Tadalafil Orodispersible Film

During sexual stimulation, the penis becomes erect due to increased blood flow to the penis caused by relaxation of the penile artery and corpus cavernosum smooth muscle. This reaction is mediated by nitric oxide (NO) released by nerve endings and endothelial cells. NO stimulates smooth muscle cells to synthesize cyclic guanosine monophosphate (eGMP). cGMP causes smooth muscle relaxation and increases blood flow to the corpus cavernosum. Inhibits phosphodiesterase 5 (PDE5) and enhances erectile function by increasing eGMP. PDES is present in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum and pancreas. In vitro studies have shown that tadalafil is a selective inhibitor of PDE5. Since sexual stimulation is required to stimulate local release of NO, tadalafil's inhibition of PDES is meaningless without sexual stimulation. PDES inhibition can affect cGMP concentrations in the corpus cavernosum and pulmonary arteries. The same situation has been observed in the smooth muscles and blood vessels of the prostate and bladder. The mechanism of action for alleviating BPH symptoms is currently unclear. In vitro studies have shown. Tadalafil has a stronger effect on PDES than on other phosphodiesterases. These studies show that tadalafil has a stronger effect on PDES than on PDE1, PDE2, PDE4 and PDE7 in the heart, brain, blood vessels, liver, white blood cells, skeletal muscle and other organs: more than 10,000 times stronger than PDE3 in the heart and blood vessels: about 700 times stronger than PDE6 involved in phototransduction in the retina: more than 9,000 times stronger than PDE8, PDE9 and PDE10: 14 times stronger than PDE11A1, and 40 times stronger than PDE11A. PDE1I is present in human prostate, testicles, skeletal muscle and other tissues. In vitro, tadalafil can inhibit recombinant PDE1IA1, and at therapeutic concentrations, the degree of inhibition of PDEI1A4 activity is low. The physiological effects and clinical effects of inhibiting PDE11 on humans are still unclear. Toxicology studies General toxicity: Vasculitis was observed in mice, rats and dogs when tadalafil was administered. When the exposure to free tadalafil reached 2-33 times the maximum recommended human dose (MRHD) of 20 mg, lymph necrosis and hemorrhage were observed in the sac, thymus and mesenteric lymph nodes of mice and rats. When the exposure reached 1-54 times, the incidence of diffuse arteritis in dogs increased: in a 12-month dog toxicity study. When the exposure reached 14-18 times, no diffuse arteritis was observed, and two dogs showed a significant decrease in white blood cells (neutrophils) and thrombocytopenia and inflammatory symptoms, which recovered after 2 weeks of drug withdrawal. Genetic toxicity: The results of the tadalafil Ames test, mouse lymphocyte forward mutation test, human lymphocyte chromosome aberration test and rat micronucleus test were all negative. Reproductive toxicity: Male or female rats were orally administered tadalafil at 400 mg/kg/day (equivalent to 14 or 26 times the MRHD based on free tadalafil exposure). No effects on fertility, reproductive behavior or reproductive organ morphology were observed. Dogs were given tadalafil for 3-~12 months, and 20%-100% of the animals showed irreversible degeneration and atrophy of the seminiferous tubule epithelial cells related to administration, and 40%-75% of the animals in the 210 mg/kg/day dose group showed a decrease in sperm production. The systemic exposure of free tadalafil at the no observed toxic effect dose (NOAEL) was similar to that at the MRHD dose. Rats or mice were given tadalafil 400 mg/kg/day for 2 consecutive years, and no testicular changes related to administration were observed. Pregnant rats or mice were given tadalafil during organogenesis, and no teratogenicity, embryotoxicity or fetotoxicity was observed when the exposure (AUC) reached 11 times the MRHD. In a rat perinatal developmental toxicity study, when the mother was given tadalafil at an exposure level (AUC) higher than 10 times the MRHD, the survival rate of the pups after birth was reduced: at exposure levels higher than 16 times the MRHD exposure level, maternal toxicity occurred, but the growth and development of the surviving pups were not affected. In a rat perinatal developmental toxicity study, the survival rate of the pups after birth was reduced at 60, 200 and 1000 mg/kg of tadalafil. The maternal no observed toxicity level (NOEL) was 200 mg/kg/day (approximately 16 times the MRHD exposure AUC), and the NOEL for developmental toxicity was 30 mg/kg/day (approximately 10 times the MRHD exposure AUC) ● Tadalafil and its metabolites can cross the placenta. Carcinogenicity: In a 2-year carcinogenicity study in rats or mice, tadalafil was administered at doses up to 400 mg/kg/day, and carcinogenicity was observed. Based on the AUC of free tadalafil, the exposure in mice was approximately 10 times that of human males taking MRHD 20 mg, and approximately 14 and 26 times that of male and female rats, respectively.

