Dosing and uses of Adcirca, Cialis (tadalafil)
Adult dosage forms and strengths
tablet (Adcirca)
- 20mg
tablet (Cialis)
- 2.5mg
- 5mg
- 10mg
- 20mg
Erectile Dysfunction
Cialis
PRN use: 10 mg PO initially before sexual activity, with or without food; may be increased to 20 mg or reduced to 5 mg on basis of efficacy and tolerability; in most patients, maximum dosing frequency is once daily
Once-daily use: 2.5 mg/day PO in single daily dose, without regard to timing of sexual activity, with or without food; may be increased to 5 mg/day on basis of efficacy and tolerability
Dosing considerations
- PRN use: Decrease dose with concomitant use of potent CYP3A4 inhibitor (eg, ritonavir, ketoconazole, itraconazole); not to exceed 10 mg/72 hr
- Once-daily use: Decrease dose with concomitant use of potent CYP3A4 inhibitor (eg, ritonavir, ketoconazole, itraconazole); not to exceed 2.5 mg/day
Benign Prostatic Hyperplasia
Treatment of signs and symptoms of benign prostatic hyperplasia (BPH); daily use also indicated for treatment of patients with both BPH and erectile dysfunction
Cialis
BPH: 5 mg PO once daily
BPH with erectile dysfunction: 5 mg PO once daily, taken at approximately same time each day without regard to timing of sexual activity
With finasteride for BPH: tadalafil 5 mg plus finasteride 5 mg PO once daily for ≤26 weeks
Pulmonary Arterial Hypertension
Adcirca
40 mg PO once daily; dividing dose for more frequent dosing is not recommended
Patients also taking ritonavir: 20 mg PO once daily initially for ≥1 week; may be increased to 40 mg/day on basis of tolerability
Dosing considerations
- If possible, avoid coadministration with CYP3A4 inhibitors; if coadministration is essential, long-term therapy is indicated, or strong CYP3A4 inhibitors are required, modify or hold dose
- Patients already taking strong CYP3A4 inhibitor who require tadalafil: 20 mg PO once daily; may be increased to 40 mg/day on basis of tolerability
- Patients already taking tadalafil who require strong CYP3A4 inhibitor: Avoid using tadalafil while starting strong CYP3A4 inhibitor; stop tadalafil ≥24 hours before starting strong CYP3A4 inhibitor; after 1 week, resume tadalafil at 20 mg PO once daily; may be increased to 40 mg/day on basis of tolerability
Geriatric Dosing
Erectile Dysfunction
- Cialis
- No dosage adjustment is warranted solely on basis of age; however, greater sensitivity to medications in some older individuals should be considered
Pulmonary Arterial Hypertension
- Adcirca
- Lower dose or reduced dosing frequency may be required in elderly because of decreased renal or hepatic clearance
Dosing Modifications
Renal impairment (erectile dysfunction)
- Cialis (PRN use)
- Mild (CrCl ≥51 mL/min): No dosage adjustment needed
- Moderate (CrCl 30-50 mL/min): Not to exceed 5 mg PO once daily initially; maximum dosage, 10 mg PO q48hr
- Severe (CrCl <30 mL/min and on hemodialysis): Not to exceed 5 mg PO q72hr
- Cialis (once-daily use)
- CrCl ≥30 mL/min: No dosage adjustment needed
- CrCl <30 mL/min: Not recommended
Renal impairment (pulmonary arterial hypertension)
- Adcirca
- Mild-to-moderate (CrCl 31-80 mL/min): 20 mg PO once daily initially; may be increased to 40 mg once daily on basis of tolerability
- Severe (CrCl <30 mL/min and on hemodialysis): Avoid use
Hepatic impairment (erectile dysfunction)
- Cialis (PRN use)
- Mild-to-moderate (Child-Pugh class A or B): Not to exceed 10 mg PO once daily
- Severe (Child-Pugh class C): Not recommended
- Cialis (once-daily use)
- Mild-to-moderate (Child-Pugh class A or B): Data limited; caution advised
- Severe (Child-Pugh class C): Not recommended
Hepatic impairment (pulmonary arterial hypertension)
- Adcirca
- Mild-to-moderate (Child-Pugh class A or B): Consider starting dosage of 20 mg PO once daily
- Severe (Child-Pugh class C): Avoid use
Muscular Dystrophy (Orphan)
Orphan designation for Duchenne muscular dystrophy (DMD)
Sponsor
- Eli Lilly and Company; Lilly Corporate Center; Indianapolis, IN 46285
Pediatric dosage forms and strengths
Use not indicated
