Tadalafil is a sexual performance-enhancing drug, whose action comes from its ability to relax smooth muscles found in the blood vessels and intensify blood circulation to the certain parts of the body (to the pelvic area, in particular). Sold under a branded name Cialis, Tadalafil is meant to manage erectile issues in men over 18. The drug is also effective against benign prostatic hypertrophy and lung arterial hypertension in both male and female patients. Sometimes, athletes consume this preparation in order to enhance exercise capacity.
Though the drug is claimed to be harmless and failure-proof, there are still some restrictions concerning the usage of Tadalafil in specific groups of patients. This is what we are going to discuss today.
Mechanism of action
To understand why Tadalafil may be contraindicated or restricted for some populations, it is necessary, first of all, to gain insight into its mechanism of action. Cialis does not directly trigger a penile engorgement and firmness but has an impact on the response to the sexual stimulation. When a male is sexually aroused, in his corpus cavernosum there is a powerful emission of nitric oxide (NO). Nitric oxide initiates the production of guanylate cyclase (a chemical substance), what initiates the formation of cyclic guanosine monophosphate (cGMP). Such a reaction gives rise to the vasodilatation of smooth blood vessel muscles and an increased flow of blood to the penile tissue.
Tadalafil steps up the activity of NO by suppressing phosphodiesterase type 5 (PDE5), a macromolecular biological catalyst playing the vital role in degradation of cGMP in the penile spongy bodies. Sexual excitement evokes local production of nitric oxide. Tadalafil blocks the activity of PDE5 causing an increased level of cGMP in a penis, which results in the smooth muscle vasodilatation and rush of blood to this genital organ. Thus, without sexual stimulation, this medicine does not work. Consequently, erection can be hampered if there are neural, vascular, endocrine or psychological disorders.
Use of Tadalafil in Geriatric Patients
Tadalafil is available in a form of oral tablets dispensed in strengths of 2.5 mg, 5 mg, 10 mg, and 20 mg.
For erectile issues, Tadalafil can be prescribed either on an as needed or once daily basis. In most subjects, the standard dose of Cialis makes 10 mg, used 30-60 minutes before an anticipated intercourse. However, the dosage may vary from 5 mg to 20 mg depending on individual effectiveness and tolerability. A maximum recommended daily dose of Tadalafil is 20 mg in most ED sufferers. When taken as needed, Tadalafil preserves its efficacy for up to 36 hours.
As for a once daily administration, the standard dose of the drug is 2.5 mg that should be consumed at one and the same time every day, irrespective of the timing of performance. An everyday dose of the medicine can be doubled to 5 mg depending on individual tolerability.
The portion of good news is that dose modifications of Tadalafil are not required in patients in their late years (over 65). During pre-marketing clinical trials, the drug was tested in men of versatile ages, from 19 to 75. During these experiments, no remarkable differences in effectiveness or safety were reported between older (over 65) and younger (under 65) probationers. Nevertheless, diarrhea was observed more frequently in older subjects. That is why the age alone is not a reason to refrain from Tadalafil if you are just not young enough. However, older individuals are prone to be more sensitive to some medications including Cialis. This should be paid a special attention when prescribing this pharmaceutical agent to geriatric patients.
Tadalafil use in the treatment of the symptoms of iperplasia prostatica benigna (IPB)
Iperplasia prostatica benigna (IPB) is better known as benign prostatic hyperplasia (BPH) is a health condition under which there is an enlargement of the prostate is observed. This disease is a culprit of lower urinary tract symptoms, which typically manifest themselves in an increased frequency of urination, involuntary urination, urinary hesitancy, a weak urine stream, a feeling of incomplete emptying, and post-micturition dribbling. These signs of IPB often come amid a severe pain in a bladder, abdominal pain, painful sensations during urination or an unending feeling of a full bladder, which can completely spoil men‘s quality of life.
Tadalafil was approved in 2011 by American FDA to manage the symptoms of IPB and for the management of IPB and erectile dysfunction when the ailments occur simultaneously.
There were a series of clinical trials under which men diagnosed with benign prostatic hyperplasia used 5 mg of Tadalafil on a daily basis, and they reported significant alleviation of their symptoms in comparison to those subjects who received a placebo. What is more, makes who suffered from both erectile dysfunction and prostatic enlargement and were receiving 5 mg of Cialis as a single daily dose, reported improvements in both disorders compared with a group who were treated with a placebo drug! Apparently, Tadalafil offers men with BPH an appropriate treatment alternative.
Men suffering from IPB or from IPB and ED are recommended to take Tadalafil at the dose of 5 mg every day, ideally, at one and the same time, without regard to food or time of an anticipated sexual activity. The treatment may last up to 27 weeks. However, the consumption of Tadalafil must not coincide with the consumption of alpha-blockers for the therapy of benign prostatic hypertrophy because these two agents pose a risk of a life-hazardous drop in blood pressure.
