Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: McNeil Products Limited, 50–100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK
Pharmacotherapeutic group: Drug used in nicotine dependence
ATC code: N07BA01
Nicotine has no therapeutic uses except as replacement therapy for the relief of abstinence symptoms in nicotine-dependent smokers.
Owing to its many actions, the overall effects of nicotine are complex. A wide variety of stimulant and depressant effects are observed that involve the central and peripheral nervous, cardiovascular, endocrine, gastro-intestinal and skeletal motor systems. Nicotine acts on specific binding sites or receptors throughout the nervous system.
Increased appetite is a recognised symptom of nicotine withdrawal and post-cessation weight gain is common. Clinical trials have demonstrated that Nicotine Replacement Therapy can help control weight following a quit attempt.
The patches are labelled by the average amount of nicotine released over 16 hours.
A linear relationship exists between released amount of nicotine (dose) and plasma levels of nicotine over the therapeutic dose range, 10-25 mg/16 hours The mean peak plasma levels of nicotine (Cmax) achieved are calculated to:
| Dose nicotine (mg/16 hours) | Cmax (ng/ml) |
|---|---|
| 10 | 15.5 |
| 10 | 25 |
| 15 | 26.5 |
The calculated peak plasma levels are in the same range as true measured peak plasma concentrations: 11 ng/mL for the 10 mg patch and 25 ng/mL for the 25 mg patch. Interpolation yelds a peak plasma concentration of 16 ng/mL for the 15 mg patch.
The maximum level of plasma concentration after administration is reached after approximately 9 hours (tmax). The plasma peak is in the afternoon/evening when the risk of relapse is highest.
The volume of distribution of nicotine is about 2 to 3 L/kg and the half-life approximately 3 hours. The major eliminating organ is the liver, and average plasma clearance is about 70 L/hour. The kidney and lung also metabolise nicotine. More than 20 metabolites of nicotine have been identified, all of which are believed to be less active than the parent compound.
Plasma protein binding of nicotine is less than 5%. Therefore, changes in nicotine binding from use of concomitant drugs or alterations of plasma proteins by disease states would not be expected to have significant effects on nicotine kinetics.
The primary metabolite of nicotine in plasma, cotinine, has a half-life of 15 to 20 hours and concentrations that exceed nicotine by 10-fold.
The primary urinary metabolites are cotinine (12% of the dose) and trans-3-hydroxy-cotinine (37% of the dose). About 10% of nicotine is excreted unchanged in the urine.
Progressive severity of renal impairment is associated with decreased total clearance of nicotine. Raised nicotine levels have been seen in smoking patients undergoing hemodialysis.
The pharmacokinetics of nicotine is unaffected in cirrhotic patients with mild liver impairment (Child score 5) and nicotine clearance is decreased in cirrhotic patients with moderate liver impairment (Child score 7).
A minor reduction in total clearance of nicotine has been demonstrated in healthy elderly patients, however, not justifying adjustment of dosage.
Plasma nicotine concentrations show dose proportionality for the three patch doses.
Preclinical data indicate that nicotine is neither mutagenic nor genotoxic.
There are no other findings derived from preclinical testing of relevance to the prescriber in determining the safety of the product which have not been considered in other relevant sections of this Summary of Product Characteristics.
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