The main ingredient of this product is tadalafil. Chemical name: (6R, 12aR)-6-(1.3-phenyl-dioxolane-5-yl) 2-methyl-2,3.6,7.1212a-hexahydro-p-diaminobenzene [‘, 2‘: 1,6] pyrido [3.4-5] indole-1, 4-dione. Molecular formula: C2HyN,O. Molecular weight: 389.41

This product is light yellow to yellow flaky film.

Treats erectile dysfunction.

It is recommended to take this product on an empty stomach. Compared with the fasting state, taking tadalafil orodispersible film with a high-fat meal will cause a significant delay in absorption (see [Pharmacokinetics] Take as needed For most patients, the recommended starting dose for as needed use is 10 mg, taken before sexual intercourse. Depending on individual efficacy and tolerability, the dose can be increased to 20 mg or reduced to 5 mg. The maximum recommended frequency of dosing for most patients is once a day. Compared with placebo, as needed use can improve erectile function for up to 36 hours. Therefore, this factor should be considered when recommending patients to take it in the best way. Take once a day Daily The recommended starting dose for a single dose is 2.5 mg, taken at approximately the same time every day, regardless of when to have sex. Depending on individual efficacy and tolerance, the once-daily dose can be increased to 5 mg. The risk-benefit ratio should be weighed according to the patient's specific situation to select an appropriate treatment plan. Instructions for use: This product is an orodispersible film. When taking it, please be sure to keep your hands dry when touching the tablets, and do not touch the tablets with wet hands. When opening the inner package, please be sure to follow the following instructions. a) Take out the medicine bag, turn the unsealed part upward, and then carefully separate the medicine bag to both sides. b) Carefully tear the two parts of the medicine bag in opposite directions. The orodispersible film tablets can be seen. c) Take out the orodispersible film tablet with a dry hand and place it directly on the tongue. The tablet will immediately dissolve in the mouth and swallow with saliva without water. If necessary, it can also be taken with water.

