Drug Monograph
Cialis (Tadalafil)
tadalafil tablets — for erectile dysfunction & benign prostatic hyperplasia
Pharmacokinetic Profile
Half-Life
17.5 h (longest among PDE5i)
Metabolism
Hepatic: CYP3A4 (predominant)
Protein Binding
94%
Bioavailability
Not determined (no food effect)
Volume of Distribution
63 L (apparent)
Clinical Information
Drug Class
PDE5 Inhibitor
Available Doses
2.5 mg, 5 mg, 10 mg, 20 mg
Route
Oral (PRN or daily)
Duration of Action
Up to 36 hours (PRN dosing)
Nitrate Interaction
CONTRAINDICATED; wait ≥48 h after last dose
Alpha-Blocker (BPH)
Combination NOT recommended for BPH
Generic Available
Yes
Schedule
Prescription only (not scheduled)
Indications
| Indication | Dosing Approach | Approved Year | Status |
|---|---|---|---|
| Erectile dysfunction (ED) | PRN (10–20 mg) or daily (2.5–5 mg) | 2003 | FDA Approved |
| Benign prostatic hyperplasia (BPH) — signs and symptoms | Daily only (5 mg) | 2011 | FDA Approved |
| ED and BPH — concomitant ED and BPH symptoms | Daily only (5 mg) | 2011 | FDA Approved |
Tadalafil is a PDE5 inhibitor distinguished by its long half-life of 17.5 hours, which provides a duration of action up to 36 hours after a single dose and supports once-daily dosing. It is the only PDE5 inhibitor approved by the FDA for both ED and the signs and symptoms of BPH. Over 9,000 men were treated with tadalafil during clinical trials worldwide. Tadalafil’s absorption is unaffected by food, providing flexible dosing. The drug is also marketed as Adcirca for pulmonary arterial hypertension at a different dose (40 mg daily); this monograph covers the ED and BPH indications only.
Limitation of Use: Combination with Finasteride
If tadalafil is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks only, because the incremental benefit of tadalafil decreases from 4 weeks until 26 weeks, and the incremental benefit beyond 26 weeks is unknown.
Dosing
Standard Dosing Regimens
| Indication / Regimen | Starting Dose | Maintenance | Maximum | Notes |
|---|---|---|---|---|
| ED — PRN (as needed) | 10 mg PRN | 5–20 mg PRN | 20 mg/day | Take prior to anticipated sexual activity; effective up to 36 h post-dose; max once daily Do not split tablets; take without regard to food |
| ED — daily | 2.5 mg once daily | 2.5–5 mg once daily | 5 mg/day | Same time every day; no regard to timing of sexual activity Steady-state reached in ~5 days; 1.6-fold accumulation |
| BPH — daily | 5 mg once daily | 5 mg once daily | 5 mg/day | Same time every day With finasteride: 5 mg tadalafil + finasteride for ≤26 weeks |
| ED + BPH — daily | 5 mg once daily | 5 mg once daily | 5 mg/day | Same time every day; addresses both conditions with a single regimen No regard to timing of sexual activity |
Renal and Hepatic Dose Adjustments
| Population | PRN (as needed) | Daily Use (ED / BPH / ED+BPH) |
|---|---|---|
| CrCl 30–50 mL/min | Start 5 mg; max 10 mg q48h | BPH/ED+BPH: start 2.5 mg, may increase to 5 mg |
| CrCl <30 or hemodialysis | Max 5 mg q72h | Not recommended (ED, BPH, or ED+BPH) |
| Hepatic impairment (Child-Pugh A/B) | Max 10 mg; once-daily not extensively evaluated | Caution advised; not extensively evaluated |
| Hepatic impairment (Child-Pugh C) | Not recommended | Not recommended |
| Potent CYP3A4 inhibitors (ketoconazole, ritonavir) | Max 10 mg q72h | Max 2.5 mg daily |
| Alpha-blockers — for ED | Must be stable on alpha-blocker first; initiate tadalafil at lowest dose | |
| Alpha-blockers — for BPH | Combination NOT recommended; discontinue alpha-blocker ≥1 day before starting tadalafil | |
Clinical Pearl: PRN vs Daily — Choosing the Right Regimen
The PRN regimen (10–20 mg) suits patients with less frequent sexual activity who prefer spontaneity within a 36-hour window. The daily regimen (2.5–5 mg) is ideal for patients with frequent sexual activity (≥2 times/week), those who prefer to dissociate medication from sexual timing, or those with concurrent BPH symptoms. Only the 5 mg daily dose is approved for BPH. Patients switching from PRN to daily should start at 2.5 mg and titrate. The daily regimen also offers the advantage of a single tablet addressing both ED and BPH.
