Triptimate

Approved Indications:

• Erectile Dysfunction (ED): For the treatment of erectile dysfunction in adult males.
• Benign Prostatic Hyperplasia (BPH): For the signs and symptoms of BPH in adult males, including urinary urgency, frequency, and hesitancy.
• ED with BPH: Indicated for patients who have both ED and BPH as a once-daily treatment.
• Pulmonary Arterial Hypertension (PAH): To improve exercise capacity in adults with PAH (WHO Group 1).

Clinically Accepted Off-Label Uses:

• Raynaud’s Phenomenon: May be used in select patients to reduce frequency and severity of vasospastic attacks.
• Female Sexual Arousal Disorder (experimental): Under limited investigation for improving genital blood flow.

For Erectile Dysfunction:

• As Needed: 10 mg orally before anticipated sexual activity; may be increased to 20 mg or decreased to 5 mg based on efficacy/tolerance. Maximum once per day.
• Once-Daily Dosing: 2.5 mg to 5 mg orally once daily, taken at the same time each day, regardless of sexual activity.

For Benign Prostatic Hyperplasia (with or without ED):

• 5 mg orally once daily.

For Pulmonary Arterial Hypertension:

• 40 mg orally once daily, taken with or without food (administered as two 20 mg tablets).

Pediatric Use:

• Not approved for use in pediatric populations.

Geriatric Use:

• No dose adjustment necessary solely based on age; consider renal and hepatic function.

Renal Impairment:

• Mild to Moderate (CrCl 31–80 mL/min): Initial dose of 5 mg for ED; max 10 mg every 48 hours.
• Severe (CrCl <30 mL/min) or on dialysis: Not recommended for daily use. Use with caution for ED (maximum 5 mg no more than once in 72 hours).

Hepatic Impairment:

• Mild to Moderate (Child-Pugh A/B): 10 mg as needed; avoid daily use.
• Severe (Child-Pugh C): Use not recommended.

Administration Route:

• Oral tablets, swallowed whole, with or without food.

Tadalafil is a selective, reversible inhibitor of phosphodiesterase type 5 (PDE5). By inhibiting PDE5, tadalafil enhances the effects of nitric oxide (NO) by increasing cyclic guanosine monophosphate (cGMP) levels in smooth muscle cells of the corpus cavernosum, pulmonary vasculature, and the prostate. Elevated cGMP causes smooth muscle relaxation, leading to improved blood flow to the penis (in ED), reduced lower urinary tract symptoms (in BPH), and decreased pulmonary vascular resistance (in PAH). Tadalafil’s longer half-life allows for a prolonged duration of action.

• Absorption: Rapidly absorbed; peak plasma concentration (Tmax) in ~2 hours.
• Bioavailability: Approximately 80% (oral).
• Distribution: Volume of distribution ~63 L; ~94% protein-bound.
• Metabolism: Primarily hepatic via CYP3A4.
• Metabolites: Inactive catechol metabolites.
• Elimination Half-life: Approximately 17.5 hours.
• Excretion: Mainly fecal (61%); renal excretion accounts for ~36%.

• Pregnancy: Not indicated for use in women. Animal studies have not shown teratogenic effects, but human data are insufficient.
• Lactation: Unknown if excreted in human milk; not recommended during breastfeeding due to lack of data.
• Note: Avoid in women of childbearing potential unless specifically indicated for PAH and prescribed under expert supervision.

• Primary Class: Phosphodiesterase-5 (PDE5) Inhibitor
• Subclass: Long-acting PDE5 Inhibitor

• Known hypersensitivity to tadalafil or any component of the formulation.
• Concurrent use with organic nitrates (e.g., nitroglycerin) due to risk of severe hypotension.
• Concomitant use with guanylate cyclase stimulators (e.g., riociguat).
• Severe hepatic impairment (Child-Pugh Class C).
• Recent history (last 90 days) of myocardial infarction or stroke (for ED/BPH indications).
• Uncontrolled hypotension (<90/50 mmHg) or hypertension.

• Cardiovascular Risk: Use with caution in patients with underlying cardiovascular conditions. Not suitable for those advised against sexual activity.
• Priapism: Risk of prolonged erections; emergency attention required if erection lasts >4 hours.
• Vision Loss: Rare reports of non-arteritic anterior ischemic optic neuropathy (NAION).
• Hearing Loss: Sudden decrease or loss of hearing has been reported.
• Renal & Hepatic Impairment: Dose adjustment or avoidance required.
• Hypotension: Especially in combination with antihypertensives or alcohol.
• Concurrent Alpha-blocker Use: May cause symptomatic hypotension; stagger dosing if used together.

Common:

• Headache
• Dyspepsia (indigestion)
• Back pain
• Nasal congestion
• Myalgia
• Flushing
• Pain in limbs

Less Common:

• Dizziness
• Visual disturbances (e.g., blue-tinged vision)
• Nausea

Serious (Rare):

• Priapism
• NAION (vision loss)
• Hearing loss
• Severe hypotension
• Cardiovascular events (angina, arrhythmias in susceptible patients)

Major Interactions:

• Nitrates: Profound hypotension; absolute contraindication.
• Alpha-blockers (e.g., tamsulosin): Additive hypotensive effect.
• Antihypertensives: May further reduce blood pressure.
• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): Increase tadalafil levels; lower starting dose recommended.
• CYP3A4 Inducers (e.g., rifampin, carbamazepine): Reduce efficacy by lowering plasma concentration.

Food/Alcohol:

• High-fat meals do not significantly affect absorption.
• Alcohol may increase the risk of orthostatic hypotension and dizziness.

• PAH Indication: Recently reaffirmed in global pulmonary hypertension guidelines for long-term management of Group 1 PAH.
• Daily Use in BPH: Gaining wider acceptance as a non-hormonal option for men with concurrent ED and LUTS (Lower Urinary Tract Symptoms).
• Ongoing Trials: Under investigation for other vascular disorders (e.g., digital ulcers, female arousal disorders).
• Regulatory: No recent FDA black box warning; safety profile considered stable.

• Temperature: Store below 30°C (86°F).
• Humidity: Protect from moisture.
• Light: Keep in original package; protect from direct sunlight.
• Handling: Do not split tablets. Keep out of reach of children.
• Shelf-life: Follow specific expiry date on packaging.