Adcirca

Name: Adcirca

What special precautions should I follow?

Before taking tadalafil,

  • tell your doctor and pharmacist if you are allergic to tadalafil, any other medications, or any of the ingredients in tadalafil tablets. Ask your pharmacist for a list of the ingredients.
  • tell your doctor if you are taking or have recently taken riociguat (Adempas) or nitrates such as isosorbide dinitrate (Isordil), isosorbide mononitrate (Monoket), and nitroglycerin (Minitran, Nitro-Dur, Nitromist, Nitrostat, others). Nitrates come as tablets, sublingual (under the tongue) tablets, sprays, patches, pastes, and ointments. Ask your doctor if you are not sure whether any of your medications contain nitrates. Your doctor will probably tell you not to take tadalafil if you are taking nitrates.
  • tell your doctor if you are taking street drugs containing nitrates ('poppers') such as amyl nitrate, butyl nitrate, or nitrite while taking tadalafil. Your doctor will probably tell you not to take tadalafil if you are taking street drugs containing nitrates.
  • you should know that tadalafil is available under the brand names Adcirca and Cialis. You should only be treated with one of these products at a time.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: alpha blockers such as alfuzosin (Uroxatral), doxazosin (Cardura), dutasteride (Avodart, in Jalyn), prazosin (Minipress), silodosin (Rapaflo), tamsulosin (Flomax, in Jalyn), and terazosin; amiodarone (Cordarone, Pacerone); certain antifungals such as fluconazole (Diflucan), griseofulvin (Grifulvin, Gris-PEG), itraconazole (Onmel, Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegel), and voriconazole (Vfend); aprepitant (Emend); bosentan (Tracleer); carbamazepine (Carbatrol, Epitol, Tegretol, Teril, others); clarithromycin (Biaxin, in Prevpac); diltiazem (Cardizem, Cartia,Tiazac, others); efavirenz (Sustiva, in Atripla); erythromycin (E.E.S., E-Mycin, Erythrocin); HIV protease inhibitors including indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir, in Kaletra), lovastatin (Altocor, in Advicor); medications for high blood pressure; nefazodone; nevirapine (Viramune); other medications or treatments for erectile dysfunction; other medications or treatments for PAH; phenobarbital; phenytoin (Dilantin, Phenytek); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); sertraline (Zoloft); telithromycin (Ketek); and verapamil (Calan, Covera,Verelan, in Tarka). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor what herbal products you are taking, especially St. John's wort.
  • tell your doctor if you smoke; if you have ever had an erection that lasted more than 4 hours; and if you have recently had diarrhea, vomiting, not been drinking enough fluids, or sweating a lot which may have caused dehydration (loss of a large amount of body fluids. Also tell your doctor if you have or have ever had pulmonary veno-occlusive disease (PVOD; blockage of veins in the lungs); any condition that affects the shape of the penis; diabetes; high cholesterol; high or low blood pressure; irregular heartbeat; a heart attack or heart failure; angina (chest pain); a stroke; ulcers in the stomach; a bleeding disorder; blood circulation problems; blood cell problems such as sickle cell anemia (a disease of the red blood cells), multiple myeloma (cancer of the plasma cells), or leukemia (cancer of the white blood cells); or heart, kidney, or liver disease. Also tell your doctor if you or any of your family members have or have ever had an eye disease such as retinitis pigmentosa (an inherited eye condition that causes loss of vision) or if you have ever had sudden severe vision loss, especially if you were told that the vision loss was caused by a blockage of blood flow to the nerves that help you see.
  • if you are a woman and you are taking tadalafil to treat PAH, tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking tadalafil, call your doctor.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tadalafil.
  • talk to your doctor about the safe use of alcoholic beverages during your treatment with tadalafil. If you drink a large amount of alcohol (more than five glasses of wine or five shots of whiskey) while you are taking tadalafil you are more likely to experience certain side effects of tadalafil such as dizziness, headache, fast heartbeat, and low blood pressure.
  • if you are taking tadalafil to treat erectile dysfunction, tell your doctor if you have ever been advised by a health care professional to avoid sexual activity for medical reasons or if you have ever experienced chest pain during sexual activity. Sexual activity may be a strain on your heart, especially if you have heart disease. If you experience chest pain, dizziness, or nausea during sexual activity, call your doctor immediately or get emergency medical treatment, and avoid sexual activity until your doctor tells you otherwise.
  • tell all your health care providers that you are taking tadalafil. If you ever need emergency medical treatment for a heart problem, the health care providers who treat you will need to know when you last took tadalafil.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Before taking tadalafil

Some medicines are not suitable for people with certain conditions, and sometimes a medicine can only be used if extra care is taken. For these reasons, before you start taking tadalafil it is important that your doctor knows:

  • If you are pregnant, trying for a baby, or breast-feeding.
  • If you have any other heart problem or blood vessel condition.
  • If you have had an eye condition causing a loss of vision.
  • If you have problems with the way your liver works, or if you have problems with the way your kidneys work.
  • If you have recently had a heart attack.
  • If you have any disease, injury or deformity of your penis.
  • If you have sickle cell disease.
  • If you have ever had bone marrow cancer or leukaemia.
  • If you are taking or using any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines, and recreational drugs.
  • If you have ever had an allergic reaction to a medicine.

