Physiology of Erection, p. 797
Oral Drugs for ED: PDE5 Inhibitors, p. 797 Sildenafil, p. 797
Vardenafil, Tadalafil, and Avanafil, p. 801 Nonoral Drugs for ED, p. 802
Alprostadil (Prostaglandin E1), p. 802 Papaverine Plus Phentolamine, p. 803 BENIGN PROSTATIC HYPERPLASIA, p. 803 Pathophysiology and Overview of Treatment,
p. 803
Pathophysiology, p. 803 Treatment Modalities, p. 803 Drug Therapy of BPH, p. 804
5-Alpha-Reductase Inhibitors, p. 804 Alpha1-Adrenergic Antagonists, p. 805 Alpha1 Blocker/5-Alpha-Reductase Inhibitor
Combination, p. 806
Tadalafil, a PDE5 Inhibitor, p. 806 Other Drugs for BPH, p. 807
Complementary and Alternative Medication (CAM) for BPH, p. 807
Key Points, p. 807
Summary of Major Nursing Implications, p. 808
include psychotherapy and surgical implantation of a penile prosthesis.
PHYSIOLOGY OF ERECTION
Before discussing drugs for ED, we need to review the physiol-ogy of erection. As shown in Fig. 66.1, the process begins with sexual arousal, which increases parasympathetic nerve traffic to the penis, causing local release of nitric oxide. Nitric oxide then activates guanylyl cyclase, an enzyme that makes cyclic guanosine monophosphate (cGMP). Through a series of steps, cGMP promotes relaxation of arterial and trabecular smooth muscle. The resultant arterial dilation increases local blood flow and blood pressure, which, in combination with relaxation of trabecular smooth muscle, causes expansion and engorgement of sinusoidal spaces in the corpus cavernosum.
This, in turn, causes venous occlusion and thereby reduces venous outflow. The combination of increased arterial pressure and arterial inflow plus reduced venous outflow causes sufficient engorgement to produce erection. Erection subsides when cGMP is removed by phosphodiesterase type 5 (PDE5), an enzyme that converts cGMP into guanosine monophosphate.
ORAL DRUGS FOR ED: PDE5 INHIBITORS
Drugs for ED fall into two major groups: oral agents and nonoral agents. The oral agents—PDE5 inhibitors—are by far the most common treatments for ED. These will constitute our primary focus. The nonoral agents—papaverine plus phentolamine, alprostadil—are considered briefly. These drugs are summarized in Table 66.2.
Four PDE5 inhibitors are available: sildenafil, tadalafil, vardenafil, and avanafil. All are considered first-line therapy for ED. Current guidelines recommend that, in the absence of a specific contraindication, all men with ED be offered one of these drugs. Which drug is preferred? Only a few trials have compared them head-to-head, so there is insufficient evidence to recommend one over the others. Accordingly, selection among them should be based on patient preference and prescriber judgment.
Sildenafil
Sildenafil [Viagra] was introduced in 1998 as the first oral treatment for ED. The drug is reliable and easy to use. Ben-efits derive from enhancing the natural response to sexual stimuli; sildenafil does not cause erection directly. Although sildenafil is generally well tolerated, it can be dangerous for
ERECTILE DYSFUNCTION
Erectile dysfunction (ED) is defined as a persistent inability to achieve or sustain an erection suitable for satisfactory sexual performance. In the United States, ED affects up to 30 million men. ED is commonly associated with chronic illnesses, especially diabetes, hypertension, and depression. Among men with diabetes, the incidence of ED is between 35% and 75%.
Some of the drugs that can cause ED are shown in Table 66.1.
The risk for ED increases with advancing age. According to the National Institutes of Health, ED affects approximately 4% of men in their 50s. Just a decade later, 17% of men in their 60s are unable to achieve any erection at all. This total inability to achieve erection affects 47% of men older than 75 years. Fortunately, new advances in medicine can rectify this problem for most patients.
First-line treatments for ED are lifestyle measures (increased exercise, smoking cessation), changing drug regimens to remove the drugs that may cause ED, and drug therapy with sildenafil [Viagra] or another drug in its class. Other interventions
Chapter 107).When used for this purpose, sildenafil is sold as Revatio.
