Crestor Nicotine Interaction Profile: What Rosuvastatin Users Need to Know

Does nicotine change rosuvastatin levels?

Rosuvastatin is not extensively metabolized. About 10% of a dose is recovered as metabolite, mainly N-desmethyl rosuvastatin, formed principally by CYP2C9 and carrying one-sixth to one-half the activity of the parent compound [4]. The label says rosuvastatin clearance does not depend on CYP3A4 to a clinically significant extent, and it lists cyclosporine among inhibitors of the transporters OATP1B1 and BCRP [4]. Its half-life is about 19 hours [4].

Nicotine runs on a different enzyme: it is a substrate of CYP2A6 [5].

The induction story belongs to smoke, not to the alkaloid. Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for the CYP1A1 and CYP1A2 induction seen in smokers [1][2]. A review of drugs affected by quitting says the effect on hepatic enzymes is not related to the nicotine component of tobacco, so nicotine replacement will not alter it [3].

One animal study adds a caveat without changing that picture: a single nicotine dose in rats raised lung CYP1A1 activity 4.4-fold at 6 hours and 14.7-fold at 12 hours, returning toward control by 24 hours, while liver CYP1A2 protein and mRNA were not significantly changed. Its relevance to people is unknown [6].

Does smoking change rosuvastatin levels?

The main drug-level interactions described for smoking involve CYP1A2 [2]. Reviews name caffeine, clozapine, fluvoxamine, olanzapine, tacrine and theophylline as the main affected drugs, with dose adjustment or monitoring clearly indicated for warfarin, olanzapine, clozapine and theophylline [2][3]. Rosuvastatin's label describes a different route: minor CYP2C9 metabolism plus transporters [4]. The Crestor dose-modification table lists transporter and enzyme inhibitors such as cyclosporine, gemfibrozil, ticagrelor and a long list of antivirals [4].

Do nicotine patches or gum interact with Crestor?

Nicotine replacement therapy is FDA-approved as a smoking cessation aid [7]. No nicotine product appears among the drugs that carry a Crestor dose limit or avoidance instruction [4].

Nicotine does have cardiovascular actions of its own: peripheral vasoconstriction, tachycardia and higher blood pressure, and tolerance does not develop to its catecholamine-releasing effects [1]. A review put those effects in context: nicotine may contribute to cardiovascular disease through sympathetic stimulation and catecholamine release, but cigarette smoke contains many other cardiovascular toxins [8]. The same review noted that cigarettes deliver nicotine faster and usually in higher doses than replacement products, that smoking raises blood coagulability while transdermal nicotine does not appear to, and that trials in stable coronary disease suggest nicotine does not raise cardiovascular risk, with replacement risk at worst no more than smoking [8]. A 2016 review reached a similar place: the risks of nicotine without tobacco combustion products are low compared with cigarette smoking but still of concern in people with cardiovascular disease [9].

Does quitting smoking change anything for Crestor users?

Quitting de-induces CYP1A2, which matters for other drugs rather than for rosuvastatin. In 12 heavy smokers (20 or more cigarettes daily) 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 [10]. An earlier study measured caffeine half-life at 3.5 hours in 13 smokers versus 6.0 hours in 13 non-smokers, with clearance of 155 versus 94 mL/kg/h [11]. Adjustment or monitoring is clearly indicated after quitting for warfarin, olanzapine, clozapine and theophylline [3].

What does the Crestor label say about its own interactions?

The interactions the label does flag are concrete. Cyclosporine raised rosuvastatin exposure about 7-fold and the label caps the dose at 5 mg daily [4][13]. Gemfibrozil raised rosuvastatin exposure about 1.9-fold; the label says to avoid the combination, or if it cannot be avoided, specifies a 5 mg starting dose and a 10 mg daily maximum [4][14]. An aluminum/magnesium hydroxide antacid taken at the same time cut rosuvastatin AUC by about 50%, and the label specifies taking Crestor at least 2 hours before such an antacid [4]. Rosuvastatin also significantly increased INR in patients on warfarin [4].

Myopathy and rhabdomyolysis lead the label's warnings. Label risk factors are age 65 or older, uncontrolled hypothyroidism, renal impairment, certain other drugs and higher dosage, and myopathy risk is greater on 40 mg daily than on lower doses [4]. In pooled placebo-controlled trials, transaminases above 3 times the upper limit of normal occurred in 1.1% on Crestor versus 0.5% on placebo [4]. Contraindications are acute liver failure or decompensated cirrhosis and hypersensitivity to rosuvastatin or an excipient [4].

Does vaping interact with Crestor?

The smoking-related CYP1A2 effect is not related to the nicotine component of tobacco [3]. A 2016 review found that electronic cigarettes deliver nicotine without combustion of tobacco and appear to pose low cardiovascular risk, at least with short-term use, in healthy users [9].