Cialis FAERS Safety Signals: What the FDA's Adverse Event Data Actually Shows

Print or save as PDF

See the public record for Tadalafil

What the Cialis label actually flags

Cialis has no boxed warning, and neither does Adcirca, the 20 mg tadalafil tablet approved 22 May 2009 for pulmonary arterial hypertension [1][4]. The contraindications are organic nitrates in any form, regularly or intermittently; guanylate cyclase stimulators such as riociguat; and serious hypersensitivity to tadalafil, including reported Stevens-Johnson syndrome and exfoliative dermatitis [1].

Sudden vision loss in one or both eyes may be non-arteritic anterior ischemic optic neuropathy (NAION), reported rarely after marketing with all PDE5 inhibitors. Two case-crossover studies suggested about a 2-fold increase in risk (2.15, 95% CI 1.06 to 4.34; and 2.27, 95% CI 0.99 to 5.20), and the label states that neither the rare reports nor those studies substantiate a causal relationship [1]. Sudden decrease or loss of hearing has been reported, and the label says it cannot determine whether it is directly related to the drug [1]. An erection lasting more than 4 hours, painful or not, needs emergency care [1].

The rates that exist come from trials

Eight 12-week placebo-controlled studies of as-needed Cialis for erectile dysfunction (placebo n=476; tadalafil 10 and 20 mg n=394 and 635) reported headache in 5% on placebo versus 11% and 15%; dyspepsia in 1% versus 8% and 10%; back pain in 3% versus 5% and 6%; and flushing in 1% versus 3% and 3%. Discontinuation for adverse events was 3.1% on 10 or 20 mg versus 1.4% on placebo [1].

Nitrates: the interaction with a measured time course

In a 150-man crossover study, men took tadalafil 20 mg or placebo daily for 7 days, then sublingual nitroglycerin 0.4 mg. Standing systolic blood pressure fell below 85 mm Hg in more men on tadalafil at 4, 8 and 24 hours (P<0.05), with no difference at 48, 72 and 96 hours [5]. Nitrates are contraindicated. In a life-threatening situation the label says at least 48 hours should elapse after the last Cialis dose before a nitrate is considered, and then only under close medical supervision with hemodynamic monitoring [1].

Melanoma: an observational signal, not a FAERS one

A nationwide Swedish case-control study published in JAMA in 2015 compared 4,065 melanoma cases diagnosed from 2006 to 2012 with 20,325 matched controls; 11% of cases and 8% of controls had filled a prescription for a PDE5 inhibitor, an adjusted odds ratio of 1.21 (95% CI 1.08 to 1.36), with similar estimates for sildenafil or vardenafil and for tadalafil [2].