Entadfi (finasteride/tadalafil)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Tadalafil, a selective phosphodiesterase (PDE) type 5 inhibitor, is a vasodilating agent.
Finasteride is aspecific inhibitor of steroid 5alpha-reductase, an intracellular enzyme necessary for conversion of testosterone to 5alpha-dihydrotestosterone (DHT).
Tadalafil is a selective inhibitor of phosphodiesterases (PDEs), with the greatest selectivity for PDE type 5, the principal isoenzyme of PDE involved in the metabolism of cyclic guanosine monophosphate (cGMP) to GMP in the vascular smooth muscle of the prostate, bladder, and corpora cavernosa of the penis. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpora cavernosa. Nitric oxide activates the enzyme guanylate cyclase, which stimulates the synthesis of cGMP. cGMP produces smooth muscle relaxation and increased blood flow into the corpora cavernosa.
By selectively inhibiting PDE type 5, tadalafil increases cGMP concentrations in the corpora cavernosa of the penis, resulting in nitric oxide-stimulated vascular relaxation. Tadalafil has no effect on erectile function in the absence of sexual stimulation.
The exact mechanism of action of tadalafil in reducing symptoms of benign prostatic hyperplasia (BPH) has not been established, but may be related to smooth muscle relaxation and increased vascular perfusion of the lower urinary tract (i.e., bladder, prostate).
Tadalafil produces modest peripheral vasodilation at usual dosages without affecting heart rate or blood pressure; such changes are not appreciably different from those observed with placebo. These effects are potentiated with concurrent use of organic nitrates, and concurrent use is contraindicated.
Tadalafil also exhibits some activity against other PDE isoenzymes. In vitro, tadalafil is >10,000-fold more potent against PDE type 5 than against PDE type 1, PDE type 2, PDE type 4, and PDE type 7 enzymes which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000-fold more potent for PDE type 5 than for PDE type 3, an enzyme found in the heart and blood vessels.
Additionally, tadalafil is 700-fold more potent for PDE type 5 than for PDE type 6, which is found in the retina and is responsible for phototransduction. Tadalafil also exhibits some affinity for PDE type 11, but the clinical importance currently is unknown.
When tadalafil is used as needed for erectile dysfunction, onset and duration of action are estimated to be 20 minutes and 24 to 36 hours, respectively.
Although pharmacologically related to other selective PDE type 5 inhibitors (e.g., sildenafil, vardenafil), tadalafil differs structurally from sildenafil and vardenafil and has a longer elimination half-life and a longer duration of action than these drugs.
The absolute bioavailability of tadalafil has not been determined. The maximum observed plasma concentration is achieved between 30 minutes and 6 hours (median time 2 hours). The rate and extent of absorption of tadalafil are not influenced by food, including a high-fat, high-calorie meal; thus tadalafil may be taken with or without food.
Administration of finasteride/tadalafil with a high-fat, high-calorie meal did not affect tadalafil or finasteride exposure (AUC). Tadalafil is distributed into tissues; less than 0.0005% of the administered dose appeared in the semen of healthy subjects. At therapeutic concentrations, the drug is 94% bound to plasma proteins.
Tadalafil clearance is reduced in patients >=65 years of age compared with younger adults, in patients with renal impairment (creatine clearance 30-80 mL/minute) including end-stage renal disease on hemodialysis, and in patients with diabetes mellitus.
Finasteride is a synthetic 4-azasteroid compound. The drug is a specific inhibitor of steroid Type II5alpha-reductase, an intracellular enzyme present in high concentrations in the liver, skin, and prostate gland. The conversion of testosterone to 5alpha-dihydrotestosterone (DHT) depends on the presence of this enzyme, and DHT appears to be the principal androgen responsible for stimulation of prostatic growth.
Finasteride inhibits 5alpha-reductase by forming a stable enzymecomplex; turnover from the complex is slow (half-life of about 30 days). Inhibition of 5alpha-reductase by finasteride, in a dose-dependent fashion, reduces serum and prostatic DHT concentrations substantially (by 70%), increases serum testosterone concentrations(by 10-20%, remaining withinthe physiologic range), and increases prostatic tissuetestosterone concentrations (by up to 10 times over pretreatment levels). In healthy men receiving finasteride for 2 weeks, serum DHT concentrations returned to pretreatment levels approximately 2 weeks after discontinuance of the drug.
In most patients with benign prostatic hypertrophy (BPH), prostatic volume decreases by an average of about 20-30% after 6-24 months of finasteride treatment and returns to baseline volume within several months after discontinuance of the drug; in one study of patients receiving finasteride for 3 months, prostatic volume declined by approximately 20% and returned to close to baseline valueapproximately 3 months following discontinuance of treatment. The drug also decreases serum and prostatic levels of prostate-specific antigen (PSA).
The mean bioavailability of finasteride 5-mg tablets is 63%; bioavailability is not affected by food. Peak plasma concentrations of the drug are achieved in 1-2 hours following a dose. Approximately 90% of circulating finasteride is bound to plasma proteins.
