Medical  Explorer

Custom Search

Drugs A to Z  :  A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  R  S  T  U  V  W  X  Y  Z
Medicinal Ingredients : A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z

Beauty Products : A  B  C  D  E  F  G  I  M  N  O  P  R  S  T  V

Aging      Allergies     Alzheimer's      Arthritis    Asthma      Bacteria   new Cancer    Chickenpox     Colds     Constipation      Diabetes      Epilepsy     Fatigue     Fever     Genetics       Haemorrhoids       newHeadaches      Hepatitis    Immunity      Infection      Insomnia       Leprosy       Menopause      Obesity      Osteoporosis     Other Diseases    Pain      PMS     Parasites     Sinusitis     newStroke     Toxicology    Urology




Arthritis medications
Acupuncture
Alcohol
Patients
newGeneral Health
Medicinal food
Chinese medicine
Nutrients
Smoking
Vitamins
OTC Drugs
Health Products
Therapy
Symptom
Parasitology
 
 

Cialis

 

NAME

Chemically, tadalafil is pyrazino[1', 2':1, 6]pyrido[3, 4-b]indole-1, 4-dione, 6-(1, 3-benzodioxol-5-yl)-2, 3, 6, 7, 12, 12a-hexahydro-2-methyl-, (6R, 12aR)-. Tadalafil has the empirical formula C22H19N3O4 representing a molecular weight of 389.41. Tadalafil is a crystalline solid that is practically insoluble in water and very slightly soluble in ethanol. The CAS number for tadalafil is 171596-29-5.

Tadalafil has the following structural formula:

DESCRIPTION
CIALIS 20 mg tablets are yellow, film coated, almond shaped tablets for oral administration, marked "C 20" on one side. CIALIS 10 mg tablets are light yellow, film coated, almond shaped tablets for oral administration, marked "C 10" on one side. Each tablet contains 20 mg or 10 mg, respectively, of tadalafil and the following excipients: croscarmellose sodium, hydroxypropylcellulose, hypromellose, iron oxide yellow CI77492, lactose, magnesium stearate, cellulose - microcrystalline, sodium lauryl sulfate, talc - purified, titanium dioxide and glycerol triacetate.

PHARMACOLOGY
Pharmacodynamics
Tadalafil is a reversible inhibitor of cyclic guanosine monophosphate (cGMP) - specific phosphodiesterase type 5 (PDE5). When sexual stimulation causes the local release of nitric oxide, inhibition of PDE5 by tadalafil produces increased levels of cGMP in the corpus cavernosum. This results in smooth muscle relaxation and inflow of blood into the penile tissues, thereby producing an erection. Tadalafil has no effect in the absence of sexual stimulation.

Studies in vitro have shown that tadalafil inhibits PDE5 more potently than other PDEs. PDE5 is an enzyme found in the corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung and cerebellum. Tadalafil is >10,000-fold more potent for PDE5 than for PDE1, PDE2 PDE4, and PDE7 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 PDE5 than for PDE3, an enzyme found in the heart and blood vessels. This selectivity for PDE5 over PDE3 is important because PDE3 is an enzyme involved in cardiac contractility. Additionally, tadalafil is approximately 700-fold more potent for PDE5 than for PDE6, an enzyme which is found in the retina and is responsible for phototransduction. Tadalafil is also >9,000-fold more potent for PDE5 than for PDE 8, 9, and 10 and 14-fold more potent for PDE5 than for PDE 11. The tissue distribution and physiological effects of the inhibition of PDE8 through PDE11 have not been elucidated.

Studies of CIALIS on vision - In a study to assess the effects of tadalafil on vision, no impairment of colour discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test. This finding is consistent with the low affinity of tadalafil for PDE6 compared to PDE5. In addition, no effects were observed on visual acuity, electroretinograms, intraocular pressure or pupillometry. Across all clinical studies, reports of changes in colour vision were rare (see ADVERSE REACT IONS).

Studies of CIALIS on blood pressure and heart rate - Tadalafil administered to healthy subjects produced no significant difference compared to placebo in supine systolic and diastolic blood pressure (mean maximal decrease of 1.6/0.8 mm Hg, respectively), in standing systolic and diastolic blood pressure (mean maximal decrease of 0.2/4.6 mm Hg, respectively) and no significant change in heart rate. Larger effects were recorded among subjects receiving concomitant nitrates (see CONTRAINDICATIONS). When tadalafil and certain oral antihypertensive medications were assessed in drug interaction studies, tadalafil did not result in clinically significant augmentation of the antihypertensive effects of those medications (see PRECAUTIONS - Interactions with Other Drugs).

