Seeing blue after the little blue pill: visual disturbances in sildenafil users

Pfizer already has employed two separate strategies that may help it hang onto sales in the ED market. It markets Revatio, a lower-dose version of sildenafil (the active ingredient in Viagra) intended for pulmonary arterial hypertension. And regulators in the United Kingdom last month approved a version of Viagra that can be sold without a prescription.

What should I know about STORAGE and DISPOSAL of this medication?

Here, well discuss the drugs mechanism of action and possible adverse effects. ED DefinedErectile dysfunction is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.10 While not life threatening, ED may result in a withdrawal from sexual intimacy and a reduced quality of life.11 The etiology of ED typically involves both organic and psychogenic factors.12 Almost any disease that alters the vascular, nervous or endocrine systemsincluding diabetes mellitus, hypertension, heart disease and depressioncan increase the risk of developing ED. Also, the risk of ED dramatically increases with age.11 Penile erections involve the coordination of psychological, neurological, endocrine, vascular and muscular components. Tumescence, the vascular filling of the corpus cavernosa (cavernous bodies) of the penis, relies on neural and hormonal mechanisms that operate at various levels of sildenafil citrate 100 mg the neural axis. The brain gathers information from a particular stimulus (touch, smell or visual) and sends that information to the base of the spine.

Sildenafil: what you need to know

There, primary nerve fibers that connect to the penis regulate blood flow during and after an erection. Specifically, blood flow regulation depends on the relaxation and constriction of the smooth muscle of the cavernous bodies, which react via nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). During sexual stimulation, the NO-cGMP pathway facilitates the relaxation of smooth muscle, thus increasing blood flow while closing venous drainage channels. The cavernous bodies become full and rigid, resulting in an erection.12 Therapies for ED include sexual counseling, external vacuum devices, vasoactive injection therapies, penile implants and oral medications such as sildenafil. Viagras ActionSildenafil itself does not cause an erection. Pharmacy websites have for some time shown men how to save by using Revatio. GoodRx says generic and branded versions of Revatio already compete with Viagra, with "the most common version of sildenafil" costing "around $14.45, 95% off the average retail price of $291.46." In a 2013 blog post, Cooper Drug Store of August, Kansas, reported saving a customer "exactly $238.72 on just one prescription by asking his physician to prescribe generic Revatio, which was covered at a generic copay, rather than brand-name Levitra." In the United Kingdom, regulators in November cited concerns about counterfeit versions of Viagra as a reason for allowing pharmacy sales of the drug without requiring prescriptions. In the past 5 years, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) investigators seized more than £50 million of unlicensed and counterfeit erectile dysfunction medicines, the agency said. "Making this medication more widely available will help direct men who might not otherwise seek help into the healthcare system and away from the risks that come with buying medicines from websites operating illegally," the UK regulators said in a statement. The MHRA said that pharmacists will be able to determine whether men can get a 50-mg version of the drug, branded as Viagra Connect. The drug is not intended for patients with severe heart, liver, or kidney conditions, the UK regulators stressed.

Over-the-Counter Viagra in US Future? For the US market, making such a switch for Viagra "would be a tricky decision, and one that's important to get right," Caleb Alexander, MD, co-director of the Center for Drug Safety and Effectiveness at the Bloomberg School of Public Health at Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News. The US Food and Drug Administration in recent years has approved switches from prescription requirements to over-the-counter status for several allergy medicines. "This would not be a slam dunk" for Viagra, Dr Alexander said of any potential bid to switch status for Viagra in the United States.

• The onset of action may be faster if taken on an empty stomach.
• It is important to avoid other erectile dysfunction treatments while using this.
• Can cause palpitations or a racing heartbeat in some individuals.
• The medication's effects can be diminished by excessive alcohol consumption.
• It is not recommended for men with low blood pressure or hypertension.
• The blue film coating protects the active ingredient from degradation.
• A sudden decrease in blood pressure upon standing (orthostasis) may occur.

