February 28, 2017
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Zingo

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Zingo

CLINICAL PHARMACOLOGY

Mechanism Of Action

ZINGO® delivers lidocaine hydrochloride monohydrate into the dermis. Lidocaine is an amidetype local anesthetic agent that blocks sodium ion channels required for the initiation and conduction of neuronal impulses, resulting in local anesthesia.

Pharmacodynamics

ZINGO® provides local dermal analgesia within 1-3 minutes of application. Analgesia diminishes within 10 minutes of treatment.

Pharmacokinetics

Absorption

A single dose of ZINGO® in adults did not produce detectable plasma concentrations of lidocaine (limit of quantitation 5 ng/ml) in any subject tested (n=38).

Application of ZINGO® to broken or inflamed skin, or multiple ZINGO® applications, could result in systemic plasma levels of lidocaine that could products systemic toxicity.

Distribution

When lidocaine is administered intravenously to healthy volunteers, the steady-state volume of distribution is approximately 0.8 to 1.3 L/kg. At much higher plasma concentrations (1 to 4 mcg/ml of free base) than those found following application of ZINGO® , the plasma protein binding of lidocaine in concentration dependent. Lidocaine crosses the placental and blood brain barriers presumably by passive diffusion. CNS toxicity may typically be observed around 5000 ng/ml of lidocaine; however a small number of patients reportedly may show signs of toxicity at approximately 1000 ng/ml.

Metabolism

It is not known if lidocaine is metabolized in the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites including monethyglycinexlidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lidocaine. The major metabolic pathway of lidocaine, sequential N-deethylation to monethylglycinexylidide (MEGX) and glucinexylidide (GX), is primarily mediated by CYP1A2 with a minor role of CYP3A4. The metabolite, 2, 6-xylidine, has unknown pharmacologic activity. Following intravenous administration of lidocaine, MEGX and GX concentrations in serum range from 11% to 36% and from 5% to 11% of lidocaine concentrations, respectively. Serum concentrations of MEGX are about one-third the serum lidocaine concentrations.

Elimination

The half-life of lidocaine elimination from the plasma following intravenous administration is approximately 1.8 hours. Lidocaine and its metabolites are excreted by the kidneys. More than 98% of an absorbed dose of lidocaine can be recovered in the urine as metabolites or parent drug. Less than 10% of lidocaine is excreted unchanged in adults, and approximately 20% is excreted unchanged in neonates. The systemic clearance is approximately 8-10 ml/min/kg. During intravenous studies, the eliminations half-life of lidocaine was statistically significantly longer in elder patients (2.5 hours) than in younger patients (1.5 hours).

Clinical Studies

Efficacy In Adults

The efficacy of ZINGO® in adults was evaluated in a randomized, double-blind, parallel-arm, shamplacebo controlled trial in which adults patients who required a venipuncture or peripheral venous cannulation received either ZINGO® or a sham placebo device.

Patients were treated with ZINGO® or a placebo device at the antecubital fossa or back of the hand between one and three minutes prior to venipuncture or peripheral venous cannulation. Measurements of pain were made immediately following the procedure. Efficacy was measured using a continuous 100 mm visual analogue scale ranging from 0 (“no pain”) to 100 (“worst possible pain”). Many of the patients had chronic medical problems such as depression, hypertension, hypothyroidism and hyperlipidemia and over one fourth of the population may have been at higher than average risk of dermal bleeding due to use of concomitant medications such as NSAIDs, aspirin, corticosteroids. Treatment with active drug resulted in less pain compared with placebo (see Table 1).

Table 1 : Visual Analogue Scale Score (Full Safety/Efficacy Population)

  Adutt Study
Active
(N = 345)
Placebo
(N=348)
Adjusted Mean, LSM1 11.61 16,23
Difference in LSMs (SE2) -4.62 (1.55)
95% Confidence Limits -7.67, -1.57
1 least squares mean 2 standard error

However, efficacy was primarily seen in patients undergoing venipuncture at the antecubital fossa, while patients undergoing cannulation at the back of the hand did not demonstrate a difference between active and sham administrations.

Efficacy In Pediatric Patients

The efficacy of ZINGO® in patients 3-18 years of age was evaluated in two randomized, double-blind, parallel-arm sham-placebo controlled trials in which pediatric patients received either ZINGO® or a sham placebo device.

The overall patient population consisted of healthy pediatric patients as well as those with acute and chronic medical conditions (i.e. diabetes, asthma, seizure disorder, juvenile rheumatoid arthritis and renal or hepatic transplantation) ages 3-18 years. All patients required peripheral venipuncture or intravenous cannulation as part of their clinical care.

Two efficacy trials (studies 1 and 2) were conducted during which patients were treated with ZINGO® or a placebo device at the back of hand or antecubital fossa, between one and three minutes prior to venipuncture or peripheral venous cannulation. Measurements of pain were made immediately following the venous procedure. Efficacy was measured using a modified version of the Wong-Baker FACES pain rating scale [a categorical 6-point scale containing 6 faces ranging from 0 (“no hurt”) to 5 (“hurts worst”)].

In both studies, treatment with active drug resulted in less pain from venipuncture or peripheral IV cannulation, compared with placebo (See Table 2).

Table 2: Modified FACES Scale Score (ITT Population), Studies 1 and 2

  Study 1 Study 2
Active
(N=292)
Placebo
(N=287)
Active
(N=269)
Placebo
(N = 266)
Adjusted Mean. LSM1 1.77 2.10 1.38 1.77
Difference in LSM& (SE2) -0.33 (0,13) -0.39 (0.13)
95% Confidence Limits -0.-50, -0,08 -0,65. -0.13
1 least squares mean 2 standard error

Last reviewed on RxList: 12/5/2016
This monograph has been modified to include the generic and brand name in many instances.

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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