Tadalafil

What is Tadalfil?

Tadalafil is a selective PDE5 inhibitor/phosphodiesterase type 5 inhibitor which has similar properties to Vardenafil and Sildenafil. This drug is usually administered orally and it is primarily indicated for the treatment of ED/Erectile Dysfunction. It is also indicated for the treatment of Benign Prostate Hypertrophy, Pulmonary Arterial Hypertension and the concurrent treatment of BPH and ED. Tadalafil is not a prostaglandin inhibitor like other agents that are used to treat Erectile Dysfunctions and unlike Sildenafil, it does not lead to the development of visual disturbances and sensory conditions. When Tadalafil is used for the treatment of ED, its duration of action can last to up to 36 hours which is longer than the action span of both Sildenafil and Vardenafil. Since PDE5 inhibitors only facilitate an erection as a response to sexual stimulation, Tadalafil’s longer duration of action generates a more spontaneous sexual stimulation and sexual action. According to the guidelines for the treatment of ED, PDE5 inhibitors should be considered as the first line of treatment before looking for additional options. Tadalafil was approved by the FDA for the clinical treatment of ED in 2003 and for the treatment of Pulmonary Arterial Hypertension in 2009. Clinical studies in patients with PAH showed an improvement in the activity and exercise capacity of their system and a diminished medical worsening of this condition during the treatment. In 2011, Tadalafil was approved by the FDA for the management of the symptoms of Benign Prostate Hyperplasia and for a concurrent treatment of ED and BPH.

Tadalafil’s Mechanism Action

Tadalafil is a selective inhibitor of cGMP- Cyclic Guanosine Monophosphate, which is a PDE5. The physiological mechanism of erection is induced by the release of nitric oxide in the corpus cavernosum during sexual stimulation. While in this system, nitric oxide activates Guanylate Cyclase which is the enzyme that is responsible for increasing the concentrations of cGMP in the serum. Cyclic Guanosine Monophosphate causes the relaxation of the smooth muscles of the corpus cavernosum, which allows more blood to flow into the tissues through the vascular system. The exact mechanism through which cGMP stimulates a relaxation action has not been established but the main function of Tadalafil is to enhance the effects of nitric oxide by inhibiting PDE5 which increases the concentration levels of cGMP in the corpus cavernosum. At normal / recommended doses, Tadalafil has no physiological effects when there is no sexual stimulation.

The mechanism through which tadalafil diminishes the symptoms of Benign Prostate Hyperplasia has not been established but its effect as a PDE5 inhibitor and its effects on cGMP concentrations in the corpus cavernosum can also be attained in the arteries and this is presumed to be responsible for its clinical effects. These effects can also be induced in the smooth muscles of the bladder, prostate and the vascular system surrounding them.

Tadalafil can also inhibit PDE5 in the esophageal smooth muscle tissues, and in the tissues of the lungs, which results in the relaxation of the pulmonary vascular smooth muscles. This facilitates pulmonary vasodilation. This property of Tadalafil makes it a very effective solution to pulmonary hypertension.

The inhibition of PDE5 in the smooth muscles of the esophagus can also minimize the instances of oesophageal motility. These effects can be highly beneficial in managing certain motor disorders that can affect the esophagus e.g. hypertensive, diffuse spasm and nutcracker esophagus.

Pharmacokinetics of Tadalafil

Tadalafil should be administered orally. Some tests that were carried out on healthy volunteers showed that once this drug is absorbed into the body, it is immediately distributed throughout the tissues where 94% of it binds to body proteins. This percentage is only attained at therapeutic concentrations. Less than 0.0005% is passed on to the semen and after its action, its primary route of elimination is through a hepatic cytochrome P450 isoenzyme which metabolizes it into a catechol metabolite. After this, the catechol metabolite is methylated into a methyl-catechol metabolite and glucuronidated  into a methyl-catechol glucuronide conjugate. These metabolites are then excreted through the feces (61%) and the urine (31%). The elimination half life of Tadalafil is estimated at 17.5 hours.

Indications for Tadalafil

Tadalafil is primarily indicated for the treatment of male Erectile Dysfunction, pulmonary artery hypertension and for benign prostate hyperplasia.

Contraindications and precautions when using Tadalafil

Your healthcare service provider needs to be informed if you are suffering from the following conditions; eye vision problems, bleeding disorders, a history of priapism ( prolonged and painful erections.) angina, a history of cardiac conditions, high or low blood pressure, irregular heartbeats, blood diseases, liver diseases, kidney diseases and allergic reactions to Tadalafil. If you notice any changes in your vision while taking this medicine, you should stop its administration immediately and contact your healthcare provider as soon as you can. You should also contact your healthcare provider and refrain from any sexual activities if you experience priapism, chest pains, dizziness, nausea, and pain in your arms upon initiation of sexual activities.

A combination of Tadalafil with other medications that are used for the treatment of ED is not recommended because the safety and efficacy of such a combination have not been established.

Tadalafil should not be used together with alpha beta blockers in the treatment of BPH because the efficacy of such a combination has not been established.

Tadalafil is contraindicated in patients who are receiving a therapy that contains nitrates or nitrites due to the known effects of this drug on nitric oxide and the cGMP pathways. This drug has a huge potential of worsening the hypotensive effects of nitrate salts.

Tadalafil should be administered cautiously to patients with renal impairment and it is not recommended for a patient who is receiving it once on a daily basis for any of its indications if their creatinine clearance rate is below 30ml/min and if the patient is currently receiving dialysis or has suffered from renal failure.

