.
Since
the theme for today seems to be "Weiner" driven it is only
appropriate to give you a sidebar story of the two most popular prescription
drugs to enhance the male performance in sexual activity.
I'm
watching campaign contributions to Anthony Weiner's mayoral campaign to see if
the erectile dysfunctional special interest community has decided to make him
the poster boy for pushing legal drugs and proving that you can always be a
bigger man than you seem.
Did
you know that sales of male enhancement drugs in America tops $5 billion annually
and Viagra and Cialis represent 90% of those sales. For comparison purposes 31.6 million low
income students receive subsidized meals at school for an annual cost of $10
billion.
So
I guess two years of male enhancement drugs costs the same as 31.6 million
students throughout America
eating breakfast and lunches for a year.
My
purpose today is to demonstrate to you how the US Food and Drug Administration
(FDA) has pretty much lost their mind by giving approval to drugs such as
these.
Part
of the FDA New Drug Approval process is to generate a list of required warnings
of the potential dangerous side effects of new drugs and precautions for their
use.
Astonishingly,
when you change the fine print to readable print you will find there are 32
pages, yes pages, warning you of the side effects and precautions before taking
these drugs.
I
suppose if you ever made it through the 32 pages of warnings and still figure
it is worth taking to gain an inch or two of enhancement you must be a Weiner
supporter.
Are you kidding me? Clever marketing people magically turned a
potential danger into a dream by suggesting you can have a "prolonged
erection" for four hours or more.
It is like a "satisfaction
guaranteed" label.
And
what is it about a prolonged erection that could become a permanent problem?
Viagra
and Cialis are the most popular pharmaceutical drugs taken to treat male
erectile dysfunction.
Viagra
was approved by FDA
on 27th March, 1998 as a prescription medicine for pulmonary arterial hypertension. The main
ingredient of Viagra is Sildenafil, the generic name for it is Sildenafil
citrate, which relaxes the muscles of penis
and increases the blood flow into the penis so that a good erection
can be gained followed by sexual stimulation. Viagra is the product of the drug
manufacturing company, Pfizer. Viagra is a blue, rounded diamond
shaped pill available in 25-mg, 50-mg and 10-mg tablets for oral
administration in the fasted state and should be taken when sexual intercourse is intended.
Cialis
was approved by the FDA on 21st November, 2003 as a prescription medicine
used to treat erectile dysfunction. The main ingredient
of Cialis is tadalafil. This relaxes the muscles of the penis and increases the
blood flow into the penis so that a good erection can be gained followed by
sexual stimulation. Cialis was developed by a small biotech
firm in US, ICOS
and was marketed by Eli Lilly. Cialis is an orange colored
pill, available in 5-mg, 10-mg, and 20-mg tablets for oral administration and
should be taken when sexual intercourse is intended.
VIAGRA SIDE
EFFECTS
Viagra (sildenafil) is used for the treatment of erectile
dysfunction. It is a phosphodiesterase-5 (PDE5) inhibitor. Common side effects
of Viagra include facial flushing, headaches, stomach pain, nasal congestion,
nausea, diarrhea, and an inability to differentiate between the colors green
and blue. Loss of hearing, ringing in the ears and dizziness may occur.
The recommended dose of Viagra is 25-100 mg taken 30
minutes to 4 hours before sexual activity. Viagra increases the effects of
blood pressure lowering medications. It also increases the blood pressure
lowering effects of nitrates (for example, isosorbide dinitrate) that are used
primarily for treating angina. Patients taking nitrates should not receive
Viagra. Viagra should not be combined with Revatio or other PDE5 inhibitors
(for example, Levitra [vardenafil], Cialis [tadalafil]). Tagamet (cimetidine),
erythromycin, ketoconazole, Sporanox (itraconazole), and Posicor (mibefradil)
can cause marked increases in the amount of Viagra in the body. Patients taking
these medications should be observed carefully if Viagra is used.
Our Viagra Side Effects Drug Center provides a comprehensive
view of available drug information on the potential side effects when taking
this medication.
This is not a complete list of side effects and others
may occur. Call your doctor for medical advice about side effects. You may
report side effects to FDA at 1-800-FDA-1088.
- sudden vision loss;
- ringing in your ears, or
sudden hearing loss;
- chest pain or heavy
feeling, pain spreading to the arm or shoulder, nausea, sweating, general
ill feeling;
- irregular heartbeat;
- swelling in your hands,
ankles, or feet;
- shortness of breath;
- vision changes;
- feeling light-headed,
fainting; or
- penis erection that is
painful or lasts 4 hours or longer.
- warmth or redness in your
face, neck, or chest;
- stuffy nose;
- headache;
- memory problems;
- upset stomach; or
- back pain.
SIDE EFFECTS: Dizziness, lightheadedness, headache, flushing,
heartburn, nosebleeds, trouble sleeping, or swollen hands/ankles/feet (edema)
may occur. Vision changes such as increased sensitivity to light, blurred
vision, or trouble telling blue and green colors apart may also occur. If any
of these effects persist or worsen, notify your doctor or pharmacist promptly.
