CAVERJECT 40 MICROGRAMS POWDER FOR SOLUTION FOR INJECTION

Active substance: ALPROSTADIL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Caverject 40 micrograms powder for solution for injection.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Alprostadil 40 micrograms
When reconstituted, each 1ml delivers a dose of 40 micrograms of alprostadil.
For excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Powder for solution for injection
Powder: A white to off-white powder.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Caverject is indicated for the treatment of erectile dysfunction in adult males
due to neurogenic, vasculogenic, psychogenic or mixed aetiology.
Caverject may be a useful adjunct to other diagnostic tests in the diagnosis of
erectile dysfunction.

4.2

Posology and method of administration
Caverject is administered by direct intracavernous injection. A half inch, 27 to
30 gauge needle is generally recommended. The dose of Caverject should be

individualised for each patient by careful titration under supervision by a
physician.
The intracavernosal injection must be done under sterile conditions. The site
of injection is usually along the dorsolateral aspect of the proximal third of the
penis. Visible veins should be avoided. Both the side of the penis that is
injected and the site of injection must be alternated; prior to the injection, the
injection site must be cleansed with an alcohol swab.
To reconstitute Caverject using the prefilled diluent syringe: flip off the plastic
cap from the vial, and use one of the swabs to wipe the rubber cap. Fit the 22
gauge needle to the syringe.
Inject the 1 ml of diluent into the vial, and shake to dissolve the powder
entirely. Withdraw slightly more than the required dose of Caverject solution,
remove the 22 gauge needle, and fit the 30 gauge needle. Adjust volume to
the required dose for injection. Following administration, any unused contents
of the vial or syringe should be discarded.
A.
i)

As an aid to aetiologic diagnosis.
Subjects without evidence of neurological dysfunction; 20 micrograms
alprostadil to be injected into the corpus cavernosum and massaged
through the penis. Should an ensuing erection persist for more than
one hour detumescent therapy (please refer to Section 4.9) should be
employed prior to the subject leaving the clinic to prevent a risk of
priapism.
Over 80% of subjects may be expected to respond to a single 20
micrograms dose of alprostadil. At the time of discharge from the
clinic, the erection should have subsided entirely and the penis must be
in a completely flaccid state.

ii)

Subjects with evidence of neurological dysfunction; these patients can
be expected to respond to lower doses of alprostadil. In subjects with
erectile dysfunction caused by neurologic disease/trauma the dose for
diagnostic testing must not exceed 10 micrograms and an initial dose
of 5 micrograms is likely to be appropriate. Should an ensuing
erection persist for more than one hour detumescent therapy (please
refer to Section 4.9) should be employed prior to the subject leaving
the clinic to prevent a risk of priapism. At the time of discharge from
the clinic, the erection should have subsided entirely and the penis
must be in a completely flaccid state.

B.

Treatment
The initial dose of alprostadil in patients with erectile dysfunction of
neurogenic origin secondary to spinal cord injury is 1.25 micrograms,
with a second dose of 2.5 micrograms, a third of 5 micrograms, and
subsequent incremental increases of 5 micrograms until an optimal
dose is achieved. For erectile dysfunction of vasculogenic,
psychogenic, or mixed aetiology, the initial dose is 2.5 micrograms.

The second dose should be 5 micrograms if there is a partial response,
and 7.5 micrograms if there is no response. Subsequent incremental
increases of 5-10 micrograms should be given until an optimal dose is
achieved. If there is no response to the administered dose, then the
next higher dose may be given within 1 hour. If there is a response,
there should be at least a 1-day interval before the next dose is given.
The usual maximum recommended frequency of injection is no more
than once daily and no more than three times weekly.
The first injections of alprostadil must be done by medically trained
personnel. After proper training and instruction, alprostadil may be
injected at home. If self-administration is planned, the physician
should make an assessment of the patient's skill and competence with
the procedure. It is recommended that patients are regularly monitored
(e.g. every 3 months) particularly in the initial stages of self injection
therapy when dose adjustments may be needed.
The dose that is selected for self-injection treatment should provide the
patient with an erection that is satisfactory for sexual intercourse. It is
recommended that the dose administered produces a duration of the
erection not exceeding one hour. If the duration is longer, the dose
should be reduced. The majority of patients achieve a satisfactory
response with doses in the range of 5 to 20 micrograms. Doses of
greater than 60 micrograms of alprostadil are not recommended. The
lowest effective dose should be used.

