Adcirca

Name: Adcirca

Overdose

Single doses up to 500 mg have been given to healthy male subjects, and multiple daily doses up to 100 mg have been given to male patients with erectile dysfunction. Adverse reactions were similar to those seen at lower doses. Doses greater than 40 mg have not been studied in patients with pulmonary arterial hypertension. In cases of overdose, standard supportive measures should be adopted as needed. Hemodialysis contributes negligibly to tadalafil elimination.

Uses For Adcirca

Tadalafil is used to treat men who have erectile dysfunction (also called sexual impotence). Tadalafil belongs to a group of medicines called phosphodiesterase 5 (PDE5) inhibitors. These medicines prevent an enzyme called phosphodiesterase type-5 from working too quickly. The penis is one of the areas where this enzyme works.

Erectile dysfunction is a condition where the penis does not harden and expand when a man is sexually excited, or when he cannot keep an erection. When a man is sexually stimulated, his body's normal response is to increase blood flow to his penis to produce an erection. By controlling the enzyme, tadalafil helps to maintain an erection after the penis is stroked by increasing blood flow to the penis. Without physical action to the penis, such as that occurring during sexual intercourse, tadalafil will not work to cause an erection.

Tadalafil is also used to treat men who have signs and symptoms of benign prostatic hyperplasia (BPH). BPH is caused by an enlarged prostate. Men with BPH usually have difficulty urinating, a decreased flow of urination, hesitation at the beginning of urination, and a need to get up at night to urinate. Tadalafil will make these symptoms less severe and reduce the chance that prostate surgery will be needed. This medicine is also used to treat erectile dysfunction and signs and symptoms of BPH.

Tadalafil is also used in both men and women to treat the symptoms of pulmonary arterial hypertension. This is high blood pressure that occurs in the main artery that carries blood from the right side of the heart (the ventricle) to the lungs. When the smaller blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump enough blood through the lungs. Tadalafil works on the PDE5 enzyme in the lungs to relax the blood vessels. This will increase the supply of blood to the lungs and reduce the workload of the heart.

This medicine is available only with your doctor's prescription. .

Proper Use of tadalafil

This section provides information on the proper use of a number of products that contain tadalafil. It may not be specific to Adcirca. Please read with care.

Use tadalafil exactly as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. If too much is used, the chance of side effects or other problems is increased.

Special patient instructions come with tadalafil. Read the directions carefully before you start using tadalafil and each time you get a refill of your medicine.

You may take this medicine with or without food.

Swallow the Cialis® tablet whole. Do not split, break, or crush it.

When using this medicine for erectile dysfunction, the ability to have sexual activity may be improved for up to 36 hours after taking the tablet.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For treatment of benign prostatic hyperplasia (daily use):
      • Adults—5 milligrams (mg) as a single dose, no more than once a day, taken at the same time each day.
      • Children—Use is not recommended.
    • For treatment of erectile dysfunction (as needed):
      • Adults—10 milligrams (mg) as a single dose, no more than once a day, taken 30 minutes before you think sexual activity may occur. Your doctor may adjust your dose if needed.
      • Children—Use is not recommended.
    • For treatment of erectile dysfunction (daily use):
      • Adults—2.5 milligrams (mg) once a day, taken at the same time each day, without regard for the timing of sexual activity. Your doctor may adjust your dose if needed.
      • Children—Use is not recommended.
    • For treatment of erectile dysfunction and benign prostatic hyperplasia (daily use):
      • Adults—5 milligrams (mg) once a day, taken at the same time each day, without regard for the timing of sexual activity.
      • Children—Use is not recommended.
    • For treatment of pulmonary arterial hypertension:
      • Adults—40 milligrams (mg) once a day.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

How is this medicine (Adcirca) best taken?

Use Adcirca as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • Read the package insert for more details.
  • Take this medicine at the same time of day.
  • To gain the most benefit, do not miss doses.
  • Keep taking Adcirca as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Adcirca (tadalafil tablets (adcirca)) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Adcirca. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Warnings and Precautions

Cardiovascular Effects

Discuss with patients the appropriate action to take in the event that they experience anginal chest pain requiring nitroglycerin following intake of Adcirca. At least 48 hours should elapse after the last dose of Adcirca before taking nitrates. If a patient has taken Adcirca within 48 hours, administer nitrates under close medical supervision with appropriate hemodynamic monitoring. Patients who experience anginal chest pain after taking Adcirca should seek immediate medical attention.

PDE5 inhibitors, including tadalafil, have mild systemic vasodilatory properties that may result in transient decreases in blood pressure. Prior to prescribing Adcirca, carefully consider whether patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. Patients with severely impaired autonomic control of blood pressure or with left ventricular outflow obstruction, (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis) may be particularly sensitive to the actions of vasodilators, including PDE5 inhibitors.

Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Since there are no clinical data on administration of Adcirca to patients with veno-occlusive disease, administration of Adcirca to such patients is not recommended. Should signs of pulmonary edema occur when Adcirca is administered, the possibility of associated PVOD should be considered.

