterone may cause severe complications
characterised by oedema with or without congestive cardiac failure. In this case,
treatment must be stopped immediately.
Testosterone should be used with caution in patients with epilepsy and migraine as
these conditions may be aggravated.
There are published reports of increased risk of sleep apnoea in hypogonadal subjects
treated with testosterone esters, especially in those with risk factors such as obesity or
chronic respiratory disease.
Improved insulin sensitivity may occur in patients treated with androgens who
achieve normal testosterone plasma concentrations following replacement therapy.
Certain clinical signs: irritability, nervousness, weight gain, prolonged or frequent
erections may indicate excessive androgen exposure requiring dosage adjustment.
If the patient develops a severe application site reaction, treatment should be
reviewed and discontinued if necessary.
In patients receiving long-term androgen therapy, the following laboratory parameters
should also be monitored regularly: haemoglobin, and haematocrit, liver function
tests and lipid profile.
Testosterone levels should be monitored at baseline and at regular intervals during
treatment. Clinicians should adjust the dosage individually to ensure maintenance of
eugonadal testosterone levels.
TESTIM should not be used to treat non-specific symptoms suggestive of
hypogonadism if testosterone deficiency has not been demonstrated and if other
aetiologies responsible for the symptoms have not been excluded. Testosterone
deficiency should be clearly demonstrated by clinical features and confirmed by 2
separate blood testosterone measurements before initiating therapy with any
testosterone replacement, including TESTIM treatment.
TESTIM is not a treatment for male infertility or sexual dysfunction/impotence in
patients without demonstrated testosterone deficiency. For the restoration of fertility
in patients with hypogonadotrophic hypogonadism, therapeutic measures in addition
to treatment with TESTIM are required.
Athletes treated for testosterone replacement in primary and secondary male
hypogonadism should be advised that the product contains an active substance which
may produce a positive reaction in anti-doping tests. Androgens are not suitable for
enhancing muscular development in healthy individuals or for increasing physical
ability.
TESTIM should not be used in women due to possible virilising effects.

As washing after TESTIM administration reduces testosterone levels, patients are
advised not to wash or shower for at least 6 hours after applying TESTIM. When
washing occurs up to six hours after the gel application, the absorption of testosterone
may be reduced.
TESTIM contains propylene glycol, which may cause skin irritation.
The contents of each tube are flammable.
Potential for Transfer
If no precaution is taken, testosterone gel can be transferred to other persons by close
skin to skin contact, resulting in increased testosterone serum levels and possibly
adverse effects (e.g. growth of facial and/or body hair, acne, deepening of the voice,
irregularities of the menstrual cycle) in case of repeat contact (inadvertent
androgenisation).
The physician should inform the patient carefully about the risk of testosterone
transfer and about safety instructions (see below). TESTIM should not be prescribed
in patients with a major risk of non-compliance with safety instructions (e.g. severe
alcoholism, drug abuse, severe psychiatric disorders).
This transfer is avoided by wearing clothes covering the application area or
showering prior to contact.
As a result, the following precautions are recommended:
For the patient:
− wash hands thoroughly with soap and water after applying the gel,
− cover the application area with clothing once the gel has dried,
− shower before any situation in which this type of contact is foreseen.
For people not being treated with TESTIM:




in the event of contact with an application area which has not been washed or is
not covered with clothing, wash the area of skin onto which testosterone may have
been transferred as soon as possible, using soap and water.
Report the development of signs of excessive androgen exposure such as acne or
hair modification.

To guarantee partner safety, the patient should be advised for example to observe a
long interval between TESTIM application and sexual intercourse, to wear a T-shirt
covering the application site during contact period, or to shower before sexual
intercourse.
Furthermore, it is recommended to wear a T-shirt covering the application site during
contact periods with children in order to avoid a contamination risk of children’s skin.
Pregnant women must avoid any contact with TESTIM application sites. In case of
pregnancy of the partner, the patient must reinforce his attention to the precautions for
use (see section 4.6).
There is limited experience on the safety and efficacy of the use of TESTIM in
patients over 65 years of age. Currently, there is no consensus about age specific
testosterone reference values. However, it should be taken into account that
physiologically testosterone serum levels are lower with increasing age.

4.5

Interaction with other medicinal products and other forms of interaction
When androgens are used simultaneously with anti-coagulants, the anticoagulant effects may be increased. Patients receiving oral anticoagulants
require close monitoring, especially when androgen therapy is started or
stopped.
The concurrent administration of testosterone with ACTH or corticosteroids
may enhance oedema formation; thus these drugs should be administered
cautiously, particularly in patients with cardiac or hepatic disease.
Laboratory Test Interactions: Androgens may decrease levels of thyroxinebinding 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.