4.3

Contraindications
Alprostadil should not be used in patients who have a known hypersensitivity
to any of the constituents of the product; in patients who have conditions that
might predispose them to priapism, such as sickle cell anaemia or trait,
multiple myeloma, or leukaemia; or in patients with anatomical deformation of
the penis, such as angulation, cavernosal fibrosis, or Peyronie's disease.
Patients with penile implants should not be treated with alprostadil.
Alprostadil should not be used in men for whom sexual activity is inadvisable
or contraindicated.

4.4

Special warnings and precautions for use
Prolonged erection and/or priapism may occur following intracavernosal
administration of alprostadil. To minimize the risk, select the lowest effective
dose. Patients should be instructed to report immediately to a physician, or if
unavailable to seek immediate medical assistance for any erection lasting for a

prolonged time period, such as 4 hours. Treatment of priapism should not be
delayed more than 6 hours (please refer to Section 4.9) and should be
according to established medical practice.
Painful erection is more likely to occur in patients with anatomical
deformations of the penis, such as angulation, phimosis, cavernosal fibrosis,
Peyronie's disease or plaques. Penile fibrosis, including angulation,
cavernosal fibrosis, fibrotic nodules and Peyronie's disease may occur
following the intracavernosal administration of alprostadil. The occurrence of
fibrosis may increase with increased duration of use. Regular follow-up of
patients, with careful examination of the penis, is strongly recommended to
detect signs of penile fibrosis or Peyronie's disease. Treatment with
alprostadil should be discontinued in patients who develop penile angulation,
cavernosal fibrosis, or Peyronie's disease.
Patients on anticoagulants such as warfarin or heparin may have increased
propensity for bleeding after the intracavernosal injection.
Underlying treatable medical causes of erectile dysfunction should be
diagnosed and treated prior to initiation of therapy with alprostadil.
Use of intracavernosal alprostadil offers no protection from the transmission
of sexually transmitted diseases. Individuals who use alprostadil should be
counselled about the protective measures that are necessary to guard against
the spread of sexually transmitted diseases, including the human
immunodeficiency virus (HIV). In some patients, injection of alprostadil can
induce a small amount of bleeding at the site of injection. In patients infected
with blood-borne diseases, this could increase the transmission of such
diseases to their partner.
Alprostadil should be used with caution in patients who have experienced
transient ischaemic attacks or those with unstable cardiovascular disorders.
Alprostadil is not intended for co-administration with any other agent for the
treatment of erectile dysfunction (see also 4.5).
The potential for abuse of alprostadil should be considered in patients with a
history of psychiatric disorder or addiction.
Sexual stimulation and intercourse can lead to cardiac and pulmonary events
in patients with coronary heart disease, congestive heart failure or pulmonary
disease. These patients when using alprostadil should engage in sexual activity
with caution.
Reconstituted solutions of alprostadil are intended for single use only, they
should be used immediately and not stored. The syringe and any remaining
solution should be properly discarded.
The solvent contains benzyl alcohol, which may cause hypersensitivity
reactions.

4.5

Interaction with other medicinal products and other forms of interaction
The effects of combinations of alprostadil with other treatments for erectile
dysfunction (e.g. sildenafil) or other drugs inducing erection (e.g. papaverine)
have not been formally studied. Such agents should not be used in
combination with alprostadil due to the potential for inducing prolonged
erections.
Sympathomimetics may reduce the effect of alprostadil. Alprostadil may
enhance the effects of antihypertensives, vasodilative agents, anticoagulants
and platelet aggregation inhibitors.

4.6

Pregnancy and lactation
Not applicable. (High doses of alprostadil (0.5 to 2.0 mg/kg subcutaneously)
had an adverse effect on the reproductive potential of male rats, although this
was not seen with lower doses (0.05 to 0.2 mg/kg). Alprostadil did not affect
rat spermatogenesis at doses 200 times greater than the proposed human
intrapenile dose.

