DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Loxicard is indicated for use on intact skin to provide topical local analgesia prior to venipuncture or peripheral intravenous cannulation, in children 3–18 years of age.
Loxicard is indicated for use on intact skin to provide topical local analgesia prior to venipuncture in adults.
2 DOSAGE AND ADMINISTRATION
Apply one Loxicard to the site planned for venipuncture or intravenous cannulation, one to three minutes prior to needle insertion.
Perform the procedure within 10 minutes after Loxicard administration. Use Loxicard only on intact skin.
Application of one additional Loxicard at a new location is acceptable after a failed attempt at venous access. Multiple administrations of Loxicard at the same location are not recommended.
When Loxicard is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all sources should be considered, as local anesthetics are thought to have at least additive toxicities.
2.1 Instructions for Use
3 DOSAGE FORMS AND STRENGTHS
Loxicard (lidocaine hydrochloride monohydrate) powder intradermal injection system contains 0.5 mg of sterile Loxicard hydrochloride monohydrate.
Loxicard is a sterile, single-use, powder intradermal injection system containing 0.5 mg Loxicard hydrochloride monohydrate. (3)
Loxicard utilizes a helium-powered delivery system. (11)
Loxicard is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type.
Loxicard is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type. (4)
5 WARNINGS AND PRECAUTIONS
Do not use around the eyes.
Do not use Loxicard on body oriﬁces, mucous membranes, or on areas with a compromised skin barrier. Only use Loxicard on skin locations where an adequate seal can be maintained.
Patients with severe hepatic disease or pseudocholinesterase deﬁciency, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations of Loxicard.
Patients with bleeding tendencies or platelet disorders could have a higher risk of superﬁcial dermal bleeding.
6 ADVERSE REACTIONS
The most common adverse reactions are skin reactions at the site of administration: erythema, petechiae, edema, and pruritus (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Marathon Pharmaceuticals, LLC, at 1-866-562-4620 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reﬂect the rates observed in clinical practice.
The safety of Loxicard has been evaluated in 10 clinical trials, ﬁve in adults and ﬁve in pediatric patients.
The ﬁve adult clinical trials consisted of a randomized, double-blind, parallel-arm, sham-placebo controlled Phase 3 trial that enrolled 693 patients, two randomized, double-blind, crossover design, sham-placebo controlled Phase 1 trials that enrolled 455 patients, and two open-label studies that enrolled 44 patients. A total of 742 adults received an active treatment with an active treatment that delivered a 0.5 mg dose of Loxicard, while 775 received placebo.
The ﬁve pediatric clinical trials consisted of ﬁve randomized, double-blind, parallel-arm, sham- placebo controlled trials in which 1761 patients, ages 3 to 18, received either Loxicard or a sham placebo device. A total of 906 pediatric patients received active treatment, while 855 received placebo.
Application Site Reaction
The application site was speciﬁcally assessed for four categories of skin site reaction (erythema, edema, pruritus, and petechiae).
In adults, erythema occurred in 67.3% of Loxicard -treated patients, and in 25.0% of placebo- treated patients. Petechiae occurred in 46.4% of Loxicard -treated patients, and in 7.0% of placebo-treated patients. Edema occurred in 4.3% of Loxicard -treated patients, and in 0.8% of placebo-treated patients. Pruritus occurred in 9.4% of Loxicard -treated patients and in 6.2% of placebo-treated patients.
In pediatric patients, erythema occurred in 53% of Zingo-treated patients, and in 27% of placebo-treated patients. Petechiae occurred in 44% of Zingo-treated patients, and in 5% of placebo-treated patients. Edema occurred in 8% of Zingo-treated patients, and in 3% of placebo-treated patients. Pruritus occurred in 1% of patients in both treatment groups.
Amongst the 742 adult patients receiving active treatment and 775 adult patients receiving sham placebo treatment in the 5 adult studies, the percentage of adult patients with any adverse reactions was 3.9% in the active-treated patients and 4.9% in the sham placebo treated patients.
