Tadalafil

Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including Tadalafil, and seek 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 rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 in males aged ≥50.

An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of "crowded" optic disc, may have contributed to the occurrence of NAION in these studies.

Neither the rare postmarketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION

Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, PDE5 inhibitors, including Tadalafil, should be used with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with "crowded" optic disc are also considered at greater risk for NAION compared to the general population; however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including Tadalafil, for this uncommon condition.

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.

If Tadalafil Tablets are used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks because the incremental benefit of Tadalafil Tablets decreases from 4 weeks until 26 weeks, and the incremental benefit of Tadalafil Tablets beyond 26 weeks is unknown

• Creatinine clearance 30 to 50 mL/min: A starting dose of 5 mg not more than once per day is recommended, and the maximum dose is 10 mg not more than once in every 48 hours.
• Creatinine clearance less than 30 mL/min or on hemodialysis: The maximum dose is 5 mg not more than once in every 72 hours
  [see Warnings and Precautions and Use in Specific Populations ]
  .

• Creatinine clearance less than 30 mL/min or on hemodialysis: Tadalafil Tablets for once daily use is not recommended
  [see Warnings and Precautions and Use in Specific Populations ]
  .

• Creatinine clearance 30 to 50 mL/min: A starting dose of 2.5 mg is recommended. An increase to 5 mg may be considered based on individual response.
• Creatinine clearance less than 30 mL/min or on hemodialysis: Tadalafil Tablets for once daily use is not recommended
  [see Warnings and Precautions and Use in Specific Populations ]
  .

• Mild or moderate (Child Pugh Class A or B): The dose should not exceed 10 mg once per day. The use of Tadalafil Tablets once per day has not been extensively evaluated in patients with hepatic impairment and therefore, caution is advised.
• Severe (Child Pugh Class C): The use of Tadalafil Tablets is not recommended
  [see Warnings and Precautions
  and Use in Specific Populations ]
  .

• Mild or moderate (Child Pugh Class A or B): Tadalafil Tablets for once daily use has not been extensively evaluated in patients with hepatic impairment. Therefore, caution is advised if Tadalafil Tablets for once daily use is prescribed to these patients.
• Severe (Child Pugh Class C): The use of Tadalafil Tablets is not recommended
  [see Warnings and Precautions
  and Use in Specific Populations ]
  .

In patients with mild or moderate hepatic impairment, the dose of Tadalafil should not exceed 10 mg. Because of insufficient information in patients with severe hepatic impairment, use of Tadalafil in this group is not recommended

Tadalafil for once daily use has not been extensively evaluated in patients with mild or moderate hepatic impairment. Therefore, caution is advised if Tadalafil for once daily use is prescribed to these patients. Because of insufficient information in patients with severe hepatic impairment, use of Tadalafil in this group is not recommended

In clinical pharmacology studies, tadalafil exposure (AUC) in subjects with mild or moderate hepatic impairment (Child-Pugh Class A or B) was comparable to exposure in healthy subjects when a dose of 10 mg was administered. There are no available data for doses higher than 10 mg of tadalafil in patients with hepatic impairment. Insufficient data are available for subjects with severe hepatic impairment (Child-Pugh Class C).

• Creatinine clearance 30 to 50 mL/min: A starting dose of 5 mg not more than once per day is recommended, and the maximum dose is 10 mg not more than once in every 48 hours.
• Creatinine clearance less than 30 mL/min or on hemodialysis: The maximum dose is 5 mg not more than once in every 72 hours
  [see Warnings and Precautions and Use in Specific Populations ]
  .

• Creatinine clearance less than 30 mL/min or on hemodialysis: Tadalafil Tablets for once daily use is not recommended
  [see Warnings and Precautions and Use in Specific Populations ]
  .

• Creatinine clearance 30 to 50 mL/min: A starting dose of 2.5 mg is recommended. An increase to 5 mg may be considered based on individual response.
• Creatinine clearance less than 30 mL/min or on hemodialysis: Tadalafil Tablets for once daily use is not recommended
  [see Warnings and Precautions and Use in Specific Populations ]
  .

• Mild or moderate (Child Pugh Class A or B): The dose should not exceed 10 mg once per day. The use of Tadalafil Tablets once per day has not been extensively evaluated in patients with hepatic impairment and therefore, caution is advised.
• Severe (Child Pugh Class C): The use of Tadalafil Tablets is not recommended
  [see Warnings and Precautions
  and Use in Specific Populations ]
  .

• Mild or moderate (Child Pugh Class A or B): Tadalafil Tablets for once daily use has not been extensively evaluated in patients with hepatic impairment. Therefore, caution is advised if Tadalafil Tablets for once daily use is prescribed to these patients.
• Severe (Child Pugh Class C): The use of Tadalafil Tablets is not recommended
  [see Warnings and Precautions
  and Use in Specific Populations ]
  .

Tadalafil should be limited to 5 mg not more than once in every 72 hours in patients with creatinine clearance less than 30 mL/min or end-stage renal disease on hemodialysis. The starting dose of Tadalafil in patients with creatinine clearance 30 – 50 mL/min should be 5 mg not more than once per day, and the maximum dose should be limited to 10 mg not more than once in every 48 hours.

Due to increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis, Tadalafil for once daily use is not recommended in patients with creatinine clearance less than 30 mL/min

Due to increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis, Tadalafil for once daily use is not recommended in patients with creatinine clearance less than 30 mL/min. In patients with creatinine clearance 30 – 50 mL/min, start dosing at 2.5 mg once daily, and increase the dose to 5 mg once daily based upon individual response

In clinical pharmacology studies using single-dose tadalafil (5 to 10 mg), tadalafil exposure (AUC) doubled in subjects with creatinine clearance 30 to 80 mL/min. In subjects with end-stage renal disease on hemodialysis, there was a two-fold increase in Cmax and 2.7- to 4.8-fold increase in AUC following single-dose administration of 10 or 20 mg tadalafil. Exposure to total methylcatechol (unconjugated plus glucuronide) was 2- to 4-fold higher in subjects with renal impairment, compared to those with normal renal function. Hemodialysis (performed between 24 and 30 hours post-dose) contributed negligibly to tadalafil or metabolite elimination. In a clinical pharmacology study (N=28) at a dose of 10 mg, back pain was reported as a limiting adverse event in male patients with creatinine clearance 30 to 50 mL/min. At a dose of 5 mg, the incidence and severity of back pain was not significantly different than in the general population. In patients on hemodialysis taking 10- or 20-mg tadalafil, there were no reported cases of back pain.