Many men have ED as a result of chronic diseases, he said. For that reason, doctors need to weigh the potential risk for complications among men in poor health posed by using drugs such as Viagra. "The same patients that have erectile dysfunction often have diabetes or heart disease or other vascular disease," said Dr Alexander, who is also a practicing primary care physician. "This is a medicine that, by virtue of the condition that it's treating, will be used [by men who] are at elevated risk for adverse events." Cite this: Little Blue Pill Goes Generic Today, and Pfizer Joins In - Medscape - Dec 11, 2017.

Erectile dysfunction (ED) affects up to 30 million men in the United States, including half of all men ages 40 to 70.1 Some 7% of men ages 18 to 29 have some form of ED, as do 18% of men ages 50 to 59.2 So, its no wonder that Viagra (sildenafil, Pfizer), the so-called little blue pill, is one of the worlds best-selling pharmaceutical agents. However, several studies have associated the drug with nonarteritic anterior ischemic optic neuropathy (NAION).3-9 In June, Pfizer agreed to include the report of NAION on the Viagra label, even though the company said its own review of 13,000 patients found no evidence that NAION occurred more frequently in men taking Viagra than in men of similar age and health who did not take the drug. Still, optometrists must know how sildenafil works and be aware of potential adverse ocular side effects. Here, well discuss the drugs mechanism of action and possible adverse effects. ED DefinedErectile dysfunction is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.10 While not life threatening, ED may result in a withdrawal from sexual intimacy and a reduced quality of life.11 The etiology of ED typically involves both organic and psychogenic factors.12 Almost any disease that alters the vascular, nervous or endocrine systemsincluding diabetes mellitus, hypertension, heart disease and depressioncan increase the risk of developing ED. Also, the risk of ED dramatically increases with age.11 Penile erections involve the coordination of psychological, neurological, endocrine, vascular and muscular components. Tumescence, the vascular filling of the corpus cavernosa (cavernous bodies) of the penis, relies on neural and hormonal mechanisms that operate at various levels of sildenafil citrate 100 mg the neural axis. The brain gathers information from a particular stimulus (touch, smell or visual) and sends that information to the base of the spine.

What OTHER INFORMATION should I know?

Pfizer already has employed two separate strategies that may help it hang onto sales in the ED market. It markets Revatio, a lower-dose version of sildenafil (the active ingredient in Viagra) intended for pulmonary arterial hypertension. And regulators in the United Kingdom last month approved a version of Viagra that can be sold without a prescription. Pharmacy websites have for some time shown men how to save by using Revatio. GoodRx says generic and branded versions of Revatio already compete with Viagra, with "the most common version of sildenafil" costing "around $14.45, 95% off the average retail price of $291.46." In a 2013 blog post, Cooper Drug Store of August, Kansas, reported saving a customer "exactly $238.72 on just one prescription by asking his physician to prescribe generic Revatio, which was covered at a generic copay, rather than brand-name Levitra." In the United Kingdom, regulators in November cited concerns about counterfeit versions of Viagra as a reason for allowing pharmacy sales of the drug without requiring prescriptions.

Off-label use for Viagra

In the past 5 years, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) investigators seized more than £50 million of unlicensed and counterfeit erectile dysfunction medicines, the agency said. "Making this medication more widely available will help direct men who might not otherwise seek help into the healthcare system and away from the risks that come with buying medicines from websites operating illegally," the UK regulators said in a statement. The MHRA said that pharmacists will be able to determine whether men can get a 50-mg version of the drug, branded as Viagra Connect. The drug is not intended for patients with severe heart, liver, or kidney conditions, the UK regulators stressed. Over-the-Counter Viagra in US Future? There, primary nerve fibers that connect to the penis regulate blood flow during and after an erection.