Clinical Research Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials worldwide, more than 6550 men have taken tadalafil. In trials of once-daily tadalafil tablets, 716, 389, and 115 patients were treated for at least 6 months, 1 year, and 2 years, respectively. For as-needed tadalafil tablets, more than 1300 and 1000 subjects were treated for at least 6 months and 1 year, respectively. In the eight major placebo-controlled Phase 3 studies lasting 12 weeks, the mean age was 59 years (range 22-88), and the percentage of patients who withdrew due to adverse events was 3.1% receiving tadalafil 10 mg or 20 mg, compared with 1.4% receiving placebo. At the recommended dosing in placebo-controlled clinical trials, as-needed tadalafil tablets have the following adverse events (see Table 1). Table 1: In the eight major placebo-controlled Phase 3 studies of as-needed tadalafil tablets, including one study in patients with diabetes, the incidence of treatment-emergent adverse events was ≥2% in the tadalafil tablet (10 or 20 mg) treatment group and was greater than that in the placebo group Adverse Events Placebo (N=476) Tadalafil 5 mg (N=151) Tadalafil 10 mg (N=394) Tadalafil 20 mg (N=635) Headache 5% 11% 11% 15% Dyspepsia 1% 4% 8 %10% Back pain 3%3%5%6% Myalgia 1%1%4%3% Nasal congestion 1%2%3%3% Hot flusha1%2%3%3% Limb pain 1%1%3%3%a Hot flushing includes: facial hot flushing and flushing Take tadalafil tablets once daily In the three placebo-controlled Phase 3 studies lasting 12 or 24 weeks, the mean age was 58 years (range 21-82), and the percentage of patients who withdrew due to adverse events was 4.1% receiving tadalafil, compared with 2.8% of patients treated with placebo. The following adverse events were reported in clinical trials lasting 12 weeks (see Table 2): Table 2. Incidence of treatment-emergent adverse events in the three primary, 12-week, placebo-controlled Phase 3 studies of once-daily tadalafil tablets, including one study in patients with diabetes, was ≥2% in the once-daily tadalafil tablets (2.5 or 5 mg) treatment group and was greater than placebo Adverse Events Placebo (N=248) Tadalafil 2.5 mg (N=196) Tadalafil 5 mg (N=304) Headache 5% 3% 6% Dyspepsia 2% 3% 5% Nasopharyngitis 4% 4% 3% Back pain 1% 3% 3% Upper respiratory tract infection 1% 3% 3% Flushing 1% 1% 3% Influenza 2% 3% 2% Myalgia 1% 2% 2% Cough 0% 4% 2% Diarrhea 0% 1% 2% Nasal congestion 0% 2% 2% Pain in extremity 0% 1% 2% Bronchitis 1% 2% 0% Urinary tract infection Infection 0% 2% 0% Gastroesophageal reflux 0% 2% 1% Abdominal pain 0% 2% 1% The following adverse events were reported in a 24-week placebo-controlled Phase 3 clinical study (see Table 3): Table 3: In a 24-week placebo-controlled Phase 3 study of once-daily tadalafil tablets, the incidence of treatment-emergent adverse events in the tadalafil tablets once-daily (2.5 or 5 mg) treatment group was ≥ 2% and was higher than the placebo group Adverse events Placebo (N= 94) Tadalafil 2.5 mg (N=96) Tadalafil 5 mg (N=97) Nasopharyngitis 5% 6% 6% Viral gastroenteritis 2% 3% 5% Influenza 3% 5% 3% Back pain 3% 5% 2% Upper respiratory tract infection 0% 3% 4% Dyspepsia 1% 4% 1% Gastroesophageal reflux disease 0% 3% 2% Myalgia 2% 4% 1% Hypertension 0% 1% 3% Nasal congestion 0% 0% 4% The incidence of back pain and myalgia is described in Tables 1 and 2. In the clinical pharmacology trials of tadalafil, back pain and myalgia generally occurred 12 to 24 hours after dosing and usually resolved within 48 hours. Back pain/myalgia caused by tadalafil treatment is characterized by diffuse discomfort in the muscles of the lower extremities, buttocks, thighs, or thoracolumbar region, which is aggravated by lying down. In general, the pain that occurred was mild or moderate in severity and resolved without treatment, but there were lower incidences of severe back pain (5% of all reports). If treatment is required, acetaminophen or nonsteroidal anti-inflammatory drugs are generally effective; however, a few subjects who required treatment used weak narcotics (such as codeine). Overall, approximately 0.5% of all subjects taking tadalafil as needed discontinued treatment because of back pain/myalgia. In the 1-year open-label extension study, back pain and myalgia were reported by 5.5% and 1.3% of patients, respectively. Diagnostic tests, including measures of inflammation, muscle damage, and renal injury, showed no medically significant pathological basis. The incidence of once-daily tadalafil tablets is described in Table 2. In studies of once-daily tadalafil tablets, back pain and myalgia events were generally mild or moderate, with a withdrawal rate of 0.3%. In all placebo-controlled clinical trials of as-needed tadalafil tablets for erectile dysfunction, patients 65 years of age and older had diarrhea more frequently when taking tadalafil tablets (2.5% of patients). In all studies of tadalafil tablets, reports of color vision changes were rare (0.1% of patients). The following subsections identify other less common (2%) adverse events reported