Cialis (Eli Lilly and Company, Indianapolis, IN, USA) is an effective drug for the treatment of erectile dysfunction. The timeline of Cialis began in 1991 when the pharmacological company GlaxoSmithKline (Brentford, UK) and the American biotechnology company ICOS Corporation (Bothell, WA, USA) initiated joint testing of a new compound under the serial number IC351.

Three years later, ICOS was able to obtain a patent for this compound and begin the first phase of clinical trials. In 1998, due to financial difficulties, ICOS merged with the American pharmaceutical company Eli Lilly and Company. Subsequently, in 2003, Eli Lilly successfully completed the last stage of clinical trials as an agent for the treatment of impotence and appealed to the United States Food and Drug Administration (FDA) for the registration of a new drug (tadalafil) and a commercial medicine based upon it (Cialis).

Clinical studies have demonstrated a high efficacy of tadalafil, which lasts up to 36 hours, which is six to eight times longer as compared with the ability of the analogs that existed at that time (i.e., Viagra from Pfizer, New York, NY, USA and Levitra from Bayer HealthCare Pharmaceuticals, Berlin, Germany). Besides, Cialis had a much smaller number and frequency of side effects as compared with other phosphodiesterase inhibitors. In October 2011, the FDA approved Cialis as a drug for the treatment of benign prostatic hyperplasia and erectile dysfunction.

Basic information

Trade name: Cialis
Manufacturer: Eli Lilly & Co. (USA)
Active Ingredient: Tadalafil 20 mg
Class: Medicines for the treatment of symptoms of erectile dysfunction, benign prostatic hyperplasia, prostate enlargement, and combinations thereof
Pharmacological group: Selective PDE5 inhibitors
Form: Almond-shaped yellow tablets
Treatment for: Erectile Dysfunction
Dosing recommendations: From 5 mg to 20 mg, depending on the purpose and recommendations of the doctor
Initiation of drug activity: The first manifestations of physiological activity occur 30 to 60 minutes after taking the drug
Duration of action: Up to 36 to 48 hours

Composition

The main active ingredient is tadalafil 10 mg or 20 mg. Fillers include lactose monohydrate, talc, hypromellose, croscarmellose sodium, hydroxypropylmethylcellulose, microcrystalline cellulose, croscarmellose, sodium lauryl sulfate, and magnesium stearate.

Mechanism of action

Tadalafil belongs to the class of selective inhibitors of phosphodiesterase-5 (PDE5). Phosphodiesterase is an enzyme that undergoes hydrolysis of cyclic guanosine monophosphate (cGMP). As a result of the increased activity of PDE5 in the male body, the reproduction of nitric oxide decreases, which is followed by a reduction in the concentration of cGMP by the smooth muscles of the vessels of the penis, prostate, and lungs. The inhibition of PDE5 with tadalafil increases the level of cGMP, leads to vascular relaxation, and increases blood flow to target organs (e.g., penis, prostate, and pulmonary vasculature).

Contraindications

Due to a lack of clinical data, Cialis isn’t recommended for use in children, seniors older 85 years, and patients with a terminal stage of renal and/or hepatic insufficiency.

Cialis is contraindicated in the case of:

  • Individual intolerance or excessive sensitivity to tadalafil or another component of the drug
  • Acute myocardial infarction occurring in the last 90 days
  • Significant hypotension with syncope
  • Anterior ischemic optic neuropathy, regardless of whether this is due to previous experience with the use of PDE5 inhibitors or not
  • Occurrence of a stroke in the last six months

Furthermore, in the presence of the following diseases, Cialis should be taken with caution:

  • Acute heart disease, including heart failure, angina pectoris, heart rhythm disturbances, or seizures
  • Narrowing of the mitral orifice and fusion of the pericardium
  • Restrictive or congestive cardiomyopathy
  • Severe left ventricular dysfunction
  • A life-threatening arrhythmia
  • Cardiac ischemia
  • Uncontrolled arterial hypertension

All PDE5 inhibitors, including tadalafil, have mild systemic vasodilator properties, which can cause a short-term reduction in blood pressure. Thus, before prescribing Cialis, doctors should carefully consider the safety of this drug in patients with cardiovascular disease.
Patients who have previously had a negative experience with the use of PDE5 inhibitors in which priapism was provoked (i.e., prolonged, painful erections lasting more than four hours) shouldn’t take tadalafil.

Overdose

Single doses of tadalafil up to 500 mg in healthy volunteers, as well as daily doses of 100 mg of tadalafil in patients with erectile dysfunction, led to side effects that are observed with therapeutic standard dosages.

Alcohol

Alcohol clearance and the time of its systemic action doesn’t depend on the joint consumption of Cialis (10 mg or 20 mg). Similarly, alcohol doesn’t affect the pharmacokinetics and concentration of tadalafil in the blood when they are used together. Tadalafil in a dose of 20 mg also didn’t reduce the average drop in arterial pressure induced by alcohol in an amount equivalent to 180 mL of 40-degree vodka for an 80-kg man. The effect of tadalafil (10 mg) and alcohol on cognitive function was not revealed.

Interaction with other medicines

Cialis should not be used by patients taking medications containing medical nitrates (e.g., nitroglycerin, isosorbide mononitrate, sodium nitroprusside), which are prescribed for angina and heart pain. Combinations of these drugs can cause a sudden and unsafe drop in blood pressure.

The administration of riociguat, which is used in the treatment of chronic thromboembolic hypertension and pulmonary arterial hypertension, in combination with tadalafil also leads to a sharp and unsafe decrease in blood pressure.

The use of Cialis with alpha-blockers and other drugs for the treatment of blood pressure can lead to an additive decrease in blood pressure. Cialis should be avoided in conjunction with potent inhibitors of CYP3A, such as ritonavir and erythromycin. Patients who require treatment with antifungal agents, such as itraconazole or ketoconazole, should reduce their dosage of tadalafil to 10 mg.

The safety and efficacy of Cialis combinations with other PDE5 inhibitors have not been studied to date, though it is suggested that combining these substances with one another can increase the possibility of side effects. Grapefruit juice and grapefruit products can increase the plasma concentrations of tadalafil, so their joint use is also not recommended.

Side effects

Clinical studies have confirmed a dose-dependent positive correlation between side effects and dosing of tadalafil. The most common side effects of Cialis that have been observed in clinical studies include headaches, runny nose or upper airway inflammation (like a common cold), hot flashes, pain in the extremities, nausea, back pain, and indigestion.

Headaches may occur at the beginning of treatment and decrease with time before completely resolving.