VIAGRA SIDE EFFECTS
Clinical Trials
|
Adverse
Event
|
Percentage
of Patients VIAGRA
N=734
|
Reporting
Event PLACEBO
N=725
|
|
Headache
|
16%
|
4%
|
|
Flushing
|
10%
|
1%
|
|
Dyspepsia
|
7%
|
2%
|
|
Nasal
Congestion
|
4%
|
2%
|
|
Urinary
Tract Infection
|
3%
|
2%
|
|
Abnormal
Vision†
|
3%
|
0%
|
|
Diarrhea
|
3%
|
1%
|
|
Dizziness
|
2%
|
1%
|
|
Rash
|
2%
|
1%
|
|
†Abnormal Vision: Mild and transient, predominantly
color tinge to vision, but also increased sensitivity to light or blurred
vision. In these studies, only one patient discontinued due to abnormal
vision.
|
Cardiovascular and cerebrovascular
Special senses
Other events
Read the entire FDA prescribing information for Viagra
(Sildenafil Citrate) »
WARNINGS
There is a potential for cardiac risk of sexual
activity in patients with preexisting cardiovascular disease. Therefore,
treatments for erectile dysfunction, including VIAGRA
(sildenafil citrate) , should not be generally used in men for whom sexual
activity is inadvisable because of their underlying cardiovascular status.
VIAGRA (sildenafil citrate) has systemic
vasodilatory properties that resulted in transient decreases in supine blood
pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), (see CLINICAL PHARMACOLOGY: Pharmacodynamics)
While this normally would be expected to be of little consequence in most
patients, prior to prescribing VIAGRA (sildenafil citrate) , physicians should
carefully consider whether their patients with underlying cardiovascular
disease could be affected adversely by such vasodilatory effects, especially in
combination with sexual activity.
Patients with the following underlying conditions
can be particularly sensitive to the actions of vasodilators including VIAGRA (sildenafil
citrate) - those with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic
subaortic stenosis) and those with severely impaired autonomic control of blood
pressure.
There is no controlled clinical data on the safety
or efficacy of VIAGRA (sildenafil citrate) in the following groups; if
prescribed, this should be done with caution.
Prolonged erection greater than 4 hours and priapism (painful erections greater than 6
hours in duration) have been reported infrequently since market approval of
VIAGRA (sildenafil citrate) . In the event of an erection that persists longer
than 4 hours, the patient should seek immediate medical assistance. If priapism
is not treated immediately, penile tissue damage and permanent loss of potency
could result.
The concomitant administration of the protease
inhibitor ritonavir substantially increases serum concentrations of sildenafil
(11-fold increase in AUC). If VIAGRA (sildenafil citrate) is prescribed
to patients taking ritonavir, caution should be used. Data from subjects
exposed to high systemic levels of sildenafil are limited. Visual disturbances
occurred more commonly at higher levels of sildenafil exposure. Decreased blood
pressure, syncope, and prolonged erection were reported in some healthy
volunteers exposed to high doses of sildenafil (200-800 mg). To decrease the
chance of adverse events in patients taking ritonavir, a decrease in sildenafil
dosage is recommended (see DRUG INTERACTIONS, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION)
PRECAUTIONS
General
The evaluation of erectile dysfunction should
include a determination of potential underlying causes and the identification
of appropriate treatment following a complete medical assessment.
Before prescribing VIAGRA (sildenafil citrate) , it
is important to note the following:
Caution is advised when Phosphodiesterase Type 5
(PDE5) inhibitors are co-administered with alpha-blockers. PDE5 inhibitors,
including VIAGRA (sildenafil citrate) , and alpha-adrenergic blocking agents
are both vasodilators with blood pressure lowering effects. When vasodilators
are used in combination, an additive effect on blood pressure may be
anticipated. In some patients, concomitant use of these two drug classes can
lower blood pressure significantly (see DRUG INTERACTIONS) leading to
symptomatic hypotension (e.g. dizziness, lightheadedness, fainting).
Consideration should be given to the following:
- Patients should be stable on alpha-blocker therapy
prior to initiating a PDE5 inhibitor. Patients who demonstrate hemodynamic
instability on alpha-blocker therapy alone are at increased risk of symptomatic
hypotension with concomitant use of PDE5 inhibitors.
- In those patients who are stable on alpha-blocker
therapy, PDE5 inhibitors should be initiated at the lowest dose.
- In those patients already taking an optimized dose of a
PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose.
Stepwise increase in alpha-blocker dose may be associated with further lowering
of blood pressure when taking a PDE5 inhibitor.
- Safety of combined use of PDE5 inhibitors and
alpha-blockers may be affected by other variables, including intravascular
volume depletion and other anti-hypertensive drugs.
Viagra (sildenafil citrate) has systemic
vasodilatory properties and may augment the blood pressure lowering effect of
other anti-hypertensive medications.
Patients on multiple antihypertensive medications
were included in the pivotal clinical trials for VIAGRA (sildenafil citrate) .
In a separate drug interaction study, when amlodipine, 5 mg or 10 mg, and
VIAGRA (sildenafil citrate) , 100 mg were orally administered concomitantly to
hypertensive patients mean additional blood pressure reduction of 8 mmHg
systolic and 7 mmHg diastolic were noted (see DRUG INTERACTIONS).
The safety of VIAGRA (sildenafil citrate) is
unknown in patients with bleeding disorders and patients with active peptic
ulceration.
VIAGRA (sildenafil citrate) should be used with
caution in patients with anatomical deformation of the penis (such as
angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have
conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
The safety and efficacy of combinations of VIAGRA
(sildenafil citrate) with other treatments for erectile dysfunction have not
been studied. Therefore, the use of such combinations is not recommended.