Use of Tadalafil in the treatment of pulmonary hypertension
Tadalafil as a phosphodiesterase-5 (PDE5) inhibitor is approved for the therapy of pulmonary arterial hypertension by the World Health Organization. The purpose of such a therapy is to elevate exercise performance and prevent clinical progression of the disease.
PDE5 is an enzyme found in the lungs (and other body parts, of course, such as corpus cavernosum). This substance degrades another enzyme known as GMP. Cyclic GMP is responsible for relaxation and widening of blood vessels. Tadalafil is capable of suppressing the degrading activity of PDE5, which increases the GMP levels inside lungs. The vasodilatation of lung blood arteries lowers the pulmonary blood pressure to the heart, what is extremely beneficial to its function. A reduced pulmonary pressure provides for being more active and physically endurable.
Patients diagnosed with PAH are advised to take 40 mg of Tadalafil as a single daily dose irrespective of timing to food. In the treatment onset, the dose may be just 20 mg to estimate a patient’s individual response to the drug. Note that Tadalafil is not recommended in pediatric PAH patients since the safety and effectiveness of this medicine in this group of people are not confirmed.
Tadalafil is avoided in PAH patients who are using Boceprevir, strong CYP3A4 inducers, and Tipranavir, as these substances can affect the serum concentration of Tadalafil, which may be fatal in this specific population.
Tadalafil use in patients with renal failure
The dosage of Tadalafil for BPH with or without co-existing erectile problems:
- CrCl greater or equal to 51 mL/minute does not involve any dosage modifications;
- Creatinine clearance varies from 30 to 50 mL/minute – the starting dosage is 2.5 mg of Tadalafil taken as a single daily dosage. The dosage must not exceed 5mg per day;
- Creatinine clearance less than 30 mL/minute: patients should refrain from taking the drug;
- End-stage renal disease requiring hemodialysis: subjects should avoid taking Tadalafil.
The dosage of Tadalafil to manage weak erection:
As for an as-needed basis:
- CrCl greater or equal to 51 mL/minute does not involve dosage corrections;
- Creatinine clearance varies from 30 to 50 mL/minute: the recommended dosage then is 5 mg taken once a day and it must not exceed 10 mg every 48 hours;
- Creatinine clearance less than 30 mL/minute: the maximum allowed dosage is 5 mg taken every 72 hours;
- End-stage renal disease that involves hemodialysis: the max dosage is 5 mg every 72 hours.
As for a once-daily basis:
- Creatinine clearance greater or equal to 31 mL/minute does not presuppose dose adjustments;
- Creatinine clearance less than 30 mL/minute: the use of Tadalafil must be abolished;
- End-stage renal disease that involves hemodialysis: the use of the drug must be avoided.
The dose of Tadalafil to cure pulmonary arterial pressure:
- Creatinine clearance varies from 31 to 80 mL/minute: the starting dosage is 20 mg of Tadalafil taken once a day; if well-tolerated, the dosage may be increased up to 40 mg taken once a day;
- Creatinine clearance less or equal to 30 mL/minute: the use is not recommended;
- End-stage renal disease involving hemodialysis: the therapy with Tadalafil must be avoided.
Tadalafil use in patients with poor hepatic function
There is no risk for patients with mild/moderate hepatic disorders after taking Tadalafil in a dose not more than 10 mg. Their exposure to the drug is similar to that in healthy patients. There is no sufficient data about safety and effectiveness of Tadalafil in individuals with a severely impaired hepatic function.
Tadalafil Posology under Hepatic Impairment is as following:
Benign prostatic hypertrophy irrespective of erectile disorders:
Mild to moderate liver decompensation: Tadalafil is not prohibited but should be prescribed with caution since the impact of Tadalafil was not properly measured in people with hepatic insufficiency.
Under a severely hampered liver function, this PDE5 inhibitor is avoided.
As for an as-needed administration:
Mild to moderate liver decompensation: the use of Tadalafil is not excluded but the dose should not be higher than 10 mg every 36 hours since the effect of Tadalafil was not properly estimated in people with hepatic insufficiency and there is no adequate clinical data supporting harmless of this medication in this group of patients.
Under severely hampered liver function, Tadalafil must be avoided.
As for a once a day administration:
Mild to moderate hepatic insufficiency: Tadalafil is taken with caution since the safety of Tadalafil for a once-daily consumption was not properly studied in people with hepatic insufficiency.
Under severe impairment treatment with Tadalafil must be avoided.
Mild to moderate hepatic insufficiency requires the Use of Tadalafil with caution. The recommended single daily dose should make 20 mg.
Severe hepatic insufficiency: the use is not advised at all since the drug was not tested in subjects with major hepatic failure.