MYTH #2: “Viagra is going to give you a heart attack”

For the US market, making such a switch for Viagra "would be a tricky decision, and one that's important to get right," Caleb Alexander, MD, co-director of the Center for Drug Safety and Effectiveness at the Bloomberg School of Public Health at Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News. The US Food and Drug Administration in recent years has approved switches from prescription requirements to over-the-counter status for several allergy medicines. "This would not be a slam dunk" for Viagra, Dr Alexander said of any potential bid to switch status for Viagra in the United States. Many men have ED as a result of chronic diseases, he said. For that reason, doctors need to weigh the potential risk for complications among men in poor health posed by using drugs such as Viagra.

Does Viagra treat ED that’s related to diabetes?

"The same patients that have erectile dysfunction often have diabetes or heart disease or other vascular disease," said Dr Alexander, who is also a practicing primary care physician. "This is a medicine that, by virtue of the condition that it's treating, will be used [by men who] are at elevated risk for adverse events." Cite this: Little Blue Pill Goes Generic Today, and Pfizer Joins In - Medscape - Dec 11, 2017. Erectile dysfunction (ED) affects up to 30 million men in the United States, including half of all men ages 40 to 70.1 Some 7% of men ages 18 to 29 have some form of ED, as do 18% of men ages 50 to 59.2 So, its no wonder that Viagra (sildenafil, Pfizer), the so-called little blue pill, is one of the worlds best-selling pharmaceutical agents. However, several studies have associated the drug with nonarteritic anterior ischemic optic neuropathy (NAION).3-9 In June, Pfizer agreed to include the report of NAION on the Viagra label, even though the company said its own review of 13,000 patients found no evidence that NAION occurred more frequently in men taking Viagra than in men of similar age and health who did not take the drug. Still, optometrists must know how sildenafil works and be aware of potential adverse ocular side effects. Specifically, blood flow regulation depends on the relaxation and constriction of the smooth muscle of the cavernous bodies, which react via nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). During sexual stimulation, the NO-cGMP pathway facilitates the relaxation of smooth muscle, thus increasing blood flow while closing venous drainage channels. The cavernous bodies become full and rigid, resulting in an erection.12 Therapies for ED include sexual counseling, external vacuum devices, vasoactive injection therapies, penile implants and oral medications such as sildenafil. Viagras ActionSildenafil itself does not cause an erection. Rather, it inhibits phosphodiesterase-5 (PDE5), an enzyme that degrades cGMP, thus increasing intracellular levels of cGMP. This, in turn, promotes relaxation of the smooth muscle of the penis to enhance erectile function. The standard recommended starting dose is 25mg to 50mg. The dose may be increased to 100mg if needed, although higher doses have an increased incidence of side effects with little gain in efficacy.

• Blue sildenafil remains one of the most prescribed medications for ED worldwide.
• Its popularity has increased with modern marketing and awareness efforts.
• The cost of blue sildenafil varies depending on the source and brand.
• Some individuals use blue sildenafil occasionally, while others use it regularly.
• Psychological factors like anxiety can influence the effectiveness of sildenafil.
• Sildenafil should not be combined with other ED medications.
• Using blue sildenafil in combination with recreational drugs can be dangerous.
• The safety profile of sildenafil is well-studied, but individual responses vary.
• Healthcare providers recommend regular health check-ups for frequent users.
• Proper hydration can help reduce side effects when using sildenafil.