In humans, VIAGRA (sildenafil citrate) has no effect
on bleeding time when taken alone or with aspirin. In vitro studies with
human platelets indicate that sildenafil potentiates the antiaggregatory effect
of sodium nitroprusside (a nitric oxide donor). The combination of heparin and
VIAGRA (sildenafil citrate) had an additive effect on bleeding time in the
anesthetized rabbit, but this interaction has not been studied in humans.
Information for Patients
Physicians should discuss with patients the
contraindication of VIAGRA (sildenafil citrate) with regular and/or
intermittent use of organic nitrates.
Physicians should advise patients of the potential
for VIAGRA (sildenafil citrate) to augment the blood pressure lowering effect
of alpha-blockers and anti-hypertensive medications. Concomitant administration
of VIAGRA (sildenafil citrate) and an alpha-blocker may lead to symptomatic
hypotension in some patients. Therefore, when VIAGRA (sildenafil citrate) is
co-administered with alpha-blockers, patients should be stable on alpha-blocker
therapy prior to initiating VIAGRA (sildenafil citrate) treatment and VIAGRA
(sildenafil citrate) should be initiated at the lowest dose.
Physicians should discuss with patients the
potential cardiac risk of sexual activity in patients with preexisting
cardiovascular risk factors. Patients who experience symptoms (e.g., angina pectoris, dizziness, nausea) upon initiation of sexual activity
should be advised to refrain from further activity and should discuss the
episode with their physician.
Physicians should advise patients to stop use of
all PDE5 inhibitors, including VIAGRA (sildenafil citrate) , and seek medical
attention in the event of a sudden loss of vision in one or both eyes. Such an
event may be a sign of non-arteritic anterior ischemic optic neuropathy
(NAION), a cause of decreased vision including permanent loss of vision, that
has been reported rarely post-marketing in temporal association with the use of
all PDE5 inhibitors. It is not possible to determine whether these events are
related directly to the use of PDE5 inhibitors or to other factors. Physicians
should also discuss with patients the increased risk of NAION in individuals
who have already experienced NAION in one eye, including whether such
individuals could be adversely affected by use of vasodilators, such as PDE5
inhibitors (see Post-Marketing Experience/Special Senses).
Physicians should advise patients to stop taking
PDE5 inhibitors, including VIAGRA (sildenafil citrate) , and seek prompt
medical attention in the event of sudden decrease or loss of hearing. These
events, which may be accompanied by tinnitus and dizziness, have been reported
in temporal association to the intake of PDE5 inhibitors, including VIAGRA
(sildenafil citrate) . It is not possible to determine whether these events are
related directly to the use of PDE5 inhibitors or to other factors (see ADVERSE REACTIONS, Clinical Trials and Post-Marketing
Experience).
Physicians should warn patients that prolonged
erections greater than 4 hours and priapism (painful erections greater than 6
hours in duration) have been reported infrequently since market approval of
VIAGRA (sildenafil citrate) . In the event of an erection that persists longer
than 4 hours, the patient should seek immediate medical assistance. If priapism
is not treated immediately, penile tissue damage and permanent loss of potency
may result.
Physicians should inform patients not to take
VIAGRA (sildenafil citrate) with other PDE5 inhibitors including REVATIO.
Sildenafil is also marketed as REVATIO for the treatment of pulmonary arterial hypertension. The safety
and efficacy of VIAGRA (sildenafil citrate) with other PDE5 inhibitors,
including REVATIO, have not been studied.
The use of VIAGRA (sildenafil citrate) offers no
protection against sexually transmitted diseases. Counseling of patients about
the protective measures necessary to guard against sexually transmitted
diseases, including the Human Immunodeficiency Virus (HIV), may be
considered.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Sildenafil was not carcinogenic when administered
to rats for 24 months at a dose resulting in total systemic drug exposure
(AUCs) for unbound sildenafil and its major metabolite of 29- and 42-times, for
male and female rats, respectively, the exposures observed in human males given
the Maximum Recommended Human Dose (MRHD) of 100 mg. Sildenafil was not
carcinogenic when administered to mice for 18-21 months at dosages up to the
Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD
on a mg/m2 basis.
Sildenafil was negative in in vitro
bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in
vitro human lymphocytes and in vivo mouse micronucleus assays to
detect clastogenicity.
There was no impairment of fertility in rats given
sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a
dose producing an AUC value of more than 25 times the human male AUC.
There was no effect on sperm motility or morphology after single 100 mg oral doses
of VIAGRA (sildenafil citrate) in healthy volunteers.
Pregnancy, Nursing Mothers and Pediatric Use
VIAGRA (sildenafil citrate) is not indicated for
use in newborns, children, or women.
Pregnancy Category B. No
evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats
and rabbits which received up to 200 mg/kg/day during organogenesis. These
doses represent, respectively, about 20 and 40 times the MRHD on a mg/m2
basis in a 50 kg subject. In the rat pre- and postnatal development study, the
no observed adverse effect dose was 30 mg/kg/day given for 36 days. In the
nonpregnant rat the AUC at this dose was about 20 times human AUC. There are no
adequate and well-controlled studies of sildenafil in pregnant women.
Geriatric Use: Healthy elderly volunteers (65 years or over) had a
reduced clearance of sildenafil (see CLINICAL PHARMACOLOGY: Pharmacokinetics in
Special Populations). Since higher plasma levels may increase both the
efficacy and incidence of adverse events, a starting dose of 25 mg should be
considered (see DOSAGE AND ADMINISTRATION).
