TADALAFIL 20 MG ADCO

Indications

• Erectile dysfunction (ED)
• Pulmonary arterial hypertension (PAH)
• Benign prostatic hyperplasia (BPH)

Dosage

Children: Not established; refer to the BNF for Children for further guidance.

Adults: Refer to the specific guidelines in the BNF for appropriate dosage.

Mechanism of action

Tadalafil selectively inhibits phosphodiesterase-5 (PDE5), leading to increased levels of cyclic guanosine monophosphate (cGMP). This enhances smooth muscle relaxation in penile tissues during sexual arousal by preventing the breakdown of cGMP, thereby facilitating increased blood flow and erection. In PAH, tadalafil promotes vasodilation of the pulmonary arteries, reducing blood pressure in these vessels. In BPH, it may decrease smooth muscle cell proliferation, alleviating urinary symptoms.

Pharmacodynamics

Tadalafil enhances sexual stimulation-dependent smooth muscle relaxation in the penis, resulting in increased blood flow and erection. In PAH, it produces vasodilation in the pulmonary vasculature, lowering pulmonary artery pressure. For BPH, tadalafil may alleviate urinary symptoms by reducing prostate size and relieving anatomical obstruction. Its lower affinity for PDE6 compared to other PDE5 inhibitors results in fewer visual side effects.

Pharmacokinetics

Tadalafil is well absorbed orally, with peak plasma concentrations occurring within 2 hours. Its bioavailability is approximately 80%, and it has a half-life of approximately 17.5 hours, allowing for once-daily dosing for some indications. Tadalafil is metabolized primarily in the liver via the cytochrome P450 system, mainly CYP3A4, and is excreted as metabolites in the feces and urine. The presence of food does not significantly affect its absorption.

Contra-indications

• Systolic blood pressure less than 90 mmHg
• Concurrent use of nitrates for angina

Adverse effects

• Headache
• Flushing
• Dyspepsia
• Nausea
• Back pain
• Myalgia
• Visual disturbances
• Hearing impairment
• Priapism
• Hypotension

Interactions

• Cobicistat + tadalafil: Moderate (increases exposure)
• Antifungals, azoles + tadalafil: Unknown (increases exposure)
• Crizotinib + tadalafil: Unknown (increases exposure)
• Idelalisib + tadalafil: Unknown (increases exposure)
• Imatinib + tadalafil: Unknown (increases exposure)
• Letermovir + tadalafil: Unknown (increases exposure)
• Nilotinib + tadalafil: Unknown (increases exposure)

Precautions

• Caution in patients with hepatic impairment
• Consider dose adjustment in mild to moderate impairment
• Discontinue if sudden visual impairment occurs

Pregnancy

Use only if potential benefit outweighs risk; no evidence of harm in animal studies.

Breast-feeding

Manufacturer advises avoiding use; no information available.

Storage

Store in a cool, dry place away from light.

Formulations

• Tadalafil 2.5 mg tablets
• Tadalafil 5 mg tablets
• Tadalafil 10 mg tablets
• Tadalafil 20 mg tablets

Indications

• Pain relief
• Inflammation
• Fever
• Musculoskeletal disorders

Dosage

Children: Refer to specific formulation guidelines for paediatric dosing, which should be based on the active ingredients and the child's weight or age.

Adults: Refer to specific formulation guidelines for dosage information, as this can vary widely depending on the active ingredients.

Mechanism of action

ADCO formulations containing NSAIDs typically act by inhibiting the cyclooxygenase (COX) enzymes, leading to decreased synthesis of prostaglandins. Prostaglandins are mediators of pain and inflammation, and by reducing their production, these drugs alleviate symptoms such as pain and fever.

Pharmacodynamics

The pharmacodynamics of ADCO formulations depend on their active ingredients. For NSAIDs, the anti-inflammatory effects are usually observed within hours of administration, while analgesic effects may be noted within 30 minutes to an hour. The degree of effectiveness can vary based on the specific formulation and individual patient response.

Pharmacokinetics

The pharmacokinetics of ADCO formulations depend on the specific active ingredients. Generally, NSAIDs are well-absorbed after oral administration, with peak plasma concentrations occurring within 1 to 3 hours. They are metabolized primarily in the liver, and their elimination half-lives can range from a few hours to several days, depending on the compound. Renal excretion is the primary route of elimination for most NSAIDs.

Pregnancy

The safety of adco during pregnancy has not been established. Consult healthcare providers for risk assessment.

Breast-feeding

Adco should be used with caution during breastfeeding. Consult healthcare providers for advice.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Dosage

Children: Refer to specific drug information for detailed dosage recommendations.

Adults: Refer to specific drug information for detailed dosage recommendations.

