Wednesday, July 24, 2013

More Weiner Worries in America

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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.



My favorite of all the warnings is the dreaded; In the unlikely event you have a painful or prolonged erection lasting 4 or more hours, stop using this drug and get medical help right away or permanent problems could occur.
 
 
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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.


Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of sildenafil.

Stop using sildenafil and call your doctor at once if you have a serious side effect such as:

  • 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.

Less serious side effects may include:

  • warmth or redness in your face, neck, or chest;
  • stuffy nose;
  • headache;
  • memory problems;
  • upset stomach; or
  • back pain.

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.

Read the entire detailed patient monograph for Viagra (Sildenafil Citrate) »

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.


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.

To minimize dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Rarely, a sudden loss of eyesight in one or both eyes (NAION) may occur. This may or may not be due to sildenafil. Stop taking sildenafil and get medical help right away if this occurs. You have a slightly greater chance of developing this serious eye problem if you have heart disease, diabetes, high cholesterol, certain other eye problems ("crowded disk"), or high blood pressure, or if you smoke or are over 50.

Sexual activity may put extra strain on your heart, especially if you have heart problems. If you have heart problems and experience any of these serious side effects while having sex, stop taking sildenafil and get medical help right away: severe dizziness, fainting, chest/jaw/left arm pain, nausea.

In the unlikely event you have a painful or prolonged erection lasting 4 or more hours, stop using this drug and get medical help right away or permanent problems could occur.

Rarely, sildenafil may cause sudden hearing problems (such as decrease/loss of hearing in one or both ears, ringing in the ears). Stop taking sildenafil and get medical help right away if these effects occur.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Viagra (Sildenafil Citrate)»

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Viagra FDA Prescribing Information: Side Effects
(Adverse Reactions)

VIAGRA SIDE EFFECTS

Clinical Trials

VIAGRA (sildenafil citrate) was administered to over 3700 patients (aged 19-87 years) during pre-marketing clinical trials worldwide. Over 550 patients were treated for longer than one year.

In placebo-controlled clinical studies, the discontinuation rate due to adverse events for VIAGRA (sildenafil citrate) (2.5%) was not significantly different from placebo (2.3%). The adverse events were generally transient and mild to moderate in nature.

In trials of all designs, adverse events reported by patients receiving VIAGRA (sildenafil citrate) were generally similar. In fixed-dose studies, the incidence of some adverse events increased with dose. The nature of the adverse events in flexible-dose studies, which more closely reflect the recommended dosage regimen, was similar to that for fixed-dose studies.

When VIAGRA (sildenafil citrate) was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials, the following adverse events were reported:

TABLE 2. ADVERSE EVENTS REPORTED BY ≥ 2% OF PATIENTS TREATED WITH VIAGRA (sildenafil citrate) AND MORE FREQUENT ON DRUG THAN PLACEBO IN PRN FLEXIBLE-DOSE PHASE II/III STUDIES

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.

Other adverse reactions occurred at a rate of > 2%, but equally common on placebo: respiratory tract infection, back pain, flu syndrome, and arthralgia.

In fixed-dose studies, dyspepsia (17%) and abnormal vision (11%) were more common at 100 mg than at lower doses. At doses above the recommended dose range, adverse events were similar to those detailed above but generally were reported more frequently.

The following events occurred in < 2% of patients in controlled clinical trials; a causal relationship to VIAGRA (sildenafil citrate) is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful:

Body as a whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury.

Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy.

Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis.

Hemic and Lymphatic: anemia and leukopenia.

Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.

Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis.

Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia.

Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased.

Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.

Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes.

Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia.

Post-Marketing Experience

Cardiovascular and cerebrovascular

Serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of VIAGRA (sildenafil citrate) . Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of VIAGRA (sildenafil citrate) without sexual activity. Others were reported to have occurred hours to days after the use of VIAGRA (sildenafil citrate) and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA (sildenafil citrate) , to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors (see WARNINGS for further important cardiovascular information).

Special senses

Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including VIAGRA (sildenafil citrate) . In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of VIAGRA (sildenafil citrate) , to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors (see PATIENT INFORMATION).

Other events

Other events reported post-marketing to have been observed in temporal association with VIAGRA (sildenafil citrate) and not listed in the clinical trial adverse reactions section above include:

Nervous: seizure, seizure recurrence, anxiety, and transient global amnesia.