Last
reviewed on RxList: 1/3/2011
This monograph has been modified to include the generic and brand name in many
instances.
CIALIS SIDE EFFECTS
Cialis (tadalafil) is an oral drug that is used for
treating impotence (erectile dysfunction, ED). It is in a class of drugs called
phosphodiesterase inhibitors. The most common side effects of Cialis are facial
flushing (reddening), headaches, stomach upset, diarrhea, flu-like symptoms,
and nausea. Cialis also may cause low blood pressure, blurred vision and
changes in color vision, abnormal ejaculation, and priapism.
The recommended dose of Cialis is 5-20 mg per day taken
before sexual activity. The breakdown and elimination of Cialis from the body
may be decreased by erythromycin, ketoconazole (Nizoral), itraconazole
(Sporanox), indinavir (Crixivan) and ritonavir (Norvir). Therefore, these drugs
may increase the levels of Cialis in the blood. Cialis exaggerates the
increases in heart rate and lowering of blood pressure caused by nitrates (for
example, nitroglycerin, isosorbide dinitrate (Isordil), isosorbide mononitrate
(Imdur). Cialis is not approved for use in women and has not been evaluated in
women who are breastfeeding.
Our Cialis Side Effects Drug Center provides a
comprehensive view of available drug information on the potential side effects
when taking this medication.
This is not a complete list of side effects and others
may occur. Call your doctor for medical advice about side effects. You may
report side effects to FDA at 1-800-FDA-1088.
- changes in vision or
sudden vision loss;
- ringing in your ears, or
sudden hearing loss;
- chest pain or heavy
feeling, pain spreading to the arm or shoulder, nausea, sweating, general
ill feeling;
- irregular heartbeat;
- shortness of breath,
swelling in your hands or feet;
- seizure (convulsions);
- feeling light-headed,
fainting; or
- penis erection that is
painful or lasts 4 hours or longer.
- redness or warmth in your
face, neck, or chest;
- cold symptoms such as
stuffy nose, sneezing, or sore throat;
- headache;
- memory problems;
- diarrhea, upset stomach;
or
- muscle pain, back pain.
SIDE EFFECTS: Headache, stomach upset, back pain, muscle pain, nasal
stuffiness, flushing, pain in arms or legs, dizziness, or vision changes may
occur. If any of these effects persist or worsen, notify your doctor or
pharmacist promptly.
Clinical Trials Experience
CIALIS for Use as Needed for ED
|
Adverse
Reaction
|
Placebo
(N=476)
|
Tadalafil
5 mg
(N=151)
|
Tadalafil
10 mg
(N=394)
|
Tadalafil
20 mg
(N=635)
|
|
Headache
|
5%
|
11%
|
11%
|
15%
|
|
Dyspepsia
|
1%
|
4%
|
8%
|
10%
|
|
Back
pain
|
3%
|
3%
|
5%
|
6%
|
|
Myalgia
|
1%
|
1%
|
4%
|
3%
|
|
Nasal
congestion
|
1%
|
2%
|
3%
|
3%
|
|
Flushinga
|
1%
|
2%
|
3%
|
3%
|
|
Pain
in limb
|
1%
|
1%
|
3%
|
3%
|
|
a
The term
flushing includes: facial flushing and flushing
|
CIALIS for Once Daily Use for ED
|
Adverse
Reaction
|
Placebo
(N=248)
|
Tadalafil
2.5 mg
(N=196)
|
Tadalafil
5 mg
(N=304)
|
|
Headache
|
5%
|
3%
|
6%
|
|
Dyspepsia
|
2%
|
4%
|
5%
|
|
Nasopharyngitis
|
4%
|
4%
|
3%
|
|
Back
pain
|
1%
|
3%
|
3%
|
|
Upper
respiratory tract infection
|
1%
|
3%
|
3%
|
|
Flushing
|
1%
|
1%
|
3%
|
|
Myalgia
|
1%
|
2%
|
2%
|
|
Cough
|
0%
|
4%
|
2%
|
|
Diarrhea
|
0%
|
1%
|
2%
|
|
Nasal
congestion
|
0%
|
2%
|
2%
|
|
Pain
in extremity
|
0%
|
1%
|
2%
|
|
Urinary
tract infection
|
0%
|
2%
|
0%
|
|
Gastroesophageal
reflux disease
|
0%
|
2%
|
1%
|
|
Abdominal
pain
|
0%
|
2%
|
1%
|
|
Adverse
Reaction
|
Placebo
(N=94)
|
Tadalafil
2.5 mg
(N=96)
|
Tadalafil
5 mg
(N=97)
|
|
Nasopharyngitis
|
5%
|
6%
|
6%
|
|
Gastroenteritis
|
2%
|
3%
|
5%
|
|
Back
pain
|
3%
|
5%
|
2%
|
|
Upper
respiratory tract infection
|
0%
|
3%
|
4%
|
|
Dyspepsia
|
1%
|
4%
|
1%
|
|
Gastroesophageal
reflux disease
|
0%
|
3%
|
2%
|
|
Myalgia
|
2%
|
4%
|
1%
|
|
Hypertension
|
0%
|
1%
|
3%
|
|
Nasal
congestion
|
0%
|
0%
|
4%
|
CIALIS for Once Daily Use for BPH and for ED
and BPH
|
Adverse
Reaction
|
Placebo
(N=576)
|
Tadalafil
5 mg
(N=581)
|
|
Headache
|
2.3%
|
4.1%
|
|
Dyspepsia
|
0.2%
|
2.4%
|
|
Back
pain
|
1.4%
|
2.4%
|
|
Nasopharyngitis
|
1.6%
|
2.1%
|
|
Diarrhea
|
1.0%
|
1.4%
|
|
Pain
in extremity
|
0.0%
|
1.4%
|
|
Myalgia
|
0.3%
|
1.2%
|
|
Dizziness
|
0.5%
|
1.0%
|
Postmarketing Experience
Evaluation of erectile dysfunction and BPH should include
an appropriate medical assessment to identify potential underlying causes, as
well as treatment options.