Pharmacology
Mechanism of Action
Tadalafil selectively inhibits PDE5, the enzyme responsible for degradation of cGMP in the corpus cavernosum. By preventing cGMP breakdown during sexual stimulation, tadalafil facilitates smooth muscle relaxation and blood inflow to the penis. In the prostate and bladder, PDE5 inhibition relaxes smooth muscle, reducing BPH-related lower urinary tract symptoms. Tadalafil is more than 10,000-fold selective for PDE5 over PDE1, PDE2, and PDE4, and 700-fold selective over PDE6 (retinal), which explains why colour vision changes are rare (<0.1%) compared with sildenafil. Tadalafil has mild systemic vasodilatory properties; tadalafil 20 mg resulted in a mean maximal supine BP decrease of only 1.6/0.8 mmHg relative to placebo in healthy subjects.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Tmax 30 min to 6 h (median 2 h); no food effect on rate or extent of absorption; dose-proportional exposure from 2.5–20 mg; steady state in ~5 days with daily dosing; 1.6-fold accumulation | Flexible dosing with meals; slower onset than sildenafil but much longer duration (up to 36 h); supports both PRN and daily regimens |
| Distribution | Apparent Vd ~63 L; 94% protein-bound (albumin, α-1 acid glycoprotein); <0.0005% of dose in semen | Moderate tissue distribution; high protein binding limits dialysis efficacy in overdose |
| Metabolism | Predominantly CYP3A4; primary metabolite is methylcatechol glucuronide (inactive); does not inhibit or induce CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 | Susceptible to CYP3A4 inhibitors (ketoconazole +312% AUC) and inducers (rifampin −88% AUC); does not alter PK of co-administered CYP substrates |
| Elimination | t½ 17.5 h; oral clearance 2.5 L/h; 61% feces, 36% urine (as metabolites); hemodialysis negligible | Longest half-life among PDE5 inhibitors; enables once-daily dosing and up to 36 h PRN window; dose adjustment needed in renal impairment due to metabolite accumulation |
Side Effects
≥2%PRN Dosing for ED (Table 1 — 8 Studies, 12 Weeks)
| Adverse Effect | Placebo (n=476) | 5 mg (n=151) | 10 mg (n=394) | 20 mg (n=635) |
|---|---|---|---|---|
| Headache | 5% | 11% | 11% | 15% |
| Dyspepsia | 1% | 4% | 8% | 10% |
| Back pain | 3% | 3% | 5% | 6% |
| Myalgia | 1% | 1% | 4% | 3% |
| Nasal congestion | 1% | 2% | 3% | 3% |
| Flushing | 1% | 2% | 3% | 3% |
| Pain in limb | 1% | 1% | 3% | 3% |
≥1%Daily Dosing for BPH and ED+BPH (Table 4 — 3 Studies, 12 Weeks)
| Adverse Effect | Placebo (n=576) | 5 mg (n=581) | Clinical Note |
|---|---|---|---|
| Headache | 2.3% | 4.1% | Most common; lower rate than PRN dosing at higher doses |
| Dyspepsia | 0.2% | 2.4% | GI-related; may be managed with food or antacids |
| Back pain | 1.4% | 2.4% | Typically occurs 12–24 h post-dose; resolves within 48 h; diffuse bilateral lower lumbar/gluteal/thigh |
| Nasopharyngitis | 1.6% | 2.1% | Not clearly drug-related |
| Diarrhea | 1.0% | 1.4% | Mild; more common in patients ≥65 |
| Pain in extremity | 0.0% | 1.4% | Similar to back pain/myalgia; PDE5 class effect |
| Myalgia | 0.3% | 1.2% | Usually mild to moderate; resolves without treatment |
| Dizziness | 0.5% | 1.0% | Vasodilation-related |
SeriousSerious Adverse Effects
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Priapism | Rare (postmarketing) | During or after sexual activity | Seek emergency care if erection >4 h; irreversible damage if untreated >6 h |
| NAION | Rare (postmarketing); ~2-fold risk with PDE5 class | Variable | Discontinue; ophthalmology referral; risk factors include “crowded disc,” age >50, diabetes, HTN |
