Tadliq

Tadalafil · Suspension · Oral

Prescription (Rx) Phosphodiesterase 5 Inhibitor

Uses

1 INDICATIONS AND USAGE TADLIQ is a phosphodiesterase 5 (PDE5) inhibitor 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%). ( 1.1 ) 1.1 Pulmonary Arterial Hypertension TADLIQ ® 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%).

Dosage and administration

40 mg (10 mL) once daily, with or without food. ( 2.1 ) Use with ritonavir requires dosage adjustments. ( 2.4 ) 2.1 Pulmonary Arterial Hypertension The recommended dose of TADLIQ is 40 mg (10 mL) taken once daily with or without food. 2.2 Dose Adjustment in Renal Impairment Mild (creatinine clearance 51 to 80 mL/min) or moderate (creatinine clearance 31 to 50 mL/min): Start dosing at 20 mg (5mL) once daily. Increase to 40 mg (10 mL) once daily based on individual tolerability. Severe (creatinine clearance <30 mL/min and on hemodialysis): Avoid use of TADLIQ because of increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis [see Use in Specific Populations ( 8.6 )] . 2.3 Dose Adjustment in 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 (5 mL) once per day. Severe (Child Pugh Class C): Patients with severe hepatic cirrhosis have not been studied. Avoid use of TADLIQ [see Use in Specific Populations ( 8.7 )] . 2.4 Dose Adjustment for Use with Ritonavir Co-administration of TADLIQ in Patients on Ritonavir In patients receiving ritonavir for at least one week, start TADLIQ at 20 mg (5 mL) once daily. Increase to 40 mg (10 mL) once daily based upon individual tolerability [see Drug Interactions ( 7.5 ) and Clinical Pharmacology ( 12.3 )] . Co-administration of Ritonavir in Patients on TADLIQ Avoid use of TADLIQ during the initiation of ritonavir. Stop TADLIQ at least 24 hours prior to starting ritonavir. After at least one week following the initiation of ritonavir, resume TADLIQ at 20 mg (5 mL) once daily. Increase to 40 mg (10 mL) once daily based upon individual tolerability [see Drug Interactions ( 7.5 ) and Clinical Pharmacology ( 12.3 )] .

Dosage forms and strengths

Oral Suspension: 20 mg/5 mL; white to off-white opaque suspension with a peppermint flavor. Oral Suspension: 20 mg/5 mL ( 3 )

Contraindications

Concomitant organic nitrates ( 4.1 ) Concomitant Guanylate Cyclase (GC) Stimulators ( 4.2 ) History of known serious hypersensitivity reaction to TADLIQ, ADCIRCA ® or CIALIS ® ( 4.3 ) 4.1 Concomitant Organic Nitrates TADLIQ is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. Do not use nitrates within 48 hours of the last dose of TADLIQ. TADLIQ potentiates the hypotensive effect of nitrates. This potentiation is thought to result from the combined effects of nitrates and TADLIQ on the nitric oxide/cGMP pathway [see Clinical Pharmacology ( 12.2 )] . 4.2 Concomitant Guanylate Cyclase (GC) Stimulators Coadministration of GC stimulators such as riociguat with TADLIQ is contraindicated. TADLIQ may potentiate the hypotensive effects of GC stimulators. 4.3 Hypersensitivity Reactions TADLIQ is contraindicated in patients with a known serious hypersensitivity to tadalafil (TADLIQ, ADCIRCA ® or CIALIS ® ). Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis [see Adverse Reactions ( 6.2 )] .

Warnings and precautions

Hypotension: Carefully consider whether patients with certain underlying cardiovascular disease could be adversely affected by vasodilatory effects of TADLIQ. Not recommended in patients with pulmonary veno-occlusive disease. ( 5.1 , 5.2 ) Effects on the eye: Sudden loss of vision could be a sign of non-arteritic ischemic optic neuropathy (NAION) and may be permanent. ( 5.3 ) Hearing impairment: Cases of sudden decrease or loss of hearing have been reported with tadalafil. ( 5.4 ) Concomitant PDE5 inhibitors: Avoid use with CIALIS, ADCIRCA or other PDE5 inhibitors. ( 5.5 ) Prolonged erection: Advise patients to seek emergency treatment if an erection lasts >4 hours. ( 5.6 ) 5.1 Hypotension TADLIQ has vasodilatory properties that may result in transient decreases in blood pressure. Prior to prescribing TADLIQ, carefully consider whether patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. Patients with preexisting hypotension, with autonomic dysfunction, with left ventricular outflow obstruction, may be particularly sensitive to the actions of vasodilators. 5.2 Worsening Pulmonary Vascular Occlusive Disease 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 TADLIQ to patients with veno-occlusive disease, administration of TADLIQ to such patients is not recommended. Should signs of pulmonary edema occur when TADLIQ is administered, the possibility of associated PVOD should be considered. 5.3 Visual Loss When used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE-5) inhibitors, including tadalafil. 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 doubling in the risk of NAION. Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. 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. 5.4 Hearing Impairment Cases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, have been reported in patients taking tadalafil. 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 )] . 5.5 Combination with Other PDE5 Inhibitors Tadalafil is also marketed for erectile dysfunction. The safety and efficacy of taking TADLIQ together with another PDE5 inhibitor has not been studied. Inform patients taking TADLIQ not to take other PDE5 inhibitors. 5.6 Prolonged Erection There have been reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds. Patients with 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) are at an increased risk. 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.

