Tadalafil side effects, risk, danger
March 6 2016

Toxicity, risk, danger, potential harm
Laryngoscope. 2013
Hearing loss with phosphodiesterase-5 inhibitors: A prospective and objective analysis with tadalafil. Department of Otolaryngology-Head and Neck Surgery, Indira Gandhi Medical College, Shimla, India.
To assess the effect of tadalafil on auditory functions. Prospective observational study in a tertiary care hospital. Twenty-five tadalafil naïve patients with erectile dysfunction or pulmonary artery hypertension were subjected to pure-tone and brainstem-evoked response audiometry before drug therapy, and 3 and 30 days following drug therapy. Results were compared using analysis of variance for repeated measures with Bonferonni correction. Fifteen patients were taking tadalafil 10 mg for erectile dysfunction, and another 10 patients were on tadalafil 20 mg once daily for pulmonary artery hypertension. No statistically significant difference was found in hearing threshold at baseline and at follow-up. However, three patients on tadalafil 20 mg showed a significant increase in hearing threshold at higher frequencies. There was no incidence of sudden sensorineural hearing loss in the study group. This is the first prospective and observational study that evaluated the effect of tadalafil on auditory functions with objective tests. Although there was no statistically significant result to confirm or refute the association between tadalafil and hearing impairment, increased threshold at higher frequencies after taking the medication supports the results from previous studies and hints at a possible relationship between the two. Similar large sample studies are warranted to know the exact association of phosphodiesterase-5 inhibitors on auditory functions.

Tuberc Respir Dis (Seoul). 2012. A case of acute pulmonary thromboembolism after taking tadalafil. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Lung Institute, Seoul National University College of Medicine, Seoul, Korea. Tadalafil is a phosphodiesterase-5 inhibitor (PDE5I), which is widely used to treat erectile dysfunction. Although PDE5Is have excellent safety profiles, and most of the side effects are mild, rare serious adverse events have been reported in association with PDE5Is. Thrombosis is one of those events, and a few previous reports have suggested the association of PDE5Is with thrombosis. We report the case of a 61-year-old male who developed pulmonary embolism combined with pulmonary infarction directly after taking tadalafil. Both the patient and the physician suspected tadalafil as the culprit drug, as the patient was in an otherwise healthy condition. However, after extensive evaluation, we noticed that factor VIII levels were elevated. Prior reports suggesting the association between thrombosis and PDEIs either lack complete information on coagulation factors, or show inconsistencies in their results. Physicians should operate caution prior to accepting the diagnosis of adverse drug reaction.

BMC Surg. 2012. Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily. Reduced libido is widely considered the most prominent symptomatic reflection of low testosterone (T) levels in men. Testosterone deficiency (TD) afflicts approximately 30% of men aged 40-79 years. This study seeks to evaluate the effect of a new natural compound "tradamixina "in order to improve male sexual function in elderly men, particularly libido and possible erectile dysfunction, versus administration of tadalafil 5 mg daily. Seventy patients (67.3 ± 3.7 years) with stable marital relations and affected by reduced libido, with or without erectile dysfunction were recruited. They were randomly separated in 2 groups A-B of 35. Group A was administered twice a day a new compound "Tradamixina" (150 mg of Alga Ecklonia Bicyclis, 396 mg of Tribulus Terrestris and 144 mg of D-Glucosamine and N-Acetyl-D-Glucosamine) for two months, while Group B was administered tadalafil 5 mg daily, for two months. At visit and after 60 days of treatment patients were evaluated by means of detailed medical and sexual history, clinical examination, laboratory investigations (Total and Free T), instrumental examination (NPTR- nocturnal penile tumescence and rigidity test- with Rigiscan). Patients completed a self-administered IIEF questionnaire (The international index of erectile function) and SQoLM questionnaire (Sexual quality of life Questionnarie-Male). The results pre and post treatment were compared by Student t test. After 2 months of treatment in group A serum TT levels and FT levels increased, while in group B serum TT levels and FT levels increased not statistically significant. The patient's numbers with negative NPTR improved after treatment in group A and B. The IIEF total score in group A increased after treatment with tradamixina; the IIEF total score in group B increased slightly. The SQoLM total score improved in both groups. The treatment twice a day with "Tradamixina" for 2 months improved libido in elderly men without side effects of Tadalafil.