Patients are typically instructed not to use sildenafil more than once in any 24-hour period and not to use the drug more than two or three times per week.13 Sildenafil reaches a peak plasma concentration between two and four hours. Because sildenafil potentiates vasodilation, the concomitant use of any nitrates is an absolute contraindication for its use, as these increase the possibility of abrupt and potentially serious hypotension.13 Also, because sildenafil is metabolized predominantly by the cytochrome P450 3A4 isoenzyme, patients who take medications that inhibit this pathway (erythromycin, ketoconazole and cimetidine) should not take sildenafil or should at least lower their dosage and/or frequency of use.14 Although sildenafil primarily affects PDE5, most potential side effects occur because the drug has a slight effect on other phosphodiesterases throughout the body, including those in the brain and cardiac tissue. The most common side effects of sildenafil include headache, flushing, dyspepsia, nasal congestion and visual disturbances.13 Serious cardiovascular, cerebrovascular and vascular eventsincluding myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhageare possible, though rare, side effects.15 The FDA has concluded that it is not possible to determine whether these events are directly related to Viagra, sexual activity, underlying cardiovascular disease, a combination of these factors or other factors.16 Ocular Side EffectsOcular side effects of sildenafil have been well documented.

The most prominent: complaints of a bluish tinge to vision, increased light sensitivity and halos.11,17 The incidence of these visual symptoms is infrequent at low doses but may be as high as 50% at 200mg.18 The mechanism for this phenomenon remains unknown. One theory: Sildenafil has up to 10% effectiveness against phosphodiesterase-6, an enzyme localized to the photoreceptors in the retina. This enzyme is important in transduction, the process in which light energy is converted to a neural signal. Because of the action against PDE6, alterations in cGMP within the cone photoreceptors may be responsible for these visual side effects.13 Higher doses of Viagra (>200mg) have been reported to cause transient visual changes, slight electroretinogram changes and subtle color-vision changes.13,19-21 There is no significant evidence that sildenafil affects visual acuity, visual field, IOP or visual evoked potentials.22,23 NAIONMore serious ocular side effects that have irreversible visual complications also have been linked with sildenafil. Since 1999, more than 20 documented cases of nonarteritic anterior ischemic optic neuropathy (NAION) occurred among individuals following sildenafil ingestion.3-9 A disc at riska crowded, small optic nerve head that has a small physiologic cup, abnormal branching of the central vessels and full nerve fiber bundles obscuring the disc marginis the typical optic nerve head seen in NAION and is almost always seen in the fellow eye (figure 4).24 Visual acuity may vary from 20/20 to a marked loss of vision, depending on which part of the optic nerve head is involved.

• The medication is metabolized primarily in the liver by cytochrome P450 enzymes.
• Patients with Peyronie's disease or anatomical deformities should use caution.
• It is not intended for continuous daily use like some other ED medications.
• The average time to peak plasma concentration is about 60 minutes.
• Can be part of a comprehensive treatment plan including lifestyle changes.
• The blue dye used is usually FD&C Blue No. 2 or a similar approved colorant.
• It is important to have realistic expectations about the medication's effects.

Structural factors of a disc at risk and subsequent alterations to perfusion pressure in the peripheral branches of the posterior ciliary arteries lead to microvascular ischemia.28 This ischemia, which occurs in the capillaries, causes axoplasmic stasis and edema of the optic nerve head. Risk is significantly increased in older patients, as their capillaries often are already compromised, potentially increasing the level of ischemia.