in controlled clinical trials with once-daily or as-needed tadalafil tablets. The causal relationship to tadalafil tablets is unclear for these events. This list does not include very mild events, events with no clear relationship to the drug, and inaccurate and meaningless reports. General - Asthenia, facial edema, fatigue, pain, peripheral edema Cardiovascular - angina, chest pain, hypotension, myocardial infarction, orthostatic hypotension, palpitations, syncope, tachycardia Digestive - abnormal liver function tests, dry mouth, dysphagia, esophagitis, gastritis, increased GGTP, loose stools, nausea, epigastric pain, vomiting Musculoskeletal - arthralgia, cervical pain Neurological - dizziness, hypoesthesia, insomnia, paresthesia, somnolence, vertigo Respiratory - dyspnea, epistaxis, pharyngitis Skin and Appendages - pruritus, rash, sweating Ocular - blurred vision, color vision changes, conjunctivitis (including conjunctival injection), eye pain, increased tearing, eyelid swelling Ear - sudden decrease or loss of hearing, tinnitus Urogenital - increased erections, spontaneous penile erections Postmarketing Experience The following adverse reactions have been identified following the approval of tadalafil. Because these adverse reactions were reported spontaneously in a population of uncertain size, their incidence cannot be reliably estimated or a causal relationship to drug exposure established. These events were selected for reasons including severity, frequency of reporting, lack of clear alternative causes, or a combination of these. Cardiovascular and cerebrovascular. Serious cardiovascular events, including myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations, and tachycardia, have been reported postmarketing in a temporal relationship with tadalafil use. Most of these patients (but not all) had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual intercourse, and rarely occurred after taking the drug but without sexual intercourse. Others were reported hours to days after taking tadalafil and engaging in sexual intercourse. It is unclear whether these events are directly related to tadalafil, sexual intercourse, the patient's preexisting cardiovascular disease, or other factors (see [Precautions]): Systemic hypersensitivity reactions, including urticaria, Stevens-Johnson syndrome, and exfoliative dermatitis. Neurology - migraine, epilepsy, and epileptic seizures, transient amnesia Eye - visual field loss, retinal vein occlusion, retinal artery occlusion Non-arteritic anterior optic neuropathy (NAION.Non-arteritic:AnteriorIschemicOpticNeuropathy), is a cause of vision loss including permanent blindness, and is rarely associated with phosphodiesterase 5 (PDE5, Phosphodiesterase5) inhibitors after marketing, including reports of temporal relationship with tadalafil. Most, but not all, of these patients had pre-existing anatomical or vascular risk factors for NAION, including but not limited to: small cup-disc size (\crowded optic disc), age over 50 years, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking (see [Precautions]). Ear - Cases of sudden hearing loss or loss have been reported postmarketing in a temporal relationship with the use of PDE5 inhibitors, including tadalafil. In some cases, medical conditions or other factors were reported that may have caused the adverse events in the ear. In most cases, medical follow-up information was limited. It is not possible to determine whether these events were directly related to the use of tadalafil, the patient's pre-existing risk factors for hearing loss, a combination of these factors, or other factors (see [Precautions]). Urogenital persistent erection (see [Precautions]).

Patients who are allergic to any of the ingredients in this product are prohibited from taking tadalafil. Nitrates: Patients who are taking any form of nitrates, whether regularly and/or intermittently, are strictly prohibited from taking tadalafil. Clinical pharmacology studies have shown that tadalafil can enhance the antihypertensive effect of nitrates (see [Drug Interactions]) Hypersensitivity: Patients with known dual allergies to tadalafil should not take tadalafil. There have been reports of hypersensitivity reactions, including Stevens-Johnson syndrome and exfoliative dermatitis (see [Adverse Reactions]): Guanylate cyclase (GC, CanointeCyenee) stimulators: Patients who are taking GC should not take tadalafil. PDE5 inhibitors, including tadalafil, may enhance the antihypertensive effect of GC stimulators.

Keep away from light and store in a sealed container at a temperature not exceeding 30°C. This product is easy to absorb moisture and should be used immediately after taking it out of the bag.

10mg x 1 tablet x 2 bags

24 months

Qilu Pharmaceutical Co., Ltd.

• Founded in:

  1992-08-21

• Address:

  No. 317, Xinluo Street, High-tech Zone, Jinan City, Shandong Province

• Tax NO.:

  91370000614073351Q

• Registered Funds:

  600 million yuan

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