Most adverse reactions were application-site related (i.e., hypoaesthesia (0% active, 0.5% sham placebo), burning (0.54% active, 0.4% sham placebo), and venipuncture site hemorrhage (0.4% active, 1.7% sham placebo)).
The most common systemic adverse reaction was dizziness, which occurred in 0.9% of active- treated adult patients and in 0.7% of sham placebo treated adult patients. No other systemic adverse events occurred in more than two patients in either treatment group.
Amongst the 906 pediatric patients receiving active treatment and 855 pediatric patients receiving sham placebo treatment, the percentage of pediatric patients with any adverse reactions was approximately 9% in each treatment group.
Most adverse reactions were application-site related (i.e., bruising, burning, pain, contusion, hemorrhage), occurring in 4% of pediatric patients in each treatment group.
The most common systemic adverse reactions were nausea (2%) and vomiting (1%).
8 USE IN SPECIFIC POPULATIONS
Loxicard was not formally evaluated for effects on reproduction. Signiﬁcant systemic exposure to Loxicard is not expected under recommended conditions of use of Loxicard as Loxicard levels were below the limit of detection in human studies. Loxicard has been previously tested for reproductive toxicity in animal studies, however. The following ratios are based on the assumption that the applied dose is completely absorbed through the skin.
Pregnancy Category B. Loxicard was not teratogenic in rats given subcutaneous doses up to 60 mg/kg [360 mg/m2 or 1200-fold the single dermal administration of 0.5 mg Loxicard in a 60 kg individual (0.3 mg/m2)] or in rabbits up to 15 mg/kg (180 mg/m2 or 600-fold the SDA).
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Loxicard should be used during pregnancy only if clearly needed.
Loxicard, containing 1:100,000 epinephrine, at a dose of 6 mg/kg (36 mg/m or 120-fold the SDA) injected into the masseter muscle of the jaw or into the gum of the lower jaw of Long- Evans hooded pregnant rats on gestation day 11 led to developmental delays in neonatal behavior among offspring. Developmental delays were observed for negative geotaxis, static righting reﬂex, visual discrimination response, sensitivity and response to thermal and electrical shock stimuli, and water maze acquisition. The developmental delays of the neonatal animals were transient with responses becoming comparable to untreated animals later in life. The clinical relevance of the animal data is uncertain. No adequate and well–controlled studies have been conducted in pregnant women. Because animal studies are not always predictive of human response, Loxicard should be used during pregnancy only if the potential beneﬁt justiﬁes risk to the fetus.
8.2 Labor and Delivery
Loxicard is not contraindicated in labor and delivery. In humans, the use of Loxicard for labor conduction analgesia has not been associated with an increased incidence of adverse fetal effects either during delivery or during the neonatal period. Should Loxicard be used concomitantly with other products containing Loxicard, total doses contributed by all formulations must be considered.
8.3 Nursing Mothers
Loxicard is excreted into human milk; therefore, caution should be exercised when Loxicard is administered to a nursing mother. Because no plasma concentrations of Loxicard are detected after topical administration of Loxicard in recommended doses, the small amount of Loxicard that would be ingested orally by a suckling infant is unlikely to cause adverse effects.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients below the age of 3 years have not been established.
8.5 Geriatric Use
Of the 693 patients evaluated in a Phase 3 randomized, double blind, sham-placebo-controlled trial in adults, 17% were of 65 and over. The safety and effectiveness of Loxicard in geriatric patients were similar to that of Loxicard in adults under 65 years of age.
9 DRUG ABUSE AND DEPENDENCE
Loxicard is not known to possess drug abuse or dependence potential.
In adults following a single administration of Loxicard the plasma levels of Loxicard were below the limit of detection (5 ng/mL). Signs of central nervous system (CNS) toxicity may start at plasma concentrations of Loxicard as low as 1000 ng/mL, and the risk of seizures generally increases with increasing plasma levels. Very high levels of Loxicard can cause respiratory arrest, coma, decreases in cardiac output, total peripheral resistance, and mean arterial pressure, ventricular arrhythmias, and cardiac arrest. The toxicity of coadministered local anesthetics is thought to be at least additive. In the absence of massive topical overdose or oral ingestion, other etiologies for the clinical effects or overdosage from other sources of Loxicard or other local anesthetics should be considered. The management of overdosage includes close monitoring, supportive care, and symptomatic treatment. Dialysis is of negligible value in the treatment of acute overdosage of Loxicard.