Mechanism of Action
Sildenafil causes selective inhibition of PDE5. By doing so, it increases and preserves cGMP levels in the penis, thereby making the erection harder and longer lasting. Please note that the drug enhances only the normal erectile response to sexual stimuli (e.g., erotic imagery, fantasies, physical contact). In the absence of sexual stimuli, nothing happens.
Pharmacokinetics
Sildenafil is well absorbed after oral administration. Bioavail-ability is about 40%. In fasting subjects, plasma levels peak about 1 hour after dosing. A high-fat meal slows absorption, resulting in a peak plasma level in 2 hours (rather than 1) and reducing the peak concentration. Sildenafil is metabolized in the liver, primarily by the 3A4 isoenzyme of cytochrome P450 (CYP3A4). Both the parent drug and its major metabolite (N-desmethyl sildenafil) are biologically active. Both compounds are eliminated primarily in the feces (80%) and partly in the urine (13%). For both compounds, the half-life is 4 hours.
Clearance of both is delayed in men older than 65 years and in men with hepatic impairment or severe renal insufficiency, causing drug levels to rise higher and persist longer.
Sexual Benefits
In Men With ED. Sildenafil has been evaluated in several thousand men (ages 19 to 87 years) with ED of organic, psychogenic, or mixed-cause origin. At least some improvement in erection hardness and duration was seen in 70% of men taking the drug, compared with 20% taking placebo. Benefits were dose related and lasted up to 4 hours, although they began to fade after 2 hours. Sildenafil was able to help a wide range of patients, including those with ED resulting from diabetes, men taking certain vasodilators, specifically alpha-adrenergic
blockers, nitroglycerin, and other nitrates used for angina pectoris.
Drug Class Representative Drug [Brand Name] Incidence of SD/EDa
RENAL/CARDIOVASCULAR DRUGS
Cardiac glycosides Digoxin [Lanoxin] 36%
Adrenergic neuron blockers Reserpine 24%–40%
Central alpha2-adrenergic agonists Methyldopa 20%–30%
Beta blockers Propranolol [Inderal] 10%–15%
Thiazide diuretics Hydrochlorothiazide 10%–20%
Aldosterone antagonists Spironolactone [Aldactone] 4%–30%
CNS DRUGS
Selective serotonin reuptake inhibitors Fluoxetine [Prozac] Up to 70%
Monoamine oxidase inhibitors Isocarboxazid [Marplan] 16%–31%
Tricyclic antidepressants Amitriptyline [Elavil] 7%–30%
Antipsychotics Chlorpromazine [Thorazine] 30%–60%
Mood stabilizers Lithium [Lithobid] 5%–50%
Social lubricant/intoxicant Alcohol 50%–75%
UROGENITAL DRUGS
5-alpha-reductase inhibitors Finasteride [Proscar] 33%
TABLE 66.1 ■ Some Drugs That Can Cause Sexual/Erectile Dysfunction
aValues for sexual dysfunction/erectile dysfunction (SD/ED) incidence are estimates based on patient reports, not on carefully controlled trials.
Prototype Drugs
DRUGS FOR ED AND BPH Drugs for ED
Phosphodiesterase Type 5 Inhibitors Sildenafil
Nonoral Drugs
Papaverine/phentolamine Alprostadil
Drugs for BPH
5-Alpha-Reductase Inhibitors Finasteride
Alpha-Adrenergic Antagonists Tamsulosin
The erection-enhancing effects of sildenafil were discovered by accident. The drug was developed as a cardiac medicine, but benefits were minimal. However, in the course of testing, some men noticed a surprising side effect: Their ED had been cured! The rest, as they say, is history. Sildenafil has been wildly popular. First-year sales were the hottest in pharmaceuti-cal history. By now, tens of millions of men in more than 100 countries have used the drug. In addition to ED, sildenafil is approved for pulmonary arterial hypertension (PAH) (see
CHAPTER 66 Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia
Deep dorsal vein
Cavernous artery Tunica albuginea Sinusoidal spaces
Corpus cavernosum Trabecular smooth muscle
GTP
cGMP GMP
↑ Parasympathetic signaling to penis
↑ Release of nitric oxide
Arterial dilation
↑ Arterial pressure and inflow
Engorgement of sinusoidal spaces
in corpus cavernosum
Venous occlusion
↓ Venous outflow Sexual arousal
Flaccid
Erect Activation of
guanylyl cyclase
Relaxation of arterial smooth muscle
Relaxation of trabecular smooth muscle
↑ Intracavernosal volume and pressure, and hence
↑ penile size and rigidity PDE5
PDE5 inhibitors
act here
Alprostadil and papaverine
act here
Fig. 66.1 ■ Physiology of penile erection.
