TADALAFILO – Calox International
ADMINISTRATION ROUTE
The oral route is the primary method of administration for Tadalafil, making it convenient for patients.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamics
Tadalafil functions as a selective inhibitor of phosphodiesterase type 5 (PDE5), which plays a crucial role in regulating blood flow within the penis. By blocking PDE5, it facilitates the accumulation of cyclic guanosine monophosphate (cGMP), a substance that promotes relaxation of smooth muscles and dilation of blood vessels, ultimately leading to an erection when sexual stimulation occurs. Importantly, the action of Tadalafil is contingent upon sexual arousal; it will not induce an erection without it.
When Tadalafil is administered, it prevents the breakdown of cGMP, thereby prolonging its effects on the vascular tissues, which supports erectile function. This mechanism highlights the drug's targeted action without overstimulation of the erectile tissues themselves.
Pharmacokinetics
Upon oral intake, Tadalafil is swiftly absorbed, achieving peak plasma concentrations typically within 2 hours. Initial effects can be noted as early as 30 minutes following administration, with a duration of action that can extend up to 36 hours. For patients on a daily regimen at 5 mg, steady-state concentrations will materialize after roughly 5 days of continuous use. Notably, food intake does not significantly alter the absorption rate of Tadalafil.
Furthermore, Tadalafil demonstrates high plasma protein binding (94%) and is extensively distributed in bodily tissues (Volume of Distribution: 63 L). The drug has a half-life of approximately 17.5 hours and undergoes metabolism primarily in the liver via the cytochrome P450 system, notably through the CYP3A4 isoenzyme. The metabolites formed are mainly inactive and are eliminated from the body, with 61% excreted in feces and 36% in urine. In cases of severe renal impairment or moderate hepatic dysfunction, the clearance of Tadalafil is significantly decreased.
In terms of preclinical safety, extensive studies have not demonstrated any carcinogenic, mutagenic, or teratogenic effects linked to Tadalafil. Additionally, the drug has shown no adverse impact on sperm quality following a single 20 mg dose in healthy subjects.
INDICATIONS
The primary indication for Tadalafil is the treatment of erectile dysfunction in adult men.
DOSAGE
Dose
Applicable only to adult patients
For on-demand use: a single dose of 20 mg is recommended. For regular daily use: 5 mg is advised.
Maximum daily dose
Prescribing higher doses is discouraged as this does not enhance therapeutic benefits and could potentially lead to increased adverse effects.
Special patient populations dosage
- Renal insufficiency: In patients with moderate insufficiency (creatinine clearance: 30-50 ml/min), it is recommended to limit doses to 10 mg every 48 hours, with a maximum daily dose of 5 mg. In severe cases (creatinine clearance < 30 ml/min), a single dose of 5 mg should not be taken more frequently than every 72 hours; daily use is contraindicated.
- Liver insufficiency: For mild to moderate insufficiency, do not exceed 10 mg as a single on-demand dose. The daily regimen has not been evaluated in these patients, while severe insufficiency warrants contraindication of the drug.
- Elderly patients: No adjustments in dosage are typically necessary for older adults.
Method of administration or usage
On-demand use: Administer orally with water approximately 30 minutes prior to sexual activity, regardless of meal timing. Re-dosing should not occur within a 36-hour window.
Daily use: Take orally with water at the same time each day, with or without food. The therapeutic effect generally manifests by the fifth day of treatment initiation.
Do not use in conjunction with other PDE5 inhibitors or different formulations of Tadalafil.
ADVERSE REACTIONS
Gastrointestinal disorders
Experiences may include dyspepsia, abdominal discomfort, gastroesophageal reflux, nausea, and, in rare cases, rectal bleeding.
Liver and biliary disorders
Potential abnormal results in liver function tests have been noted.
Renal and urinary disorders
Incidences of hematuria have been reported.
Cardiovascular disorders
Adverse effects may include flushing, palpitations, tachycardia, hypotension, and potential myocardial infarction.
Neurological disorders
Common side effects involve headaches, dizziness, and insomnia. Rare but severe reactions may include strokes and seizures.
Respiratory disorders
Symptoms like nasal congestion and dyspnea may manifest.
Musculoskeletal disorders
Myalgia and back pain may occur as side effects.
Ocular disorders
Visual disturbances, including blurred vision and color perception alteration, have been observed.
Skin disorders
Reports of rashes and urticaria have been noted following Tadalafil usage.
WARNINGS AND PRECAUTIONS
Prior to initiating Tadalafil therapy, a comprehensive medical history and physical assessment are essential to identify potential contraindications, particularly in individuals with cardiovascular conditions.
Patients with existing heart issues should receive thorough evaluation before using Tadalafil as sexual activity poses inherent cardiac risks.
The drug’s vasodilatory effects can result in transient blood pressure drops, which may be particularly concerning for those with pre-existing cardiovascular diseases.
Close monitoring is necessary for patients concurrently taking antihypertensives or alpha-adrenergic blockers, as these combinations may further heighten hypotensive risk.
Patients should also be warned against the simultaneous use of Tadalafil with nitrates, as this can lead to markedly decreased blood pressure and serious adverse events.
PREGNANCY AND LACTATION
Tadalafil is not intended for use in women, and its safety during pregnancy or lactation has not been established.
CONTRAINDICATIONS
Hypersensitivity to Tadalafil, concurrent use with nitrates, severe hepatic insufficiency, among others, constitute critical contraindications.
OVERDOSAGE
Should overdose occur, supportive treatment is the mainstay, as dialysis is ineffective due to Tadalafil's high protein binding.