| Sudden hearing loss | Rare (postmarketing) | Variable; may include tinnitus/dizziness | Discontinue; prompt ENT evaluation |
| Hypersensitivity (Stevens-Johnson syndrome, exfoliative dermatitis) | Rare (postmarketing) | Variable | Discontinue immediately; contraindicated for re-challenge |
| CV events (MI, sudden cardiac death, stroke) | Rare (postmarketing) | During/after sexual activity | Emergency care; most patients had pre-existing CV risk; causality uncertain |
DiscontinuationDiscontinuation Rates
PRN for ED (12 weeks)
3.1% vs 1.4% placebo
Daily for BPH/ED+BPH (12 weeks)
3.6% vs 1.6% placebo
Back Pain / Myalgia
Back pain and myalgia generally occur 12 to 24 hours after dosing and resolve within 48 hours. The pain is characteristically diffuse, bilateral, involving lower lumbar, gluteal, thigh, or thoracolumbar muscles, and is exacerbated by recumbency. Approximately 0.5% of PRN users discontinued due to back pain/myalgia. When treatment was necessary, paracetamol or NSAIDs were generally effective. Colour vision changes were rare (<0.1% of all patients).
Drug Interactions
Tadalafil is predominantly metabolised by CYP3A4. Unlike sildenafil, it does not inhibit or induce any CYP isoforms at therapeutic concentrations. The critical interaction is with nitrates (contraindicated) and GC stimulators (riociguat — contraindicated). Clinicians prescribing daily tadalafil should be aware that continuous plasma levels increase the window for drug interactions compared with PRN dosing.
MajorOrganic nitrates (nitroglycerin, isosorbide, amyl nitrite)
EffectPotentiates hypotensive effect of nitrates via synergistic NO/cGMP pathway
ManagementABSOLUTELY CONTRAINDICATED; if nitrate needed in a life-threatening situation, at least 48 hours must elapse after last tadalafil dose before nitrate can be considered, under close hemodynamic monitoring
FDA PIMajorGC stimulators (riociguat)
EffectPDE5 inhibitors may potentiate hypotensive effects of GC stimulators
ManagementCONTRAINDICATED; do not co-administer
FDA PIMajorKetoconazole (potent CYP3A4 inhibitor)
EffectKetoconazole 400 mg daily: tadalafil AUC +312%, Cmax +22%; ketoconazole 200 mg daily: AUC +107%, Cmax +15%
ManagementPRN: max 10 mg q72h; daily: max 2.5 mg; applies also to itraconazole
FDA PIMajorRitonavir (HIV protease inhibitor / potent CYP3A4 inhibitor)
EffectRitonavir 200 mg BID: tadalafil AUC +124%, no Cmax change; ritonavir 500–600 mg BID: AUC +32%, Cmax −30%
ManagementPRN: max 10 mg q72h; daily: max 2.5 mg
FDA PIModerateRifampin (potent CYP3A4 inducer)
EffectTadalafil AUC −88%, Cmax −46%; expect decreased efficacy
ManagementNo dose adjustment; efficacy of daily dosing may be substantially reduced; also applies to carbamazepine, phenytoin, phenobarbital
FDA PIModerateAlpha-blockers (doxazosin, tamsulosin, alfuzosin)
EffectAdditive hypotension risk; clinical studies with doxazosin, tamsulosin, and alfuzosin showed significant blood pressure augmentation
ManagementED: stable on alpha-blocker first, initiate tadalafil at lowest dose; BPH: combination NOT recommended; discontinue alpha-blocker ≥1 day before starting tadalafil for BPH
FDA PIMonitoring
- CV StatusBefore prescribing
RoutineAssess fitness for sexual activity; avoid in patients with MI <90 days, stroke <6 months, NYHA Class 2+ HF <6 months, unstable angina, uncontrolled arrhythmias, hypotension (<90/50), or uncontrolled hypertension - Nitrate / GC Stimulator ScreenEvery visit