How to store tadalafil

  • Keep all medicines out of the reach and sight of children.
  • Store in a cool, dry place, away from direct heat and light.

Patient information

No information provided. Please refer to the WARNINGS AND PRECAUTIONS sections.

Precautions While Using Adcirca

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 this medicine 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.

This medicine 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. This medicine can cause serious side effects in patients with heart problems.

Do not use this medicine 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 this medicine. Grapefruit and grapefruit juice may change the amount of this medicine 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.

What are some things I need to know or do while I take Adcirca?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how Adcirca affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Do not take this medicine with other drugs used to treat a change in sex ability.
  • Talk with your doctor before you drink alcohol.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • Very bad and sometimes deadly side effects like a heartbeat that does not feel normal, heart attack, stroke, and very bad high blood pressure have happened with Adcirca. Talk with the doctor.
  • A very bad eye problem has rarely happened with this medicine. This may lead to a change in eyesight and sometimes loss of eyesight, which may not come back. Talk with the doctor.
  • If you are 65 or older, use Adcirca with care. You could have more side effects.
  • This medicine is not approved for use in children. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Indications and Usage for Adcirca

Pulmonary Arterial Hypertension

Adcirca® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%).

Dosing & Uses

Dosage Forms & Strengths

tablet (Adcirca)

  • 20mg

tablet (Cialis)

  • 2.5mg
  • 5mg
  • 10mg
  • 20mg

Erectile Dysfunction (ED)

Cialis

  • PRN use: 10 mg PO initially before sexual activity, with or without food; may be increased to 20 mg or reduced to 5 mg on basis of efficacy and tolerability; in most patients, maximum dosing frequency is once daily
  • Once-daily use: 2.5 mg/day PO in single daily dose, without regard to timing of sexual activity, with or without food; may be increased to 5 mg/day on basis of efficacy and tolerability

Dosing considerations

  • PRN use: Decrease dose with concomitant use of potent CYP3A4 inhibitor (eg, ritonavir, ketoconazole, itraconazole); not to exceed 10 mg/72 hr
  • Once-daily use: Decrease dose with concomitant use of potent CYP3A4 inhibitor (eg, ritonavir, ketoconazole, itraconazole); not to exceed 2.5 mg/day

Benign Prostatic Hyperplasia

Treatment of signs and symptoms of benign prostatic hyperplasia (BPH); daily use also indicated for treatment of patients with both BPH and erectile dysfunction

Cialis

  • BPH: 5 mg PO once daily
  • BPH with erectile dysfunction: 5 mg PO once daily, taken at approximately same time each day without regard to timing of sexual activity
  • With finasteride for BPH: tadalafil 5 mg plus finasteride 5 mg PO once daily for ≤26 weeks

Pulmonary Arterial Hypertension (PAH)

Adcirca

  • 40 mg PO once daily; dividing dose for more frequent dosing is not recommended
  • Patients also taking ritonavir: 20 mg PO once daily initially for ≥1 week; may be increased to 40 mg/day on basis of tolerability

Dosing considerations

  • If possible, avoid coadministration with CYP3A4 inhibitors; if coadministration is essential, long-term therapy is indicated, or strong CYP3A4 inhibitors are required, modify or hold dose
  • Patients already taking strong CYP3A4 inhibitor who require tadalafil: 20 mg PO once daily; may be increased to 40 mg/day on basis of tolerability
  • Patients already taking tadalafil who require strong CYP3A4 inhibitor: Avoid using tadalafil while starting strong CYP3A4 inhibitor; stop tadalafil ≥24 hours before starting strong CYP3A4 inhibitor; after 1 week, resume tadalafil at 20 mg PO once daily; may be increased to 40 mg/day on basis of tolerability

Geriatric Dosing

Erectile Dysfunction (ED)

  • Cialis: No dosage adjustment is warranted solely on basis of age; however, greater sensitivity to medications in some older individuals should be considered

Pulmonary Arterial Hypertension (PAH)

  • Adcirca: Lower dose or reduced dosing frequency may be required in elderly because of decreased renal or hepatic clearance

Dosing Modifications

Renal impairment (ED)

  • Cialis (PRN use)
    • Mild (CrCl ≥51 mL/min): No dosage adjustment needed
    • Moderate (CrCl 30-50 mL/min): Not to exceed 5 mg PO once daily initially; maximum dosage, 10 mg PO q48hr
    • Severe (CrCl <30 mL/min and on hemodialysis): Not to exceed 5 mg PO q72hr
  • Cialis (once daily use)
    • CrCl ≥30 mL/min: No dosage adjustment needed
    • CrCl <30 mL/min: Not recommended

Renal impairment (PAH)