Urogenital: prolonged erection, priapism (see WARNINGS), and hematuria.

Special Senses: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal vascular disease or bleeding, vitreous detachment/traction, paramacular edema and epistaxis.

Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA (sildenafil citrate) . Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors (see PATIENT INFORMATION).
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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.


Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

If you become dizzy or nauseated during sexual activity, or if you have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of tadalafil.

Stop using tadalafil and call your doctor at once if you have any of these serious side effects:

  • 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.

Less serious side effects may include:

  • 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.

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.

Read the entire detailed patient monograph for Cialis (Tadalafil) »

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.


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.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Rarely, a sudden loss of eyesight in one or both eyes (NAION) may occur. This may or may not be due to tadalafil. If this serious problem occurs, seek immediate medical attention. You have a slightly greater chance of developing this serious eye problem if you have heart disease, diabetes, high cholesterol, certain eye problems ("crowded disk"), high blood pressure, are over 50 years of age, or if you smoke.

Sexual activity may put extra strain on your heart, especially if you have heart problems. If you have heart problems or experience any of the following serious side effects during sex, stop and seek immediate medical attention: severe dizziness, fainting, chest pain.

For males, in the very unlikely event you have a painful or prolonged erection lasting 4 or more hours, stop using this drug and seek immediate medical attention, or permanent problems could occur.

Rarely, tadalafil may cause sudden hearing problems, or ringing in the ears. Stop taking this medication and tell your doctor immediately if these effects occur.

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Cialis (Tadalafil)»

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Cialis FDA Prescribing Information: Side Effects
(Adverse Reactions)

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Tadalafil was administered to over 9000 men during clinical trials worldwide. In trials of CIALIS for once daily use, a total of 1434, 905, and 115 were treated for at least 6 months, 1 year, and 2 years, respectively. For CIALIS for use as needed, over 1300 and 1000 subjects were treated for at least 6 months and 1 year, respectively.

CIALIS for Use as Needed for ED

In eight primary placebo-controlled clinical studies of 12 weeks duration, mean age was 59 years (range 22 to 88) and the discontinuation rate due to adverse events in patients treated with tadalafil 10 or 20 mg was 3.1%, compared to 1.4% in placebo treated patients.

When taken as recommended in the placebo-controlled clinical trials, the following adverse reactions were reported (see Table 1) for CIALIS for use as needed:

Table 1: Treatment-Emergent Adverse Reactions Reported by ≥ 2% of Patients Treated with CIALIS (10 or 20 mg) and More Frequent on Drug than Placebo in the Eight Primary Placebo-Controlled Clinical Studies (Including a Study in Patients with Diabetes) for 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

In three placebo-controlled clinical trials of 12 or 24 weeks duration, mean age was 58 years (range 21 to 82) and the discontinuation rate due to adverse events in patients treated with tadalafil was 4.1%, compared to 2.8% in placebo-treated patients.

The following adverse reactions were reported (see Table 2) in clinical trials of 12 weeks duration:

Table 2: Treatment-Emergent Adverse Reactions Reported by ≥ 2% of Patients Treated with CIALIS for Once Daily Use (2.5 or 5 mg) and More Frequent on Drug than Placebo in the Three Primary Placebo-Controlled Phase 3 Studies of 12 weeks Treatment Duration (Including a Study in Patients with Diabetes) for 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%

The following adverse reactions were reported (see Table 3) over 24 weeks treatment duration in one placebo-controlled clinical study:

Table 3: Treatment-Emergent Adverse Reactions Reported by ≥ 2% of Patients Treated with CIALIS for Once Daily Use (2.5 or 5 mg) and More Frequent on Drug than Placebo in One Placebo-Controlled Clinical Study of 24 Weeks Treatment Duration for CIALIS for Once Daily Use for ED

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

In three placebo-controlled clinical trials of 12 weeks duration, two in patients with BPH and one in patients with ED and BPH, the mean age was 63 years (range 44 to 93) and the discontinuation rate due to adverse events in patients treated with tadalafil was 3.6% compared to 1.6% in placebo-treated patients. Adverse reactions leading to discontinuation reported by at least 2 patients treated with tadalafil included headache, upper abdominal pain, and myalgia. The following adverse reactions were reported (see Table 4).