Before prescribing CIALIS, it is important to note
the following:
Cardiovascular
Physicians should consider the cardiovascular
status of their patients, since there is a degree of cardiac risk associated
with sexual activity. Therefore, treatments for erectile dysfunction, including CIALIS, should not
be used in men for whom sexual activity is inadvisable as a result of their
underlying cardiovascular status. Patients who experience symptoms upon
initiation of sexual activity should be advised to refrain from further sexual
activity and seek immediate medical attention.
Physicians should discuss with patients the
appropriate action in the event that they experience anginal chest pain requiring nitroglycerin
following intake of CIALIS. In such a patient, who has taken CIALIS, where
nitrate administration is deemed medically necessary for a life-threatening
situation, at least 48 hours should have elapsed after the last dose of CIALIS
before nitrate administration is considered. In such circumstances, nitrates
should still only be administered under close medical supervision with
appropriate hemodynamic monitoring. Therefore, patients who experience anginal
chest pain after taking CIALIS should seek immediate medical attention. [See CONTRAINDICATIONS and PATIENT INFORMATION].
Patients with left ventricular outflow obstruction,
(e.g., aortic stenosis and idiopathic hypertrophic
subaortic stenosis) can be sensitive to the action of vasodilators, including PDE5 inhibitors.
The following groups of patients with cardiovascular disease were not included in
clinical safety and efficacy trials for CIALIS, and therefore until further
information is available, CIALIS is not recommended for the following groups of
patients:
- myocardial infarction within the last
90 days
- unstable angina or angina occurring during
sexual intercourse
- New York Heart
Association Class 2 or greater heart failure in the last 6 months
- uncontrolled arrhythmias,
hypotension ( < 90/50 mm Hg), or
uncontrolled hypertension
- stroke within the last 6 months.
As with other PDE5 inhibitors, tadalafil has mild systemic vasodilatory properties that may
result in transient decreases in blood pressure. In a clinical pharmacology
study, tadalafil 20 mg resulted in a mean maximal decrease in supine blood pressure, relative to placebo, of 1.6/0.8 mm Hg in healthy
subjects [see CLINICAL PHARMACOLOGY]. While this
effect should not be of consequence in most patients, prior to prescribing
CIALIS, physicians should carefully consider whether their patients with
underlying cardiovascular disease could be affected adversely by such
vasodilatory effects. Patients with severely impaired autonomic control of
blood pressure may be particularly sensitive to the actions of vasodilators,
including PDE5 inhibitors.
Potential for Drug Interactions When Taking CIALIS for
Once Daily Use
Physicians should be aware that CIALIS for once
daily use provides continuous plasma tadalafil levels and should consider
this when evaluating the potential for interactions with medications (e.g.,
nitrates, alpha-blockers, anti-hypertensives and potent inhibitors of CYP3A4)
and with substantial consumption of alcohol [see DRUG INTERACTIONS].
Prolonged Erection
There have been rare reports of prolonged erections
greater than 4 hours and priapism (painful erections greater than 6
hours in duration) for this class of compounds. Priapism, if not treated
promptly, can result in irreversible damage to the erectile tissue. Patients
who have an erection lasting greater than 4 hours, whether painful or not,
should seek emergency medical attention.
Eye
Physicians should advise patients to stop use of
all PDE5 inhibitors, including CIALIS, and seek medical attention in the event
of a sudden loss of vision in one or both eyes. Such an event may be a sign of
non-arteritic anterior ischemic optic neuropathy (NAION),
a cause of decreased vision, including permanent loss of vision that has been
reported rarely postmarketing in temporal association with the use of all
PDE5 inhibitors. It is not possible to determine whether these events are
related directly to the use of PDE5 inhibitors or other factors. Physicians should
also discuss with patients the increased risk of NAION in individuals who have
already experienced NAION in one eye, including whether such individuals could
be adversely affected by use of vasodilators such as PDE5 inhibitors [see ADVERSE REACTIONS].
Patients with known hereditary degenerative retinal disorders, including retinitis
pigmentosa, were not included in the clinical trials, and use in these patients
is not recommended.
Sudden Hearing Loss
Physicians should advise patients to stop taking
PDE5 inhibitors, including CIALIS, and seek prompt medical attention in the
event of sudden decrease or loss of hearing. These events, which may be
accompanied by tinnitus and dizziness, have been reported in temporal
association to the intake of PDE5 inhibitors, including CIALIS. It is not
possible to determine whether these events are related directly to the use of
PDE5 inhibitors or to other factors [see ADVERSE REACTIONS].