4.7

Effects on ability to drive and use machines
Alprostadil would not be expected to have an influence on the ability to drive
or operate machines.

4.8

Undesirable effects
The most frequent adverse reaction after intracavernosal injection of
alprostadil is penile pain. Thirty percent of the patients reported penile pain at
least once; however, this event was associated with only 11% of the
administered injections. In the majority of the cases, penile pain was rated
mild or moderate in intensity. 3% of patients discontinued treatment because
of penile pain.
Prolonged erection (defined as an erection that lasts for 4 to 6 hours) after
intracavernosal administration of alprostadil was reported in 4% of patients.
The frequency of priapism (defined as an erection that lasts 6 hours or longer)
was 0.4%. In the majority of cases, spontaneous detumescence occurred.

Penile fibrosis, including angulation, fibrotic nodules and Peyronie's disease
was reported in 3% of clinical trial patients overall, however, in one selfinjection study in which the duration of use was up to 18 months, the
incidence of penile fibrosis was higher, approximately 8%.
Haematoma and ecchymosis at the site of injection, which is related to the
injection technique rather than to the effects of alprostadil, occurred in 3% and
2% of patients, respectively. Penile oedema or rash was reported by 1% of
alprostadil treated patients.
Adverse drug reactions reported during clinical trials and post marketing
experience are presented in the table below, frequencies are very common
(≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100).
System Organ
Class
Infections and
Infestations
Nervous System
Disorders
Eye Disorders
Cardiac Disorders
Vascular Disorders

Gastrointestinal
Disorders
Skin and
Subcutaneous
Tissue Disorders
Musculoskeletal
and Connective
Tissue Disorders
Renal and Urinary
Disorders
Reproductive
System and Breast
Disorders

Frequency

Undesirable effects

Uncommon

Fungal infection, Common cold

Uncommon

Hypoaesthesia, Hyperaesthesia, Presyncope

Uncommon
Uncommon
Uncommon

Uncommon

Mydriasis
Supraventricular extrasystoles
Vein disorder, Hypotension, Peripheral
vascular disorder, Vasodilatation, Venous
haemorrhage
Nausea, Dry mouth

Uncommon

Erythema, Hyperhidrosis, Rash, Pruritus

Common

Muscle spasms

Uncommon

Dysuria, Haematuria, Pollakiuria,
Micturition urgency, Urethral haemorrhage
Penile pain

Very
common
Common
Uncommon

General Disorders
and Administration

Common

Erection increased, Peyronie’s disease,
Penis disorder
Erectile dysfunction, Ejaculation disorder,
Balanitis, Painful erection, Phimosis,
Priapism, Testicular pain, Scrotal disorder,
Scrotal erythema, Scrotal pain,
Spermatocele, Scrotal oedema, Testicular
disorder, Testicular swelling, Testicular
oedema, Testicular mass, Pelvic pain
Injection site haematoma, Haematoma,
Ecchymosis

Site Conditions

Investigations

4.9

Uncommon

Uncommon

Asthenia, Injection site haemorrhage,
Injection site inflammation, Injection site
pruritus, Injection site swelling, Injection
site oedema, Injection site warmth,
Injection site irritation, Haemorrhage,
Inflammation, Oedema peripheral, Oedema,
Injection site anaesthesia, Injection site pain
Blood pressure decreased, Heart rate
increased, Blood creatinine increased