Side effects

The following serious adverse reactions are discussed elsewhere in the labeling: Hypotension [see Warnings and Precautions ( 5.1 )] Visual Loss [see Warnings and Precautions ( 5.3 )] Hearing loss [see Warnings and Precautions ( 5.4 )] Priapism [see Warnings and Precautions ( 5.6 )] The most common adverse reaction is headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact CMP Development, LLC at 1-844-321-1443, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 tadalafil, 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 tadalafil 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 tadalafil 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 tadalafil 40 mg group and occurring more frequently than with placebo. Table 1: Treatment-Emergent Adverse Events Reported by ≥9% of Patients in Tadalafil and More Frequent than Placebo by 2% EVENT Placebo (%) (N=82) Tadalafil 20 mg (%) (N=82) Tadalafil 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 6.2 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 [see Contraindications ( 4.1 )] . 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. 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, retinal artery occlusion, and NAION [see Warnings and Precautions ( 5.3 )]. 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 ( 5.4 )] . Urogenital — Priapism [see Warnings and Precautions ( 5.6 )] .

Drug interactions

7.1 Nitrates Administration of nitrates within 48 hours after the last dose of TADLIQ is contraindicated [see Contraindications ( 4.1 )] . 7.2 Alpha-Blockers PDE5 inhibitors, including TADLIQ, 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 Clinical Pharmacology ( 12.2 )] . 7.3 Antihypertensives PDE5 inhibitors, including TADLIQ, 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 Clinical Pharmacology ( 12.2 )] . 7.4 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 TADLIQ 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 Clinical Pharmacology ( 12.2 )] . 7.5 CYP3A Inhibitors/Inducers 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 ( 2.4 ) and Clinical Pharmacology ( 12.3 )] . 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 TADLIQ [see Clinical Pharmacology ( 12.3 )] . Potent Inducers of CYP3A For patients chronically taking potent inducers of CYP3A, such as rifampin, avoid use of TADLIQ [see Clinical Pharmacology ( 12.3 )] .

Use in specific populations

Renal Impairment ( 2.2 , 8.6 , 12.3 ) Mild or moderate: Start with 20 mg once daily. ( 2.2 , 8.6 ) Severe: Avoid use of TADLIQ. ( 2.2 , 8.6 ) Hepatic Impairment ( 2.2 , 8.7 , 12.3 ) Mild or moderate: Consider starting dose of 20 mg once daily. ( 2.3 , 8.7 ) Severe: Avoid use of TADLIQ. ( 2.3 , 8.7 ) 8.1 Pregnancy Risk Summary Pregnant women with untreated pulmonary arterial hypertension are at risk for adverse maternal and fetal outcomes (see Clinical Considerations) . Available data from a randomized controlled trial, observational studies, and case series with tadalafil use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats or mice during organogenesis at exposures 7 times the exposure at the maximum recommended human dose (MRHD) of 40 mg/day based on AUC (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. Data Animal Data Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. 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 exposure at the maximum recommended human dose (MRHD) of 40 mg/day during organogenesis based on AUC. In one of two perinatal/postnatal developmental studies in rats, a reduction of postnatal pup survival was observed at dose levels of 60, 200 and 1000 mg/kg. The no-observed-effect-level (NOEL) for developmental toxicity was 30 mg/kg, which provided maternal exposure to unbound tadalafil concentrations approximately 5 times the exposure at the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 200 mg/kg/day, which produced AUCs greater than 8 times the exposure at the MRHD. Surviving offspring had normal development and reproductive performance. 8.2 Lactation Risk Summary There are no data on the presence of tadalafil and/or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Tadalafil and/or its metabolites are present in the milk of lactating rats at concentrations approximately 2.4-times that found in the plasma. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TADLIQ and any potential adverse effects on the breastfed child from TADLIQ or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Infertility Males Based on the data from 3 studies in adult males, tadalafil decreased sperm concentrations in the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. There was no adverse effect of tadalafil 10 mg or 20 mg on mean concentrations of testosterone, luteinizing hormone or follicle stimulating hormone. The clinical significance of the decreased sperm concentrations in the two studies is unknown. There have been no studies evaluating the effect of tadalafil on fertility in men or women [see Clinical Pharmacology ( 12.2 )] . 8.4 Pediatric Use Safety and effectiveness of TADLIQ in pediatric patients have not been established. 8.5 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 Clinical Pharmacology ( 12.3 )] . 8.6 Renal Impairment For patients with mild or moderate renal impairment, start TADLIQ at 20 mg (5 mL) once daily. Increase the dose to 40 mg (10 mL) 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 TADLIQ because of increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis [see Clinical Pharmacology ( 12.3 )] . 8.7 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 TADLIQ 20 mg (5 mL) once daily. Patients with severe hepatic cirrhosis (Child-Pugh Class C) have not been studied, thus avoid use of TADLIQ in such patients [see Dosage and Administration ( 2.3 ) and Clinical Pharmacology ( 12.3 )] .

