TADALAFIL tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TADALAFIL (UNII: 742SXX0ICT) (TADALAFIL - UNII:742SXX0ICT)

Available from:

Teva Pharmaceuticals USA, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Tadalafil tablets are indicated for the treatment of erectile dysfunction (ED). Tadalafil tablets are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Tadalafil tablets are indicated for the treatment of ED and the signs and symptoms of BPH (ED/BPH). 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 [see Clinical Studies (14.3)]. Administration of tadalafil tablets to patients who are using any form of organic nitrate, either regularly and/or intermittently, is contraindicated. In clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates [see Clinical Pharmacology (12.2) ]. Tadalafil tablets are contraindicated in patients with a known serious hypersensitivity to tadalafil (or ADCIRCA® ). Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis [see Adverse Reactions (6.2) ]. Do not use tadalafil in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including tadalafil, may potentiate the hypotensive effects of GC stimulators. Risk Summary Tadalafil tablets are not indicated for use in females. There are no data with the use of tadalafil tablets in pregnant women to inform any drug-associated risks for adverse developmental 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 up to 11 times the maximum recommended human dose (MRHD) of 20 mg/day (see Data). Data Animal Data Animal reproduction studies showed no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given orally to pregnant rats or mice at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg/day during organogenesis. In a prenatal/postnatal developmental study in rats, postnatal pup survival decreased following maternal exposure to tadalafil doses greater than 10 times the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 16 times the MRHD based on AUC. Surviving offspring had normal development and reproductive performance. In another rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was observed. The no observed effect level (NOEL) for maternal toxicity was 200 mg/kg/day and for developmental toxicity was 30 mg/kg/day. This gives approximately 16 and 10 fold exposure multiples, respectively, of the human AUC for the MRHD of 20 mg. Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. Risk Summary Tadalafil tablets are not indicated for use in females. There is no information on the presence of tadalafil and/or 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-fold greater than found in the plasma. Infertility 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 [see Clinical Pharmacology (12.2)] . Based on studies in animals, a decrease in spermatogenesis was observed in dogs, but not in rats [see Nonclinical Toxicology (13.1)] . Tadalafil tablets are not indicated for use in pediatric patients. Safety and efficacy in patients below the age of 18 years have not been established. A randomized, double-blind, placebo-controlled trial in pediatric patients (7 to 14 years of age) with Duchenne muscular dystrophy, who received tadalafil tablets 0.3 mg/kg, tadalafil tablets 0.6 mg/kg, or placebo daily for 48 weeks failed to demonstrate any benefit of treatment with tadalafil tablets on a range of assessments of muscle strength and performance. Juvenile Animal Study No adverse effects were observed in a study in which tadalafil was administered orally at doses of 60, 200, and 1000 mg/kg/day to juvenile rats on postnatal days 14 to 90. The highest plasma tadalafil exposures (AUC) achieved were approximately 10-fold that observed at the MRHD. Of the total number of subjects in ED clinical studies of tadalafil, approximately 19 percent were 65 and over, while approximately 2 percent were 75 and over. Of the total number of subjects in BPH clinical studies of tadalafil (including the ED/BPH study), approximately 40 percent were over 65, while approximately 10 percent were 75 and over. In these clinical trials, no overall differences in efficacy or safety were observed between older (>65 and ≥75 years of age) and younger subjects (≤65 years of age). However, in placebo-controlled studies with tadalafil for use as needed for ED, diarrhea was reported more frequently in patients 65 years of age and older who were treated with tadalafil (2.5% of patients) [see Adverse Reactions (6.1)] . 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)]. 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) [see Dosage and Administration (2.6) and Warnings and Precautions (5.8)]. 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 [see Dosage and Administration (2.6) and Warnings and Precautions (5.7)].

Product summary:

Tadalafil tablets, USP are available as follows: 2.5 mg: light yellow, round, film-coated tablets, debossed with “TEVA” on one side of the tablet and with “3016” on the other side, in the following package sizes: Bottles of 30 (NDC 0093-3016-56) Unit-Dose Boxes of 30 (2 cards of 15 tablets) (NDC 0093-3016-65) 5 mg: yellow, round, film-coated tablets, debossed with “TEVA” on one side of the tablet and with “3017” on the other side, in the following package sizes: Bottles of 30 (NDC 0093-3017-56) Unit-Dose Boxes of 30 (2 cards of 15 tablets) (NDC 0093-3017-65) 10 mg: yellow, oval-shaped, film-coated tablets, debossed with “TEVA” on one side of the tablet and with “3018” on the other side, in bottles of 30 (NDC 0093-3018-56). 20 mg: yellow, oval-shaped, film-coated tablets, debossed with “TEVA” on one side of the tablet and with “3019” on the other side, in bottles of 30 (NDC 0093-3019-56). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep this and all medications out of the reach of children.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

TADALAFIL- TADALAFIL TABLET, FILM COATED
TEVA PHARMACEUTICALS USA, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TADALAFIL TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR TADALAFIL
TABLETS.
TADALAFIL TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2003
INDICATIONS AND USAGE
Tadalafil tablets are a phosphodiesterase 5 (PDE5) inhibitor indicated
for the treatment of:
erectile dysfunction (ED) (1.1)
the signs and symptoms of benign prostatic hyperplasia (BPH) (1.2)
ED and the signs and symptoms of BPH (ED/BPH) (1.3)
If tadalafil tablets are used with finasteride to initiate BPH
treatment, such use is recommended for up to
26 weeks (1.4).
DOSAGE AND ADMINISTRATION
_Tadalafil tablets for use as needed:_
ED: Starting dose: 10 mg as needed prior to sexual activity. Increase
to 20 mg or decrease to 5 mg
based upon efficacy/tolerability. Improves erectile function compared
to placebo up to 36 hours post
dose. Not to be taken more than once per day (2.1).
_Tadalafil tablets for once daily use:_
ED: 2.5 mg taken once daily, without regard to timing of sexual
activity. May increase to 5 mg based
upon efficacy and tolerability (2.2).
BPH: 5 mg, taken at approximately the same time every day (2.3)
ED and BPH: 5 mg, taken at approximately the same time every day (2.3,
2.4)
Tadalafil tablets may be taken without regard to food (2.5).
DOSAGE FORMS AND STRENGTHS
Tablets: 2.5 mg, 5 mg, 10 mg, 20 mg (3).
CONTRAINDICATIONS
Administration of tadalafil tablets to patients using any form of
organic nitrate is contraindicated.
Tadalafil tablets were shown to potentiate the hypotensive effect of
nitrates (4.1).
History of known serious hypersensitivity reaction to tadalafil or
ADCIRCA (4.2).
Administration with guanylate cyclase (GC) stimulators, such as
riociguat (4.3).
WARNINGS AND PRECAUTIONS
Patients should not use tadalafil if sex is inadvisable due to
cardiovascular status (5.1).
Use of tadalafil with alpha-blockers, antihypertensives or subs