Overdose
The pharmacotoxic signs of alprostadil are similar in all animal species and
include depression, soft stools or diarrhoea and rapid breathing. In animals,
the lowest acute LD50 was 12 mg/kg which is 12,000 times greater than the
maximum recommended human dose of 60 micrograms.
In man, prolonged erection and/or priapism are known to occur following
intracavernous administration of vasoactive substances, including alprostadil.
Patients should be instructed to report to a physician any erection lasting for a
prolonged time period, such as 4 hours or longer.
Overdosage was not observed in clinical trials with alprostadil. If
intracavernous overdose of alprostadil occurs, the patient should be placed
under medical supervision until any systemic effects have resolved and/or
until penile detumescence has occurred. Symptomatic treatment of any
systemic symptoms would be appropriate.
The treatment of priapism (prolonged erection) should not be delayed more
than 6 hours. Initial therapy should be by penile aspiration. Using aseptic
technique, insert a 19-21 gauge butterfly needle into the corpus cavernosum
and aspirate 20-50 ml of blood. This may detumesce the penis. If necessary,
the procedure may be repeated on the opposite side of the penis until a total of
up to 100 ml blood has been aspirated. If still unsuccessful, intracavernous
injection of alpha-adrenergic medication is recommended. Although the usual
contra-indication to intrapenile administration of a vasoconstrictor does not
apply in the treatment of priapism, caution is advised when this option is
exercised. Blood pressure and pulse should be continuously monitored during
the procedure. Extreme caution is required in patients with coronary heart
disease, uncontrolled hypertension, cerebral ischaemia, and in subjects taking
monoamine oxidase inhibitors. In the latter case, facilities should be available
to manage a hypertensive crisis. A 200 microgram/ml solution of
phenylephrine should be prepared, and 0.5 to 1.0 ml of the solution injected
every 5 to 10 minutes. Alternatively, a 20 microgram/ml solution of
adrenaline should be used. If necessary, this may be followed by further
aspiration of blood through the same butterfly needle. The maximum dose of

phenylephrine should be 1 mg, or adrenaline 100 micrograms (5 ml of the
solution). As an alternative metaraminol may be used, but it should be noted
that fatal hypertensive crises have been reported. If this still fails to resolve
the priapism, urgent surgical referral for further management, which may
include a shunt procedure, is required.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Alprostadil is present in various mammalian tissues and fluids. It has a diverse
pharmacologic profile, among which some of its more important effects are
vasodilation, inhibition of platelet aggregation, inhibition of gastric secretion,
and stimulation of intestinal and uterine smooth muscle. The pharmacologic
effect of alprostadil in the treatment of erectile dysfunction is presumed to be
mediated by inhibition of alpha1-adrenergic activity in penile tissue and by its
relaxing effect on cavernosal smooth muscle.

5.2

Pharmacokinetic properties
Following intracavernous injection of 20 micrograms of alprostadil, mean
peripheral levels of alprostadil at 30 and 60 minutes after injection are not
significantly greater than baseline levels of endogenous PGE1. Peripheral
levels of the major circulating metabolite, 15-oxo-13,14-dihydro-PGE1,
increase to reach a peak 30 minutes after injection and return to pre-dose
levels by 60 minutes after injection. Any alprostadil entering the systemic
circulation from the corpus cavernosum will be rapidly metabolised.
Following intravenous administration, approximately 80% of the circulating
alprostadil is metabolised in one pass through the lungs, primarily by beta- and
omega-oxidation. The metabolites are excreted primarily by the kidney and
excretion is essentially complete within 24 hours. There is no evidence of
tissue retention of alprostadil or its metabolites following intravenous
administration.

5.3

Preclinical safety data
No relevant information additional to that already contained in this SPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose
sodium citrate
hydrochloric acid
sodium hydroxide

6.2

Incompatibilities
Caverject is not intended to be mixed or coadministered with any other products.

6.3

Shelf life
24 months under refrigerated conditions (2-8°C). After dispensing, 3 months
at room temperature, (do not store above 25°C), included in 24 months shelf
life. After reconstitution, the product may be stored for 6 hours below 25°C.

6.4

Special precautions for storage
Store at 2-8°C until dispensed. After dispensing, may be stored at room
temperature (do not store above 25°C), included in 24 months shelf life. The
reconstituted solution can be kept below 25°C for up to 6 hours.
Do not refrigerate or freeze.

6.5

Nature and contents of container
Single packs containing a vial of Caverject 40 microgram powder and a
syringe of diluent.
Packs also each contain a sterile 22 G and a 30 G needle plus pre-injection
swab.

6.6

Special precautions for disposal
The presence of benzyl alcohol in the reconstitution vehicle decreases the
degree of binding to package surfaces. Therefore, a more consistent product

delivery is produced when Bacteriostatic Water for Injection containing benzyl
alcohol is used.
Use immediately after reconstitution.

7

MARKETING AUTHORISATION HOLDER
Pfizer Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 00057/0943

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23rd June 1998 / April 2003.

10

DATE OF REVISION OF THE TEXT
19/12/2012

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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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