Safety and efficacy in pediatric patients not established
Adcirca, Cialis (tadalafil) adverse (side) effects
>10%
Headache (11-42%)
Myalgia (1-14%)
Respiratory tract infection (3-13%)
Nasopharyngitis (2-13%)
Dyspepsia (1-13%)
Flushing (1-13%)
Back pain (2-12%)
Nausea (10-11%)
1-10%
Nasal congestion (≤9%)
Gastroesophageal reflux disease (1-3%)
Hypertension (1-3%)
Bronchitis (≤2%)
Genitourinary tract infection (≤2%)
<1%
Amnesia
Angina pectoris
Arthralgia
Change in color vision
Conjunctival hyperemia
Dyspnea
Epistaxis
Postmarketing reports
Hypotension
Visual Loss
Hearing loss
Priapism
Warnings
Contraindications
Hypersensitivity, including Stevens-Johnson syndrome and exfoliative dermatitis
Soluble guanylate cyclase (sGC) stimulators (eg, riociguat); concomitant use can cause hypotension
Coadministration with nitrates
- Coadministration with nitrates (either regularly and/or intermittently) and nitric oxide donors
- Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors may potentiate the hypotensive effects of nitrates
- A suitable time interval following PDE5 dosing for the safe administration of nitrates or nitric oxide donors has not been determined
Cautions
Use caution in patients with anatomic deformation of penis, cardiovascular disease, left ventricular outflow obstruction, myocardial infarction in preceding 90 days, unstable angina, angina occurring during sexual intercourse, NYHA class 2 or greater heart failure in preceding 6 months, uncontrolled arrhythmias, hypotension, uncontrolled hypertension, cerebrovascular accident in preceding 6 months, bleeding disorders, active peptic ulcer disease, liver disease, renal impairment, conditions predisposing to priapism, concomitant use of CYP3A4 inhibitors
May cause dose-related impairment of color discrimination; use caution in patients with retinitis pigmentosa
Evaluate underlying causes of erectile dysfunction or BPH before initiating therapy
May increase risk of sudden vision loss attributed to nonarteritic ischemic optic neuropathy; if vision problems arise, discontinue, and contact physician
Risk of sudden hearing loss
CYP3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, indinavir, ritonavir) may significantly increase tadalafil serum levels
CYP3A4 inducers (eg, rifampin, St John’s wort) may decrease tadalafil serum levels
Potentiates hypotensive effect of nitrates (see Contraindications)
Concomitant use with alpha blockers (other than tamsulosin 0.4 mg/day) should be stabilized before initiation of phosphodiesterase (PDE)-5 inhibitors; patients with instability on alpha-blocker therapy alone are at increased risk for symptomatic hypotension with concurrent PDE-5 inhibitor therapy
Not to be taken with other PDE-5 inhibitors (eg, sildenafil, vardenafil)
Not recommended in patients with pulmonary veno-occlusive disease
Advise patients to seek emergency treatment if an erection lasts >4 hr
Pregnancy and lactation
Pregnancy category: B
Lactation: Use not recommended in nursing women
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Adcirca, Cialis (tadalafil)
Mechanism of action
Erectile dysfunction: Inhibits PDE-5, increasing cyclic guanosine monophosphate (cGMP) to allow smooth-muscle relaxation and inflow of blood into corpus cavernosum
Pulmonary arterial hypertension (PAH): Inhibits PDE-5, increasing cGMP to allow relaxation of pulmonary vascular smooth-muscle cells and vasodilation of pulmonary vasculature
Absorption
Duration: ≤36 hr
Peak plasma time: Erectile dysfunction, 0.5-6 hr; PAH, 2-8 hr
Distribution
Protein bound: 94%
Vd: Erectile dysfunction, 63 L; PAH, 77 L
Metabolism
Metabolized in liver by CYP3A4
Elimination
Half-life: Erectile dysfunction, 15-17.5 hr; PAH (not on bosentan), 35 hr
Total body clearance: Erectile dysfunction, 2.5 L/hr; PAH (not on bosentan), 1.6 L/hr
Excretion: Feces (61%), urine (36%)
Administration
Instructions
Erectile dysfunction (PRN use): Take before anticipated sexual activity
Erectile dysfunction (once-daily use): Take at approximately same time each day without regard to timing of sexual activity