Alpha-blockers and Antihypertensives
Caution is advised when PDE5 inhibitors are
coadministered with alpha blockers. PDE5 inhibitors, including CIALIS, and
alpha-adrenergic blocking agents are both vasodilators with
blood-pressure-lowering effects. When vasodilators are used in combination, an
additive effect on blood pressure may be anticipated. In some patients,
concomitant use of these two drug classes can lower blood pressure
significantly [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY], which may lead
to symptomatic hypotension (e.g., fainting). Consideration should be given to
the following:
ED
- Patients should be stable
on alpha-blocker therapy prior to initiating a PDE5
inhibitor. Patients who demonstrate hemodynamic instability on
alpha-blocker therapy alone are at increased risk of symptomatic
hypotension with concomitant use of PDE5 inhibitors.
- In those patients who are
stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at
the lowest recommended dose.
- In those patients already
taking an optimized dose of PDE5 inhibitor, alpha-blocker therapy should
be initiated at the lowest dose. Stepwise increase in alpha-blocker dose
may be associated with further lowering of blood pressure when taking a
PDE5 inhibitor.
- Safety of combined use of
PDE5 inhibitors and alpha-blockers may be affected by other variables,
including intravascular volume depletion and other antihypertensive drugs.
[See DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS].
BPH
- The efficacy of the
co-administration of an alpha-blocker and CIALIS for the treatment of BPH
has not been adequately studied, and due to the potential vasodilatory
effects of combined use resulting in blood pressure lowering, the
combination of CIALIS and alpha-blockers is not recommended for the
treatment of BPH. [See DOSAGE AND ADMINISTRATION, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].
- Patients on alpha-blocker
therapy for BPH should discontinue their alpha-blocker at least one day
prior to starting CIALIS for once daily use for the treatment of BPH.
Renal Impairment
CIALIS for Use as Needed
CIALIS should be limited to 5 mg not more than once
in every 72 hours in patients with creatinine clearance less than 30 mL/min or end-stage renal disease on hemodialysis. The starting dose of CIALIS
in patients with creatinine clearance 30 – 50 mL/min should be 5 mg not more
than once per day, and the maximum dose should be limited to 10 mg not more
than once in every 48 hours. [See Use in Specific Populations].
CIALIS for Once Daily Use
ED
Due to increased tadalafil exposure (AUC), limited
clinical experience, and the lack of ability to influence clearance by dialysis, CIALIS for once daily use is not
recommended in patients with creatinine clearance less than 30 mL/min [see Use
In Specific Populations].
BPH and ED/BPH
Due to increased tadalafil exposure (AUC), limited
clinical experience, and the lack of ability to influence clearance by
dialysis, CIALIS for once daily use is not recommended in patients with
creatinine clearance less than 30 mL/min. In patients with creatinine clearance
30 – 50 mL/min, start dosing at 2.5 mg once daily, and increase the dose to 5
mg once daily based upon individual response [see DOSAGE AND ADMINISTRATION, Use In
Specific Populations, and CLINICAL PHARMACOLOGY].
Hepatic Impairment
CIALIS for Use as Needed
In patients with mild or moderate hepatic
impairment, the dose of CIALIS should not exceed 10 mg. Because of insufficient
information in patients with severe hepatic impairment, use of CIALIS in this
group is not recommended [see Use in Specific Populations].
CIALIS for Once Daily Use
CIALIS for once daily use has not been extensively
evaluated in patients with mild or moderate hepatic impairment. Therefore,
caution is advised if CIALIS for once daily use is prescribed to these
patients. Because of insufficient information in patients with severe hepatic
impairment, use of CIALIS in this group is not recommended [see Use In
Specific Populations].
Alcohol
Patients should be made aware that both alcohol and
CIALIS, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are
taken in combination, blood-pressure-lowering effects of each individual
compound may be increased. Therefore, physicians should inform patients that
substantial consumption of alcohol (e.g., 5 units or greater) in combination
with CIALIS can increase the potential for orthostatic signs and symptoms,
including increase in heart rate, decrease in standing blood
pressure, dizziness, and headache [see CLINICAL PHARMACOLOGY].
Concomitant Use of Potent Inhibitors of Cytochrome P450
3A4 (CYP3A4)
CIALIS is metabolized predominantly by CYP3A4 in
the liver. The dose of CIALIS for use as needed
should be limited to 10 mg no more than once every 72 hours in patients taking
potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, and itraconazole
[see DRUG INTERACTIONS]. In patients taking
potent inhibitors of CYP3A4 and CIALIS for once daily use, the maximum
recommended dose is 2.5 mg [see DOSAGE AND ADMINISTRATION].
Combination With Other PDE5 Inhibitors or Erectile
Dysfunction Therapies
The safety and efficacy of combinations of CIALIS
and other PDE5 inhibitors or treatments for erectile dysfunction have not been
studied. Inform patients not to take CIALIS with other PDE5 inhibitors,
including ADCIRCA.
Effects on Bleeding
Studies in vitro have demonstrated that
tadalafil is a selective inhibitor of PDE5. PDE5 is found in platelets. When
administered in combination with aspirin, tadalafil 20 mg did not prolong
bleeding time, relative to aspirin alone. CIALIS has not been administered to
patients with bleeding disorders or significant active peptic ulceration. Although CIALIS has not been
shown to increase bleeding times in healthy subjects, use in patients with
bleeding disorders or significant active peptic ulceration should be based upon
a careful risk-benefit assessment and caution.