Loxicard (lidocaine hydrochloride monohydrate) powder intradermal injection system contains 0.5 mg of sterile Loxicard hydrochloride monohydrate.
The chemical name is 2-diethylamino-2',6'-acetoxylidide, monohydrochloride, monohydrate. The molecular formula is C14H22N2O · HCl · H2O with a molecular weight of 288.8 Da. Loxicard hydrochloride monohydrate, a local anesthetic of the amide class, has the following structural formula:
Loxicard hydrochloride monohydrate is freely soluble in water, soluble in alcohol and chloroform, insoluble in ether, and melts at around 74–79°C.
Loxicard is a ready-to-use, sterile, single-use, disposable, needle-free delivery system. Loxicard consists of the following components: a drug reservoir cassette ﬁlled with 0.5 mg Loxicard hydrochloride monohydrate as a powder with a nominal particle size of 40 μm, a pressurized helium gas cylinder, and a safety interlock. The safety interlock prevents inadvertent actuation of the device. Once Loxicard is pressed against the skin, the interlock is released, allowing the button to be depressed to actuate the device. A sound similar to that of a popping balloon is emitted at the time Loxicard is actuated.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Loxicard delivers Loxicard hydrochloride monohydrate into the dermis. Loxicard is an amide- type local anesthetic agent that blocks sodium ion channels required for the initiation and conduction of neuronal impulses, resulting in local anesthesia.
Loxicard provides local dermal analgesia within 1–3 minutes of application. Analgesia diminishes within 10 minutes of treatment.
A single dose of Loxicard in adults did not produce detectable plasma concentrations of Loxicard (limit of quantitation 5 ng/mL) in any subject tested (n = 38).
Application of Loxicard to broken or inﬂamed skin, or multiple Loxicard applications, could result in systemic plasma levels of Loxicard that could produce systemic toxicity.
When Loxicard 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 Loxicard, the plasma protein binding of Loxicard is concentration dependent. Loxicard crosses the placental and blood brain barriers, presumably by passive diffusion. CNS toxicity may typically be observed around 5000 ng/mL of Loxicard; however a small number of patients reportedly may show signs of toxicity at approximately 1000 ng/mL.
It is not known if Loxicard is metabolized in the skin. Loxicard is metabolized rapidly by the liver to a number of metabolites including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of Loxicard. The major metabolic pathway of Loxicard, sequential N-deethylation to monoethylglycinexylidide (MEGX) and glycinexylidide (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 Loxicard, MEGX and GX concentrations in serum range from 11% to 36% and from 5% to 11% of Loxicard concentrations, respectively. Serum concentrations of MEGX are about one-third the serum Loxicard concentrations.
The half-life of Loxicard elimination from the plasma following intravenous administration is approximately 1.8 hours. Loxicard and its metabolites are excreted by the kidneys. More than 98% of an absorbed dose of Loxicard can be recovered in the urine as metabolites or parent drug. Less than 10% of Loxicard 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 elimination half-life of Loxicard was statistically signiﬁcantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours).
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Loxicard.
No mutagenic potential of Loxicard was demonstrated in the in vitro Ames Bacterial Reverse Mutation Assay, the in vitro chromosome aberration assay using Chinese hamster ovary cells, and the in vivo mouse micronucleus assay.
Impairment of Fertility
Loxicard was not formally evaluated for effects on fertility. Significant systemic exposure to Loxicard is not expected under recommended conditions of use of Loxicard, as Loxicard levels were below the limit of detection in human studies. Loxicard has been previously tested in animal studies for effects on fertility, however. The following ratios are based on the assumption that the applied dose is completely absorbed through the skin.