In the flaccid state, there is free outflow of venous blood and restricted inflow of arterial blood. During sexual arousal, cyclic guanosine monophosphate (cGMP) relaxes arterial and trabecular smooth muscle, permitting free inflow of arterial blood and subsequent engorge-ment of sinusoidal spaces, whose expansion compresses penile veins, restricting blood outflow.
The resultant accumulation of blood at elevated pressure increases penile size and rigidity.
Removal of cGMP by PDE5 restores penile smooth muscle to the nonaroused state, and detumescence ensues. (cGMP, Cyclic guanosine monophosphate; GMP, guanosine mono-phosphate; GTP, guanosine trimono-phosphate; PDE5, phosphodiesterase type 5.)
in irreversible blurring or loss of vision. The cause is blockage of blood flow to the optic nerve. In most cases, there were underlying anatomic or vascular risk factors for NAION. Also, although NAION developed during sildenafil use, a direct causal relationship has not been established. Nonetheless, patients with NAION in one eye should not use sildenafil, owing to a potential risk for developing NAION in the other eye.
Sudden Hearing Loss. Very rarely, men taking sildenafil have experienced sudden hearing loss, usually in one ear, sometimes in association with dizziness, vertigo, and tinnitus (ringing in the ears). Hearing loss may be partial or complete.
Hearing returned by the time the loss was reported in one-third of cases, but had not returned in the remaining two-thirds.
To date, a direct causal relationship between sildenafil and hearing loss has not been established. Nonetheless, the drug is suspected because (1) sudden hearing loss is unusual and (2) it developed when sildenafil was taken. Men who experience sudden hearing loss should discontinue the drug—but only if they are taking it for ED; men taking the drug for PAH should continue treatment.
Other Adverse Effects. The most common adverse effects are headache, flushing, and dyspepsia. Sildenafil may also cause nasal congestion, diarrhea, rash, and dizziness. About 3% of patients experience mild transient visual disturbances (blue color tinge to vision, increased sensitivity to light, blur-ring). In addition, sildenafil may intensify symptoms of obstructive sleep apnea (perhaps by relaxing pharyngeal muscles and/or dilating pulmonary blood vessels).
Drug Interactions
Nitrates. Both sildenafil and nitrates (e.g., nitroglycerin, isosorbide dinitrate) promote hypotension, and they both spinal cord injury, and transurethral prostate resection, as well
as ED of no known physical cause.
In Men Without ED. Despite anecdotal reports to the contrary, sildenafil has little or no effect on erection quality or duration in men who do not have ED. Any apparent benefits in healthy men are likely the result of a placebo response.
In Women. Sildenafil is not approved for use in women and probably won’t be. Although several large-scale studies showed the drug is safe in women, they failed to show much enhancement of sexual arousal. Thus the manufacturer decided not to seek U.S. Food and Drug Administration (FDA) approval for the treatment of female hypoactive sexual desire disorder or any other condition in women.
Adverse Effects
Hypotension. At recommended doses, sildenafil produces a small (8.4/5.5 mm Hg) reduction in blood pressure. However, in men taking nitrates or alpha blockers, severe hypotension can develop.
Priapism. A few cases of priapism (painful erection lasting more than 6 hours) have been reported. If an erection persists more than 4 hours, immediate medical intervention is required.
Left untreated, priapism can cause permanent damage of penile tissue. If priapism persists longer than 24 hours, chances are very high that the patient will never be able to have sexual intercourse again. Persistent erection can be relieved by aspirat-ing blood from the corpus cavernosum followed by irrigation with a solution containing a vasoconstrictor (e.g., epinephrine, phenylephrine, metaraminol). If this is unsuccessful, surgery is required.
