Safety Profile

CIALIS has been administered to over 6550 men in worldwide clinical trials. In trials of CIALIS for once daily use, a total of 716, 389, and 115 were treated for at least 6 months, 1 year, and 2 years, respectively. For CIALIS for use as needed, over 1300 and 1000 subjects were treated for at least 6 months and 1 year, respectively.

• CIALIS was generally well tolerated in clinical trials
• Cardiovascular safety
• Important Safety Information for CIALIS

CIALIS was generally well tolerated in clinical trials*

Discontinuation rate due to adverse events for patients taking CIALIS as needed was 3.1% (placebo: 1.4%)1

Discontinuation rate due to adverse events for patients taking CIALIS once daily was 4.1% (placebo: 2.8%)1

Not studied in head-to-head trials.

Cardiovascular safety
Pooled results from 36 controlled and open-label clinical trials are presented in the table below. Doses of CIALIS ranged from 2 mg to 50 mg, with most patients receiving 20 mg. Patients were excluded from trials if they had an underlying cardiovascular disorder sufficiently severe or unstable to make sexual intercourse inadvisable.²

• CIALIS taken as needed n=12,978; CIALIS taken once daily n=1077²
• The incidence of serious cardiovascular treatment-emergent adverse events with CIALIS taken once daily was comparable to placebo^§2
• One patient with comorbid hypertension and hyperlipidemia who received CIALIS 2.5 mg for once daily use had a nonfatal MI³

Indication
CIALIS^® (tadalafil) is indicated for the treatment of erectile dysfunction.

Important Safety Information for CIALIS

• CIALIS for use as needed. Starting dose: 10 mg up to once daily. Increase to 20 mg or decrease to 5 mg based upon efficacy/tolerability. Improves erectile function compared to placebo up to 36 hours post dose
• CIALIS for once daily use. Starting dose: 2.5 mg taken once daily, without regard to timing of sexual activity. May increase to 5 mg based upon efficacy and tolerability
• Renal Insufficiency:
  • Moderate: For use as needed: Dosage adjustment may be needed. For once daily use: No dose adjustment is needed
  • Severe: For use as needed: Dose should not exceed 5 mg every 72 hours. Once daily use is not recommended
• Hepatic Impairment:
  • Mild or Moderate: Dosage adjustment may be needed
  • Severe: Use is not recommended
• Concomitant use of potent inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, itraconazole): limited to CIALIS 10 mg for use as needed once every 72 hours. Dosing should not exceed 2.5 mg for CIALIS for once daily use
• When CIALIS is co-administered with an alpha blocker, patients should be stable on alpha-blocker therapy prior to initiating treatment with CIALIS, and CIALIS should be initiated at the lowest recommended dose

Contraindications

Nitrates: CIALIS should not be used in patients using any form of organic nitrate, either regularly and/or intermittently, as the combination could cause a sudden, unsafe drop in blood pressure.

Hypersensitivity reactions: CIALIS is contraindicated in patients with a known serious hypersensitivity to CIALIS or ADCIRCA^™ (tadalafil). Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis.

Warnings and Precautions

Cardiovascular: Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Treatments for erectile dysfunction, including CIALIS, should not be used in men for whom sexual activity is inadvisable as a result of their underlying cardiovascular status. Patients who experience symptoms upon initiation of sexual activity should be advised to refrain from further sexual activity and seek immediate medical attention. PDE5 inhibitors, including CIALIS, are mild systemic vasodilators. While this effect should not be of consequence in most patients, physicians should consider this potential when prescribing CIALIS.

Patients with left ventricular outflow obstruction (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators, including PDE5 inhibitors.

CIALIS was not studied and is not recommended in patients who have recently suffered a heart attack (within 90 days) or stroke (within 6 months), or patients with uncontrolled hypertension, hypotension, uncontrolled arrhythmias, heart failure (NYHA ≥ Class 2 in last 6 months), unstable angina or angina occurring during sexual activity.

Potential Drug Interactions: Due to potential increased blood-pressure-lowering effects, caution is advised when CIALIS is co-administered with alpha blockers, antihypertensives, and/or substantial consumption of alcohol (5 units or greater). CIALIS for once daily use provides continuous plasma tadalafil levels. Physicians should consider this when evaluating the potential for interactions.

Combination with other PDE5 inhibitors: CIALIS is also marketed as ADCIRCA for the treatment of pulmonary arterial hypertension. Do not take both CIALIS and ADCIRCA or other PDE5 inhibitors.

Potent inhibitors of CYP3A4: For patients taking potent inhibitors of CYP3A4, dose should be adjusted: CIALIS for use as needed: ≤10mg every 72 hours. CIALIS for once daily use: dose not to exceed 2.5 mg.

Special Populations: For patients with severe hepatic impairment use of CIALIS is not recommended. For patient with severe renal impairment CIALIS for daily use is not recommended. Additional dose adjustments may be required for mild and moderate renal and hepatic impairment or with other concomitant medications. See Dosing Guidelines and full Prescribing Information for complete dosing instructions.

Prolonged Erection: There have been rare reports of priapism with this class of compounds. Patients should be advised to seek immediate medical attention should this occur. Use CIALIS with caution in patients who have conditions that might predispose them to priapism.

Vision/Hearing: The following events have been reported in men taking PDE5 inhibitors including CIALIS: (1) sudden decrease or loss of vision in one or both eyes; (2) sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness. It is not possible to determine whether these events are related directly to the medicines, other health conditions, or to a combination of these. If a patient experiences a sudden decrease or loss in vision or hearing he should stop taking CIALIS, and call a healthcare provider right away.

Adverse Reactions

Most common adverse reactions (≥2%) include headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and pain in limb.

For more complete information see Important Safety Information and full Prescribing Information.

1. *Safety profile demonstrated in more than 6550 subjects in worldwide trials.
2. †Treatment-emergent adverse events reported by >2% of patients treated with CIALIS (20 mg) and more frequent on drug than placebo in 8 primary, placebo-controlled, Phase 3 studies (including a study in patients with diabetes).
3. ‡Treatment-emergent adverse events reported by >2% of patients treated with CIALIS (2.5 and 5 mg) and more frequent on drug than placebo in the primary, placebo-controlled, Phase 3 studies (including a study in patients with diabetes) for CIALIS for once daily use.
4. §Serious CVTEAEs included MI, cardiovascular death, and cerebrovascular death (no cerebrovascular deaths occurred).

1. Cialis [package insert]. Indianapolis, Ind: Eli Lilly and Company; 2008.
2. Kloner RA, Jackson G, Hutter AM, et al. Cardiovascular safety update of tadalafil: retrospective analysis of data from placebo-controlled and open-label clinical trials of tadalafil with as needed, three times-per-week or once-a-day dosing. Am J Cardiol. 2006;97:1778-1784.
3. Rajfer J, Aliotta PJ, Steidle CP, et al. Tadalafil dosed once a day in men with erectile dysfunction: a randomized, double-blind, placebo-controlled study in the US. Int J Impot Res. 2007;19:95-103.