Loxicard did not affect fertility in female rats when given via continuous subcutaneous infusion via osmotic minipumps up to doses of 250 mg/kg/day [1500 mg/m2 or 5000-fold higher than the SDA of 0.5 mg Loxicard in a 60 kg individual (0.3 mg/m2)]. Although Loxicard treatment of male rats increased the copulatory interval and led to a dose-related decreased homogenization resistant sperm head count, daily sperm production, and spermatogenic efficiency, the treatment did not affect overall fertility in male rats when given subcutaneous doses up to 60 mg/kg (360 mg/m2 or 1200-fold the SDA).
14 CLINICAL STUDIES
Efficacy in Adults
The efficacy of Loxicard in adults was evaluated in a randomized, double-blind, parallel-arm, sham-placebo controlled trial in which adult patients who required a venipuncture or peripheral venous cannulation received either Loxicard or a sham placebo device.
Patients were treated with Loxicard 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, and corticosteroids.
Treatment with active drug resulted in less pain compared with placebo.
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 Loxicard 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 Loxicard 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 Loxicard 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.
1 least squares mean 2 standard error
16 HOW SUPPLIED/STORAGE AND HANDLING
NDC 61388-001-48 Loxicard (lidocaine hydrochloride monohydrate) powder intradermal injection system contains 0.5 mg of sterile Loxicard hydrochloride monohydrate. Loxicard is a single-use device packaged in an individual clear pouch. Twelve pouched devices are placed in labeled cartons.
Cartons are stored at controlled room temperature (15–30°C, 59–86°F).
17 PATIENT COUNSELING INFORMATION
Patients should be made aware that a sound similar to that of a popping balloon is emitted at the time Loxicard is actuated.
Patients should be informed that skin reactions including erythema, petechiae, pruritus and edema may occur.
Powder Pharmaceuticals, Inc.
Hong Kong, China
Loxicard is a trademark of Powder
Medline Industries, Inc.,
Mundelein, IL 60060, USA (RA14)
Under license by Marathon Pharmaceuticals, LLC.
(lidocaine hydrochloride monohydrate)
powder intradermal injection system
Powder Pharmaaceuticals, Inc.
Hong Kong, China
NDC 61388-001-48 Loxicard (lidocaine hydrochloride monohydrate) powder intradermal injection system 0.5mg RX only. Manufactured by: Powder Pharmaceuticals, Inc. Hong Kong, China
Loxicard pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Loxicard available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Loxicard destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Loxicard Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Loxicard pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Loxicard?
Depending on the reaction of the Loxicard after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Loxicard not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Loxicard addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
ReviewsDrugs.com conducted a study on Loxicard, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Loxicard consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Two visitors reported side effectsDid you get side effects while taking the Loxicard drug, or were there no side effects?
According to the survey conducted by website sDrugs.com users, the below-mentioned percentages indicate the number of people experiencing the side effects and the number of people not experiencing the side effects when taking Loxicard medicine. Every drug produces minimal side effects, and they are negligible most times, when compared to the desired effect [use] of the medicine. Side effects depend on the dose you are taking, any drug interactions that happen when you are on other medications, if the patient is sensitive, and other associated conditions. If you cannot tolerate the side effects, consult your doctor immediately, so he can either adjust the dose or change the medication.
One visitor reported price estimatesWhat is your opinion about drug cost? Did you feel the cost is apt, or did you feel it is expensive?
The report given by the sDrugs.com website users shows the following figures about several people who felt the medicine Loxicard is expensive, and the medicine is not expensive. The results are mixed. The perception of the cost of the medicine to be expensive or not depends on the brand name of the medicine, country, and place where it is sold, and the affordability of the patient. You can choose a generic drug in the place of the branded drug to save the cost. The efficiency of the medicine will not vary if it is generic or a branded one.
One visitor reported dosesWhat is the dose of Loxicard drug you are taking?
According to the survey conducted among sDrugs.com website users, the maximum number of people are using the following dose 501mg-1g. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
One visitor reported administrationThe drugs are administered in various routes, like oral or injection form. They are administered before food or after food. How are you taking Loxicard drug, before food or after food?
Click here to find out how other users of our website are taking it. For any doubts or queries on how and when the medicine is administered, contact your health care provider immediately.
Four visitors reported age
The information was verified by Dr. Arunabha Ray, MD Pharmacology