Mechanism of action

The mechanism of action varies depending on the specific drug that 'contains' certain active ingredients. Each compound will have its own unique pharmacological pathway and target within the body, which can include receptor modulation, enzyme inhibition, or other biochemical interactions.

Pharmacodynamics

Pharmacodynamics will depend on the active ingredients in the formulation. It generally encompasses the biochemical and physiological effects of the drug and its mechanisms of action, including the relationship between drug concentration and effect.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of the specific active ingredients within the formulation. This can vary significantly based on the drug's chemical properties, route of administration, and individual patient factors.

Pregnancy

Consult with a healthcare provider before use, as safety during pregnancy has not been established.

Breast-feeding

Consult with a healthcare provider before use, as it is not known if this drug is excreted in human milk.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Mechanism of action

Tadalafil is a selective phosphodiesterase-5 (PDE5) inhibitor that produces several downstream effects with the most common therapeutic effect being smooth muscle relaxation. Patients may experience ED due to a variety of causes including psychogenic, neurogenic, vasculogenic, iatrogenic, or endocrine. These causes result in dysfunction of penile smooth muscle relaxation through either disrupted neuronal signaling or direct influence on smooth muscle cells. During sexual arousal, non-adrenergic non-cholinergic (NANC) neurons release nitric oxide (NO). Nitric oxide stimulates guanylate cyclase which converts guanosine triphosphate to cyclic guanosine monophosphate (cGMP). cGMP activates the cGMP-dependent kinase (PKG) in a signal cascade which activates K+ channels leading to inhibition of Ca2+ channels, inhibits platelet activation, and inhibits smooth muscle cell proliferation while inducing apoptosis. This signal cascade is attenuated by PDE5 which breaks the phosphodiester bond of cGMP, converting it to GMP. Inhibition of PDE5 by tadalafil increases signaling via the PKG cascade which supports penile smooth muscle relaxation during sexual arousal by decreasing Ca2+ entry into smooth muscle cells. This smooth muscle relaxation allows blood to fill the corpus cavernosum thereby producing an erection. In PAH, blood pressure in the pulmonary arteries is raised due to a variety of mechanisms stemming from endothelial dysfunction. Decreased production of NO and prostacyclin reduce vasodilatory signaling while overproduction of endothelin-1 and thromboxane increase vasoconstriction. Inflammation, thromboses, and hypoxia later contribute to vascular remodeling which further reduces luminal size. The resultant increase in blood pressure reduces the capacity for gas exchange and increases afterload at the right ventricle, producing symptoms of dyspnea, fatigue, and dizziness as well as leading to right-sided heart failure. Tadalafil exerts its therapeutic effect in PAH through boosting NO-cGMP signaling to contribute to smooth muscle relaxation as with ED. Lastly, tadalafil is used to treat BPH. BPH produces urinary dysfunction through hyperproliferation of the epithelial and smooth muscle layers of the prostate. The increased size of the prostate blocks urine flow through the urethra resulting in higher residual volumes due to incomplete emptying. Tadalafil does not appear to exert its benefit via smooth muscle relaxation of the prostate. It may instead exert its effect through a mix of increased oxygenation and decreased inflammation, which decreases tissue remodeling, and inhibition of cell proliferation through the cGMP cascade. The decreased affinity for PDE6 compared to other PDE5 inhibitors may explain the decreased incidence of visual side effects as PDE6 is present in the eye and contributes to color vision. In vitro studies have shown that the effect of tadalafil is more potent on phosphodiesterase type 5 (PDE5) than on other phosphodiesterases. These studies have shown that tadalafil is >10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, tadalafil is 700-fold more potent for PDE5 than for PDE8, PDE9, PDE10 and 14-fold more potent for PDE5 than for PDE11A1, an enzyme found in human skeletal muscle. Tadalafil inhibits human recombinant PDE11A1 activity at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined. Studies in vitro have demonstrated that tadalafil is a selective inhibitor of phosphodiesterase type 5 (PDE5). PDE5 is found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas. Penile ere

Pharmacodynamics

Tadalafil exerts a therapeutic effect in ED by increasing sexual stimulation-dependant smooth muscle relaxation in the penis, allowing the corpus cavernosum to fill with blood to produce an erection. Smooth muscle relaxation in the pulmonary vasculature helps to produce vasodilation in PAH which reduces blood pressure in the pulmonary arteries. In BPH, tadalafil may contribute to decreased smooth muscle cell proliferation which may reduce the size of the prostate and relieve the anatomical obstruction which produces urinary symptoms of BPH. The decreased affinity of tadalafil for PDE6 compared to other PDE5 inhibitors may explain the reduced incidence of visual side effects.