Cialis, Adcirca (Tadalafil) - Complete Drug Information

Cialis and adcirca are brand names of the drug tadalafil among others. Tadalafil is a phosphodiesterase inhibitor that causes smooth muscle relaxation. It increases the blood flow to the penis resulting in an erection. It also increases the blood supply to the lungs reducing pulmonary vascular pressures.

Other phosphodiesterase inhibitors include Vardenafil (Levitra) and sildenafil (Viagra)

It is used to treat the following conditions:

Benign prostatic hyperplasia (Cialis only):
- It is used in the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).
Erectile dysfunction (Cialis only):
- It is used in the treatment of erectile dysfunction.
Erectile dysfunction and benign prostatic hyperplasia (Cialis only):
- It is used in the treatment of erectile dysfunction and the signs and symptoms of BPH.
Pulmonary arterial hypertension (Adcirca only):
- It is used in the treatment of pulmonary arterial hypertension (World Health Organization group 1) to improve exercise ability.
Off Label Use of Tadalafil in Adults:
- It is used in Raynaud Phenomenon

Tadalafil (Cialis, adcirca) Dose in Adults

Dose in the treatment of Benign prostatic hyperplasia (with or without concomitant erectile dysfunction) (Cialis):

5 mg orally once daily given.

Dosing adjustment with concomitant medications:
- Alpha-blockers:
  - It is Not recommended for use in combination with alpha-blockers for the treatment of BPH.
- CYP3A4 inhibitors (strong):
  - 2.5 mg once daily given
  - the maximum dose is 2.5 mg once daily

Dose in the treatment of Erectile dysfunction (Cialis):

As-needed dosing:
- 10 mg at least 30 minutes before anticipated sexual activity as one single dose and not more than once daily.
- The dose may be adjusted based on tolerability
- dosing range is 5 to 20 mg

Once-daily dosing:
- 5 mg once daily given at approximately the same time daily without regard to timing of sexual activity.
- The dose may be adjusted based on tolerability
- the dosage range is 2.5 to 5 mg/day.
Dosing adjustment with concomitant medications: Oral:
- Alpha-blockers:
  - Patients should be stable on alpha-blocker therapy before initiating tadalafil treatment, and tadalafil should be initiated at the lowest recommended dose.
- CYP3A4 inhibitors (strong):
  - As-needed dosing:
  - The maximum dose is 10 mg, not more frequently than every 72 hours
  - Once-daily dosing is Maximum: 2.5 mg once daily

Dose in the treatment of Pulmonary arterial hypertension (Adcirca):

Oral: 40 mg once daily given
Dosing adjustment with concomitant medications:
- Concurrent use with ritonavir:
  - Initiation of tadalafil in patients currently receiving ritonavir for at least 7 days:
  - Initiate tadalafil at 20 mg once daily
  - Then increase the dose to 40 mg once a day if it is tolerated.
- Initiation of ritonavir in patients currently receiving tadalafil:
  - Stop tadalafil at least 24 hours prior to the initiation of ritonavir.
  - After at least 1 week of ritonavir, resume tadalafil at 20 mg once daily
  - Then increase the dose to 40 mg once a day if it is tolerated.

Dose in the treatment of Raynaud phenomenon (off-label):

20 mg orally given every other day.

Tadalafil (Cialis, adcirca) Dose in Childrens

Not recommended for use in chiildren

Pregnancy Risk Factor B

Tadalafil can likely cross the placenta
Avoid pregnancy for women with pulmonary arterial hypertension.

Tadalafil use during breastfeeding:

It is unknown if breast milk contains tadalafil.
Manufacturer advises that pregnant women should exercise caution when administering tadalafil.

Tadalafil (Cialis, adcirca) Dose in Renal Disease:

Benign prostatic hyperplasia (with or without concomitant erectile dysfunction) (Cialis):

CrCl ≥51 mL/minute:
- No dosage adjustment required.
CrCl 30 to 50 mL/minute:
- Initial: 2.5 mg once daily given & maximum dose is 5 mg once daily.
CrCl <30 mL/minute:
- Use not advised.
ESRD requiring hemodialysis:
- Use not advised.

Erectile dysfunction (Cialis):

As-needed use:
- CrCl ≥51 mL/minute:
  - No dosage adjustment required.
- CrCl 30 to 50 mL/minute:
  - Initial: 5 mg once daily given & maximum dose of 10 mg (not more frequently than every 48 hours).
- CrCl <30 mL/minute:
  - The maximum dose is 5 mg (not more frequently than every 72 hours).
- ESRD requiring hemodialysis:
  - The maximum dose is 5 mg (not more frequently than every 72 hours).
Once-daily use:
- CrCl ≥31 mL/minute:
  - No dosage adjustment required.
- CrCl <30 mL/minute:
  - Use not advised.
- ESRD requiring hemodialysis:
  - Use not advised.

