ADCIRCA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADCIRCA (ADCIRCA).
Phosphodiesterase-5 (PDE5) inhibitor; increases cGMP in pulmonary vascular smooth muscle, leading to vasodilation.
| Metabolism | Primarily metabolized by CYP3A4 (major) and CYP2C9 (minor) hepatic enzymes. |
| Excretion | Renal: ~70% (metabolites and unchanged drug), Fecal: ~20%, Biliary: minor |
| Half-life | Terminal half-life: 10–15 hours in healthy adults; prolonged in hepatic impairment (Child-Pugh B/C: up to 30 hours); clinical context: supports twice-daily dosing |
| Protein binding | 96% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 0.4–0.7 L/kg; suggests distribution into total body water and moderate tissue binding |
| Bioavailability | Oral: 80%; absolute bioavailability: 50% due to first-pass metabolism |
| Onset of Action | Oral: 30–60 minutes; maximal hemodynamic effects at 1–2 hours |
| Duration of Action | 6–8 hours based on pulmonary hemodynamic effects; clinical note: sustained improvement in exercise capacity observed with continuous dosing |
10 mg orally three times daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; avoid use in severe impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): 10 mg orally once daily; severe hepatic impairment (Child-Pugh C): contraindicated. |
| Pediatric use | Not established for patients <18 years. |
| Geriatric use | No specific dose adjustment, but caution due to increased sensitivity; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADCIRCA (ADCIRCA).
| Breastfeeding | Not recommended. Excretion in human milk unknown. M/P ratio not established. Risk of hypotension in neonate. Alternative feeding method advised during therapy and for 48 hours after last dose. |
| Teratogenic Risk | Pregnancy Category B. Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. First trimester: risk cannot be ruled out; use only if clearly needed. Second and third trimesters: no known fetal risks, but caution advised due to maternal hypotension risk. |
■ FDA Black Box Warning
Do not use in patients taking nitrates (regularly or intermittently) due to risk of severe hypotension.
| Serious Effects |
["Concomitant use of nitrates (any form) or nitric oxide donors.","Concomitant use with riociguat or other guanylate cyclase stimulators.","Known hypersensitivity to tadalafil or any component of the product.","Severe hepatic impairment (Child-Pugh class C)."]
| Precautions | ["Risk of hypotension, especially with nitrates or alpha-blockers.","Hematologic effects: increased risk of bleeding due to antiplatelet activity; caution with bleeding disorders or anticoagulants.","Vision loss: non-arteritic anterior ischemic optic neuropathy (NAION) has been reported; discontinue if sudden vision loss occurs.","Hearing loss: sudden decrease or loss of hearing; may be accompanied by tinnitus or dizziness.","Use caution in patients with left ventricular outflow obstruction (e.g., aortic stenosis) or severely impaired autonomic control of blood pressure.","Dose adjustment required with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir)."] |
| Food/Dietary |
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| Fetal Monitoring |
| Monitor maternal blood pressure and heart rate. Assess fetus via ultrasound for growth and well-being if used in pregnancy. Monitor for signs of hypotension or bleeding in mother. |
| Fertility Effects | Preclinical studies showed no impairment of fertility. Human data lacking; no known adverse effects on spermatogenesis or ovarian function. |
| Avoid grapefruit and grapefruit juice as they may increase tadalafil levels and risk of side effects. No other significant food interactions. High-fat meals may delay absorption but do not require dose adjustment. |
| Clinical Pearls | Adcirca (tadalafil) is a PDE5 inhibitor indicated for pulmonary arterial hypertension (PAH) to improve exercise ability. It is dosed at 40 mg once daily, not as needed. Avoid use with nitrates due to risk of severe hypotension. Monitor for vision loss (non-arteritic anterior ischemic optic neuropathy) and hearing loss. Use caution in patients with hepatic impairment (Child-Pugh class B: reduce dose; class C: contraindicated). Dose adjustment required with potent CYP3A4 inhibitors (e.g., ketoconazole: reduce to 20 mg). Not recommended for severe renal impairment (CrCl <30 mL/min) or on hemodialysis. |
| Patient Advice | Take Adcirca exactly as prescribed, 40 mg once daily, at the same time each day. Do not take it as needed for erectile dysfunction. · Do not take Adcirca if you are taking any form of nitrate medication (e.g., nitroglycerin) or recreational drugs called 'poppers' (amyl nitrate) as this can cause a sudden dangerous drop in blood pressure. · Seek immediate medical attention if you experience sudden vision loss or decrease in hearing, as these may be signs of a serious side effect. · Avoid drinking large amounts of alcohol (e.g., 3 or more drinks) within a short time while taking Adcirca, as it may increase the risk of dizziness, lightheadedness, and fainting. · Inform your healthcare provider about all medications you take, including prescription, over-the-counter, and herbal products, especially alpha-blockers, erythromycin, or ritonavir. · Adcirca may cause dizziness. Do not drive or operate machinery until you know how the medicine affects you. |