Cialis Explained: Mechanism, Onset, Duration, and Who It’s For

Author: Sylvia (Xi) He – Medical / Scientific Editor & Writer

Cialis is the trade name for tadalafil, one of the three major prescription medicines in the class known as PDE5 inhibitors. It is approved by the U.S. Food and Drug Administration (FDA) and the EMA (European Medicines Agency) for the treatment of erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and the combination of both conditions.

What sets Cialis apart from other ED medicines is its long duration of action — up to 36 hours, which has earned it the nickname “the weekend pill.” This prolonged effect allows for greater flexibility in timing sexual activity, and in lower daily doses it can be used continuously for ongoing symptom control.

In this article, we explain what Cialis is, how it works in the body, how quickly it starts working and how long it lasts, and who it may or may not be suitable for.

What Is Tadalafil (Cialis)?

Cialis is the brand name for tadalafil, a selective phosphodiesterase type 5 (PDE5) inhibitor. It was first approved by the U.S. Food and Drug Administration (FDA) in 2003 for erectile dysfunction, with later approvals for benign prostatic hyperplasia (BPH) and combined ED+BPH treatment. The European Medicines Agency (EMA) granted its first marketing authorization in the same year. The active ingredient in Cialis and its generic equivalents is identical — tadalafil. Generic versions have been available since 2018 in many markets, often at significantly lower cost. Both brand and generic are available in 2.5 mg, 5 mg, 10 mg, and 20 mg tablets, enabling both daily low-dose regimens and on-demand use.

Unlike sildenafil (Viagra) and vardenafil (Levitra), tadalafil is notable for its long plasma half-life of approximately 17.5 hours, which underlies its extended window of effect — up to 36 hours after a single dose, as noted in the FDA label. (Cialis vs Viagra (and Avanafil): Which PDE5 Inhibitor Fits Your Profile?)

In addition to sexual medicine, tadalafil is also approved under the brand Adcirca for pulmonary arterial hypertension at different doses, reflecting the same PDE5-inhibiting mechanism but targeting vascular tone in the lungs.

The primary difference between brand-name Cialis and generic tadalafil lies in the manufacturer, price, and appearance; regulatory authorities require generics to meet bioequivalence standards so that therapeutic effects are consistent.

Mechanism of Action: PDE5, NO–cGMP Pathway, and Selectivity

Erection of the penis is a neurovascular event triggered by sexual stimulation, during which nitric oxide (NO) is released from nerve terminals and endothelial cells in the corpus cavernosum. NO activates guanylate cyclase, increasing levels of cyclic guanosine monophosphate (cGMP). This molecule causes smooth muscle relaxation in penile arteries and erectile tissue, allowing increased blood inflow and engorgement. Under normal physiology, phosphodiesterase type 5 (PDE5) breaks down cGMP, ending the erection. Tadalafil works by selectively inhibiting PDE5, thereby slowing cGMP degradation and prolonging smooth muscle relaxation. The result is improved erectile quality in response to sexual stimulation — tadalafil does not initiate an erection without sexual arousal.

One distinguishing feature of tadalafil is its selectivity profile. It is highly selective for PDE5 over PDE6 (present in the retina) and PDE1 (found in vascular smooth muscle), which may contribute to a lower incidence of visual side effects compared to sildenafil. However, tadalafil also inhibits PDE11, found in skeletal muscle and the prostate, which is thought to be related to the muscle aches and back pain occasionally reported by users.

The FDA prescribing information and EMA Summary of Product Characteristics both emphasize that tadalafil’s effect is site-specific because PDE5 is abundantly expressed in penile tissue and the lower urinary tract, explaining its utility in ED, BPH, and ED+BPH.

Onset, Peak, and Duration (“Weekend Pill” Myth)

Tadalafil is often called the “weekend pill” because a single dose can remain effective for up to 36 hours, allowing greater flexibility in sexual activity compared to shorter-acting PDE5 inhibitors. This extended action is directly related to its elimination half-life of around 17.5 hours.

Onset of action is typically within 30 to 60 minutes after oral administration. In some individuals, noticeable effects may occur in as little as 15–20 minutes, but this is less common and should not be relied upon for timing. The peak plasma concentration is generally reached at about 2 hours post-dose, as reported in both the FDA label and EMA SmPC.

