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Author: Admin | 2025-04-28
Serum concentrations of bosentan and reduced levels of sildenafil. Hypotension and Alpha-Blockers: Sildenafil should be started at the lowest dose in patients on alpha-blockers due to the potential for significant systemic hypotension. Caution is also advised when sildenafil is coadministered with mixed alpha/beta-blockers, unless specific information is available regarding the safety of such combinations. Special Populations: Increased caution is advised when prescribing sildenafil to elderly patients, those with renal or hepatic impairment, and individuals taking multiple medications that could interact with sildenafil. Contraindications Nitrates and Severe Hypotension: Sildenafil is contraindicated in patients who are using nitrates in any form, due to the risk of severe, life-threatening hypotension. Nitrates increase cyclic guanosine monophosphate (cGMP) formation, while sildenafil inhibits its degradation, leading to a synergistic effect that can cause significant drops in blood pressure. Therefore, sildenafil should not be coadministered with nitrates, and nitrates should only be considered safe for administration at least five sildenafil elimination half-lives (24 or more hours) after the last dose of sildenafil. Other Causes of Hypotension: Severe hypotension from any cause, such as volume depletion, contraindicates the use of sildenafil. Hypersensitivity: Sildenafil is contraindicated in individuals with a known hypersensitivity to any component of the formulation. Specific Medical Conditions: Pulmonary Veno-Occlusive Disease (PVOD): Sildenafil is contraindicated in patients with pulmonary veno-occlusive disease due to the potential for significant adverse effects. Left Ventricular Outflow Obstruction: Patients with conditions causing left ventricular outflow obstruction should not use sildenafil, as it can exacerbate hemodynamic instability. PAH Associated with Sickle Cell Anemia: The use of sildenafil in patients with pulmonary arterial hypertension associated with sickle cell anemia is contraindicated due to the risk of severe complications. Multiple System Atrophy: Patients with multiple system atrophy should not use sildenafil due to the risk of severe hypotension. Ocular Conditions: Sildenafil is contraindicated in patients with a history of ischemic optic neuropathy or inherited degenerative retinal disorders. If a patient experiences sudden vision loss, sildenafil should be discontinued immediately. Monitoring UVA CLINICAL PHARMACOLOGY / COMPREHENSIVE REVIEW OF SILDENAFIL While routine monitoring is generally not required for sildenafil use, certain situations may warrant closer observation. Patients may need to monitor their blood pressure and pulse, especially after starting sildenafil, adjusting the dose, or adding CYP3A4 inhibitors. During routine clinical evaluations, assessing for visual changes is recommended. For patients treated with sildenafil for pulmonary arterial hypertension, monitoring for signs and symptoms of pulmonary edema is essential. Toxicity In studies with healthy subjects, single doses of sildenafil up to 800 mg have been associated with adverse effects similar to those observed at therapeutic doses, but with greater frequency and severity. There is no specific antidote for sildenafil overdose; treatment involves supportive care. In cases of overdose, dose-related visual disturbances are more common, although significant changes in blood pressure are less frequently correlated with toxic levels. Since sildenafil is highly protein-bound and not significantly excreted renally, dialysis is ineffective in enhancing drug clearance. The metabolite N-desmethyl-sildenafil, which has a lower potency but still retains specificity for PDE5, can
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