Tadaflo is a medication that contains Tadalafil, a PDE5 inhibitor used to treat ED in men. It helps to relax blood vessels in the penis, allowing increased blood flow during sexual stimulation.

How does Tadaflo Work?

Tadalafil inhibits the Phosphodiesterase Type 5 enzyme, that leads to nitric oxide release, and results into smooth muscle relaxation.

Mechanism

• Inhibition of PDE5 enzyme: This Phosphodiesterase Type-5 enzyme enhances cyclic guanosine monophosphate (cGMP) levels by causing dilation of blood vessels in the penis.
• Increasing nitric oxide release: It leads to nitric oxide release, with sexual excitement, release of nitric oxide is intensified, leading to elevated levels of cGMP.
• Smooth muscle relaxation: Tadalafil reduces symptoms of BPH by enhancing urine flow in bladder and prostate gland.

Dosage

• Initial dose is Tadaflo 5 mg.
• The dose can be adjusted to 10 mg according to tolerance.

Applications of Tadalafil

Tadalafil is most commonly prescribed for:

• Erectile Dysfunction: Managing ED in men, facilitating achieving and sustaining erections.
• Benign Prostatic Hyperplasia: Managing symptoms such as urgency to urinate, poor stream, and incontinence.
• Pulmonary Arterial Hypertension: Decreasing pulmonary blood vessel pressure, enhancing exercise capacity.

Benefits of using Tadalafil medication

• Long duration of action up to 36 hours, enabling more spontaneity.
• Enhanced erectile function, more confidence, and satisfaction.
• Enhanced urine flow and lessened symptoms for Benign Prostatic Hyperplasia.

Interactions

Tadaflo interactions are classified into several categories:

1. Drug interactions
2. Food interactions
3. Disease interactions

Drug Interactions:

• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): Increase Tadalafil levels, CYP3A4 inhibitors can retard the metabolism of Tadalafil, with consequent higher levels and a greater risk of adverse effects.
• CYP3A4 Inducers (e.g., rifampicin, bosentan): Reduce tadalafil concentration, CYP3A4 inducers may speed up Tadalafil metabolism, weakening is efficacy.
• Nitrates (e.g., nitroglycerin, isosorbide dinitrate): Severe hypotension, Tadalafil may enhance the blood pressure-lowering effects of nitrates and cause potentially hazardous reductions in blood pressure.
• Alpha-blockers (e.g., doxazosin, tamsulosin): Increase risk of hypotension, Tadalafil has the potential to increase alpha-blockers hypotensive effects.
• Antihypertensives: (e.g., ACE inhibitors, beta-blockers): Additive hypotensive effects, Tadalafil has the potential to enhance the blood pressure-reducing effects of these medications, so the risk of hypotension is increased.
• Alcohol: Increased the risk of hypotension and side effects: Alcohol can potentiate the blood pressure-lowering action of Tadalafil and enhance the risk of side effects such as dizziness and headache.
• Other PDE5 Inhibitors: Increased risk of side effects, Concomitant use of Tadalafil with other PDE5 (e.g., Sildenafil, Vardenafil) may raise the risk of side effects because of additive effects.

Therapeutic Suggestions

• Adjustments in dose can be made when Tadalafil is administered with CYP3A4 inhibitors or inducers.
• Concomitant use should be avoided of Tadalafil with nitrates or other PDE5 inhibitors.
• Blood pressure should be monitored when Tadalafil is administered with antihypertensives or alpha-blockers.
• Alcohol should be consumed in limited amounts to prevent side effects.

Pharmacokinetics

Pharmacokinetic Interaction takes place when a drug influences the Absorption, Distribution, Metabolism, or excretion (ADME) of another drug. This may result in an alteration in the concentration of one or both drugs in the body and thus may alter their effects or enhance the risk of side effects.

There are various categories of Pharmacokinetic interactions:

• Absorption interaction
• Distribution interaction
• Metabolism interaction
• Erection Interaction

Pharmacokinetic interactions are very important in anticipating and managing future drug interactions, allowing for safe and effective therapy.

Does Tadaflo have any pharmacokinetic interaction?

Yes, Tadaflo also has a number of pharmacokinetic interactions. Tadaflo can be metabolized by cytochrome P450 (CYP) 3A4, and as bosentan induces CYP2C9 and CYP3A4, a pharmacokinetic interaction is possible between these agents.

Food Interactions

• Grapefruit: Grapefruit and grapefruit juice may raise levels of tadalafil in the blood, which could result in higher side effects.
• Alcohol: Drinking a lot of alcohol with tadalafil might cause side effects to be greater, such as dizziness, headache, and low blood pressure. Taking moderate alcohol is recommended.

Disease Interactions

• Cardiovascular disease: People with heart disease or high blood pressure might have increased risks when using tadalafil.
• Liver or kidney impairment: Abnormal liver or kidney function may change the metabolism and elimination of tadalafil, requiring dose modification.
• Retinal disorders: Diseases such as retinitis pigmentosa might be worsened by tadalafil.
• Priapism: Priapism, a lasting erection of the penis, may occur with tadalafil in some patients.

Contraindications of Tadaflo

Tadaflo, a drug employed to cure erectile dysfunction (ED) and benign prostatic hyperplasia (BPH), has specific contraindications:

1. Nitrates

• Forbidden usage: Tadalafil must not be used with nitrates, for it results in a remarkable fall in blood pressure.
• Examples of nitrates: Nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate.

2. Guanylate Cyclase Stimulators

• Forbidden use: Tadalafil is not recommended to be used with guanylate cyclase stimulators like riociguat since it can also lead to a sudden drop in blood pressure.