Pulmonary arterial hypertension (Adcirca):

CrCl 31 to 80 mL/minute: Initial:
- 20 mg once daily given
- increase to 40 mg once daily based on individual tolerability.
CrCl ≤30 mL/minute:
- Avoid use due to increased tadalafil exposure
ESRD requiring hemodialysis:
- Avoid use due to increased tadalafil exposure, limited clinical experience, and lack of ability to influence clearance by dialysis.

Tadalafil (Cialis, adcirca) Dose in Liver Disease:

Benign prostatic hyperplasia (with or without concomitant erectile dysfunction) (Cialis):

Mild to moderate hepatic impairment (Child-Pugh class A or B):
- Use with caution
Severe hepatic impairment (Child-Pugh class C):
- Use is not advised.

Erectile dysfunction (Cialis):

As-needed use:
- Mild to moderate impairment (Child-Pugh class A or B):
  - Use with caution
  - The dose should not exceed 10 mg once daily.
- Severe impairment (Child-Pugh class C):
  - Use is not advised.
Once-daily use:
- Mild to moderate impairment (Child-Pugh class A or B):
  - Use with caution
- Severe impairment (Child-Pugh class C):
  - Use is not advised.

Pulmonary arterial hypertension (Adcirca):

Mild to moderate hepatic impairment (Child-Pugh class A or B):
- Use with caution
- consider an initial dose of 20 mg once daily.
Severe hepatic impairment (Child-Pugh class C):
- Avoid use

Common Side Effects of Tadalafil (Cialis, adcirca) Include:

Cardiovascular:
- Flushing
Central Nervous System:
- Headache
Gastrointestinal:
- Nausea
Neuromuscular & Skeletal:
- Myalgia
- Limb Pain
Respiratory:
- Respiratory Tract Infection
- Nasopharyngitis

Less Common Side Effects of Tadalafil (Cialis) Include:

Cardiovascular:
- Hypertension
- Angina Pectoris
- Chest Pain
- Facial Edema
- Hypotension
- Myocardial Infarction
- Orthostatic Hypotension
- Palpitations
- Peripheral Edema
- Syncope
- Tachycardia
Central Nervous System:
- Dizziness
- Drowsiness
- Fatigue
- Hypoesthesia
- Insomnia
- Pain
- Paresthesia
- Vertigo
Dermatologic:
- Diaphoresis
- Pruritus
- Skin Rash
Endocrine & Metabolic:
- Increased Gamma-Glutamyl Transferase
Gastrointestinal:
- Dyspepsia
- Gastroenteritis
- Gastroesophageal Reflux Disease
- Diarrhea
- Abdominal Pain
- Dysphagia
- Esophagitis
- Gastritis
- Hemorrhoidal Bleeding
- Loose Stools
- Upper Abdominal Pain
- Vomiting
- Xerostomia
Genitourinary:
- Urinary Tract Infection
- Prolonged Erection
- Spontaneous Erections
Hematologic & Oncologic:
- Rectal Hemorrhage
Hepatic:
- Abnormal Hepatic Function Tests
Neuromuscular & Skeletal:
- Back Pain
- Arthralgia
- Asthenia
- Neck Pain
Ophthalmic:
- Blurred Vision
- Conjunctival Hyperemia
- Conjunctivitis
- Eyelid Edema
- Eye Pain
- Increased Lacrimation
- Vision Color Changes
Otic:
- Hearing Loss
- Tinnitus
Renal:
- Renal Insufficiency
Respiratory:
- Nasal Congestion
- Paranasal Sinus Congestion
- Upper Respiratory Tract Infection
- Cough
- Dyspnea
- Epistaxis
- Pharyngitis

Contraindication to (Cialis, Adcirca) Tadalafil Include:

Severe hypersensitivity to tadalafil and any part of its formulation
Concurrent use of riociguat, a guanylate-cyclase stimulator, or organic nitrate (regularly or intermittently).
An anterior episode of non-arteritic optic neuropathy.