Nonarteritic Ischemic Optic Neuropathy (NAION). Very rarely, men taking sildenafil have developed NAION, resulting
Parameter
Drug
Sildenafil [Viagra] Tadalafil [Cialis] Vardenafil [Levitra,
Staxyn] Avanafil [Stendra]
Date approved 3/27/1998 11/21/2003 8/19/2003 4/28/2012
Dosing schedule PRN only PRN or once daily PRN only PRN
Median time to peak level 1 hr 2 hr 1 hr 30–45 min
Half-life 4 hr 17.5 hr 4–5 hr 5 hr
Duration of action 4 hr 36 hr 4 hr 4 hr
Major mode of metabolism CYP3A4 CYP3A4 CYP3A4 CYP3A4
Drug interactions
Nitrates Contraindicated: Wait
24 hr before giving a nitrate
Contraindicated: Wait 48 hr before giving a nitrate
Contraindicated: Wait 24 hr before giving a nitrate
Contraindicated: Wait 12 hr before giving a nitrate
Alpha blockers Use with caution Contraindicated (except for tamsulosin, 0.4 mg once daily)
Contraindicated Use with caution
CYP3A4 inhibitors Reduce sildenafil
dosage Reduce tadalafil dosage
to no more than 10 mg every 72 hr
Reduce vardenafil
dosage Do not take with strong
CYP3A4 inhibitors;
reduce dosage with moderate inhibitors Class I and class III
antidysrhythmic drugs No interaction No interaction Vardenafil prolongs the QT interval—avoid class I and class III antidysrhythmics
No interaction TABLE 66.2 ■ Comparison of PDE5 Inhibitors
CHAPTER 66 Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia
Vardenafil, Tadalafil, and Avanafil
Vardenafil, tadalafil, and avanafil are very similar to sildenafil. All three drugs inhibit PDE5, and all three are approved for oral therapy of ED. Vardenafil is unique in that it prolongs the QT interval, and tadalafil is unique in that its effects last 36 hours. Avanafil is unique in that it has the fastest onset of action. Otherwise, the clinical effects of all four PDE5 inhibitors appear about equal, although some patients may respond better to one than to the others.
Pharmacokinetics and other properties of all four are shown in Table 66.2.
Preparation, dosage, and administration guidelines for these drugs are provided in Table 66.3.
Vardenafil
Actions and Use. Vardenafil [Levitra, Staxyn] was the second selective PDE5 inhibitor approved for ED. As with sildenafil, benefits derive from relaxing arterial and trabecular smooth muscle in the penis. Effects begin about 60 minutes after dosing and persist about 4 hours. There is no evidence that vardenafil works faster, longer, or better than sildenafil.
Adverse Effects. The most common adverse effects are headache, flushing, and rhinitis. Like other PDE5 inhibitors, vardenafil can lower blood pressure. Like sildenafil, vardenafil can cause visual changes, and has been associated with sudden hearing loss and vision loss from NAION.
Vardenafil can prolong the cardiac QT interval and might thereby pose a risk for serious dysrhythmias. However, dysrhythmias have not been reported.
Nonetheless, to reduce risk, vardenafil should be used with caution in patients taking other drugs that cause QT prolongation.
Drug Interactions. Vardenafil is contraindicated for use with alpha-adrenergic blockers and with nitroglycerin and other nitrates. Plasma levels can be increased by inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir), and hence such combinations must be used with caution. As noted, caution is needed in patients taking drugs that prolong the QT interval.
Tadalafil
Actions and Uses. Tadalafil [Cialis] was approved mere months after vardenafil. Like sildenafil and vardenafil, the drug is indicated for oral therapy of ED. As with other PDE5 inhibitors, benefits derive from relaxation of penile arterial and trabecular smooth muscle brought on by accumulation of cGMP. On average, therapeutic levels of the drug are reached by 2 hours after dosing and persist about 36 hours—much longer than with sildenafil or vardenafil. As a result, the timing of dosing and sexual activity needn’t be tightly coupled. Furthermore, in addition to being approved for PRN dosing (like sildenafil and vardenafil), tadalafil is also approved for daily dosing (but only for men who anticipate sexual activity at least twice a week).
As discussed later, tadalafil is also used for benign prostatic hyperpla-sia (BPH). In addition, like sildenafil, tadalafil, sold as Adcirca, is used for PAH.
Adverse Effects. The most common adverse effects are headache, dyspepsia, back pain, myalgia, limb pain, flushing, and nasal congestion. Like other PDE5 inhibitors, tadalafil can lower blood pressure. Very rarely, the drug alters color vision. A few cases of NAION and sudden hearing loss have been reported, but a causal relationship has not been established. Because tadalafil has a long duration of action, adverse effects may persist for many hours.