How to save on Viagra

Because of the action against PDE6, alterations in cGMP within the cone photoreceptors may be responsible for these visual side effects.13 Higher doses of Viagra (>200mg) have been reported to cause transient visual changes, slight electroretinogram changes and subtle color-vision changes.13,19-21 There is no significant evidence that sildenafil affects visual acuity, visual field, IOP or visual evoked potentials.22,23 NAIONMore serious ocular side effects that have irreversible visual complications also have been linked with sildenafil. Since 1999, more than 20 documented cases of nonarteritic anterior ischemic optic neuropathy (NAION) occurred among individuals following sildenafil ingestion.3-9 A disc at riska crowded, small optic nerve head that has a small physiologic cup, abnormal branching of the central vessels and full nerve fiber bundles obscuring the disc marginis the typical optic nerve head seen in NAION and is almost always seen in the fellow eye (figure 4).24 Visual acuity may vary from 20/20 to a marked loss of vision, depending on which part of the optic nerve head is involved. Structural factors of a disc at risk and subsequent alterations to perfusion pressure in the peripheral branches of the posterior ciliary arteries lead to microvascular ischemia.28 This ischemia, which occurs in the capillaries, causes axoplasmic stasis and edema of the optic nerve head. Risk is significantly increased in older patients, as their capillaries often are already compromised, potentially increasing the level of ischemia. The role of sildenafil in NAION is unknown, but reports suggest that the effect on blood pressure through the NO-cGMP pathway may be responsible.3-5,21,22,29-31 Just as NO can regulate blood pressure through vasodilation, NO may also dilate blood vessels around the optic nerve head and influence its perfusion, subsequently interfering with the autoregulation of ocular blood flow.5,22,29-31 The circulation of the optic disc, peripapillary choroid and choroid depends upon the difference in perfusion pressure of the posterior ciliary arteries and IOP.28 If sildenafil accentuates hypotension enough, the perfusion pressure in the posterior ciliary arteries may decrease and cause an oxygen imbalance, and ultimately an ischemic optic nerve head.

When to take

The role of sildenafil in NAION is unknown, but reports suggest that the effect on blood pressure through the NO-cGMP pathway may be responsible.3-5,21,22,29-31 Just as NO can regulate blood pressure through vasodilation, NO may also dilate blood vessels around the optic nerve head and influence its perfusion, subsequently interfering with the autoregulation of ocular blood flow.5,22,29-31 The circulation of the optic disc, peripapillary choroid and choroid depends upon the difference in perfusion pressure of the posterior ciliary arteries and IOP.28 If sildenafil accentuates hypotension enough, the perfusion pressure in the posterior ciliary arteries may decrease and cause an oxygen imbalance, and ultimately an ischemic optic nerve head.

About the Company

Rather, it inhibits phosphodiesterase-5 (PDE5), an enzyme that degrades cGMP, thus increasing intracellular levels of cGMP. This, in turn, promotes relaxation of the smooth muscle of the penis to enhance erectile function. The standard recommended starting dose is 25mg to 50mg. The dose may be increased to 100mg if needed, although higher doses have an increased incidence of side effects with little gain in efficacy. Patients are typically instructed not to use sildenafil more than once in any 24-hour period and not to use the drug more than two or three times per week.13 Sildenafil reaches a peak plasma concentration between two and four hours.

What should I do if I miss a dose of sildenafil?

Because sildenafil potentiates vasodilation, the concomitant use of any nitrates is an absolute contraindication for its use, as these increase the possibility of abrupt and potentially serious hypotension.13 Also, because sildenafil is metabolized predominantly by the cytochrome P450 3A4 isoenzyme, patients who take medications that inhibit this pathway (erythromycin, ketoconazole and cimetidine) should not take sildenafil or should at least lower their dosage and/or frequency of use.14 Although sildenafil primarily affects PDE5, most potential side effects occur because the drug has a slight effect on other phosphodiesterases throughout the body, including those in the brain and cardiac tissue. The most common side effects of sildenafil include headache, flushing, dyspepsia, nasal congestion and visual disturbances.13 Serious cardiovascular, cerebrovascular and vascular eventsincluding myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhageare possible, though rare, side effects.15 The FDA has concluded that it is not possible to determine whether these events are directly related to Viagra, sexual activity, underlying cardiovascular disease, a combination of these factors or other factors.16 Ocular Side EffectsOcular side effects of sildenafil have been well documented. The most prominent: complaints of a bluish tinge to vision, increased light sensitivity and halos.11,17 The incidence of these visual symptoms is infrequent at low doses but may be as high as 50% at 200mg.18 The mechanism for this phenomenon remains unknown. One theory: Sildenafil has up to 10% effectiveness against phosphodiesterase-6, an enzyme localized to the photoreceptors in the retina. This enzyme is important in transduction, the process in which light energy is converted to a neural signal.