Warnings and precautions

Angina chest pain
- Patients with anginal chest pain following tadalafil administration need immediate medical attention.
Color discrimination:
- Can cause color discrimination impairment due to dose.
- Patients with retinitis pigmentosa should be cautious. A minority of patients have retinal phosphodiesterases genetic disorders (no safety information).
Hearing loss:
- Rarely is sudden loss or decrease in hearing.
- Hearing changes can be accompanied with tinnitus or dizziness.
- For sudden hearing loss or a decrease in hearing, instruct patients to seek medical attention.
Hypotension
- Vasodilator effects can cause blood pressure to drop.
- Patients with left ventricular obstruction (aortic Steen or hypertrophic-obstructive cardiomyopathy), should be used with caution
- Hypotensive actions can make you more sensitive.
- Hypotension can be caused by concurrent use of alpha-adrenergic antagonist treatment.
- Patients should limit or avoid concurrent large amounts of ethanol as it may increase the risk for symptomatic hypotension.
Priapism
- A painful erection lasting more than 6 hours has been observed
- For an erection that lasts more than four hours, inform the patient to seek medical attention.
- Patients with pre-existing conditions such as multiple myeloma, sickle cell, or leukemia should be cautious.
Vision loss:
- Vision loss (rarely) is a sign that there is non-arteritic anterior Ischemia optic Neuropathy (NAION); it is not known if there is any causal relationship with PDE5 inhibitors.
- For sudden vision loss in one or both eyes, instruct patients to discontinue therapy and seek medical help.
- Patients who have had NAION before are at a higher risk of experiencing recurrence.
- Another risk factor for NAION is a low cup to-disc ratio ("crowded disk"), CAD and diabetes.
- These patients should be treated with caution and only if the benefits are greater than the risks.
- Patients with known hereditary retinal disorders (eg, Retinitis Pigmentosa) have not been evaluated for safety and therefore it is not recommended to use this medication.
Anatomical penis deformation:
- Patients with anatomical deformations of the penis (angulation or cavernosal fissis) should be avoided.
Bleeding disorders:
- Patients with bleeding disorders should be cautious; safety and effectiveness have not been established.
- Studies in vitro have shown a decrease in platelet aggregation.
Cardiovascular disease
- Patients with hypotension (>90/50mm Hg), uncontrolled hypertension (170/100mm Hg), NYHA Class II-IV Heart Failure within the past 6 months, NYHA class I-IV heart failure within 3 months, MI within three months, and unstable angina (or angina during sexual intercourse) are not recommended. Safety and efficacy of these patients have not been evaluated.
- Patients with left ventricular obstruction (eg, hypertrophic-obstructive cardiomyopathy, aorticstensis) should be cautious. They may be more sensitive than others to vasodilator effect.
- Sexual activity can pose a slight risk to the heart. Therefore, doctors may want to assess their cardiovascular health before prescribing any treatment for erectile dysfunction.
Hepatic impairment
- Use cautiously in patients with mild to moderate hepatic impairment; dosage adjustment/limitation is needed.
- Patients with severe cirrhosis or hepatic impairment should not use this medication.
Peptic ulcer disease:
- Patients with active peptic ulcer diseases should be cautious because of the potential effect on platelets (bleeding).
Pulmonary Venoocclusive Disease (PVOD),
- Patients with PVOD may experience an increase in cardiovascular disease if they take pulmonary vasodilators.
- It is not recommended to use
Renal impairment
- Use cautiously in patients with renal impairment; dosage adjustment/limitation is needed

Monitor:

Blood pressure response and adverse effects
urine flow
PSA

How to administer Tadalafil (Cialis, adcirca)?

It may be administered orally with or without food.

Adcirca:

Give daily dose all at once
dividing doses throughout the day is not advised.

Cialis:

Do not split tablets
the entire dose should be taken.
When used on an as-needed basis, it should be taken at least 30 minutes before sexual activity.
When used on a once-daily basis, should be taken at the same time each day, without regard to timing of sexual activity.

Mechanism of action of Cialis (Tadalafil):

BPH (benign prostate hypertrophy):

Unknown exact mechanism
PDE-5 may have caused a decrease in smooth muscle and endothelial cells proliferation, decreased nerve activity and increased smooth muscles relaxation.

Erectile dysfunction:

Although it does not cause penile erections, it affects sexual stimulation.
The physiological mechanism for the erection and stimulation of the penis is the release of nitric dioxide (NO) from the corpus cavernosum. The enzyme guanylate-cyclase is activated by NO.
It promotes smooth muscle relaxation and blood flow to the corpus cavernosum through the increase in cyclic Guanosine monophosphate.
Tadalafil increases the NO effect by inhibiting phosphodiesterase 5 (PDE-5), responsible for the degradation of cGMP within the corpus cavernosum.
When sexual stimulation results in local release of Nitric Ox, inhibition of PDE-5 with tadalafil causes higher levels of cGMP within the corpus Cavernosum. This causes smooth muscle relaxation and blood flow to the corpus Cavernosum.
It does not cause erection if there is no sexual stimulation.

Hypertension in the pulmonary arterial system:

It inhibits phosphodiesterase 5 (PDE-5) in the smooth muscles of the pulmonary vasculature, where PDE-5 is responsible to the degradation of cyclic Guanosine monophosphate.
An increase in cGMP levels results in relaxation of the pulmonary vasculature
It causes vasodilation of the pulmonary bed and a lesser extent in the systemic circulation.

The onset of action: