| Medication | Mechanism and clinical use | Adverse effects and precautions | Drug interactions* | Usual dosing¶ |
| Phosphodiesterase type 5 (PDE5) inhibitors | ||||
| Sildenafil | Inhibits enzyme phosphodiesterase 5, allowing cyclic GMP to accumulate within penis. Effective for as-needed treatment of organic, psychogenic, or mixed type ED. | Applies to all PDE5 inhibitors:
| Sildenafil is metabolized by CYP3A4. Strong inhibitors of CYP3A4 (eg, protease inhibitors§, systemic-azole antifungals, certain macrolide antibiotics) elevate sildenafil concentrations. Inducers of CYP3A4 may reduce sildenafil concentrations. A list of CYP3A4 inhibitors and inducers is provided in a separate table*. We suggest avoidance of large amounts of grapefruit and its juice (a CYP3A4 inhibitor) as well as alcohol, which may enhance hypotensive effect. Use with nitrates or guanylate cyclase stimulators (eg, riociguat) is contraindicated (refer to adverse effects/precautions in this table and accompanying text). | Taken 1 hour before sex and effective up to 4 hours. Dose: 50 to 100 mg on empty stomach.¶ Administration with a high-fat meal may delay absorption. A reduced dose of 25 mg is recommended if coadministered with a strong inhibitor of CYP3A4 or an alpha-1 blocker and in patients with renal impairment (Crcl <30 mL/minute) or moderate hepatic impairment. Applies to all PDE5 inhibitors: Stimulation needed for erection. |
| Vardenafil | Same as sildenafil. | Similar efficacy, adverse effects, and precautions to sildenafil, EXCEPT visual color distortions reported much less frequently◊. Use not recommended in hemodialysis or severe hepatic impairment. | Same as sildenafil. | Similar onset and duration of action as sildenafil. Dose: 10 to 20 mg on empty stomach about 60 minutes before sexual activity.¶ Patients ≥65 years old: 5 mg initially. Orally disintegrating tablet (ODT): 10 mg on empty stomach (no titration). Administration with a high-fat meal may delay absorption. A reduced dose of 2.5 or 5 mg is recommended if coadministered with a strong inhibitor of CYP3A4 or an alpha-1 blocker, respectively*. Dose adjustment for moderate hepatic impairment needed. |
| Tadalafil | Similar onset of action as sildenafil. Duration of action up to 36 hours. Effective for as-needed or daily treatment of organic, psychogenic, or mixed type ED. | Similar efficacy, side effects, and precautions to sildenafil, EXCEPT visual color distortions reported much less frequently◊. Daily use not recommended in severe renal or hepatic impairment. | Same as sildenafil. | Tadalafil has a much longer duration of action than sildenafil. Dose for as-needed treatment: 10 to 20 mg about 30 minutes before sexual activity.¶ 10 mg not more than once every 72 hours is recommended if coadministered with a strong inhibitor of CYP3A4. Dose adjustment for renal or hepatic impairment is necessary when used as-needed. or Daily treatment: 2.5 to 5 mg once daily (assumes normal renal and hepatic function). 2.5 mg once daily is recommended if coadministered with a strong inhibitor of CYP3A4 or alpha-1 blocker*. Administration with a high-fat meal does not alter absorption. |
| Avanafil | Onset of action of 15 to 30 minutes is more rapid than sildenafil. | Similar efficacy, adverse effects, and precautions to sildenafil, EXCEPT visual color distortions reported much less frequently◊. Use not recommended in severe renal or hepatic impairment. | Same as sildenafil, EXCEPT use of avanafil with medications that are strong inhibitors of CYP3A4 is not recommended. A list of strong inhibitors of CYP3A4 (to be avoided with avanafil) is provided separately*. Grapefruit and grapefruit juice should be avoided within 24 hours of use. | 100 to 200 mg as early as 15 minutes before sexual activity. Administration with a high-fat meal may delay absorption. A reduced dose of 50 mg is recommended if coadministered with an alpha-1 blocker or moderate inhibitor of CYP3A4*. 50 mg dose should be taken about 30 minutes before sexual activity. |
| Other therapies | ||||
| Yohimbine In the United States, yohimbine is available as an ingredient in some nonprescription dietary supplements (yohimbe)¥. | Blocks presynaptic alpha-2 receptors. Stimulates mid-brain, increases libido. Might increase local blood flow or decrease outflow. Used for psychogenic ED. May have placebo effect. Alternative to testosterone for libido. | Dizziness, flushing, nausea, headache, anxiety, insomnia, elevated blood pressure, and increased heart rate; avoid with benign prostatic hyperplasia. Potency and purity of dietary supplements may not be assured. Long-term use is not recommended. | May interact with antihypertensives, antidepressants, or stimulant medications*. | 15 to 30 mg daily in 2 or 3 divided doses. |
| Trazodone | Serotonin modulation and alpha-1 antagonism. Used for psychogenic ED. May benefit males suffering from premature ejaculation. Low dose for psychogenic ED may not be effective for treatment of depression. | Dizziness, lethargy, sedation. Dose-related orthostatic hypotension, gastrointestinal toxicity, QTc prolongation, and weight gain. May cause priapism. | Trazodone is metabolized by CYP1A2, 2D6, and 3A4; it is an inducer of P-gp*. | 25 to 100 mg before sleep. |
CYP: cytochrome P450 drug metabolism; ED: erectile dysfunction; NAION: non-arteritic anterior ischemic optic neuropathy; P-gp: P-glycoprotein efflux transporters; SSRI: selective serotonin reuptake inhibitor; UDP-GT: glucuronyltransferase drug metabolism (glucuronidation).
* A list of strong inhibitors and inducers of CYP3A4 that can interact with PDE5 inhibitors is provided separately. This table does not provide a complete list of drug interactions. Specific drug interactions and management suggestions may be determined by using Lexi-Interact, the drug interactions program included with UpToDate.
¶ One-half of the usual PDE5 dose shown above may have adequate effect and better tolerability in some patients. The co-administration of more than one PDE5 inhibitor or use more than once per day is not recommended. Dose recommendations are based upon product information approved in United States and assume normal renal and hepatic function. Specific recommendations for use in setting of renal or hepatic impairment may be found in the Lexicomp drug monographs. Dose recommendations approved in other countries may differ. Consult locally approved product information.
Δ Riociguat is used in treatment of pulmonary arterial hypertension.
◊ Rarely, vision loss and non-arteritic anterior ischemic optic neuropathy (NAION) described in temporal association with PDE5 inhibitor in post-marketing reports. Precise causality (ie, PDE5 and/or patient-specific risk factors) not determined.
§ Protease inhibitors include atazanavir, boceprevir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, telaprevir and tipranavir. Interaction is of greater significance in ritonavir- or cobicistat-boosted regimens.
¥ Additional information on yohimbe-containing supplements is available from the US National Library of Medicine MedlinePlus database.