Tadalafil

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

The breakdown and elimination of tadalafil 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 tadalafil in the blood. If these drugs are being used at the same time as tadalafil, the dose of tadalafil should be reduced to 10 mg every 72 hours when used as needed or 2.5 mg when used daily in order to avoid side effects from high levels of tadalafil.

Rifampin, carbamazepine (Tegretol, Tegretol XR, Equerto, Carbatrol), phenytoin (Dilantin, Dilantin-125), and phenobarbital may decrease blood levels of tadalafil, possibly reducing the effect of tadalafil.

Tadalafil exaggerates the increases in heart rate and lowering of blood pressure caused by nitrates, for example, nitroglycerin, isosorbide dinitrate (Isordil), isosorbide mononitrate (Imdur, Ismo, Monoket), nitroglycerin (Nitro-Dur, Transderm-Nitro) that are used primarily for treating heart pain (angina). In patients who take nitrates for angina, tadalafil could cause heart pain or possibly even a heart attack by exaggerating the increase in heart rate and the lowering of blood pressure. Therefore, tadalafil should not be used with nitrates.

Tadalafil also exaggerates the blood pressure lowering effects of some alpha-blocking drugs for example, terazosin (Hytrin) that primarily are used for treating high blood pressure or enlargement of the prostate (BPH). Individuals who take these alpha-blockers should be on a stable dose of the alpha-blocker before tadalafil is started. In such situations, tadalafil should be started at the lowest dose. If the patient is already taking tadalafil, the alpha-blocker should be started at the lowest dose. Combining tadalafil with alpha-blockers for treatment of BPH is not recommended.

Tadalafil and alcohol both lower blood pressure. Therefore, combining tadalafil with alcohol may cause excessive drops in blood pressure and cause dizziness, headaches, and increased heart rate.

PDE5 inhibitors may affect platelet function and therefore prolong bleeding. Tadalafil should be used cautiously in patients with bleeding disorders or active ulcers. Tadalafil should not be combined with Adcirca (another form of tadalafil) or other PDE5 inhibitors, for example, vardenafil (Levitra) or sildenafil (Viagra, Revatio).

Tadalafil is part of the drug class:

• Drugs used in erectile dysfunction

Take tadalafil exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

Tadalafil for Use as Needed for Erectile Dysfunction

• The recommended starting dose of tadalafil for use as needed in most patients is 10 mg, taken prior to anticipated sexual activity.
• The dose may be increased to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. The maximum recommended dosing frequency is once per day in most patients.
• Tadalafil for use as needed was shown to improve erectile function compared to placebo up to 36 hours following dosing. Therefore, when advising patients on optimal use of tadalafil, this should be taken into consideration.

Tadalafil for Once Daily Use for Erectile Dysfunction

• The recommended starting dose of tadalafil for once daily use is 2.5 mg, taken at approximately the same time every day, without regard to timing of sexual activity.
• The tadalafil dose for once daily use may be increased to 5 mg, based on individual efficacy and tolerability.

Tadalafil for Once Daily Use for Benign Prostatic Hyperplasia

The recommended dose of tadalafil for once daily use is 5 mg, taken at approximately the same time every day.

Tadalafil for Once Daily Use for Erectile Dysfunction and Benign Prostatic Hyperplasia

The recommended dose of tadalafil for once daily use is 5 mg, taken at approximately the same time every day, without regard to timing of sexual activity.

Tadalafil for use in PAH:

• The dose for treating PAH is 40 mg once daily, with or without food.
• Dividing the dose over the course of the day is not recommended. (2.1)
• Use with ritonavir requires dosage adjustments.

You should not take tadalafil if you are allergic to it.

Taking tadalafil with certain other medicines can cause a sudden and serious decrease in blood pressure. Do not take tadalafil if you also use:

• riociguat (to treat pulmonary arterial hypertension); or

• a nitrate drug (for chest pain or heart problems) such as nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, or recreational drugs such as amyl nitrate or nitrite "poppers".

Some tadalafil can remain in your bloodstream for 2 or more days after each dose you take (longer if you have liver or kidney disease). Avoid nitrate use during this time.

