Tadalafil (Generic) Potentially Permanent Side Effects: What the Evidence Actually Shows

Which tadalafil side effects can last?

Generic tadalafil 2.5, 5, 10 and 20 mg tablets follow the Cialis indications for erectile dysfunction and benign prostatic hyperplasia [3][1].

In the eight 12-week placebo-controlled studies of as-needed Cialis (placebo 476 men, tadalafil 20 mg 635 men), headache occurred in 15% versus 5% on placebo, dyspepsia in 10% versus 1%, back pain in 6% versus 3%, myalgia in 3% versus 1% and flushing in 3% versus 1%; 3.1% of men on 10 or 20 mg stopped because of adverse events versus 1.4% on placebo [1]. Back pain and myalgia generally started 12 to 24 hours after dosing and typically resolved within 48 hours [1]. Tadalafil's mean terminal half-life is about 17.5 hours [1].

Three label warnings are different in kind. For NAION and for priapism, the label describes damage that can be permanent [1]. For sudden hearing loss, it reports the event but says it cannot determine whether it is directly related to the drug [1].

NAION: the optic-nerve risk

The Cialis label describes NAION as a rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely after marketing with all PDE5 inhibitors [1]. The Adcirca label says sudden loss of vision could be a sign of NAION and may be permanent [2].

The label gives the background rate in men 50 and older as 2.5 to 11.8 cases per 100,000 per year [1]. Two observational case-crossover studies, which compared PDE5 inhibitor use in the period immediately before NAION onset with the same person's use in an earlier period, suggested roughly a doubling of risk: an estimate of 2.15 (95% CI 1.06 to 4.34) in the first and 2.27 (95% CI 0.99 to 5.20) in the second [1]. The label states that neither the postmarketing reports nor these studies substantiate a causal relationship, and notes that other risk factors, such as a crowded optic disc, may have contributed [1].

The Adcirca label lists the underlying factors most reported patients had: a low cup-to-disc ratio, age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking [2]. The Cialis label advises caution in patients with a history of NAION or a crowded optic disc, and says use is not recommended in hereditary retinal disorders such as retinitis pigmentosa [1]. The label says to stop Cialis and seek medical attention for sudden loss of vision in one or both eyes [1].

Priapism and the 4-hour line

The label describes rare reports of prolonged erections longer than 4 hours and priapism, defined as painful erections longer than 6 hours, for this class of drugs, and states that priapism not treated promptly can result in irreversible damage to the erectile tissue [1]. The label tells patients with an erection lasting more than 4 hours, whether painful or not, to seek emergency medical attention [1].

The Adcirca label lists priapism among postmarketing reactions, where it says frequency cannot be estimated reliably [2]. The label also advises caution in people with conditions that predispose to priapism — sickle cell anemia, multiple myeloma, leukemia — or with anatomical deformation of the penis such as angulation, cavernosal fibrosis or Peyronie's disease [1].

Sudden hearing loss

The Cialis label tells patients who notice a sudden decrease or loss of hearing to stop Cialis and seek prompt medical attention [1]. Cases may be accompanied by tinnitus and dizziness, and the label states that it is not possible to determine whether these events are related directly to PDE5 inhibitors or to other factors [1][2]. In many cases, the Adcirca label says, medical follow-up information was limited [2]. Like priapism, hearing loss sits in the Adcirca label's postmarketing list, where frequency cannot be reliably estimated [2].

Nitrates and tadalafil: a contraindicated interaction

Nitrates in any form are contraindicated with tadalafil, whether used regularly or intermittently [1]. The interaction has a measured time course. In a crossover study, 150 men took tadalafil 20 mg or placebo daily for 7 days and then received 0.4 mg sublingual nitroglycerin at set times; standing systolic pressure fell below 85 mm Hg in more men on tadalafil at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours [4].

The label's provision for emergencies is narrow: where a nitrate is medically necessary in a life-threatening situation, at least 48 hours should elapse after the last Cialis dose, and the nitrate should still only be given under close medical supervision with hemodynamic monitoring [1]. That is an emergency rule, not a safe interval for planned use [1].

The Adcirca label's postmarketing list includes serious cardiovascular events (myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations and tachycardia) reported in temporal association with tadalafil, mostly in patients with preexisting cardiovascular risk factors; it says it is not possible to determine whether they relate to tadalafil, to sexual activity, to underlying cardiovascular disease or to other factors [2].

Peyronie's disease

Peyronie's disease appears in the Cialis label as one of the penile conditions warranting caution, alongside angulation and cavernosal fibrosis, in the same paragraph as priapism [1]. The label does not list it as an effect the drug is reported to cause.

Once-daily dosing and interactions

The label says once-daily Cialis provides continuous plasma levels (steady state within 5 days, with about 1.6-fold the exposure of a single dose) and that this should be considered when evaluating interactions with nitrates, alpha-blockers, antihypertensives, potent CYP3A4 inhibitors and substantial alcohol [1]. The NAION case-crossover estimates come from studies of PDE5 inhibitor use as a class [1]. HealthRX.com offers tadalafil by prescription.