Added illegally to over the counter products
Yakugaku Zasshi. 2014. Analysis and identification of illegal constituents in health food products implicitly advertizing tonic or slimming effect in the national institute of health sciences in Japan. With the prefectural governments' aid of the purchase, the Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences (NIHS) successively has surveyed illegal constituents in health food products implicitly advertizing tonic or slimming effect since the fiscal year of 2002 (slimming type) or 2003 (tonic type). The average numbers of the analyzed products per year are about 100 (slimming type) and 150 (tonic type), respectively. We also continuously distribute standards of authentic samples of several illegal components such as N-nitrosofenfluramine (NFF) and sildenafil to prefectural institutes and the average gross number per year is about 140. In the case of slimming type, the fact that the products containing NFF were widely sold in Japanese markets in 2002 is well known. In addition, phenolphthalein, fenfluramine, sibtramine, desdimethylsibtramine, orlistat, mazindol, Rhubarb, Senna Leaf, etc. have been found as illegal constituents. In the tonic type products, we have identified more than 20 synthetic compounds relating to the erectile dysfunction (ED) treatment drugs, sildenafil, vardenafil and tadalafil. Since 2005, their synthetic intermediates and the patented but non-approved PDE5 inhibitors also have been found. It should be noted that tadalafil was found in the shells of capsule in 2009 and that mutaprodenafil was found as pro-drug type illegal component in 2010.

J Pharm Biomed Anal. 2015 Identification and structural elucidation of three new tadalafil analogues found in a dietary supplement. Compounds elucidated as new tadalafil analogues were found to be adulterated in a dietary supplement and detected during routine analysis by HPLC with photodiode array detection. The UV spectra of these compounds were found to be almost identical to that of tadalafil. The unknown compounds were isolated by preparative HPLC and elucidated by quadrupole-time-of-flight MS and NMR spectroscopy. Two compounds were identified as cyclopentyltadalafil and trans-cyclopentyltadalafil, from the substitution of the tadalafil N-methyl group with a cyclopentyl group. Another analogue was a dimeric form of tadalafil with an N-cyclopentyl group. This represents the first report of the elucidation of compounds used as adulterants in a dietary supplement.

Erectile function
In recommended doses, oral PDE5-Is are more effective than placebo for ED, and tadalafil seems to be the most effective agent, followed by vardenafil.

Correction of erectile dysfunction in patients with benign prostate hyperplasia using daily administration of tadalafil 5 mg against the background of combined drug therapy]. Urologiia. 2013 Sep-Oct.

BJU Int. 2013. Effects of 12 weeks of tadalafil treatment on ejaculatory and orgasmic dysfunction and sexual satisfaction in patients with mild to severe erectile dysfunction: integrated analysis of 17 placebo-controlled studies. Department of Urology and Reproductive Medicine, Weill Cornell Medical College, New York, NY, USA. Tadalafil treatment was associated with significant improvements in ejaculatory function, orgasmic function and sexual satisfaction. Proportions of subjects reporting improved ejaculatory or orgasmic function were ≈ twofold higher with tadalafil than with placebo. These findings warrant corroboration in prospective trials of patients with EjD or OD (without ED).

J Sex Med. 2013. Assessment of the efficacy of combination therapy with folic Acid and tadalafil for the management of erectile dysfunction in men with type 2 diabetes mellitus. Department of Urology, Urology Research Center, Guilan University of Medical Sciences, Rasht, Iran. Phosphodiesterase type 5 inhibitors PDE5Is are less effective in diabetic men with erectile dysfunction (ED); however, the effect of combination therapy with folic acid and PDE5Is in these patients has not been investigated.  Eighty-three patients with type 2 diabetes mellitus and ED were included in this randomized double-blind clinical trial. They were randomly divided into two groups. Group A was treated with tadalafil 10 mg every other day plus folic acid 5 mg daily and group B received tadalafil 10 mg every other day plus placebo daily for 3 months.  Sexual function in diabetic patients with ED treated with the combination of tadalafil and folic acid improved significantly as compared with the placebo group. The use of folic acid and tadalafil is safe.

Prostate function
Tadalafil is a phosphodisesterase (PDE)-5 inhibitor approved by the United States Food and Drug Administration for lower urinary tracts symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). The mechanism for improved LUTS is thought to be related to three principal theories: alterations in nitric oxide levels, Rho-associated protein kinase deactivation, and reductions in pelvic atherosclerosis.

J Sex Med. 2013. Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin-controlled, 12-week double-blind study. Neuro-Uro-Andrology Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France. Tadalafil 5 mg once daily significantly improved ejaculation and orgasm, intercourse and overall satisfaction, and erectile function. Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo, with no significant effect on erectile function.

Comparison to natural products
Tradamix TX1000 tablets uses the same ingredients as the patented Tradamixina has substances such as saponins of tribulus terrestris; glucosamine from Biovis; and the phlorotannins from ecklonia bicyclis algae. The product claims to promote the welfare of the male urinary tract and corpora cavernosa [penile tissue].
BMC Surg. 2012. Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily. The treatment twice a day with Tradamixina for 2 months improved libido in elderly men without side effects of tadalafil.