The drug has been shown to cross the blood brain barrier, but does not appear to distribute preferentially into the CSF. Finasteride is extensively metabolized in the liver, primary by cytochrome P-450 (CYP) 3A4. The mean elimination half-life of the drug in healthy individuals was 6 hours (range 3 to 16 hours).
Following administration of an oral dose, approximately 39% of the dose is excreted in urine as metabolites and 57% is ecreted in feces.
USES: This combination medication contains 2 drugs: finasteride and tadalafil. It is used to treat signs and symptoms of an enlarged prostate (benign prostatic hyperplasia-BPH). This medication may help shrink an enlarged prostate and lessen symptoms of BPH such as difficulty starting urination, weak stream, feeling that the bladder is not completely emptied, and frequent urge to urinate (including at night).
Finasteride works by decreasing the amount of a natural body hormone (DHT) that causes growth of the prostate. Tadalafil is thought to work by relaxing muscles in the prostate and bladder. Women and children should not use this medication.
Generic name: finasteride/tadalafil
Pronunciation: (fin-AS-ter-ide/ ta-DA-la-fil)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Entadfi
Indications
The following indications are listed for Entadfi:
- Benign Prostatic Hyperplasia
Also known as: Benign Prostatic Hypertrophy, Nodular Hyperplasia Of The Prostate, Prostatic Hypertrophy.
Dosing
No dosing information is available for this tab.
Tadalafil is administered orally without regard to meals.
Finasteride is administered orally without regard to meals. The fixed combination of finasteride/tadalafil is administered orally on an empty stomach.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Tadalafil is metabolized principally via hepatic cytochrome P-450 (CYP) isoenzyme 3A4. Inhibitors and inducers of CYP3A4 may increase or decrease tadalafil exposure, respectively.
Tadalafil does not appear to induce or inhibit the clearance of other drugs metabolized by P-glycoprotein (P-gp) or CYP isoforms 1A2, 3A4, 2C9, 2C19, 2D6, or 2E1.
When tadalafil in fixed combination with finasteride is used, the drug interactions associated with each drug must be considered. The manufacturer states no drug interactions of clinical importance have been identified for finasteride.
Finasteride does not affect the cytochrome P-450 (CYP) enzyme system. No clinically meaningful drug interactions have been identified. Drugs that have been tested for drug interaction potential with finasteride includedigoxin, propranolol, theophylline, and warfarin.
Although specific drug interaction studies have not been performed, in clinical studies,finasteridewas used concomitantly with acetaminophen, acetylsalicylic acid, alpha-blockers, analgesics, angiotensin-converting enzyme (ACE) inhibitors, anticonvulsants, benzodiazepines, beta-blockers, calcium-channel blockers, cardiac nitrates, diuretics, H2 antagonists, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory agents, and quinolone anti-infectives without evidence of clinically significant adverse interactions.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Concomitant use of organic nitrates or nitrites, either regularly and/or intermittently.
Concomitant use of guanylate cyclase stimulators (e.g., riociguat).
Known hypersensitivity to tadalafil, finasteride, or any ingredient in the formulations.
Finasteride/tadalafil fixed combination: Pregnancy.
*Pregnancy.
*Hypersensitivity to any components of the medication.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Tadalafil (Cialis(R) and generic equivalents): Most common adverse effects reported in at least 2% of patients receiving tadalafil for the treatment of ED and/or BPH include headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and limb pain.
Finasteride/tadalafil: Most common adverse effects associated with finasteride monotherapy (>=1%) in a 4-year study were impotence, decreased libido, decreased volume of ejaculate, breast enlargement, breast tenderness, and rash. Most common adverse effects (>=2%) associated with tadalafil were headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and limb pain.
The most common adverse effects of finasteride reported in >=1% of patients in clinical studiesinclude impotence, decreased libido, decreased volume of
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Use of tadalafil has not been evaluated for the treatment of BPH or ED in individuals younger than 18 years of age.
Finasteride is not indicated for use in pediatric patients; safety and efficacy have not been established.
The manufacturer of tadalafil (Cialis(R)) states that the drug is not indicated for use in women.
Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. 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.
Finasteride/tadalafil: Contraindicated in pregnancy and not indicated for use in females. Based on animal studies and the mechanism of action of finasteride, finasteride/tadalafil may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female.
Reproduction studies in pregnant rats receiving finasteride dosages ranging from 0.1 to 86 times the MRHD of 5 mg daily resulted in dose-dependent development of hypospadias in 3.6-100% of male offspring. Pregnant rats produced male offspring with decreased prostatic and seminal vesicular weights, delayed preputial separation, and transient nipple development when given dosages 0.03 times the MRHD and decreased anogenital distance in male offspring at maternal doses approximately 0.003 times the MRHD. These effects are expected pharmacologic effects of 5alpha-reductase inhibitors and are similar to those reported in male infants with a genetic deficiency of 5alpha-reductase.