RoutineConfirm absence of organic nitrate use (including recreational “poppers”) and GC stimulators (riociguat); both are absolutely contraindicated; at least 48 h must elapse after last tadalafil dose before nitrate use - BPH AssessmentBaseline; 4–12 weeks; then periodically
RoutineAssess IPSS or AUA-SI score; exclude prostate cancer before attributing symptoms to BPH; re-evaluate at 26 weeks if using with finasteride - Renal FunctionBaseline
RoutineCheck CrCl to guide dosing: CrCl 30–50 requires adjustment; CrCl <30/HD: daily use not recommended; PRN limited to 5 mg q72h - Vision / HearingIf symptoms occur
Trigger-basedDiscontinue and seek immediate evaluation for sudden vision loss (NAION risk) or sudden hearing loss (may include tinnitus/dizziness)
Contraindications & Cautions
Absolute Contraindications
- Concurrent nitrate use: Organic nitrates or nitric oxide donors in any form (regular or intermittent), including recreational amyl nitrite/nitrate
- Known serious hypersensitivity: To tadalafil (Cialis or Adcirca) or excipients; includes history of Stevens-Johnson syndrome or exfoliative dermatitis
- GC stimulators: Concurrent use with riociguat or any guanylate cyclase stimulator
Not Recommended
- MI within last 90 days: Not studied; sexual activity poses cardiovascular risk
- Unstable angina or angina during intercourse
- NYHA Class 2+ heart failure in the last 6 months
- Uncontrolled arrhythmias, hypotension (<90/50), or uncontrolled hypertension
- Stroke within the last 6 months
- Severe hepatic impairment (Child-Pugh C)
- Alpha-blocker combination for BPH: Efficacy not studied; hypotension risk
Critical: Nitrate Timing
48-Hour Minimum After Tadalafil Before Nitrate Administration
Unlike sildenafil (where the timing is unknown), the Cialis FDA label specifically states that if nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last tadalafil dose. Even then, nitrates should only be given under close medical supervision with hemodynamic monitoring. The 17.5-hour half-life means significant tadalafil levels persist longer than with shorter-acting PDE5 inhibitors.
Patient Counselling
Critical: Nitrate / “Poppers” Warning
Tell patientNever take tadalafil if you use any form of nitrate medication for chest pain or recreational “poppers.” If you develop chest pain after taking tadalafil, tell the emergency team you have taken a PDE5 inhibitor so they avoid giving nitrates. At least 48 hours must pass since your last tadalafil dose before a nitrate can be considered.
PRN vs Daily Dosing
Tell patientPRN: Take 10–20 mg before anticipated sexual activity. The medication can work for up to 36 hours. Do not take more than one dose per day. Daily: Take 2.5–5 mg at the same time every day regardless of when you plan sexual activity. Full benefit develops over approximately 5 days. Do not split tablets.
Back Pain / Muscle Aches
Tell patientSome patients develop lower back pain or muscle aches 12–24 hours after taking tadalafil. This usually resolves within 48 hours and can be managed with over-the-counter pain relievers such as paracetamol or ibuprofen. Contact your doctor if the pain is severe or persistent.
Vision / Hearing / Erection Emergencies
Tell patientStop tadalafil and seek immediate medical attention if you experience: a sudden loss of vision in one or both eyes; a sudden decrease in hearing (with or without ringing/dizziness); or an erection lasting longer than 4 hours. These are medical emergencies requiring prompt treatment.