4.6

Fertility, pregnancy and lactation
TESTIM is not indicated for women and must not be used in pregnant or
breastfeeding women.
Testosterone may induce virilising effects on the female foetus.
Pregnant women should avoid skin contact with TESTIM application sites.
In the event that unwashed or unclothed skin to which TESTIM has been
applied does come into direct contact with the skin of a pregnant woman, the
general area of contact on the woman should be washed with soap and water
immediately.

4.7

Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been
performed.

4.8

Undesirable effects
a. Summary of the safety profile
In double-blind clinical trials comparing TESTIM to placebo, the most frequently
observed adverse drug reactions in TESTIM treated patients were application site
erythema and increased PSA, both occurring in approximately 4% of patients.
b. Tabulated summary of adverse events
Adverse Drug Reactions terminology used for the classification of incidence: 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).
The cumulative safety experience of TESTIM is derived from Phase I to Phase III
clinical trials and post-marketing experience.
The adverse reactions listed in the table below have been observed in clinical studies
with TESTIM and/or post-marketing experience.

MedDRA
System Organ
Class (SOC)

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)

Gastrointestinal
disorders
General
disorders and
administration
site conditions

Nausea
Application
site reaction
(including
erythema,
rash and
pruritus)

Peripheral
oedema

Hepatobiliary
disorders

Investigations

Not Known*

Jaundice and
liver function
test
abnormalities
Altered blood
lipid levels,
reduction in
HDL cholesterol
and weight gain

PSA
increased,
haematocrit
increased,
haemoglobin
increased,
red blood
cell count
increased

Metabolism and
nutrition
disorders

Electrolyte
changes
(retention of
sodium,
chloride,
potassium,
calcium,
inorganic
phosphate and
water)

Musculoskeletal
and connective
tissue disorders

Muscle cramps

Neoplasms
benign,
malignant and
unspecified

Prostate Cancer

(incl cysts and
polyps)
Nervous system
disorders

Headache

Paresthesia
generalised

Psychiatric
disorders

Reproductive
system and
breast disorders

Decreased
libido, anxiety,
emotional
lability
Gynecomastia
(may develop
and persist in
patients being
treated for

Azoospermia

Increased
frequency of
erections;
testosterone
replacement
therapy of

hypogonadism
with
testosterone)

hypogonadism
can in rare cases
cause persistent,
painful erections
(priapism), and
prostate
abnormalities

Skin and
subcutaneous
tissue disorders

Acne

Pruritus

Various skin
reactions may
occur including
hirsutism,
alopecia and
seborrhoea

Vascular
disorders

Hypertension
worsened

Hot flushes/
flushing

Hypertension

*cannot be estimated from the available data, majority from post-marketing reports
and class effects of testosterone.
Patients should be instructed to report any of the following to a physician; too
frequent or persistent erections of the penis; any changes in skin colour, ankle
swelling or unexplained nausea or vomiting; any breathing disturbances including
those associated with sleep.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Reports describing overdose have included doses up to Testim 150mg. No dose
limiting toxicity has been reported from these spontaneous cases.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Androgens. ATC code: G03B A03.
Testosterone and dihydrotestosterone (DHT), endogenous androgens, are responsible
for the normal growth and development of the male sex organs and for the
maintenance of secondary sex characteristics. These effects include the growth and
maturation of the prostate, seminal vesicles, penis and scrotum; the development of
male hair distribution on the face, chest, axillae and pubis; laryngeal enlargement,
vocal chord thickening, alterations in body musculature and fat distribution.
Insufficient secretion of testosterone due to testicular failure, pituitary pathology or
gonadotropin or luteinising hormone-releasing hormone deficiency results in male
hypogonadism and low serum testosterone concentration. Symptoms associated with
low testosterone include decreased sexual desire with or without impotence, fatigue,
loss of muscle mass, mood depression and regression of secondary sexual

characteristics. Restoring testosterone levels to within the normal range can result in
improvements over time in muscle mass, mood, sexual desire, libido and sexual
function including sexual performance and number of spontaneous erections.
During exogenous administration of testosterone to normal males, endogenous
testosterone release may be decreased through feedback inhibition of pituitary
luteinising hormone (LH). With large doses of exogenous androgens,
spermatogenesis may also be suppressed through inhibition of pituitary follicle
stimulating hormone (FSH).
Androgen administration causes retention of sodium, nitrogen, potassium, phosphorus
and decreased urinary excretion of calcium. Androgens have been reported to
increase protein anabolism and decrease protein catabolism. Nitrogen balance is
improved only when there is sufficient intake of calories and protein. Androgens have
been reported to stimulate production of red blood cells by enhancing the production
of erythropoietin.