Table 4: Treatment-Emergent Adverse Reactions Reported by ≥ 1% of Patients Treated with CIALIS for Once Daily Use (5 mg) and More Frequent on Drug than Placebo in Three Placebo-Controlled Clinical Studies of 12 Weeks Treatment Duration, including Two Studies for CIALIS for Once Daily Use for BPH and One Study 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%

Additional, less frequent adverse reactions ( < 1%) reported in the controlled clinical trials of CIALIS for BPH or ED and BPH included: gastroesophageal reflux disease, upper abdominal pain, nausea, vomiting, arthralgia, and muscle spasm.

Back pain or myalgia was reported at incidence rates described in Tables 1 through 4. In tadalafil clinical pharmacology trials, back pain or myalgia generally occurred 12 to 24 hours after dosing and typically resolved within 48 hours. The back pain/myalgia associated with tadalafil treatment was characterized by diffuse bilateral lower lumbar, gluteal, thigh, or thoracolumbar muscular discomfort and was exacerbated by recumbency. In general, pain was reported as mild or moderate in severity and resolved without medical treatment, but severe back pain was reported with a low frequency ( < 5% of all reports). When medical treatment was necessary, acetaminophen or non-steroidal anti-inflammatory drugs were generally effective; however, in a small percentage of subjects who required treatment, a mild narcotic (e.g., codeine) was used. Overall, approximately 0.5% of all subjects treated with CIALIS for on demand use discontinued treatment as a consequence of back pain/myalgia. In the 1-year open label extension study, back pain and myalgia were reported in 5.5% and 1.3% of patients, respectively. Diagnostic testing, including measures for inflammation, muscle injury, or renal damage revealed no evidence of medically significant underlying pathology. Incidence rates for CIALIS for once daily use for ED, BPH and BPH/ED are described in Tables 2, 3 and 4. In studies of CIALIS for once daily use, adverse reactions of back pain and myalgia were generally mild or moderate with a discontinuation rate of < 1% across all indications.

Across all studies with any CIALIS dose, reports of changes in color vision were rare ( < 0.1% of patients).

The following section identifies additional, less frequent events ( < 2%) reported in controlled clinical trials of CIALIS for once daily use or use as needed. A causal relationship of these events to CIALIS is uncertain. Excluded from this list are those events that were minor, those with no plausible relation to drug use, and reports too imprecise to be meaningful:

Body as a Whole - asthenia, face edema, fatigue, pain


Digestive - abnormal liver function tests, dry mouth, dysphagia, esophagitis, gastritis, GGTP increased, loose stools, nausea,

upper abdominal pain, vomiting, gastroesophageal reflux disease, hemorrhoidal hemorrhage, rectal hemorrhage

Musculoskeletal - arthralgia, neck pain

Nervous - dizziness, hypesthesia, insomnia, paresthesia, somnolence, vertigo

Renal and Urinary - renal impairment

Respiratory - dyspnea, epistaxis, pharyngitis

Skin and Appendages - pruritus, rash, sweating

Ophthalmologic - blurred vision, changes in color vision, conjunctivitis (including conjunctival hyperemia), eye pain, lacrimation increase, swelling of eyelids

Otologic - sudden decrease or loss of hearing, tinnitus

Urogenital - erection increased, spontaneous penile erection

Postmarketing Experience

The following adverse reactions have been identified during post approval use of CIALIS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion either due to their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors.

Cardiovascular and Cerebrovascular - Serious cardiovascular events, including myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations, and tachycardia, have been reported postmarketing in temporal association with the use of tadalafil. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of CIALIS without sexual activity. Others were reported to have occurred hours to days after the use of CIALIS and sexual activity. It is not possible to determine whether these events are related directly to CIALIS, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONS].

Body as a Whole - hypersensitivity reactions including urticaria, Stevens-Johnson syndrome, and exfoliative dermatitis

Nervous - migraine, seizure and seizure recurrence, transient global amnesia

Ophthalmologic - visual field defect, retinal vein occlusion, retinal artery occlusion

Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including CIALIS. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONS].

Otologic - Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including CIALIS. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of CIALIS, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONS].

Urogenital - priapism [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Cialis (Tadalafil) »

CIALIS PRECAUTIONS

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.

CIALIS should be used with caution in patients who have conditions that might predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease).

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

Physicians should discuss with patients the potential for CIALIS to augment the blood-pressure-lowering effect of alpha blockers and antihypertensive medications [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

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

“See FDA-approved Patient Labeling (PATIENT 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.

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