Drug: Adcirca

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.

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The following serious adverse reactions are discussed elsewhere in the labeling:
  • Hypotension [see WARNINGS AND PRECAUTIONS]
  • Visual Loss [see WARNINGS AND PRECAUTIONS and PATIENT INFORMATION]
  • Hearing loss [see WARNINGS AND PRECAUTIONS]
  • Priapism [see WARNINGS AND PRECAUTIONS]
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 398 patients with PAH during clinical trials worldwide. In trials of ADCIRCA, a total of 311 and 251 subjects have been treated for at least 182 days and 360 days, respectively. The overall rates of discontinuation because of an adverse event (AE) in the placebo-controlled trial were 9% for ADCIRCA 40 mg and 15% for placebo. The rates of discontinuation because of AEs, other than those related to worsening of PAH, in patients treated with ADCIRCA 40 mg was 4% compared to 5% in placebo-treated patients. In the placebo-controlled study, the most common AEs were generally transient and mild to moderate in intensity. Table 1 presents treatment-emergent adverse events reported by ≥ 9% of patients in the ADCIRCA 40 mg group and occurring more frequently than with placebo. TABLE 1: Treatment-Emergent Adverse Events Reported by ≥ 9% of Patients in ADCIRCA and More Frequent than Placebo by 2%
EVENT Placebo (%)
(N=82) ADCIRCA 20 mg (%)
(N=82) ADCIRCA 40 mg (%)
(N=79) Headache 15 32 42 Myalgia 4 9 14 Nasopharyngitis 7 2 13 Flushing 2 6 13 Respiratory Tract Infection (Upper and Lower) 6 7 13 Pain in Extremity 2 5 11 Nausea 6 10 11 Back Pain 6 12 10 Dyspepsia 2 13 10 Nasal Congestion (Including sinus congestion) 1 0 9 Postmarketing Experience The following adverse reactions have been identified during post-approval use of tadalafil. These events have been chosen for inclusion either because of their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. The list does not include adverse events that are reported from clinical trials and that are listed elsewhere in this section. 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 tadalafil without sexual activity. Others were reported to have occurred hours to days after the use of tadalafil and sexual activity. It is not possible to determine whether these events are related directly to tadalafil, 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, and transient global amnesia Ophthalmologic Visual field defect, retinal vein occlusion, and retinal artery occlusion Otologic Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including tadalafil. 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 tadalafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONS and PATIENT INFORMATION]. Urogenital Priapism [see WARNINGS AND PRECAUTIONS]. Read the Adcirca (tadalafil tablets) Side Effects Center for a complete guide to possible side effectsLearn More »

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Pulmonary Arterial Hypertension The recommended dose of ADCIRCA is 40 mg (two 20 mg tablets) taken once daily with or without food. Dividing the dose (40 mg) over the course of the day is not recommended. Use In Special Populations Renal Impairment
  • Mild (creatinine clearance 51 to 80 mL/min) or moderate (creatinine clearance 31 to 50 mL/min): Start dosing at 20 mg once daily. Increase to 40 mg once daily based on individual tolerability.
  • Severe (creatinine clearance < 30 mL/min and on hemodialysis): Avoid use of ADCIRCA because of increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis [see WARNINGS AND PRECAUTIONS and Use in Specific Populations].
Hepatic Impairment
  • Mild or moderate (Child Pugh Class A or B): Because of limited clinical experience in patients with mild to moderate hepatic cirrhosis, consider a starting dose of 20 mg once per day.
  • Severe (Child Pugh Class C): Patients with severe hepatic cirrhosis have not been studied. Avoid use of ADCIRCA [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Geriatric Patients
  • No dose adjustment is required in patients > 65 years of age without renal impairment or hepatic impairment.
Use With Ritonavir 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 WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]. 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 WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