Pregnant females should not handle crushed or open finasteride/tadalafil capsules because of the potential for absorption of finasteride and the subsequent potential risk to a male fetus. Wash the contact area immediately with soap and water if contact occurs.
Finasteride is not indicated for use in women and is contraindicated in women who are pregnant or may potentially be pregnant. Because of the ability of 5alpha-reductase inhibitors to inhibit the conversion of testosterone to DHT, finasteride may cause abnormalities of the external genitalia of male fetuses exposed to the drug during pregnancy. Studies have shown that low doses of finasteride administered to female rats during pregnancy can produce abnormalities of the external genitalia in male offspring. If finasteride is administered during pregnancy, the patient should be apprised of the potential fetal hazard. In addition, because of the possibility of drug absorption and subsequent risk to a male fetus, women who are pregnant or who potentially may be pregnant should not handlebrokenorcrushed finasteride tablets; if such contact occurs, the affected area should be washed immediately with soap and water and the woman should inform her clinician. Intact finasteride tablets are coated, and the coating will prevent contact with finasteride during normal handling.
Reproduction studies in pregnant rats receiving finasteride dosages ranging from 100 mcg/kg daily to 100 mg/kg daily (up to 86 times the maximumrecommended human dosage (MRHD)) resulted in dose-dependent development of hypospadias in 3.6-100% of male offspring. Pregnant rats produced male offspring with decreased prostatic and seminal vesicular weights, delayed preputial separation, and transient nipple development when given dosages of 30 mcg/kg daily (0.03times the MRHD) and decreased anogenital distance when given dosages of 3 mcg/kg daily (0.003times the MRHD). The critical period during which these effects can be induced in male rats has been determined to be days 16-17 of gestation. These effects are expected pharmacologic effects of 5alpha-reductase inhibitors and are similar to those reported in male infants with a genetic deficiency of 5alpha-reductase. No abnormalities were observed in female offspring exposed to any finasteride dosage in utero.
No developmental abnormalities were observed in first filial generation (F1) male or female offspring resulting from mating of male rats receiving finasteride 80 mg/kg daily (61 times the MRHD) with untreated females. Administration of the drug at a dosage of 3 mg/kg daily (30 times the MRHD) during the late gestation and lactation period resulted in slightly decreased fertility in F1 male offspring. No effects were seen in female offspring. No evidence of malformations was observed in rabbit fetuses exposed to finasteride in utero from days 6-18 of gestation at dosages up to 100 mg/kg daily; however, effects on male genitalia would not be expected as the exposure did not occur during the critical period of genital system development in rabbits.
No abnormalities were observed in male fetuses when pregnant rhesus monkeys were given finasteride IV at dosages up to 800 ng daily (143 times the highest estimated exposure of a pregnant woman to finasteride via the semen of a sexual partner receiving finasteride 5 mg daily) during days 20-100 of gestation. However, external genital abnormalities were observed in male rhesus monkey fetuses in studies using an oral finasteride dosage of 2 mg/kg daily (18,000 times the highest estimated blood levels of finasteride from semen in men receiving 5 mg daily). No other abnormalities were observed in male fetuses, and no abnormalities were observed in female fetuses exposed to finasteride at any dosage in utero.
Tadalafil (Cialis(R)) and finasteride/tadalafil (Entadfi(R)) are not indicated for use in women. Tadalafil and/or its metabolites are present in the milk of lactating rats at concentrations approximately 2.4 times that found in the plasma.
It is not known whether finasteride is distributed into human milk, but the drug is not indicated for use in women.
Tadalafil or finasteride/tadalafil dosage adjustment based solely on age is not necessary in geriatric patients.
Dosage adjustment is not necessary in geriatric patients.
Safety and efficacy of tadalafil in geriatric patients (older than 65 years of age) are similar to those in younger patients. Substantial age-related differences in pharmacokinetics of tadalafil were not observed between patients 65 years of age or older and younger individuals; therefore, the manufacturer states that modification of tadalafil dosage is not needed in geriatric patients solely on the basis of age. However, the possibility of greater sensitivity in some geriatric individuals should be considered.
Because BPH occurs mainly in men 55 years of age or older, efficacy and safety of finasteride in this age group have been established, although only limited data are available on use of the drug in men older than 80 years of age. Of the 3040 patients enrolled in a long-term (4 years) controlled clinical trial of the drug, 1480 (49%) were 65 years of age or older and 105 (3.5%) were 75 years of age or older. No overall differences in efficacy or safety were observed in this trial between geriatric and younger patients, and other clinical experience has revealed no evidence of age-related differences. Generally, finasteride is well tolerated in geriatric men.
The elimination rate of finasteride is decreased in geriatric individuals; however, the findings are not clinically significant anddosage adjustment is not necessary. The mean terminal half-life of finasteride in individuals 70 years of age or older was approximately 8 hours (range: 6-15 hours) compared with 6 hours (range: 4-12 hours) in individuals 45-60 years of age; consequently, the mean daily AUC after 17 days of dosing was 15% higher in individuals 70 years of age or older.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.