Tadalafil (tadalafil)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Tadalafil, a selective phosphodiesterase (PDE) type 5 inhibitor, is a vasodilating agent.
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.
USES: Tadalafil is used to treat male sexual function problems (impotence or erectile dysfunction-ED). In combination with sexual stimulation, tadalafil works by increasing blood flow to the penis to help a man get and keep an erection. Tadalafil is also used to treat the symptoms of an enlarged prostate (benign prostatic hyperplasia-BPH).
It helps to relieve symptoms of BPH such as difficulty in beginning the flow of urine, weak stream, and the need to urinate often or urgently (including during the middle of the night). Tadalafil is thought to work by relaxing the smooth muscle in the prostate and bladder. This drug does not protect against sexually transmitted diseases (such as HIV, hepatitis B, gonorrhea, syphilis).
Using an effective barrier method (latex or polyurethane condom/dental dams) during sexual activity will help to decrease your risk of infection.
Generic name: tadalafil
Pronunciation: (tah-DA-la-fil)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Tadalafil
Indications
The following indications are listed for Tadalafil:
- Benign Prostatic Hyperplasia With Lower Urinary Tract Symptom
- Erectile Dysfunction
Also known as: Impotency, Symptomatic Benign Prostatic Hyperplasia, Symptomatic Benign Prostatic Hypertrophy, Symptomatic Bph, Symptomatic Prostatic Hypertrophy.
Dosing
No dosing information is available for this tab.
Tadalafil is administered orally without regard to meals.
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.
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.
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.
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.
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.
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.
Tadalafil or finasteride/tadalafil dosage adjustment based solely on age 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.
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.