Drug Interactions. Tadalafil is contraindicated for use with nitrates or alpha blockers (except tamsulosin [Flomax]). As with sildenafil and vardenafil, CYP3A4 inhibitors can cause levels of tadalafil to rise. To avoid toxicity, men taking CYP3A4 inhibitors should limit tadalafil dosage to 10 mg every 72 hours.
Avanafil
Actions and Use. Avanafil [Stendra], approved in 2012, is the latest selective PDE5 inhibitor approved for ED. Actions are the same as for the other PDE5 inhibitors; however, effects begin about 15 minutes after dosing and last about 2 hours.
Adverse Effects. Headache is the only adverse effect, occurring in at least 10% of patients. A few patients will experience flushing, nasal congestion, and nasopharyngitis. Like other PDE5 inhibitors, avanafil can lower blood pressure.
Drug Interactions. Avanafil is contraindicated for use with nitroglycerin and other nitrates. It can increase the hypotensive effects of alcohol and antihypertensive drugs, especially alpha-adrenergic antagonists. A starting dose of 50 mg (the lowest strength available) is recommended if prescribed for patients taking antihypertensive drugs.
Plasma levels can be increased when taken with CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, and erythromycin). For this reason, dosing should not exceed 50 mg in 24 hours for patients taking CYP3A4 inhibitors.
do so by increasing cGMP (nitrates increase cGMP forma-tion and sildenafil slows cGMP breakdown). If these drugs are combined, life-threatening hypotension could result.
Therefore, sildenafil is absolutely contraindicated for men taking nitrates. At least 24 hours should elapse between the last dose of sildenafil and giving a nitrate. If elimination of sildenafil is slowed (owing to a CYP3A4 inhibitor or hepatic or renal impairment), an even longer time should elapse before nitrate use.
Alpha Blockers. Alpha-adrenergic antagonists—including doxazosin [Cardura] and other alpha blockers used for prostatic hyperplasia (discussed later)—dilate arterioles and can thereby lower blood pressure. Combined use with sildenafil has caused symptomatic postural hypotension. Accordingly, these combina-tions should be used with caution.
Inhibitors of CYP3A4. Inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, erythromycin, cimetidine, saquinavir, ritonavir, grapefruit juice) can suppress metabolism of sildenafil, thereby increasing its levels. These combinations should be used with caution.
Is Sildenafil Safe for Men With CHD?
Reports of adverse cardiovascular events, including at least 130 cardiac deaths, raised concern about the safety of sildenafil in men with coronary heart disease (CHD). However, there was a question as to what caused the adverse events: sildenafil or the sexual activity that sildenafil permitted. When attempting to answer this question, researchers made two important observations: First, giving sildenafil to resting men with severe CHD produced no harmful effects on coronary blood flow or any other hemodynamic parameter. Second, in men with stable CHD who were performing exercise, sildenafil had no effect on CHD symptoms, exercise tolerance, or exercise-induced ischemia. Taken together, these results suggest that, in men with CHD, sexual activity—and not sildenafil—is the likely cause of ischemic events. However, even though sildenafil itself appears safe for men with CHD, sexual activity may not be. Accordingly, the drug should be used with caution by men with the following conditions:
• Myocardial infarction, stroke, or life-threatening dys-rhythmia within the past 6 months
• Resting hypotension (blood pressure below 90/50 mm Hg)
• Resting hypertension (blood pressure above 170/
110 mm Hg)
• Heart failure
• Unstable angina
In addition, sildenafil should not be used at all by men taking nitroglycerin or any other drug in the nitrate family.
To reduce the risk for adverse events, candidates for sildenafil therapy should undergo a careful evaluation of cardiovascular function. Those with impaired function should be counseled about the risks posed by sexual activity and all other moderate to intense physical activity.
Preparations, Dosage, and Administration
For treatment of ED, sildenafil is available in 25-, 50-, and 100-mg tablets sold as Viagra. The usual dose is 50 mg taken 1 hour before sexual activity.
The dosage range is 25 to 100 mg taken 30 minutes to 4 hours before sexual activity. A low dose (25 mg) should be considered for men older than 65, men with hepatic dysfunction or severe renal dysfunction, and men taking alpha blockers or drugs that inhibit CYP3A4. Dosing should not be done more than once a day.
