Cialis and Nicotine Interaction: What the Evidence Actually Shows

Does nicotine change how tadalafil is broken down?

Tadalafil and nicotine are handled by different enzymes. The Cialis label states that tadalafil is a substrate of and predominantly metabolised by CYP3A4, and that it does not inhibit or induce CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 [1]. Nicotine is a CYP2A6 substrate [2].

The main pharmacokinetic interactions with smoking occur with drugs that are CYP1A2 substrates: caffeine, clozapine, fluvoxamine, olanzapine, tacrine and theophylline [3]. The Cialis label says tadalafil does not inhibit or induce CYP1A2 [1].

Nicotine itself is not what induces the enzyme. The effect on hepatic enzymes is not related to the nicotine component of tobacco, so nicotine replacement will not alter it [5]. The polycyclic aromatic hydrocarbons in smoke are the inducers of CYP1A1 and CYP1A2 [4][3].

What the Cialis label does list

Nitrates are contraindicated [1]. Alpha-blockers add to blood pressure lowering, and for BPH the label does not recommend combining Cialis with an alpha-blocker [1]. Antihypertensives produce small additional reductions in blood pressure [1]. Five units or more of alcohol with Cialis can increase orthostatic signs and symptoms [1]. Ketoconazole 400 mg daily raised tadalafil 20 mg exposure (AUC) by 312%, and rifampin 600 mg daily cut tadalafil 10 mg AUC by 88% [1].

Blood pressure, heart rate and blood vessels

In healthy volunteers, tadalafil 20 mg lowered supine blood pressure by a mean maximal 1.6/0.8 mm Hg compared with placebo [1]. Nicotine works in the other direction: it causes peripheral vasoconstriction, tachycardia and higher blood pressure, and tolerance does not develop to its catecholamine-releasing effects [4]. In a study of 28 people, 11 of them chronic smokers, smoking one cigarette increased brachial and aortic blood pressure, the augmentation index and pulse wave velocity [6]. Smoking also raises blood coagulability, which transdermal nicotine does not appear to do [7].

The label's specific cautions about additive blood pressure lowering name alpha-blockers, antihypertensives and substantial alcohol, not nicotine [1].

The contraindication that matters here: nitrates

The Cialis label contraindicates any form of organic nitrate, taken regularly or intermittently [1]. For a life-threatening situation where a nitrate is medically necessary, the label says at least 48 hours should have elapsed since the last Cialis dose before a nitrate is considered, and that the nitrate should still only be given under close medical supervision with hemodynamic monitoring [1]. This is an emergency rule, not permission to combine them. In a crossover study of 150 men given tadalafil 20 mg or placebo daily for 7 days and then sublingual nitroglycerin 0.4 mg, 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 [8]. Guanylate cyclase stimulators such as riociguat are also contraindicated [1]. The nitrate rule applies to a smoker who uses nitroglycerin for angina just as it does to anyone else.

Quitting smoking while taking tadalafil

Stopping smoking reverses CYP1A2 induction. In 12 heavy smokers taking 20 or more cigarettes a day who stopped abruptly, caffeine clearance fell 36.1%, from 2.47 to 1.53 mL/min/kg, with an apparent half-life of the decline of 38.6 hours [9]. Reviews of smoking cessation put warfarin, olanzapine, clozapine and theophylline among the drugs where dose adjustment or monitoring is clearly indicated as that induction fades [5].

Tadalafil is predominantly metabolised by CYP3A4, while the documented enzyme change after quitting concerns CYP1A2 [1][5]. Nothing in the evidence shows that quitting changes tadalafil exposure. Nicotine replacement does not prevent the CYP1A2 change, because the enzyme effect is not nicotine-related [5].

Smoking, nicotine and erectile dysfunction

A 2015 review says the nitric oxide signalling pathway appears to be the main physiologic mechanism affected in the link between cigarette smoking and erectile dysfunction, and it also covers dose dependency and the effects of quitting [10]. In a prospective study of 281 smokers who requested nicotine replacement and reported erectile dysfunction, 118 stopped smoking and 163 continued. After a year, erectile function had improved in at least 25% of the ex-smokers and in none of those still smoking, and had worsened in 2.5% versus 6.8%. Ex-smokers had significantly better erectile function (P=0.009), and pack-years of smoking correlated with the severity of the dysfunction [11].

Doses, and whether smoking changes them

The label gives these Cialis doses [1]:

• ED as needed: start at 10 mg, adjust between 5 and 20 mg, no more than once a day.
• ED once daily: start at 2.5 mg, may increase to 5 mg.
• BPH, and ED with BPH: 5 mg once daily.

The label also says not to split the tablets [1]. Its dose reductions are tied to kidney function, liver function and strong CYP3A4 inhibitors such as ketoconazole, and it recommends the lowest starting dose for ED in men on alpha-blockers; smoking is not among them [1].

Cialis tadalafil tablets are prescription-only products [12]. HealthRX.com offers tadalafil by prescription.