Tadalafil


Generic Medicine Info
Indications and Dosage
Oral
Erectile dysfunction
Adult: As needed dosing: Initially, 10 mg as a single dose, taken at least 30 minutes before sexual activity; may be increased to 20 mg, or decreased to 5 mg depending on patient response and tolerability. Max dosing frequency: Once daily. In patients anticipating frequent use (e.g. at least twice weekly), a regular once-daily regimen with the lowest dose may be considered suitable. Regular daily dosing: 5 mg once daily, taken at the same time each day; may be decreased to 2.5 mg once daily depending on patient response and tolerability. Alternatively, start with 2.5 mg once daily, taken at the same time each day; may be increased to 5 mg once daily according to efficacy and tolerability. Periodically reassess the appropriateness of continued use of the daily regimen. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Oral
Benign prostatic hyperplasia
Adult: 5 mg once daily, taken at the same time each day. For men being treated for both benign prostatic hyperplasia (BPH) and erectile dysfunction (ED): 5 mg once daily, taken at the same time each day; without regard to the timing of sexual activity.

Oral
Pulmonary arterial hypertension
Adult: To improve exercise ability: 40 mg once daily.
Special Patient Group
Erectile dysfunction:
Patients taking potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir): For as-needed dosing: Max: 10 mg once every 72 hours. For regular daily dosing: Max: 2.5 mg once daily.

Patients taking α-blockers: Initiate at the lowest recommended dose. Patient must be stable on α-blocker therapy before starting treatment.

Benign prostatic hyperplasia (with or without concomitant erectile dysfunction):
Patients taking potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir): Max: 2.5 mg once daily.

Pulmonary arterial hypertension:
Patients taking ritonavir for at least 1 week: Initially, 20 mg once daily, increased to 40 mg once daily as tolerated.

For concurrent use of ritonavir in patients taking tadalafil: Avoid use during ritonavir initiation; stop tadalafil treatment at least 24 hours before starting ritonavir. After at least 1 week of starting ritonavir, resume tadalafil at 20 mg once daily, increased to 20 mg once daily as tolerated.
Renal Impairment
Erectile dysfunction:
Patient on haemodialysis: As needed dosing: Max: 5 mg once every 72 hours. Regular daily dosing: Not recommended.

CrCl (mL/min) Dosage
<30 As needed dosing: Max: 5 mg once every 72 hours. Regular daily dosing: Not recommended.
30-50 As needed dosing: Initially, 5 mg once daily. Max: 10 mg once every 48 hours.

Benign prostatic hyperplasia:
Patient on haemodialysis: Not recommended.

CrCl (mL/min) Dosage
<30 Not recommended.
30-50 For cases with or without concomitant erectile dysfunction: Initially, 2.5 mg once daily, may be increased up to Max 5 mg once daily if needed according to patient response.

Pulmonary arterial hypertension:
Patient on haemodialysis: Avoid.

CrCl (mL/min) Dosage
<30 Avoid.
31-80 Initially, 20 mg once daily, may be increased to 40 mg once daily according to patient tolerability.
Hepatic Impairment
Erectile dysfunction:
Mild to moderate (Child-Pugh class A or B): As needed dosing: Max: 10 mg taken before sexual activity, once daily. Severe (Child-Pugh class C): Not recommended.

Benign prostatic hyperplasia:
Severe (Child-Pugh class C): Not recommended.