Importantly, tadalafil’s efficacy is not significantly affected by food, including high-fat meals. This contrasts with sildenafil, which can have a delayed onset if taken with heavy or fatty foods. Alcohol, however, should be consumed cautiously, as excessive intake can increase the risk of hypotension and dizziness when combined with tadalafil.

For erectile dysfunction, tadalafil may be prescribed on demand (usually at doses of 10 mg or 20 mg taken prior to anticipated sexual activity) or as a low-dose daily regimen (2.5 mg or 5 mg once daily) for men who prefer spontaneity or who also require treatment for benign prostatic hyperplasia (BPH).

The “weekend pill” label can be misleading if interpreted as providing a continuous erection. In reality, tadalafil simply extends the window of responsiveness to sexual stimulation. Its prolonged duration means that men do not have to precisely time dosing in relation to sexual activity, which can improve psychological comfort and reduce performance anxiety.

In clinical trials, tadalafil maintained statistically significant erectile function improvement at up to 36 hours post-dose, supporting its unique position among PDE5 inhibitors.

Indications: ED, BPH, and ED + BPH

Tadalafil is approved by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for three main uses in adult men: erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and the combination of ED with BPH.

Erectile Dysfunction (ED):
Clinical trials have consistently shown that tadalafil improves erectile function across a wide range of patient populations, including men with diabetes, post-prostatectomy, and spinal cord injury. In pivotal phase III studies, men taking tadalafil had significantly higher International Index of Erectile Function (IIEF) scores compared with placebo. Its long duration allows for greater flexibility and reduces the need for strict timing before sexual activity.

Benign Prostatic Hyperplasia (BPH):
Tadalafil is the only PDE5 inhibitor with regulatory approval for the treatment of lower urinary tract symptoms (LUTS) due to BPH. The mechanism is thought to involve relaxation of smooth muscle in the bladder, prostate, and associated vasculature, improving urinary flow and reducing symptoms such as frequency and urgency. Clinical trials using the International Prostate Symptom Score (IPSS) have demonstrated statistically significant reductions in LUTS versus placebo.

ED + BPH Combination:
For men experiencing both erectile dysfunction and LUTS, tadalafil 5 mg once daily can address both conditions simultaneously, eliminating the need for two separate medications. This dual benefit is reflected in both the FDA label and the EMA SmPC.

Tadalafil is not indicated for use in women or in pediatric populations, and its safety and efficacy outside approved uses, except for pulmonary arterial hypertension under the brand name Adcirca, have not been fully established in controlled trials.

Who Should and Shouldn’t Consider It

Cialis (tadalafil) can be an appropriate option for adult men with erectile dysfunction, benign prostatic hyperplasia, or both, provided they have undergone a medical evaluation to confirm the diagnosis and assess cardiovascular fitness for sexual activity. Candidates often include men who value the extended duration of action or who prefer a low-dose daily regimen for greater spontaneity.

However, certain individuals should not take tadalafil due to potentially dangerous interactions or health risks. The most important absolute contraindication is concurrent nitrate therapy (e.g., nitroglycerin for angina) or riociguat (a guanylate cyclase stimulator for pulmonary hypertension), as these combinations can cause severe, potentially life-threatening hypotension. (Tadalafil: Contraindications, Interactions, and Red-Flag Symptoms)

Tadalafil should also be avoided, or used with extreme caution, in men with:

Severe cardiovascular disease (e.g., recent heart attack or stroke within the past 90 days, unstable angina, severe heart failure)
Severe liver impairment (Child-Pugh Class C)
Severe hypotension or uncontrolled hypertension
Rare inherited eye disorders such as non-arteritic anterior ischemic optic neuropathy (NAION) linked to PDE5 inhibitor use

Men taking strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may experience increased tadalafil exposure and require lower doses, while strong CYP3A4 inducers (e.g., rifampin, carbamazepine) may reduce effectiveness.

A full medical history, medication review, and cardiovascular assessment are essential before initiating therapy, ensuring the benefits outweigh potential risks for each individual.

If you are thinking about buying Cialis for a long course of treatment, then you should study our article How to legally reduce your costs for buying Cialis online

References

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