For patients with ALT (SGPT) greater than 3–5 times normal, decrease the dose by 40 mg/day and resume the normal dose when ALT (SGPT) returns to normal. For patients with ALT (SGPT) greater than 5 times normal, stop treatment and resume it when ALT (SGPT) returns to normal.
! Overdose can cause cholinergic crisis, marked by increased salivation, lacrimation, bradycardia, respiratory depression, hypotension, and increased muscle weakness. Treatment usually consists of supportive measures and an anticholinergic, such as atropine.
Variably absorbed after PO administration (food reduces absorption). Protein binding: 75%–97%. Extensively metabolized in the liver. Excreted in urine. Not removed by hemodialysis. Half-life: 11.7 hr.
Concurrent use with cyclosporine (increases the risk of nephrotoxicity), hypersensitivity to HCO-60 polyoxyl 60 hydrogenated castor oil (used in solution for injection), hypersensitivity to tacrolimus
! Nephrotoxicity (characterized by increased serum creatinine level and decreased urine output), neurotoxicity (including tremor, headache, and mental status changes), and pleural effusion are common adverse reactions. Thrombocytopenia, leukocytosis, anemia, atelectasis, sepsis, and infection occur occasionally.
Inhibits phosphodiesterase type 5 (PDE-5) in smooth muscle of pulmonary vasculature where PDE-5 is responsible for the degradation of cyclic guanosine monophosphate (cGMP). Increased cGMP concentration results in pulmonary vasculature relaxation; vasodilation in the pulmonary bed and the systemic circulation (to a lesser degree) may occur.
Hypersensitivity to tadalafil or any component of the formulation. Concurrent use of nitrates in any form. May cause auditory and visual disturbances, including hearing and vision loss. Not recommended for use in patients with severe cardiovascular disease (hypotension, uncontrolled hypertension, angina, arrhythmias, stroke) and bleeding disorders.
Advanced breast carcinoma that has not responded to other therapy in estrogen receptor-positive patients (usually postmenopausal), to reduce the incidence of breast cancer in healthy women with high risk of developing the disease; ductal carcinoma in situ
! First-dose syncope (hypotension with sudden loss of consciousness) may occur within 30–90 min after administration of initial dose and may be preceded by tachycardia (pulse rate of 120–160 beats/min).
Limited oral bioavailability (32%) due to extensive hepatic first-pass metabolism. Peak concentration reached at 1.25 hr, widely distributed. Protein binding: 20%. Metabolized in the liver, primarily by glucuronide conjugation. Half-life: 4 hr. 99% excreted by the kidneys. No active metabolites.
Hypotension, bradycardia, tachycardia, agitation, ataxia, euphoria, depressed consciousness, restlessness, syncope, seizures, delayed gastric emptying, urinary retention, involuntary muscle contractions, cough, dyspnea, drug withdrawal, hypersensitivity
Rapidly absorbed. Widely distributed. Protein binding: 98%. Metabolized by hydrolysis in the stomach and by oxidation and conjugation of the primary metabolite. Primarily excreted in feces. Half-life: 11 hr.