  • Adcirca
    • Mild-to-moderate (CrCl 31-80 mL/min): 20 mg PO once daily initially; may be increased to 40 mg once daily on basis of tolerability
    • Severe (CrCl <30 mL/min and on hemodialysis): Avoid use

Hepatic impairment (ED)

  • Cialis (PRN use)
    • Mild-to-moderate (Child-Pugh class A or B): Not to exceed 10 mg PO once daily
    • Severe (Child-Pugh class C): Not recommended
  • Cialis (once daily use)
    • Mild-to-moderate (Child-Pugh class A or B): Data limited; caution advised
    • Severe (Child-Pugh class C): Not recommended

Hepatic impairment (PAH)

  • Adcirca
    • Mild-to-moderate (Child-Pugh class A or B): Consider starting dosage of 20 mg PO once daily
    • Severe (Child-Pugh class C): Avoid use

Muscular Dystrophy (Orphan)

Orphan designation for Duchenne muscular dystrophy (DMD)

Sponsor

  • Eli Lilly and Company; Lilly Corporate Center; Indianapolis, IN 46285

Pulmonary Arterial Hypertension (Orphan)

Orphan designation of a fixed dose combination of macitentan and tadalafil for treatment of pulmonary arterial hypertension

Sponsor

  • Actelion Clinical Research, Inc; 1820 Chapel Avenue West, Suite 300; Cherry Hill, New Jersey 08002

Safety and efficacy not established

Warnings

Contraindications

Hypersensitivity, including Stevens-Johnson syndrome and exfoliative dermatitis

Soluble guanylate cyclase (sGC) stimulators (eg, riociguat); concomitant use can cause hypotension

Coadministration with nitrates

  • Coadministration with nitrates (either regularly and/or intermittently) and nitric oxide donors
  • Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors may potentiate the hypotensive effects of nitrates
  • A suitable time interval following PDE5 dosing for the safe administration of nitrates or nitric oxide donors has not been determined

Cautions

Use caution in patients with anatomic deformation of penis, cardiovascular disease, left ventricular outflow obstruction, myocardial infarction in preceding 90 days, unstable angina, angina occurring during sexual intercourse, NYHA class 2 or greater heart failure in preceding 6 months, uncontrolled arrhythmias, hypotension, uncontrolled hypertension, cerebrovascular accident in preceding 6 months, bleeding disorders, active peptic ulcer disease, liver disease, renal impairment, conditions predisposing to priapism, concomitant use of CYP3A4 inhibitors

May cause dose-related impairment of color discrimination; use caution in patients with retinitis pigmentosa

Evaluate underlying causes of erectile dysfunction or BPH before initiating therapy

May increase risk of sudden vision loss attributed to nonarteritic ischemic optic neuropathy; if vision problems arise, discontinue, and contact physician

Risk of sudden hearing loss

CYP3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, indinavir, ritonavir) may significantly increase tadalafil serum levels

CYP3A4 inducers (eg, rifampin, St John’s wort) may decrease tadalafil serum levels

Potentiates hypotensive effect of nitrates (see Contraindications)

Concomitant use with alpha blockers (other than tamsulosin 0.4 mg/day) should be stabilized before initiation of phosphodiesterase (PDE)-5 inhibitors; patients with instability on alpha-blocker therapy alone are at increased risk for symptomatic hypotension with concurrent PDE-5 inhibitor therapy

Not to be taken with other PDE-5 inhibitors (eg, sildenafil, vardenafil)

Not recommended in patients with pulmonary veno-occlusive disease

Advise patients to seek emergency treatment if an erection lasts >4 hr

Pharmacology

Mechanism of Action

Erectile dysfunction: Inhibits PDE-5, increasing cyclic guanosine monophosphate (cGMP) to allow smooth-muscle relaxation and inflow of blood into corpus cavernosum

Pulmonary arterial hypertension (PAH): Inhibits PDE-5, increasing cGMP to allow relaxation of pulmonary vascular smooth-muscle cells and vasodilation of pulmonary vasculature

Absorption

Duration: ≤36 hr

Peak plasma time: Erectile dysfunction, 0.5-6 hr; PAH, 2-8 hr

Distribution

Protein bound: 94%

Vd: Erectile dysfunction, 63 L; PAH, 77 L

Metabolism

Metabolized in liver by CYP3A4

Elimination

Half-life: Erectile dysfunction, 15-17.5 hr; PAH (not on bosentan), 35 hr

Total body clearance: Erectile dysfunction, 2.5 L/hr; PAH (not on bosentan), 1.6 L/hr

Excretion: Feces (61%), urine (36%)

What is tadalafil (adcirca, cialis)?

Tadalafil relaxes muscles and increases blood flow to particular areas of the body.

Tadalafil under the name of Cialis is used to treat erectile dysfunction (impotence) and symptoms of benign prostatic hypertrophy (enlarged prostate). Another brand of tadalafil is Adcirca, which is used to treat pulmonary arterial hypertension and improve exercise capacity in men and women.

Tadalafil may also be used for purposes not listed in this medication guide.

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