To make sure tadalafil is safe for you, tell your doctor if you have ever had:

• heart disease or heart rhythm problems;

• a heart attack or stroke;

• angina (chest pain), high or low blood pressure;

• pulmonary hypertension (unless you are taking tadalafil for this);

• a condition called pulmonary veno-occlusive disease (narrowing of the veins that carry blood from the lungs to the heart);

• liver or kidney disease (or if you are on dialysis);

• vision loss, or retinitis pigmentosa (an inherited condition of the eye);

• a bleeding disorder;

• a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;

• a physical deformity of the penis (such as Peyronie's disease), or an erection lasting longer than 4 hours;

• a stomach ulcer; or

• health problems that make sexual activity unsafe.

Sudden vision loss has occurred in a small number of people taking medicines like tadalafil (Viagra or others). Most of these people already had certain eye problems or risk factors for blood vessel disorders (heart disease, diabetes, high blood pressure, high cholesterol, coronary artery disease, smoking, or being over 50 years old). It is not clear whether the medicine was the actual cause of vision loss.

Tadalafil is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether tadalafil passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Tadalafil is not approved for use by anyone younger than 18 years old.

If tadalafil is used as needed, you are not likely to be on a dosing schedule.

If you take tadalafil every day and you miss a dose, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Drinking alcohol with this medicine can cause side effects.

Grapefruit and grapefruit juice may interact with tadalafil and lead to unwanted side effects. Avoid the use of grapefruit products while taking this medicine.

It is important that you tell all of your doctors that you take tadalafil. If you need emergency medical care for a heart problem, it is important that your doctor knows when you last took tadalafil.

If you will be taking tadalafil for pulmonary arterial hypertension, your doctor will want to check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

If you take tadalafil for pulmonary arterial hypertension, do not take Cialis® or other PDE5 inhibitors, such as sildenafil (Revatio® or Viagra®) or vardenafil (Levitra®). Cialis® also contains tadalafil. If you take too much tadalafil or take it together with these medicines, the chance for side effects will be higher.

If you experience a prolonged or painful erection for 4 hours or more, contact your doctor immediately. This condition may require prompt medical treatment to prevent serious and permanent damage to your penis.

tadalafil does not protect you against sexually transmitted diseases (including HIV or AIDS). Use protective measures and ask your doctor if you have any questions about this.

It is important to tell your doctor about any heart problems you have now or may have had in the past. tadalafil can cause serious side effects in patients with heart problems.

Do not use tadalafil if you are also using riociguat or a nitrate medicine, often used to treat angina (chest pain). Nitrate medicines include nitroglycerin, isosorbide, Imdur®, Nitro-Bid®, Nitrostat®, Nitro-Dur®, Transderm Nitro®, Nitrol® Ointment, and Nitrolingual® Spray. Some illegal ("street") drugs called "poppers" (such as amyl nitrate, butyl nitrate, or nitrite) also contain nitrates.

Do not drink excessive amounts of alcohol (eg, 5 glasses of wine or 5 shots of whiskey) when taking tadalafil. When taken in excess, alcohol can increase your chances of getting a headache or getting dizzy, increase your heart rate, or lower your blood pressure.

If you experience sudden loss of vision in one or both eyes, contact your doctor immediately.

Check with your doctor right away if you have a sudden decrease in hearing or loss of hearing, which may be accompanied by dizziness and ringing in the ears.

Do not eat grapefruit or drink grapefruit juice while you are using tadalafil. Grapefruit and grapefruit juice may change the amount of tadalafil that is absorbed in the body.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• chest tightness or heaviness
• chills
• cold sweats
• confusion
• dizziness
• fainting
• faintness or lightheadedness when getting up suddenly from a lying or sitting position
• fast or irregular heartbeat
• headache
• hearing loss
• nausea
• nervousness
• pain or discomfort in the arms, jaw, back, or neck
• pounding in the ears
• shortness of breath
• slow or fast heartbeat
• sweating
• unusual tiredness or weakness
• vomiting