Alcohol
Tell patientConsuming large amounts of alcohol (5 or more drinks) with tadalafil can increase the chances of dizziness, headache, and rapid heartbeat due to additive blood pressure lowering. Moderate alcohol consumption is acceptable.
Sources
Regulatory (PI / SmPC)
- Cialis (tadalafil) tablets — Full Prescribing Information. Eli Lilly and Company. Revised February 2018. FDA LabelPrimary regulatory source: 3 indications (ED, BPH, ED+BPH), dosing Tables 1–4, renal/hepatic adjustments, CYP3A4 interaction data, alpha-blocker guidance, finasteride limitation.
- Cialis (tadalafil) tablets — FDA Label 2011 (BPH approval). FDA Label 2011Label revision adding BPH and ED+BPH indications; source for Table 4 (BPH adverse reactions) and alpha-blocker contraindication in BPH.
Key Clinical Trials
- Brock GB, McMahon CG, Chen KK, et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol. 2002;168(4 Pt 1):1332–1336. PubMed: 12352386Integrated analysis from 5 pivotal RCTs establishing PRN tadalafil efficacy across ED severities and aetiologies; 36-hour duration of action confirmed.
- Porst H, Roehrborn CG, Gratzke C, et al. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: analyses of pooled data from four randomized, placebo-controlled tadalafil clinical studies. J Sex Med. 2013;10(8):2044–2052. PubMed: 23782456Pooled analysis from 4 BPH trials demonstrating tadalafil 5 mg daily improves both LUTS-BPH and ED in men with both conditions.
- Oelke M, Giuliano F, Mirone V, et al. Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur Urol. 2012;61(5):917–925. PubMed: 22297243Head-to-head trial demonstrating tadalafil 5 mg non-inferior to tamsulosin for LUTS-BPH, supporting the BPH FDA indication.
- Glina S, Roehrborn CG, Engelen S, et al. Tadalafil 5 mg plus finasteride 5 mg versus finasteride 5 mg combination therapy for benign prostatic hyperplasia: a 26-week randomized double-blind study. J Urol. 2014;192(3):830–838. PubMed: 24704009The pivotal combination trial of tadalafil + finasteride showing early BPH symptom benefit that diminishes by 26 weeks; basis for the FDA limitation of use.
Guidelines
- Burnett AL, Nehra A, Breau RH, et al. Erectile dysfunction: AUA guideline. J Urol. 2018;200(3):633–641. PubMed: 29746858AUA guideline positioning PDE5 inhibitors as first-line for ED; recommends daily tadalafil for concurrent ED+BPH.
- Lerner LB, McVary KT, Barry MJ, et al. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline part 1 — initial work-up and medical management. J Urol. 2021;206(4):806–817. PubMed: 34384237AUA BPH guideline including tadalafil 5 mg daily as a medical management option for LUTS-BPH.
Pharmacokinetics
- Forgue ST, Patterson BE, Bedding AW, et al. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2006;61(3):280–288. PubMed: 16487221Definitive PK study: t½ 17.5 h (5th–95th: 11.5–29.6 h), CL/F 2.48 L/h, Vz/F 62.6 L, linear PK, no food effect, steady state by day 5, 1.6-fold accumulation.
- Tadalafil — StatPearls. National Center for Biotechnology Information. Updated March 2024. NCBI BookshelfComprehensive clinical review covering mechanism, pharmacokinetics (t½ 17.5 h, 94% protein-bound, 61% fecal/36% renal excretion), dosing, and adverse effects for all tadalafil indications.
Mechanistic / Selectivity
- Corbin JD, Francis SH. Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract. 2002;56(6):453–459. PubMed: 12166544PDE selectivity profile review: tadalafil >10,000-fold selective for PDE5 vs PDE1–4; 700-fold vs PDE6; explains low rate of visual side effects compared with sildenafil.
- Andersson KE, de Groat WC, McVary KT, et al. Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action. Neurourol Urodyn. 2011;30(2):292–301. PubMed: 21284020Discusses the pathophysiological rationale for PDE5 inhibition in BPH/LUTS: smooth muscle relaxation in prostate, bladder, and urethra; improved pelvic blood flow.