Pulmonary arterial hypertension:
Mild to moderate (Child-Pugh class A or B): Initially, 20 mg once daily. Severe (Child-Pugh class C): Not recommended.
Administration
May be taken with or without food.
Contraindications
MI within the last 90 days, hypotension (<90/50 mmHg); vision loss in 1 eye due to non-arteritic anterior ischaemic optic neuropathy (NAION). When used for ED or BPH: Cardiac disease wherein sexual activity is inadvisable; unstable angina or angina during sexual activity, NYHA class ≥II heart failure in the last 6 months; uncontrolled arrhythmias, uncontrolled hypertension, stroke within the last 6 months. Concurrent use with any form of organic nitrate (regularly or intermittently), and guanylate cyclase stimulators (e.g. riociguat).
Special Precautions
Patient with pre-existing CV disease or risk factors, left ventricular outflow obstruction (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy); anatomical penis deformation (e.g. angulation, cavernosal fibrosis, Peyronie’s disease); conditions which may be predisposed to priapism (e.g. sickle cell anaemia, multiple myeloma, leukaemia); risk factors of NAION (e.g. history of NAION, low cup-to-disc ratio [“crowded disc”], coronary artery disease, diabetes, hypertension, hyperlipidaemia, smoking, >50 years); peptic ulcer disease, bleeding disorders. Not recommended in patients with hereditary degenerative retinal disorders, including retinitis pigmentosa. When used for pulmonary arterial hypertension (PAH): Not recommended in patients with pulmonary veno-occlusive disease (PVOD), significant aortic or mitral valve disease, life-threatening arrhythmias, restrictive or congestive cardiomyopathy, coronary artery disease, significant left ventricular dysfunction, and pericardial constriction. Not indicated for use in women (when used for ED and BPH). Therapy in patients with severe renal impairment (CrCl <30 mL/min), including haemodialysis is avoided when used for PAH, and not recommended for BPH and ED (regular daily dosing). Not recommended in patients with severe hepatic impairment (Child-Pugh class C). Patients taking potent CYP3A4 inhibitors, or α-blockers (when used for ED). Concomitant use with α-blockers is not recommended when used for BPH. Renal and mild to moderate hepatic impairment. Pregnancy and lactation (when used for PAH).
Adverse Reactions
Significant: Anginal chest pain, palpitations, tachycardia; impairment of colour discrimination (dose-related), hypotension; may worsen CV status of patients with PVOD. Rarely, sudden hearing loss (may be accompanied by dizziness and tinnitus), priapism or prolonged erections (>4 hours), sudden vision loss or NAION.
Eye disorders: Blurred vision.
General disorders and administration site conditions: Facial oedema.
Gastrointestinal disorders: Dyspepsia, nausea, vomiting, abdominal pain, GERD.
Immune system disorders: Hypersensitivity reactions.
Musculoskeletal and connective tissue disorders: Back pain, pain in extremity, myalgia.
Nervous system disorders: Headache, migraine, syncope.
Reproductive system and breast disorders: Increased uterine bleeding.
Respiratory, thoracic and mediastinal disorders: Nasal congestion, epistaxis, dyspnoea, nasopharyngitis, respiratory tract infection.
Skin and subcutaneous tissue disorders: Rash, exfoliative dermatitis, Stevens-Johnson syndrome.
Vascular disorders: Flushing.
Potentially Fatal: Serious CV events (e.g. MI, stroke, TIA, sudden cardiac death, ventricular arrhythmia, unstable angina pectoris).
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Evaluate CV status of the patient, and possible underlying causes of ED or BPH (to rule out the presence of prostate cancer) before starting therapy. Monitor blood pressure, urine flow, prostate-specific antigen; signs of postural hypotension.
Drug Interactions
May enhance the hypotensive effects of α-blockers and other antihypertensive drugs. Increased serum concentration with potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, ritonavir, saquinavir, erythromycin, clarithromycin). Decreased plasma concentration with CYP3A4 inducers (e.g. rifampicin, phenobarbital, phenytoin, carbamazepine). May cause a slight increase in heart rate with theophylline. May increase the oral bioavailability of ethinylestradiol and terbutaline. Bosentan may reduce serum levels of tadalafil.
Potentially Fatal: Enhanced hypotensive effects of organic nitrates (any form), and guanylate cyclase stimulators (e.g. riociguat).
Food Interaction
May increase serum concentration with grapefruit juice. May increase the risk of orthostatic hypotension with alcohol.
Action
Description: Tadalafil is a potent and selective inhibitor of phosphodiesterase type-5 (PDE-5), the enzyme responsible for the metabolism of cyclic guanosine monophosphate (cGMP). For ED, sexual stimulation causes the local release of nitric oxide in the corpus cavernosum then PDE-5 inhibition leads to increased cGMP levels. This effect causes smooth muscle relaxation and increased blood flow into the corpus cavernosum of the penile tissues, thereby producing an erection. For BPH, effects of PDE-5 inhibition results in decreased bladder nerve activity, and increased smooth muscle relaxation and blood perfusion of the bladder and prostate. For PAH, PDE-5 inhibition elevates cGMP concentrations leading to relaxation of pulmonary smooth muscle and vasodilation of the pulmonary vascular bed.
Onset: Within 1 hour.
Duration: Erectile dysfunction: Up to 36 hours.
Pharmacokinetics:
Absorption: Readily absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 2 hours (range: 0.5-6 hours).
Distribution: Widely distributed in the tissues. Detected in semen (small amounts). Volume of distribution: 63-77 L. Plasma protein binding: Approx 94%.
Metabolism: Metabolised in the liver primarily by CYP3A4 isoenzyme into methylcatechol glucuronide (major inactive metabolite).
Excretion: Via faeces (approx 61%, mainly as metabolites); urine (approx 36%, primarily as metabolites). Elimination half-life: 15-17.5 hours.
Chemical Structure

Chemical Structure Image
Tadalafil

Source: National Center for Biotechnology Information. PubChem Database. Tadalafil, CID=110635, https://pubchem.ncbi.nlm.nih.gov/compound/Tadalafil (accessed on Jan. 23, 2020)

Storage
Store between 15-30°C. Protect from moisture.
MIMS Class
Drugs for Bladder & Prostate Disorders / Drugs for Erectile Dysfunction & Ejaculatory Disorders / Other Antihypertensives
ATC Classification
G04BE08 - tadalafil ; Belongs to the class of drugs used in erectile dysfunction.
References
Adcirca 20 mg Film-Coated Tablets (Eli Lilly Nederland B.V.). European Medicines Agency [online]. Accessed 20/04/2021.

Adcirca Tablet (United Therapeutics Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/03/2021.

Anon. Tadalafil. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 03/03/2021.

Anon. Tadalafil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/03/2021.

Buckingham R (ed). Tadalafil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/03/2021.

Caliberi Orodispersible Film 5 mg and 20 mg (Abbott Laboratories [Singapore] Pte. Ltd.). MIMS Singapore. http://www.mims.com/singapore. Accessed 20/04/2021.

Cialis 5 mg Film-Coated Tablets (Zuellig Pharma Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/03/2021.

Cialis Tablet, Film Coated (Eli Lilly and Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 20/04/2021.

Eli Lilly and Company (NZ) Limited. Cialis 2.5 mg, 5 mg, 10 mg, 20 mg Film-Coated Tablets data sheet 18 March 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 01/03/2021.

Joint Formulary Committee. Tadalafil. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/03/2021.

Tadalafil 5 mg Film-Coated Tablets (Aspire Pharma Ltd). MHRA. https://products.mhra.gov.uk. Accessed 01/03/2021.

Disclaimer: This information is independently developed by MIMS based on Tadalafil from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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