Counseling Patients About Sexually Transmitted Diseases
The use of CIALIS offers no protection against
sexually transmitted diseases. Counseling patients about the protective
measures necessary to guard against sexually transmitted diseases, including
Human Immunodeficiency Virus (HIV) should be considered.
Consideration of Other Urological Conditions Prior to
Initiating Treatment for BPH
Prior to initiating treatment with CIALIS for BPH,
consideration should be given to other urological conditions that may cause
similar symptoms. In addition, prostate cancer and BPH may coexist.
Patient Counseling Information
Nitrates
Physicians should discuss with patients the contraindication of CIALIS with regular
and/or intermittent use of organic nitrates. Patients should be
counseled that concomitant use of CIALIS with nitrates could cause blood
pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope,
or even heart attack or stroke.
Physicians should discuss with patients the
appropriate action in the event that they experience anginal chest pain
requiring nitroglycerin following intake of CIALIS. In such a patient, who has
taken CIALIS, where nitrate administration is deemed medically necessary for a
life-threatening situation, at least 48 hours should have elapsed after the
last dose of CIALIS before nitrate administration is considered. In such
circumstances, nitrates should still only be administered under close medical
supervision with appropriate hemodynamic monitoring. Therefore, patients who
experience anginal chest pain after taking CIALIS should seek immediate medical
attention [see CONTRAINDICATIONS and WARNINGS AND
PRECAUTIONS].
Cardiovascular Considerations
Physicians should consider the potential cardiac
risk of sexual activity in patients with preexisting cardiovascular disease.
Physicians should advise patients who experience symptoms upon initiation of
sexual activity to refrain from further sexual activity and seek immediate
medical attention [see WARNINGS AND PRECAUTIONS].
Concomitant Use with Drugs Which Lower Blood Pressure
Physicians should discuss with patients the
potential for CIALIS to augment the blood-pressure-lowering effect of
alpha-blockers and antihypertensive medications [see WARNINGS AND
PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].
Potential for Drug Interactions When Taking CIALIS for
Once Daily Use
Physicians should discuss with patients the
clinical implications of continuous exposure to tadalafil when prescribing
CIALIS for once daily use, especially the potential for interactions with
medications (e.g., nitrates, alpha-blockers, antihypertensives and potent
inhibitors of cytochrome P450 3A4) and with substantial consumption of alcohol.
[See DOSAGE AND ADMINISTRATION, WARNINGS
AND PRECAUTIONS, DRUG INTERACTIONS, CLINICAL PHARMACOLOGY, and Clinical Studies].
Priapism
There have been rare reports of prolonged erections
greater than 4 hours and priapism (painful erections greater than 6 hours in
duration) for this class of compounds. Priapism, if not treated promptly, can
result in irreversible damage to the erectile tissue. Physicians should advise
patients who have an erection lasting greater than 4 hours, whether painful or
not, to seek emergency medical attention.
Vision
Physicians should advise patients to stop use of
all PDE5 inhibitors, including CIALIS, and seek medical attention in the event
of a sudden loss of vision in one or both eyes. Such an event may be a sign of
non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased
vision, including permanent loss of vision that has been reported rarely
postmarketing in temporal association with the use of all PDE5 inhibitors. It
is not possible to determine whether these events are related directly to the
use of PDE5 inhibitors or other factors. Physicians should also discuss with
patients the increased risk of NAION in individuals who have already
experienced NAION in one eye, including whether such individuals could be
adversely affected by use of vasodilators such as PDE5 inhibitors [see Clinical Studies].
Sudden Hearing Loss
Physicians should advise patients to stop taking
PDE5 inhibitors, including CIALIS, and seek prompt medical attention in the
event of sudden decrease or loss of hearing. These events, which may be
accompanied by tinnitus and dizziness, have been reported in temporal
association to the intake of PDE5 inhibitors, including CIALIS. It is not
possible to determine whether these events are related directly to the use of
PDE5 inhibitors or to other factors [see ADVERSE REACTIONS].
Alcohol
Patients should be made aware that both alcohol and
CIALIS, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are
taken in combination, blood-pressure-lowering effects of each individual
compound may be increased. Therefore, physicians should inform patients that
substantial consumption of alcohol (e.g., 5 units or greater) in combination
with CIALIS can increase the potential for orthostatic signs and symptoms,
including increase in heart rate, decrease in standing blood pressure,
dizziness, and headache [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].
Sexually Transmitted Disease
The use of CIALIS offers no protection against
sexually transmitted diseases. Counseling of patients about the protective
measures necessary to guard against sexually transmitted diseases, including
Human Immunodeficiency Virus (HIV) should be considered.
Recommended Administration
Physicians should instruct patients on the
appropriate administration of CIALIS to allow optimal use.
For CIALIS for use as needed in men with ED,
patients should be instructed to take one tablet at least 30 minutes before
anticipated sexual activity. In most patients, the ability to have sexual
intercourse is improved for up to 36 hours.
For CIALIS for once daily use in men with ED or
ED/BPH, patients should be instructed to take one tablet at approximately the
same time every day without regard for the timing of sexual activity. Cialis is
effective at improving erectile function over the course of therapy.