There is a lack of data on safety and efficacy in the following groups who were specifically excluded from the PAH clinical trials:

  • Patients with clinically significant aortic and mitral valve disease
  • Patients with pericardial constriction
  • Patients with restrictive or congestive cardiomyopathy
  • Patients with significant left ventricular dysfunction
  • Patients with life-threatening arrhythmias
  • Patients with symptomatic coronary artery disease
  • Patients with hypotension (<90/50 mm Hg) or uncontrolled hypertension

Use with Alpha Blockers and Antihypertensives

PDE5 inhibitors, including Adcirca, and alpha–adrenergic blocking agents are 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 (7.1) and Clinical Pharmacology (12.2)], which may lead to symptomatic hypotension (e.g., fainting). Safety of combined use of PDE5 inhibitors and alpha blockers may be affected by other variables, including intravascular volume depletion and use of other antihypertensive drugs [see Drug Interactions (7.1)].

Use with Alcohol

Both alcohol and tadalafil are mild vasodilators. When mild vasodilators are taken in combination, blood pressure-lowering effects are increased [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)].

Use with Potent CYP3A Inhibitors or Inducers

Co-administration of Adcirca in Patients on Ritonavir

In patients receiving ritonavir for at least one week, start Adcirca at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability [see Dosage and Administration (2.3), Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

Co-administration of Ritonavir in Patients on Adcirca

Avoid use of Adcirca during the initiation of ritonavir. Stop Adcirca at least 24 hours prior to starting ritonavir. After at least one week following the initiation of ritonavir, resume Adcirca at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability [see Dosage and Administration (2.3), Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

Other Potent Inhibitors of CYP3A

Tadalafil is metabolized predominantly by CYP3A in the liver. In patients taking potent inhibitors of CYP3A such as ketoconazole and itraconazole, avoid use of Adcirca [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

Potent Inducers of CYP3A

For patients chronically taking potent inducers of CYP3A, such as rifampin, avoid use of Adcirca [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

Use in Renal Impairment

In patients with mild or moderate renal impairment

Start dosing at 20 mg once daily. Increase the dose to 40 mg once daily based upon individual tolerability [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

In patients with severe renal impairment

Avoid use of Adcirca because of increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

Use in Hepatic Impairment

In patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A and B)

Because of limited clinical experience in patients with mild to moderate hepatic cirrhosis, consider a starting dose of 20 mg once daily Adcirca [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

In patients with severe hepatic cirrhosis (Child-Pugh Class C)

Patients with severe hepatic cirrhosis have not been studied. Avoid use of Adcirca [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

Visual Loss

Physicians should advise patients to seek immediate 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 postmarketing in temporal association with the use of all PDE5 inhibitors. 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. Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 in males aged ≥50 in the general population. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, typical of erectile dysfunction treatment, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies.

Neither the rare postmarketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [see Adverse Reactions (6.2)].

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.

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.

Hearing Impairment

Physicians should advise patients to seek immediate 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 Adcirca. 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 (6.2)].

Combination with Other PDE5 Inhibitors

Tadalafil is also marketed as CIALIS. The safety and efficacy of taking Adcirca together with CIALIS or other PDE5 inhibitors have not been studied. Inform patients taking Adcirca not to take CIALIS or other PDE5 inhibitors.

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.

Adcirca 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).

Effects on Bleeding

PDE5 is found in platelets. When administered in combination with aspirin, tadalafil 20 mg did not prolong bleeding time, relative to aspirin alone. Adcirca has not been administered to patients with bleeding disorders or significant active peptic ulceration. Although Adcirca 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.

Adcirca Description

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

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

Adcirca is available as orange, film–coated, almond–shaped tablets for oral administration. Each tablet contains 20 mg of tadalafil and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, talc, titanium dioxide, and triacetin.

How Supplied/Storage and Handling

How Supplied

Adcirca (tadalafil) is supplied as follows:

20 mg orange, film–coated, almond–shaped tablets (not scored), debossed with “4467”

           Bottles of 60           NDC 66302-467-60

Storage

Store at 25°C (77°F): excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Keep out of reach of children.

Important information

Do not take Adcirca if you are also using a nitrate drug for chest pain or heart problems, including nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, and some recreational drugs such as "poppers". Taking tadalafil with a nitrate medicine can cause a sudden and serious decrease in blood pressure.

Some medicines can cause unwanted or dangerous effects when used with Adcirca. Tell your doctor about all your current medicines, especially riociguat (Adempas).

Get medical help at once if you have nausea, chest pain, or dizziness during sex.

Stop using Adcirca and get emergency medical help if you have sudden vision loss.

What happens if I miss a dose?

If 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.

Adcirca side effects

Get emergency medical help if you have signs of an allergic reaction to Adcirca: 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 Adcirca 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 Adcirca 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.

Tadalafil Breastfeeding Warnings

This drug and/or its metabolites were excreted in the milk of lactating rats at concentrations up to 2.4-fold higher than the maximal maternal plasma concentration. A risk to the breastfed child cannot be excluded. There are no human data on the excretion of this drug into breast milk.

This drug is not indicated for use in women Adcirca (R): UK: Use should be avoided. AU and US: Caution is recommended. Excreted into human milk: Data not available Excreted into animal milk: Yes Comments: The effects in the nursing infant are unknown.

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