• Painful or prolonged erection of the penis

• Abdominal or stomach pain
• blindness
• blistering, peeling, or loosening of the skin
• cough
• cracks in the skin
• decrease or change in vision
• diarrhea
• difficulty with speaking
• double vision
• fast, irregular, pounding, or racing heartbeat or pulse
• headache, severe and throbbing
• hives or welts
• inability to move the arms, legs, or facial muscles
• inability to speak
• itching
• joint or muscle pain
• loss of heat from the body
• numbness or tingling of the face, hands, or feet
• red irritated eyes
• red skin lesions, often with a purple center
• red, swollen skin
• redness of the skin
• redness or soreness of the eyes
• scaly skin
• skin rash
• slow speech
• sores, ulcers, or white spots in the mouth or on the lips
• sudden cardiac death
• swelling of the feet or lower legs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• heartburn
• indigestion
• stomach discomfort, upset, or pain

• Bloody nose
• body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• burning, dry, or itching eyes
• burning feeling in the chest or stomach
• congestion
• difficulty with moving
• difficulty with swallowing
• dry mouth
• dryness or soreness of the throat
• excessive eye discharge
• eye pain
• feeling of constant movement of self or surroundings
• feeling of warmth, redness of the face, neck, arms and occasionally, upper chest
• fever
• hoarseness
• increased erection
• lack or loss of strength
• loose stools
• muscle aching or cramping
• muscle stiffness
• nasal congestion
• neck pain
• pain
• pain in the arms or legs
• pain or burning in the throat
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• reduced sensitivity to touch
• runny nose
• sensation of spinning
• sleepiness or unusual drowsiness
• sleeplessness
• spontaneous penile erection
• stomach upset
• swelling of the eyelids
• swelling or puffiness of the eyes or face
• swollen joints
• tearing
• tender, swollen glands in the neck
• tenderness in the stomach area
• trouble with sleeping
• unable to sleep
• upper abdominal or stomach pain
• voice changes
• watering of the eyes

• Changes in color vision

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

Diabetes mellitus: The AUC was reduced approximately 19% and Cmax was 5% lower in patients with diabetes mellitus than in healthy subjects.

Benign prostatic hyperplasia (Cialis only): Treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).

Erectile dysfunction (Cialis only): Treatment of erectile dysfunction.

Erectile dysfunction and benign prostatic hyperplasia (Cialis only): Treatment of erectile dysfunction and the signs and symptoms of BPH.

Pulmonary arterial hypertension (Adcirca only): Treatment of pulmonary arterial hypertension (World Health Organization group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with New York Heart Association (NYHA) functional class II to III symptoms and etiologies of idiopathic or heritable pulmonary arterial hypertension (61%) or pulmonary arterial hypertension associated with connective tissue diseases (23%).

You should not take tadalafil if you are allergic to it.

Taking tadalafil with certain other medicines can cause a sudden and serious decrease in blood pressure. Do not take this medicine if you also use:

• riociguat (to treat pulmonary arterial hypertension); or

• a nitrate drug (for chest pain or heart problems) such as nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, or recreational drugs such as amyl nitrate or nitrite "poppers".

Some tadalafil can remain in your bloodstream for 2 or more days after each dose you take (longer if you have liver or kidney disease). Avoid nitrate use during this time.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• heart disease or heart rhythm problems;

• a heart attack or stroke;

• angina (chest pain), high or low blood pressure;

• pulmonary hypertension (unless you are taking tadalafil for this);

• a condition called pulmonary veno-occlusive disease (narrowing of the veins that carry blood from the lungs to the heart);

• liver or kidney disease (or if you are on dialysis);

• vision loss, or retinitis pigmentosa (an inherited condition of the eye);

• a bleeding disorder;

• a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;

• a physical deformity of the penis (such as Peyronie's disease), or an erection lasting longer than 4 hours;

• a stomach ulcer; or

• health problems that make sexual activity unsafe.

Sudden vision loss has occurred in a small number of people taking medicines like tadalafil (Viagra or others). Most of these people already had certain eye problems or risk factors for blood vessel disorders (heart disease, diabetes, high blood pressure, high cholesterol, coronary artery disease, smoking, or being over 50 years old). It is not clear whether the medicine was the actual cause of vision loss.

Tadalafil is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether tadalafil passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Tadalafil is not approved for use by anyone younger than 18 years old.

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

Stop and get medical help at once if you have nausea, chest pain, or dizziness during sex. You could be having a life-threatening side effect.