Pregnancy

8.1 Pregnancy Risk Summary Pregnant women with untreated pulmonary arterial hypertension are at risk for adverse maternal and fetal outcomes (see Clinical Considerations) . Available data from a randomized controlled trial, observational studies, and case series with tadalafil use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats or mice during organogenesis at exposures 7 times the exposure at the maximum recommended human dose (MRHD) of 40 mg/day based on AUC (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. Data Animal Data Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. 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 exposure at the maximum recommended human dose (MRHD) of 40 mg/day during organogenesis based on AUC. In one of two perinatal/postnatal developmental studies in rats, a reduction of postnatal pup survival was observed at dose levels of 60, 200 and 1000 mg/kg. The no-observed-effect-level (NOEL) for developmental toxicity was 30 mg/kg, which provided maternal exposure to unbound tadalafil concentrations approximately 5 times the exposure at the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 200 mg/kg/day, which produced AUCs greater than 8 times the exposure at the MRHD. Surviving offspring had normal development and reproductive performance.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of TADLIQ in pediatric patients have not been established.

Geriatric use

8.5 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 Clinical Pharmacology ( 12.3 )] .

Overdosage

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.

Description

11 DESCRIPTION TADLIQ contains tadalafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)–specific phosphodiesterase type 5 (PDE5). Tadalafil has the empirical formula C 22 H 19 N 3 O 4 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. TADLIQ oral suspension contains 20 mg/5 mL of tadalafil and the following inactive ingredients: 30% simethicone emulsion, citric acid monohydrate, glycerin, peppermint flavor, polysorbate 80, purified water, sodium benzoate, sucralose, trisodium citrate dihydrate, xanthan gum. Structural Formula

Mechanism of action

12.1 Mechanism of Action Tadalafil is an inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Pulmonary arterial hypertension is associated with impaired release of nitric oxide by the vascular endothelium and consequent reduction of cGMP concentrations in the pulmonary vascular smooth muscle. PDE5 is the predominant phosphodiesterase in the pulmonary vasculature. Inhibition of PDE5 by tadalafil increases the concentrations of cGMP resulting in relaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed. Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in pulmonary vascular smooth muscle, visceral smooth muscle, corpus cavernosum, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas. In vitro studies have shown that the effect of tadalafil is more potent on PDE5 than on other phosphodiesterases. These studies have shown that tadalafil is >10,000 times as potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000 times as potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, tadalafil is 700–fold as potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Tadalafil is >9,000-fold as potent for PDE5 than for PDE8, PDE9, and PDE10. Tadalafil is 14 times as potent for PDE5 than for PDE11A1 and 40 times as potent for PDE5 than for PDE11A4, two of the four known forms of PDE11. PDE11 is an enzyme found in human prostate, testes, skeletal muscle and in other tissues. In vitro , tadalafil inhibits human recombinant PDE11A1 and, to a lesser degree, PDE11A4 activities at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined.

How supplied

16.1 How Supplied TADLIQ (tadalafil) Oral Suspension, 20 mg/5 mL is a white to off-white, opaque, peppermint-flavored suspension. It is available in a 150 mL bottle (NDC 46287-045-15). 16.2 Storage Store at 20°C to 25°C (68°F to 77°F): excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Shake well for 30 seconds before use. Dispense in a tight container as defined in the USP. Keep out of reach of children. 16.1 How Supplied TADLIQ (tadalafil) Oral Suspension, 20 mg/5 mL is a white to off-white, opaque, peppermint-flavored suspension. It is available in a 150 mL bottle (NDC 46287-045-15).

Storage

16.2 Storage Store at 20°C to 25°C (68°F to 77°F): excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Shake well for 30 seconds before use. Dispense in a tight container as defined in the USP. Keep out of reach of children.

Patient information

Advise patient to read the FDA-Approved patient labeling ( Patient Information ) 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 TADLIQ 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 TADLIQ. Such an event may be a sign of NAION. Also discuss with patients that there is an 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. Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking TADLIQ. These events may be accompanied by tinnitus and dizziness.

Label text from the FDA structured product label by CMP Pharma, Inc. (revised Oct 15, 2022). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Tadalafil in 1 product

Tadliq NDC products (1)

NDC	Strength & form	Labeler	Type
46287-045	Tadalafil 20 mg/5mL Suspension	CMP Pharma, Inc.	NDA

Frequently asked questions

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Who makes Tadliq?

Tadliq is listed by 1 labeler in the FDA NDC directory, including CMP Pharma, Inc..