10 OVERDOSAGE

Available on the World Wide Web at: Food and Drug Administration (US FDA) Drug Safety Communication. Revatio (sildenafil)-FDA clarifies warning about pediatric use for pulmonary arterial hypertension. Available on the World Wide Web at: Abman SH, Kinsella JP, Rosenzweig EB, et al. Implications of the U.S. Food and Drug Administration Warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension. The Top 100 Drug Interactions: A Guide to Patient Management. includes table of CYP450 and drug transporter substrates and modifiers (appendices).

Overdose/Missed Dose

Transient global amnesia has been reported during post-marketing use of sildenafil. The frequency is unknown and causality has not been established. Two cases of tonic-clonic seizures have been reported with sildenafil use.84 Seizure recurrence has also been included in post-marketing reports. Other gastrointestinal and urogenital adverse reactions reported by persons receiving sildenafil include nausea (25%), gastritis (< 3%), and hematuria. Adverse reactions affecting the musculoskeletal system and occurring in < 2% of patients in controlled clinical trials of sildenafil include arthritis, arthrosis, bone pain, myasthenia, synovitis, tendon rupture, and tenosynovitis.

Warnings and Precautions

Myalgia was reported by <= 7% of persons receiving sildenafil during clinical trials. Adverse reactions affecting the skin and appendages and occurring in < 2% of patients in controlled clinical trials of sildenafil include contact dermatitis, diaphoresis, exfoliative dermatitis, herpes simplex, pruritus, skin ulcer, and urticaria. During clinical trials, erythema was reported by 6% of sildenafil recipients. Adverse reactions affecting hearing or otic special senses and occurring in < 2% of patients in controlled clinical trials of sildenafil include hearing loss, otalgia, and tinnitus. In addition, 29 reports of sudden changes in hearing including hearing loss or decrease in hearing, usually in 1 ear only, have been reported to the FDA during post-marketing surveillance in patients taking sildenafil, tadalafil, or vardenafil; the reports are associated with a strong temporal relationship to the dosing of these agents.

Why it’s used

Many times, the hearing changes are accompanied by vestibular effects including dizziness, tinnitus, and vertigo. Follow-up has been limited in many of the reports; however, in approximately one-third of the patients, the hearing loss was temporary. Concomitant medical conditions or patient factors may play a role, although risk factors for the onset of sudden hearing loss have not been identified. Patients should be instructed to contact their physician if they experience changes in hearing. [12][15] A thorough ophthalmic examination, in addition to cardiovascular risk assessment, should be considered for patients prior to prescribing phosphodiesterase inhibitors. Indianapolis, IN: Lilly ICOS, LLC; 2011 Oct.

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Indianapolis, IN: Lilly ICOS, LLC; 2007 Jan. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2014 Aug. Hall MCS, Ahmad S. Interaction between sildenafil and HIV-1 combination therapy. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.

Use Case	Description	Typical Dosage	Onset of Action	Duration
Erectile Dysfunction	Helps achieve and maintain erections during sex	125 mg	30-60 minutes	Up to 4-6 hours
Pulmonary Hypertension	Relieves high blood pressure in lung arteries	125 mg	15-30 minutes	4-6 hours
Off-Label Uses	Potential uses in other vascular conditions	Varies	Varies	Varies

Research Triangle Park, NC: ViiV Healthcare; 2013 Apr. Research Triangle Park, NC: GlaxoSmithKline; 2005 Nov. Princeton, NJ: Bristol-Myers Squibb Company; 2014 Jun. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2014 Apr. Foster City, CA: Gilead Sciences, Inc; 2014 Sept. Princeton, NJ: Bristol-Myers Squibb Company; 2015 Jan.

Product Overview

[85] It is not yet possible to determine if these adverse events are related directly to the use of PDE5 inhibitors, to the patient’s underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors. Sickle-cell crisis (vaso-occlusive crisis) requiring hospitalization has been reported in patients treated with sildenafil for pulmonary hypertension secondary to sickle cell disease. The manufacturer warns the safety and efficacy of sildenafil have not been established in this population (see Contraindications/Precautions). You are encouraged to report negative side effects of prescription drugs to the FDA. The prescribing information for Revatio recommends caution when the drug is administered to a nursing mother.

Drug Interactions

[15] Sildenafil is not indicated for use in women. [12] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date.

5.8 Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease

Do not flush unused medications or pour down a sink or drain. New treatment options for erectile dysfunction in patients with diabetes mellitus. The role of sildenafil in the treatment of erectile dysfunction in patients with pelvic fracture urethral disruption. Sildenafil citrate for erectile dysfunction in men receiving multiple antihypertensive agents: A randomized controlled trial. Chapter 1: The management of erectile dysfunction: an AUA update. Prezcobix (darunavir and cobicistat) tablets package insert. Interaction of sildenafil and indinavir when co-administered to HIV-patients. North Chicago, IL: AbbVie Inc; 2015 Jan. Research Triangle Park, NC: ViiV Healthcare Company; 2013 May. Princeton, NJ: Bristol-Myers Squibb Company; 2014 May. Walters JS, Woodring JH, Stelling CB, Rosenbaum HD: Salicylate-induced pulmonary edema. Balon R. Fluvoxamine-induced erectile dysfunction responding to sildenafil. Whitehouse Station, NJ: Merck & Co., Inc.; 2007 Nov. North Chicago, IL: AbbVie, Inc.; 2015 Jan.

