Tadalafil

Tadalafil is an oral phosphodiesterase type 5 (PDE5) inhibitor. FDA-approved products include Cialis tablets and generics for erectile dysfunction (ED) and benign prostatic hyperplasia (BPH), and Adcirca and Alyq tablets and Tadliq oral suspension for pulmonary arterial hypertension (PAH). Lake Hills Pharmacy compounds tadalafil as a 503A pharmacy, pursuant to patient-specific prescriptions, in oral capsules, rapid dissolve tablets and combination preparations. Tadalafil is not a controlled substance.

• Cialis (oral): ED; the signs and symptoms of BPH; and ED with BPH. When used with finasteride to start BPH treatment, labeling covers up to 26 weeks.
• Adcirca (oral): PAH (WHO Group 1) to improve exercise ability.
• Prescribers use compounded tadalafil when a strength or dosage form not available commercially is needed, including in combination with other actives.

Sexual stimulation releases nitric oxide in the corpus cavernosum, activating guanylate cyclase and raising cGMP, which relaxes smooth muscle and increases blood inflow. Tadalafil selectively inhibits PDE5, which degrades cGMP, so it enhances this response but has no effect without stimulation. PDE5 inhibition also relaxes prostate, bladder neck and pulmonary vascular smooth muscle. Tadalafil has some PDE11 activity of unknown significance and little PDE6 activity.

After oral dosing, peak plasma concentration is reached at a median of 2 hours (range 0.5 to 6 hours). Absorption is not affected by food. Volume of distribution is about 63 L and protein binding is about 94%. Tadalafil is metabolized mainly by CYP3A4 to an inactive catechol metabolite and excreted as metabolites, about 61% in feces and 36% in urine. Mean half-life is about 17.5 hours in healthy adults, which underlies labeled efficacy for up to 36 hours after a dose. Exposure rises in renal impairment and with strong CYP3A4 inhibitors.

• Use of nitrates or nitric oxide donors in any form, regularly or intermittently, because of potentiated hypotension. If a nitrate is medically necessary in a life-threatening situation, at least 48 hours should pass after the last tadalafil dose, with hemodynamic monitoring.
• Concomitant riociguat or other guanylate cyclase stimulators, because of hypotension.
• Known serious hypersensitivity to tadalafil, including Stevens-Johnson syndrome and exfoliative dermatitis.

• Cardiovascular: assess cardiac status before use, as sexual activity carries cardiac risk. Not recommended after myocardial infarction within 90 days, with unstable angina or angina during intercourse, NYHA class II or greater heart failure within 6 months, uncontrolled arrhythmias, hypotension (<90/50 mmHg), uncontrolled hypertension or stroke within 6 months. Left ventricular outflow obstruction (aortic stenosis, idiopathic hypertrophic subaortic stenosis) increases sensitivity to vasodilators.
• Prolonged erection and priapism: an erection lasting more than 4 hours needs immediate care. Use caution with anatomic penile deformity or conditions predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia).
• Sudden vision loss from non-arteritic anterior ischemic optic neuropathy (NAION) has been reported; stop and seek care. Use is not recommended in hereditary degenerative retinal disorders such as retinitis pigmentosa. Sudden decrease or loss of hearing, sometimes with tinnitus and dizziness, has been reported.
• Renal impairment: on-demand use no more than 10 mg once per 48 hours for creatinine clearance 30 to 50 mL/min and no more than 5 mg once per 72 hours below 30 mL/min or on hemodialysis; once-daily use is not recommended below 30 mL/min. Hepatic impairment: Child-Pugh A or B, on-demand no more than 10 mg once daily; Child-Pugh C not recommended.
• Alcohol: substantial intake (for example, 5 or more units) with tadalafil increases orthostatic signs, dizziness and headache. Use with other PDE5 inhibitors or other ED therapies has not been studied and is not recommended. Use caution with bleeding disorders or active peptic ulceration. Evaluate for prostate cancer and other urologic conditions before treating BPH.

• Nitrates and nitric oxide donors, and riociguat: contraindicated.
• Alpha-blockers: additive blood-pressure lowering. For ED, patients should be stable on alpha-blocker therapy before starting tadalafil, at the lowest dose; tadalafil with an alpha-blocker is not recommended for BPH. Other antihypertensives and alcohol: additive lowering of blood pressure.
• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir and other HIV protease inhibitors, clarithromycin) raise exposure: on-demand use no more than 10 mg once per 72 hours, and once-daily use no more than 2.5 mg. Adcirca labeling gives separate guidance for ritonavir in PAH.
• CYP3A4 inducers (rifampin, and bosentan, which induces CYP3A4) lower tadalafil exposure and may reduce its effect.

The most common adverse reactions are headache, dyspepsia, back pain, myalgia, nasal congestion, flushing and pain in the limbs. Back pain and myalgia typically begin 12 to 24 hours after a dose. Less common or serious reactions include hypotension, syncope, chest pain, myocardial infarction, priapism, NAION, sudden hearing loss, visual disturbance and hypersensitivity reactions, including Stevens-Johnson syndrome and exfoliative dermatitis.

Cialis is not indicated for use in women. Adcirca labeling notes no adverse developmental effects in animal studies and limited human data in pregnancy. It is not known whether tadalafil is present in human milk; it is present in rat milk. The prescriber weighs benefits and risks for any use during pregnancy or breastfeeding.

Assess cardiovascular status and blood pressure before starting and when other blood-pressure-lowering drugs are added. Review renal and hepatic function and current CYP3A4 inhibitors or inducers to apply labeled dose limits. Ask about visual or hearing changes, prolonged erections and orthostatic symptoms. For BPH, evaluate for prostate cancer before treatment.

• Cialis (tadalafil) tablets Prescribing Information, Eli Lilly and Company.
• Adcirca (tadalafil) tablets Prescribing Information, Eli Lilly and Company.
• USP General Chapter <795> Pharmaceutical Compounding, Nonsterile Preparations.