Tadalafil should be used cautiously in patients with hepatic dysfunction that is due to hepatic diseases. This is because data on its effects is still insufficient to ensure its safety and efficacy.

A notable degree of cardiac risks and conditions are associated with sexual activities in ED patients, so, physiians should carry out a thorough evaluation of a patient’s cardiovascular condition before initiating a treatment for ED using this medication. Patients with cardiac conditions should be treated very cautiously and in certain developed conditions, this medication should be avoided completely.

All patients on a treatment with Tadalafil should be informed that this medication does not protect them from any sexually transmitted diseases and infections including HIV so, additional caution should be taken during a sexual engagement with sexual partners.

Tadalafil is classified under the FDA pregnancy risk category B. there are no comprehensive studies on the effects of this medication on women because it is not indicated for women. It is not known if Tadalafil is excreted in breast milk and not many studies have been carried out on this issue, but in any case where a breastfeeding infant suffers from adverse effects after maternally ingesting this drug, health service providers are encouraged to report this matter to the FDA immediately.

Tadalafil is a PDE5 inhibitor and since PDE5 is found in blood platelets, this medication should be administered cautiously in patients with severe hematological diseases.

This list does not contain all the possible contraindications, so all patients are advised to communicate with their health service providers whenever they are in need of any information concerning this medication.

Drug interactions

Some possible chemicals and substances that can interact with Tadalafil can be found in drugs that are used to treat high blood pressure, drugs used to manage HIV/AIDS, drugs used for yeast and fungal infections, seizures and prostate problems. This list may not contain all the possible drug interactions, so it is advisable to inform your physician of all the medicines that you are currently using and this should include all the prescription and non-prescription drugs, vitamins, additives, and supplements. You should also inform your healthcare provider if you smoke, drink alcohol, if you use herbs or any illegal drugs and any additional substances that might interact with your medication.

Tadalafil should not be used concurrently with phosphodiesterase inhibitors because the safety and efficacy of this combination have not been established.

PDE5 inhibitors such as Tadalafil should be used with caution in patients who are receiving protease inhibitors like darunavir, atazanavir, ritonavir, fosamprenavir, tipranavir, saquinavir, and nelfinavir because these drugs may influence the efficacy of this medication.

Tadalafil should never be administered concurrently with CYP3A4 inhibitors because this drug is usually metabolized by CYP3A4, these inhibitors may reduce the clearance rate of this drug which will increase its concentration levels in the body system. Some of these drugs include; cimetidine, amiodarone, clarithromycin, fluoxetine, and ketoconazole.

Ethanol and PDE5 inhibitors like Tadalafil are mild systemic vasodilators, so an administration of this medication plus a substantial intake of alcohol should be avoided because this may dispose a patient to severe orthostatic signs and symptoms e.g dizziness, low blood pressure, increased heart rates and headaches.

Various studies have proved that Tadalafil does not induce or inhibit cytochrome P450 enzymes, so, this medication is not expected to have any clinical significance on the serum clearance of any drugs that are metabolized by CYP450 enzymes.

Adverse reactions and side effects that are associated with Tadalafil.

Some immediate side effects of Tadalafil can include; back pains, dizziness, flushing, indigestion, nausea, muscle aches, running nose, irregular heartbeats, changes in vision, changes in hearing and headaches. This list does not include all the side effects of this medication, so in the case of any signs of an allergic reaction, you are advised to contact your health service provider immediately.

After some clinical trials on the adverse effects of Tadalafil when used as a treatment for ED, the most frequently reported problems were hypotension, chest pains, angina, myocardial infarction, palpitations, sinus tachycardia and syncope. Sudden strokes and cardiac deaths were also reported but these were in patients with a history of cardiac diseases.

In patients with Pulmonary Arterial Hypotension, dyspepsia was reported more frequently. Other effects on the gastrointestinal system included; viral gastroenteritis, nausea, diarrhea, abdominal pains and gastro esophageal reflex. Other common effects of tadalafil can include; nasal congestion, gastritis, xerostomia, rectal hemorrhage, swelling of the eyelids, epistaxis, ocular pain, increased lacrimation, blurred vision, tinnitus, facial edema, fatigue, and pain.

There have been reports of priapism and prolonged erections that can last for more than 4 hours and some even greater than 6 hours but these are very rare.

You should contact your health service provider in case of any allergic reactions to this medication which may include but are not limited to; chest pain and chest tightness, the appearance of blue tints on your skin, skin rashes, painful swollen areas on your leg, swelling of your face, lips or tongue, difficulty in breathing, wheezing and dizziness.

How should this medication be administered?

Tadalafil should be taken orally and only by mouth. You should follow all the instructions on your prescription label.

If you administer this medication in the correct way, you should be able to attain sexual arousal and perform sexual activities from 30 minutes to 36 hours after taking this drug. You should never take more than one dose in a day and you should never administer it more often than you are required to/instructed.

This medicine should be stored at 59 – 86 degrees Farads. This should be away from heat, light, and moisture. You should never share your medicine or take someone else’s medicine and you should always remember to consult your physician in case you want to change your dose or if you prefer switching to other medications.

Conclusion

Tadalafil is commonly prescribed for the treatment of erectile dysfunction, and the Dosage strengths of Tadalafil available in our pharmacy are 10mg and 20mg.

The dosage form available is a troche and Absolute Pharmacy’s troches are compounded under the strict rules and guidelines of the USP 795. We also have a quality-assurance process that ensures the absolute consistency, potency, uniformity, and beyond use dating (BUD) of every drug and compound that we dispense. For more information on this medication and its administration, feel free to contact us.

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