For CIALIS for once daily use in men with BPH,
patients should be instructed to take one tablet at approximately the same time
every day.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Tadalafil was not carcinogenic to rats or mice when
administered daily for 2 years at doses up to 400 mg/kg/day. Systemic drug
exposures, as measured by AUC of unbound tadalafil, were approximately 10-fold
for mice, and 14and 26-fold for male and female rats, respectively, the
exposures in human males given Maximum Recommended Human Dose (MRHD) of 20 mg.
Mutagenesis
Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells. Tadalafil was not
clastogenic in the in vitro chromosomal aberration test in human lymphocytes or the
in vivo rat micronucleus assays.
Impairment of Fertility
There were no effects on fertility, reproductive
performance or reproductive organ morphology in male or female rats given
oral doses of tadalafil up to 400 mg/kg/day, a dose producing AUCs for unbound
tadalafil of 14-fold for males or 26-fold for females the exposures observed in
human males given the MRHD of 20 mg. In beagle dogs given tadalafil daily for 3
to 12 months, there was treatment-related non-reversible degeneration and atrophy of the seminiferous tubular epithelium in the testes in 20-100% of the dogs that resulted
in a decrease in spermatogenesis in 40-75% of the dogs at
doses of ≥ 10 mg/kg/day. Systemic exposure (based on AUC) at
no-observed-adverse-effect-level (NOAEL) (10 mg/kg/day) for unbound tadalafil
was similar to that expected in humans at the MRHD of 20 mg.
There were no treatment-related testicular findings
in rats or mice treated with doses up to 400 mg/kg/day for 2 years.
Use In Specific Populations
Pregnancy
Pregnancy Category B
CIALIS (tadalafil) is not indicated for use in
women. There are no adequate and well controlled studies of CIALIS use in pregnant women. Animal reproduction studies in rats and mice
revealed no evidence of fetal harm.
Animal reproduction studies showed no evidence of
teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to
pregnant rats or mice at exposures up to 11 times the maximum recommended human
dose (MRHD) of 20 mg/day during organogenesis. In one of two
perinatal/postnatal developmental studies in rats, postnatal pup survival
decreased following maternal exposure to tadalafil doses
greater than 10 times the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 16
times the MRHD based on AUC. Surviving offspring had normal development and
reproductive performance.
In a rat prenatal and postnatal development study at
doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was
observed. The no observed effect level (NOEL) for maternal toxicity was 200
mg/kg/day and for developmental toxicity was 30 mg/kg/day. This gives
approximately 16 and 10 fold exposure multiples, respectively, of the human AUC
for the MRHD of 20 mg.
Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in
rats.
Nursing Mothers
CIALIS is not indicated for use in women. It is not
known whether tadalafil is excreted into human milk. While tadalafil or some
metabolite of tadalafil was excreted into rat milk, drug levels in animal breast milk may not accurately predict levels
of drug in human breast milk.
Tadalafil and/or its metabolites were secreted into
the milk in lactating rats at concentrations approximately 2.4-fold greater
than found in the plasma.
Pediatric Use
CIALIS is not indicated for use in pediatric
patients. Safety and efficacy in patients below the age of 18 years has not
been established.
Geriatric Use
Of the total number of subjects in ED clinical
studies of tadalafil, approximately 25 percent were 65 and over, while
approximately 3 percent were 75 and over. Of the total number of subjects in
BPH clinical studies of tadalafil (including the ED/BPH study), approximately
40 percent were over 65, while approximately 10 percent were 75 and over. In
these clinical trials, no overall differences in efficacy or safety were
observed between older ( > 65 and ≥ 75 years of age) and younger subjects (
≤ 65 years of age). Therefore no dose adjustment is warranted based on age
alone. However, a greater sensitivity to medications in some older
individuals should be considered. [See CLINICAL PHARMACOLOGY].
Hepatic Impairment
In clinical pharmacology studies, tadalafil exposure
(AUC) in subjects with mild or moderate hepatic impairment (Child-Pugh Class A
or B) was comparable to exposure in healthy subjects when a dose of 10 mg was
administered. There are no available data for doses higher than 10 mg of
tadalafil in patients with hepatic impairment. Insufficient data are available
for subjects with severe hepatic impairment (Child-Pugh Class C). [See DOSAGE AND ADMINISTRATION and WARNINGS
AND PRECAUTIONS].
Renal Impairment
In clinical pharmacology studies using single-dose
tadalafil (5 to 10 mg), tadalafil exposure (AUC) doubled in subjects with
creatinine clearance 30 to 80 mL/min. In subjects with end-stage renal disease
on hemodialysis, there was a two-fold increase in Cmax and 2.7- to 4.8-fold
increase in AUC following single-dose administration of 10 or 20 mg tadalafil.
Exposure to total methylcatechol (unconjugated plus glucuronide) was 2- to
4-fold higher in subjects with renal impairment, compared to those with normal
renal function. Hemodialysis (performed between 24 and 30 hours post-dose)
contributed negligibly to tadalafil or metabolite elimination. In a clinical
pharmacology study (N=28) at a dose of 10 mg, back pain was reported as a
limiting adverse event in male patients with
creatinine clearance 30 to 50 mL/min. At a dose of 5 mg, the incidence and severity of back pain was not significantly different
than in the general population. In patients on hemodialysis taking 10- or 20-mg
tadalafil, there were no reported cases of back pain. [See DOSAGE AND ADMINISTRATION and WARNINGS
AND PRECAUTIONS].
Last
reviewed on RxList: 10/14/2011
This monograph has been modified to include the generic and brand name in many
instances.