(arterial, venous, and trabecular) causes a rapid inflow of arterial blood. As explained when discussing the physiology of erection, the blood fills the vascular sinusoidal spaces of the corpus cavernosum, resulting in an erection.
Pressure from the engorged penis helps block venous outflow to promote maintenance of the erect state.
Adverse Effects
The most common adverse effect, dull ache in the penis, occurs in 32% of users. Another 12% report urethral burning. Minor bleeding or spotting and testicular pain occur in about 5% of patients. Systemic symptoms are rare when taken as directed and approximate those of placebo use.
NONORAL DRUGS FOR ED
Unlike the PDE5 inhibitors, which are administered orally, the drugs discussed in this section—alprostadil and papaverine/phentolamine—are administered by nonoral routes. Specifically, they are administered either by injection into the penis or by insertion into the urethra. Because of this inconvenient dosing, these drugs are second-line agents for ED.
Alprostadil (Prostaglandin E1)
Mechanism of Action
Alprostadil’s active ingredient has the same chemical structure as prostaglandin E1 (PGE1), which has vasodilating properties. Relaxation of smooth muscle
Drug Preparation Dosage for ED Administration
PDE5 INHIBITORS
Avanafil [Stendra] Tablets: 50, 100, 200 mg 100 mg taken approximately 15 minutes before sexual activity. May be increased to 200 mg if needed.
Decrease to lowest effective dose.
May be taken with or without food, but avoid grapefruit juice.
High-fat foods delay the time to onset. Do not take more than once a day.
Sildenafil [Viagra] Tablets: 25, 50, 100 mg 50 mg once daily approximately 60 minutes before sexual activity. May be increased to 100 mg if needed.
Decrease to lowest effective dose.
May be taken with or without food, but avoid grapefruit juice.
High-fat foods may delay onset by as much as 60 minutes.
Do not take more than once a day.
Tadalafil [Cialis] Tablets: 2.5, 5, 10, 20 mg PRN use: 10 mg before sexual activity. May be increased to 20 mg if needed. Decrease to lowest effective dose.
Daily use: 2.5 mg once daily; timing unrelated to sexual activity. May increase to 5 mg if needed.
May be taken with or without food, but avoid grapefruit juice.
Do not take more than once a day.
If administered for daily use, take at the same time each day.
Vardenafil [Levitra,
Staxyn] Tablets (Levitra): 2.5, 5, 10, 20 mg
Orally disintegrating tablets (Staxyn): 10 mg
Levitra: 10 mg taken approximately 60 minutes before sexual activity. May be increased to 20 mg if needed.
Decrease to lowest effective dose.
Decrease starting dose to 5 mg for patients age 65 and older.
Staxyn: 10 mg taken approximately 60 minutes before sexual activity. Do not increase dosage.
Levitra: May be taken with or without food, but avoid grapefruit juice and fatty foods.
Staxyn: Place tablet on tongue and allow to disintegrate. Do not take with food or drink.
Both: Do not take more than once a day.
PROSTAGLANDIN E1
Alprostadil intracavernosal injection [Caverject, Caverject Impulse, Edex]
Intracavernosal Kit (Caverject Impulse): 10, 20 mcg Intracavernosal Kit (Edex):
10, 20, 40 mcg
Solution for Intracavernosal Injection (Caverject): 20, 40 mcg
Typical dosages range from 5–40 mcg.
Dosing is individualized;
determination is made in the healthcare setting. Maximum dosing is 60 mcg for Caverject and 40 mcg for Edex.
Patients self-administer injection into the penis.
Do not take more than once in 24 hours. Limit total dosing to 3 times a week.
Alprostadil intraurethral
insertion [Muse] Urethral pellets (Muse): 125,
250, 500, 1000 mcg Intraurethral insertion: Initial dosing is 125–250 mcg 5–10 minutes before sexual activity. (Effect lasts 30–60 minutes.) Increase, if needed, to lowest effective dose.
Patients self-insert the pellet into the urethra.
Limit use to twice daily.
VASODILATOR + ALPHA-ADRENERGIC ANTAGONIST Papaverine with
phentolamine Papaverine 30 mg/mL with
phentolamine 1 mg/mL Dosing is individualized;
determination is made in the healthcare setting. As little as 0.1 mL may be sufficient.
Patients self-administer injection into the penis.
TABLE 66.3 ■ Drugs for Erectile Dysfunction: Preparation, Dosage, and Administration