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Potential For Pharmacodynamic Interactions With ADCIRCA Nitrates Do not use ADCIRCA in patients who are using any form of organic nitrate [see CONTRAINDICATIONS]. In clinical pharmacology studies ADCIRCA potentiated the hypotensive effect of nitrates [see CLINICAL PHARMACOLOGY]. In a patient who has taken ADCIRCA, where nitrate administration is deemed medically necessary in a life–threatening situation, at least 48 hours should elapse after the last dose of ADCIRCA before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring. Alpha-Blockers PDE5 inhibitors, including ADCIRCA, 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. Clinical pharmacology studies have been conducted with coadministration of tadalafil with doxazosin, alfuzosin or tamsulosin [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Antihypertensives PDE5 inhibitors, including ADCIRCA, are mild systemic vasodilators. Clinical pharmacology studies were conducted to assess the effect of tadalafil on the potentiation of the blood–pressure–lowering effects of selected antihypertensive medications (amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalapril, and metoprolol). Small reductions in blood pressure occurred following coadministration of tadalafil with these agents compared with placebo [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Alcohol Both alcohol and tadalafil, 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. Substantial consumption of alcohol (e.g., 5 units or greater) in combination with ADCIRCA can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Tadalafil (10 mg or 20 mg) did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations. [See WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Potential For Other Drugs To Affect ADCIRCA Ritonavir Ritonavir initially inhibits and later induces CYP3A, the enzyme involved in the metabolism of tadalafil. At steady state of ritonavir (about 1 week), the exposure to tadalafil is similar as in the absence of ritonavir [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY]. 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 WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Potent Inducers of CYP3A For patients chronically taking potent inducers of CYP3A, such as rifampin, avoid use of ADCIRCA [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Potential For ADCIRCA To Affect Other Drugs Cytochrome P450 Substrates Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms (e.g., theophylline, warfarin, midazolam, lovastatin, bosentan) [see CLINICAL PHARMACOLOGY]. Aspirin Tadalafil (10 mg and 20 mg once daily) does not potentiate the increase in bleeding time caused by aspirin [see CLINICAL PHARMACOLOGY]. P-glycoprotein (e.g., digoxin) Coadministration of tadalafil (40 mg once daily) for 10 days did not significantly alter digoxin pharmacokinetics in healthy subjects [see CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 4/21/2015
This monograph has been modified to include the generic and brand name in many instances.

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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%).

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Concomitant Organic Nitrates Do not use ADCIRCA in patients who are using any form of organic nitrate, either regularly or intermittently. ADCIRCA potentiates the hypotensive effect of nitrates. This potentiation is thought to result from the combined effects of nitrates and ADCIRCA on the nitric oxide/cGMP pathway [see CLINICAL PHARMACOLOGY]. Concomitant Guanylate Cyclase (GC) Stimulators Do not use ADCIRCA in patients who are using a GC stimulator, such as riociguat. ADCIRCA may potentiate the hypotensive effects of GC stimulators. Hypersensitivity Reactions ADCIRCA is contraindicated in patients with a known serious hypersensitivity to tadalafil (ADCIRCA or CIALIS). Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis [see ADVERSE REACTIONS]. Last reviewed on RxList: 4/21/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

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.

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Dosage Forms And Strengths 20 mg, orange, film-coated, almond-shaped tablets (not scored) debossed with “4467”. Storage And Handling 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. Manufactured by: Eli Lilly and Company, Indianapolis, IN 46285, USA Marketed by: Lung Biotechnology Inc., a wholly-owned subsidiary of United Therapeutics Corporation. Revised Apr 2015 Last reviewed on RxList: 4/21/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

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 venoocclusive 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 and CLINICAL PHARMACOLOGY], 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]. 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 and CLINICAL PHARMACOLOGY]. 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, DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]. 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, DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]. 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 and CLINICAL PHARMACOLOGY]. Potent Inducers of CYP3A For patients chronically taking potent inducers of CYP3A, such as rifampin, avoid use of ADCIRCA [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]. 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 and CLINICAL PHARMACOLOGY]. 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 and CLINICAL PHARMACOLOGY]. 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 and CLINICAL PHARMACOLOGY]. 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 and CLINICAL PHARMACOLOGY]. 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 study evaluated whether recent episodic use of PDE5 inhibitors, as a class, typical of erectile dysfunction treatment, was associated with acute onset of NAION. The results suggest an approximate 2-fold increase in the risk of NAION within 1 to 4 days of PDE5 inhibitor use. 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. 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]. 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. Patient Counseling Information See FDA-Approved Patient Labeling (PATIENT INFORMATION)
  • Inform patients of contraindication of ADCIRCA with any use of organic nitrates or GC stimulators.
  • Inform patients that tadalafil is also marketed as CIALIS for erectile dysfunction (ED) and for the signs and symptoms of benign prostatic hyperplasia (BPH). Advise patients taking ADCIRCA not to take CIALIS or other PDE5 inhibitors.
  • Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking ADCIRCA. Such an event may be a sign of NAION.
  • Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking ADCIRCA. These events may be accompanied by tinnitus and dizziness.
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 5–fold for mice, and 7– and 14–fold for male and female rats, respectively, the exposures at the maximum recommended human dose (MRHD) of 40 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 6–fold for males or 17–fold for females the exposures at the MRHD of 40 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 40 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 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. Non–teratogenic effects 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]. 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 ADCIRCA is administered to a nursing woman. Pediatric Use Safety and effectiveness of ADCIRCA 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 and CLINICAL PHARMACOLOGY]. Renal Impairment For patients with mild or moderate renal impairment, start ADCIRCA at 20 mg once daily. Increase the dose to 40 mg once daily based upon individual tolerability [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. 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 WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. 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 ADCIRCA 20 mg once daily. Patients with severe hepatic cirrhosis (Child-Pugh Class C) have not been studied, thus avoid use of ADCIRCA in such patients [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 4/21/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

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