6. Adverse Reactions/Side Effects

Ophthalmic adverse events reported by >= 2% of patients treated with sildenafil and which were more frequent on drug than placebo in clinical studies include visual impairment (3-11% vs. 0%) including mild and transient color tinge to vision and blurred vision (3% vs. 0%). In these studies, only 1 patient discontinued drug due to abnormal vision. Abnormal vision (11%) was more common at 100 mg doses than at lower doses.

2.1 Recommended Dosage in Adults

Other ophthalmic adverse reactions occurring in < 2% of patients in controlled clinical trials of sildenafil include cataracts, conjunctivitis, mydriasis, ocular hemorrhage, ocular pain, photophobia, and xerophthalmia. Post-marketing reports have included diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular irritation/burning, ocular swelling/pressure, increased intraocular pressure (ocular hypertension), retinal vascular disease or retinal hemorrhage (1.4%), vitreous detachment/traction, and paramacular edema, and epistaxis (9-13%). Non-arteritic anterior ischemic optic neuropathy (NAION) has also been reported rarely in patients using phosphodiesterase type 5 (PDE5) inhibitors. [85][86][87][88] Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 males >= 50 years of age per year in the general population. An observational study found that episodic use of PDE5 inhibitors was associated with acute onset of NAION and suggested an approximate 2-fold increase in the risk of NAION within 5 half-lives of PDE5 inhibitor use.

Figure 3.5.1

It is thought that the vasoconstrictive effect of phosphodiesterase inhibitors may decrease blood flow to the optic nerve, especially in patients with a low cup to disc ratio. Symptoms, such as blurred vision and loss of visual field in one or both eyes, are usually reported within 24 hours of use. Most, but not all, of these patients who reported this adverse effect had underlying anatomic or vascular risk factors for development of NAION. These risk factors include, but are not limited to: low cup to disc ratio (‘crowded disc’), age over 50 years, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. Additionally, 2 patients had retinal detachment, and 1 patient had hypoplastic optic neuropathy. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2008 Dec. Indianapolis, IN: Eli Lilly and Company; 2003 Nov. Princeton, NJ: Bristol-Myers Squibb Company; 2003 Sep.

• Sildenafil is sometimes used off-label for other health issues.
• Its interaction with blood thinners should be monitored.
• Men with retinitis pigmentosa should avoid sildenafil.
• Always inform healthcare providers about all treatments.
• Use sildenafil in conjunction with a healthy lifestyle.
• Avoid unnecessary medication to prevent side effects.
• Be aware of potential drug interactions with sildenafil.
• Proper storage maintains medication efficacy over time.

Quinidex Extentabs (quinidine sulfate extended-release tablets) package insert. Richmond, VA: A.H.

• Recreational use of sildenafil without prescription is risky.
• The drug is not intended for daily use unless directed.
• Overuse can increase the risk of adverse effects.
• Always discuss health concerns with a healthcare professional.
• Managing stress and anxiety can improve ED symptoms.
• Patients should report persistent side effects promptly.
• Combining sildenafil with certain medications can be dangerous.
• Education on proper use enhances safety and effectiveness.

Robbins Company; 2000 Sept. Ranexa (ranolazine extended-release tablets) package insert. Foster City, CA: Gilead Sciences, Inc. 2013 Dec. Research Triangle Park, NC: Bertek Pharmaceuticals; 2003 Feb.

Region	Average Cost per Pack	Pack Quantity	Notes
USA	$30 - $50	30 tablets	Generic versions available
UK	£15 - £25	30 tablets	Prescribed or OTC in some areas
India	₹150 - ₹300	10-30 tablets	Widely available, generic options
Australia	AUD 40 - AUD 70	30 tablets	Prescription required

South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2007 Feb. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2008 Jun. Rifampin and rifabutin drug interactions: an update.

• Common side effects include headaches and facial flushing.
• Less common effects may include nasal congestion or upset stomach.
• Do not use sildenafil if allergic to it or similar drugs.
• Pregnant women should consult a healthcare provider before use.
• Be aware of the signs of allergic reactions.
• Sildenafil may also be indicated for certain heart conditions.
• Emergency services should be contacted if adverse reactions occur.
• Keep a record of any side effects experienced.

Morris Plains, NJ: Parke-Davis; 1999 June. NOTE: Troglitazone was removed from the US market in response to FDA concerns in March 2000. NOTE: As of May 2000; Propulsid has only been available in the United States via an investigational limited access program to ensure proper patient screening and pres New York, NY: Danco Laboratories, LLC; 2009 Apr. Menlo Park, CA: Corcept Therapeutics Incorporated; 2013 Jun. Interactions of sildenafil and tacrolimus in men with erectile dysfunction after kidney transplantation.

8.1 Pregnancy

Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension. Sildenafil Inhibits the altitude-induced hypoxemia sildenafil 100 mg cost and pulmonary hypertension. Effects of sildenafil on esophageal motility of normal subjects.

Adverse Reactions/Side Effects

Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease. Sildenafil inhibits β-adrenergic-stimulated cardiac contractility in humans. Treatment of erectile dysfunction in patients with Peyronie’s disease using sildenafil citrate. Food and Drug Administration (US FDA) News Release. FDA recommends against use of Revatio in children with pulmonary hypertension.