Stop using tadalafil and call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• an erection is painful or lasts longer than 4 hours (prolonged erection can damage the penis);

• vision changes or sudden vision loss;

• ringing in your ears or sudden hearing loss; or

• heart attack symptoms - chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating.

Common tadalafil side effects may include:

• headache;

• flushing (warmth, redness, or tingly feeling);

• nausea, upset stomach;

• stuffy nose; or

• muscle pain, back pain, pain in your arms or legs.

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.

Use as needed for ED:
-Initial dose: 10 mg orally once a day, as needed, prior to sexual activity
-Maintenance dose: 5 to 20 mg orally once a day, as needed, prior to sexual activity based on individual efficacy and tolerability

Comment: Consider that this drug has shown to improve erectile dysfunction up to 36 hours following dosing, when used as needed.

Once a day use for ED:
-Initial dose: 2.5 mg orally once a day at approximately the same time, without regard to timing of sexual activity
-Maintenance dose: 2.5 to 5 mg orally once a day based on individual efficacy and tolerability.

Once daily use for ED and Benign Prostatic Hyperplasia (BPH):
-5 mg orally once a day at approximately the same time, without regard to timing of sexual activity

Use: Treatment of erectile dysfunction (ED)

Data not available

Pregnancy

Animal reproduction studies in rats and mice revealed no evidence of fetal harm. There are, however, no adequate and well-controlled studies of Tadalafil in pregnant women. Because animal reproduction studies are not always predictive of human response, Tadalafil should be used during pregnancy only if clearly needed.

Animal reproduction studies showed no evidence of teratogenicity, embryotoxicity, or fetotoxicity when Tadalafil was given to pregnant rats or mice at unbound Tadalafil exposures up to 7 times the maximum recommended human dose (MRHD) of 40 mg/day during organogenesis. In one of two perinatal/postnatal developmental studies in rats, postnatal pup survival decreased following maternal exposure to unbound Tadalafil concentrations greater than 5 times the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 8 times the MRHD based on AUC. Surviving offspring had normal development and reproductive performance [see Nonclinical Toxicology (13.3)].

Nursing Mothers

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. Because many drugs are excreted in human milk, caution should be exercised when Tadalafil tablets are administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Tadalafil tablets in pediatric patients have not been established.

Geriatric Use

Of the total number of subjects in the clinical study of Tadalafil for pulmonary arterial hypertension, 28 percent were 65 and over, while 8 percent were 75 and over. No overall differences in safety were observed between subjects over 65 years of age compared to younger subjects or those over 75 years of age. No dose adjustment is warranted based on age alone; however, a greater sensitivity to medications in some older individuals should be considered. [See Dosage and Administration (2.2) and Clinical Pharmacology (12.3).]

Renal Impairment

For patients with mild or moderate renal impairment, start Tadalafil tablets at 20 mg once daily. Increase the dose to 40 mg once daily based upon individual tolerability [see Dosage and Administration (2.2), Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

In patients with severe renal impairment, avoid use of Tadalafil tablets because of increased Tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

Hepatic Impairment

Because of limited clinical experience in patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A or B), consider a starting dose of Tadalafil tablets 20 mg once daily. Patients with severe hepatic cirrhosis (Child-Pugh Class C) have not been studied, thus avoid use of Tadalafil tablets in such patients [see Dosage and Administration (2.2), Warnings and Precautions (5.4) and Clinical Pharmacology (12.3)].

Tadalafil tablets, USP, an oral treatment for pulmonary arterial hypertension, are a selective inhibitor of cyclic guanosine monophosphate (cGMP)–specific phosphodiesterase type 5 (PDE5). Tadalafil has the molecular formula C22H19N3O4 representing a molecular weight of 389.41. The structural formula is:

The chemical designation is (6R-trans)-6-(1,3-benzodioxol-5-yl)- 2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino [1', 2':1,6] pyrido[3,4-b]indole-1,4-dione. It is a crystalline solid that is practically insoluble in water and very slightly soluble in ethanol.

Tadalafil is available as yellow, film-coated, round, unscored tablets for oral administration. Each tablet contains 20 mg of Tadalafil and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium lauryl sulfate, talc, titanium dioxide and yellow iron oxide.

See FDA-Approved Patient Labeling (Patient Information)