3. Hypersensitivity

• Allergic reactions: If you are hypersensitive or allergic to tadalafil or any component of the drug, you should avoid taking it.

4. Severe Health Conditions

• Heart conditions: Some heart conditions, e.g., severe heart failure or uncontrolled hypertension, might necessitate caution or contraindication.
• Liver or kidney problems: Severe liver or kidney dysfunction can necessitate dose modification or contraindication.

5. Other Considerations

• Age and health status: Elderly or patients with specific health conditions might need dose adjustment or more intensive monitoring.
• Interactions with other medications: Tadalafil may interact with other drugs, so it’s important to tell your physician all the medications you’re taking.

Reducing Interactions

• Discuss medication lists with healthcare professionals on a regular basis
• Follow dosage directions.
• Reduce alcohol intake.
• Avoid grapefruit and grapefruit juice.
• Inform medical professionals regarding any health conditions or medication being used.

Side effects of

• Headache
• Muscle pain
• Flushing
• Nausea
• Back pain
• Dizziness

Clinical Trials

Tadalafil has been investigated in numerous clinical trials across a range of conditions such as pulmonary arterial hypertension (PAH), erectile dysfunction, and chronic obstructive pulmonary disease (COPD).

Some significant trials are:

1. Pulmonary Arterial Hypertension (PAH)

• A DUE Trial: This trial demonstrated that macitentan 10 mg daily + tadalafil 40 mg daily fixed-dose combination therapy is superior to either drug as monotherapy in lowering pulmonary vascular resistance (PVR) at 6 weeks in patients with PAH.
• Pediatric PAH Trial: A phase 3 trial assessed the safety and effectiveness of tadalafil in pediatric patients with PAH, between the ages of 6 months and 17 years. The trial had a 6-month double-blind and 2-year open-label extension phase.

2. Erectile Dysfunction

• Actual Use Trial: Opella, the consumer healthcare division of Sanofi, is performing an actual use trial (AUT) to facilitate the potential transition of Cialis (tadalafil) from prescription to over-the-counter (OTC) medication for erectile dysfunction. The FDA had put the trial on hold in 2022 because of issues regarding protocol design, but the hold has been removed.

3. Chronic Obstructive Pulmonary Disease (COPD)

• BETTER COPD-PH Trial: This phase 2 trial is examining the impact of tadalafil on patient-reported dyspnea in patients with pulmonary hypertension and COPD. The trial is exploring the effectiveness and safety of tadalafil in decreasing severity of patient-reported dyspnea.

Clinical Trial (Erectile Dysfunction)

• EndoPAT Device for Endothelial Dysfunction in ED: This trial assesses endothelial dysfunction in young men with vasculogenic ED using EndoPAT before and after daily low-dose phosphodiesterase type 5 (PDE5) inhibitor therapy.
• Efficacy of Low-intensity Shockwave vs Radial Wave for Treatment of Erectile Dysfunction and Pelvic Pain: This trial compares the effectiveness of focused shockwave and radial wave therapies for treating ED and chronic pelvic pain syndrome.
• External Device for Erectile Dysfunction (3D-Erect): This trial tests the safety and feasibility of a non-invasive 3D-printed external penile device to achieve successful and satisfactory sexual intercourse in men with ED.
• Double-S: A Wearable Device for Erectile Dysfunction: This trial evaluates the effectiveness of a wearable device for treating ED.
• SAFE Nerve Sparing Guided by Micro-ultrasound (MUS): This trial investigates the impact of normal saline solution hydro dissection on erectile function outcomes after robotic-assisted radical prostatectomy.
• Safety and Efficacy of Bi-Polar Radiofrequency for the Treatment of Erectile Dysfunction: This trial assesses the safety and efficacy of bi-polar radiofrequency for treating ED.
• The Impact of a Plant-based Meat Meal Versus an Animal Meat Meal on Erectile Function: This trial examines the differential impact of plant-based and animal-based meals on erectile function in healthy men.
• Actual Use Trial of Tadalafil 5 mg: This trial evaluates the appropriateness of selection and use of tadalafil 5 mg tablets with a digital tool.
• Evaluating the Efficacy of Platelet-Rich-Plasma (PRP) for Erectile Dysfunction: This trial assesses the effectiveness of PRP for treating ED.
• Concurrent Low Intensity Shockwave Therapy on Collagenase Clostridium Histolyticum for Peyronie’s Disease: This trial investigates the effectiveness of low-intensity shockwave therapy with Xiaflex treatment for Peyronie’s disease and ED.

Precautions

• Tadaflo should be used cautiously in patients with cardiovascular disease.
• Tadaflo should be used cautiously in patients with severe hepatic impairment.
• Tadaflo should be used cautiously in patients with severe renal impairment.

Conclusion

Tadaflo is a potent drug for the treatment of ED with an action time of as long as 36 hours. Although generally well tolerated, Tadaflo can produce side effects and interact with some drugs. Patients need to discuss with their doctor prior to taking Tadaflo, particularly if they have any pre-existing medical conditions or are on other drugs.

FAQs

1. What is Tadaflo used for?

Tadaflo is used to treat erectile dysfunction AND Benign Prostatic Hyperplasia.

2. How does Tadaflo work?

Tadaflo works by increasing blood flow to the penis during sexual stimulation, helping to achieve and maintain an erection.

3. How long does Tadaflo last?

The effects of Tadaflo can last up to 36 hours.

4. Can Tadaflo be taken with food?

Yes, Tadaflo can be taken with or without food.

5. Who should avoid Tadaflo?

Men with Certain medical conditions like Liver, Heart, and Kidney should avoid Tadaflo.