5.2

Pharmacokinetic properties
TESTIM dries very quickly when applied to the skin surface. The skin acts as a
reservoir for the sustained release of testosterone into the systemic circulation.
With once daily application of TESTIM 50mg or 100mg to adult males with early
morning serum testosterone levels ≤300ng/dL, follow up measurements at 30, 60 and
90 days after starting treatment have confirmed that serum testosterone concentrations
are generally maintained within the normal range.
Absorption
Following 50mg TESTIM daily in hypogonadal men, the Cavg was shown to be 365 ±
187ng/dL (12.7 ± 6.5nmol/L), Cmax was 538 ± 371ng/dL (18.7 ± 12.9nmol/L) and
Cmin was 223 ± 126ng/dl (7.7 ± 4.4nmol/L), measured at steady-state. The
corresponding concentrations following 100mg TESTIM daily were Cavg = 612 ±
286ng/dL (21.3 ± 9.9nmol/L), Cmax = 897 ± 566ng/dL (31.1 ± 19.6nmol/L) and Cmin =
394 ± 189ng/dL (13.7 ± 6.6nmol/L). Steady state is reached by day 7. Steady state
may be reached at an earlier time-point although the timing for this was not
determined from the clinical studies.
In the young eugonadal man, normal levels of serum testosterone are in the range of
300 - 1000ng/dL (10.4 - 34.6nmol/L).
The measurement of serum testosterone levels can be variable depending on the
laboratory and method of assay used (see section 4.2).
Distribution
Circulating testosterone is chiefly bound in the serum to sex hormone-binding
globulin (SHBG) and albumin. The albumin-bound fraction of testosterone easily
dissociates from albumin and is presumed to be bioactive. The portion of testosterone
bound to SHBG is not considered biologically active. Approximately 40% of
testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is
bound to albumin and other proteins.
Biotransformation
There is considerable variation in the half-life of testosterone as reported in the
literature, ranging from ten to 100 minutes.

Testosterone is metabolised to various 17-keto steroids through two different
pathways. The major active metabolites of testosterone are oestradiol and
dihydrotestosterone (DHT). Testosterone is metabolised to DHT by steroid 5α
reductase located in the skin, liver and the urogenital tract of the male. DHT binds
with greater affinity to SHBG than does testosterone. In many tissues, the activity of
testosterone depends on its reduction to DHT, which binds to cytosol receptor
proteins. The steroid-receptor complex is transported to the nucleus where it initiates
transcription and cellular changes related to androgen action. In reproductive tissues,
DHT is further metabolised to 3-α and 3-β androstanediol.
Inactivation of testosterone occurs primarily in the liver.
DHT concentrations increased during TESTIM treatment. After 90 days of treatment,
mean DHT concentrations remained within the normal range for TESTIM treated
subjects.
Elimination
About 90% of testosterone given intramuscularly is excreted in the urine as
glucuronic and sulphuric acid conjugates of testosterone and its metabolites; about
6% of a dose is excreted in the faeces, mostly in the unconjugated form.
Special Patient groups:
In patients treated with TESTIM no differences in the average daily serum
testosterone concentration at steady state were observed based on age or cause of
hypogonadism.

5.3

Preclinical safety data
Toxicological studies have not revealed effects other than those which can be
explained based on the hormonal profile of Testim.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Purified water
Pentadecalactone
Carbomer 980
Carbomer copolymer
Propylene glycol
Glycerol
Macrogol 1000
Ethanol
Trometamol

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
24 months

6.4

Special precautions for storage
Do not store above 25ºC
This medicinal product is flammable and should be protected from direct
sunlight.

6.5

Nature and contents of container
Testim is supplied in unit dose aluminium tubes with epoxy phenolic liners and screw
caps, each containing 5g gel.
The tubes are packed in cartons containing 7, 14, 30 or 90 tubes.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in
accordance with local requirements.

7

MARKETING AUTHORISATION HOLDER
Ferring Pharmaceuticals Ltd
Drayton Hall
Church Road
West Drayton
UB7 7PS

8

MARKETING AUTHORISATION NUMBER(S)
PL 03194/0105

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
20/06/2003

10

DATE OF REVISION OF THE TEXT
18/12/2015

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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