Studies on Spermatogenesis - Three studies were conducted in men to assess the potential effect on spermatogenesis of tadalafil 10 mg (one 6-month study) and 20 mg (one 6-month and one 9-month study) administered daily. There were no adverse effects on sperm morphology or sperm motility in any of the three studies. In the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months, results showed a decrease in mean sperm concentrations relative to placebo. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. In the 9-month study, decreases in sperm concentration were associated with higher ejaculatory frequency. Ejaculation frequency was not assessed in the 6 month studies. In addition there was no adverse effect on mean concentrations of reproductive hormones, testosterone, luteinizing hormone or follicle stimulating hormone with either 10 or 20 mg of tadalafil compared to placebo.

Pharmacokinetics
Absorption - Tadalafil is rapidly absorbed after oral administration and the mean maximum observed plasma concentration (Cmax) is achieved at a median time of 2 hours after dosing. There is no clinically relevant effect of food on the rate and extent of absorption of tadalafil, thus tadalafil may be taken with or without food. The time of dosing (morning versus evening) has no clinically relevant effects on the rate and extent of absorption. The absolute bioavailability of oral tadalafil has not been established. The mean bioavailability of the tadalafil 20 mg tablet has been estimated to be 88% relative to an oral suspension dosage form.

Distribution -The mean volume of distribution after oral dosing is approximately 63 L. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Protein binding is not affected by impaired renal function. Less than 0.0005% of the administered dose appears in the semen of healthy subjects.

Metabolism -Tadalafil is metabolised mainly (>80%) by the cytochrome P450 (CYP) 3A4 isoform, with minor contributions by CYPs 2C8, 2C9, 2C19 and 2D6 (<20% collectively). The major circulating metabolite is the methylcatechol glucuronide. This metabolite is at least 13,000-fold less potent than tadalafil for PDE5. Consequently, it is not expected to be clinically active at observed metabolite concentrations.

Elimination -The mean oral clearance for tadalafil is 2.5 L/hr and the mean half-life is 17.5 hours in healthy subjects. Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

Tadalafil pharmacokinetics in healthy subjects are linear with respect to time and dose. Over a dose range of 2.5 to 20 mg, exposure (AUC) increases proportionally with dose. Steady-state plasma concentrations are attained within 5 days of once-daily dosing.

Pharmacokinetics determined with a population approach in patients with erectile dysfunction are similar to pharmacokinetics in subjects without erectile dysfunction.

Table 1: Summary of Geometric Mean (CV%) Single Dose Pharmacokinetic Parameters of tadalafil (20 mg) in Healthy Volunteers

 

AUC

(μg*h/L)

Cmax

(μg/L)

tmax

(h)

t1/2

(h)

Geometric

mean (CV%)

8066 (39.3)

378 (27.6)

2.0

(0.5 to 12.0)a

17.5 (32.3)

a Median and range

 

Pharmacokinetics in Special Populations
Elderly - Healthy elderly subjects (65 years or over) had a lower clearance of tadalafil, resulting in a half life of 22 hours and 25% higher exposure (AUC), relative to healthy subjects aged 19 to 45 years (half life of 16-17 hours). This effect does not appear to warrant a dose adjustment (see DOSAGE AND ADMINISTRATION - Elderly Patients).The half life of tadalafil in the elderly increases the period after the last dose of CIALIS during which nitrates should be avoided (see CONTRAINDICATIONS).

Renal Impairment In subjects with renal insufficiency, including those on hemodialysis, tadalafil exposure AUC was higher than in healthy subjects. Therefore, the recommended starting dose of tadalafil in patients with renal impairment is 10 mg (see DOSAGE and ADMINISTRATION).

Hepatic Impairment - Tadalafil exposure (AUC) in subjects with mild and moderate hepatic impairment (Child-Pugh Class A and B) is comparable to exposure in healthy subjects. No data are available in patients with severe hepatic impairment (Child-Pugh Class C).


Patients with Diabetes - Tadalafil exposure (AUC) in patients with diabetes was approximately 19% lower than the AUC value for healthy subjects. This difference in exposure does not warrant a dose adjustment.

 

1   2   3   4

Abdomen
Blood
Bone
Breast
Ear

Eye

Face
Hair

Head

Heart
Kidney
Liver
Limbs
Lungs
newMind
Mouth
Muscles
Nails

Neck

newNerves
Nose

Skin

Teeth

Throat

Tongue
 
Health news
 
Cardiovascular Guide
 
Natural Remedies
 
Treatment of Cancer
 
Women's Health
 
Irritable bowel syndrome
 
Common Childhood Illnesses
 
Prescribed Drugs
 
 

     
         
     

 

Disclaimer