Ztlido Drug Information

is indicated for relief of pain associated with post-herpetic neuralgia (PHN) in adults. ZTLIDO contains lidocaine, an amide local anesthetic, and is indicated for relief of pain associated with post-herpetic neuralgia (PHN) in adults.

Important Dosage and

Administration Instructions Because of the difference in bioavailability of ZTLIDO compared to Lidoderm (lidocaine patch 5%), a different dosage strength is required to be administered to the patient. One ZTLIDO (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm (lidocaine patch 5%). When ZTLIDO is used concomitantly with other products containing local anesthetic agents, the total amount of drug absorbed from all formulations must be considered. Clearly instruct and advise patients: to wash hands immediately after handling ZTLIDO and to avoid contact with eyes . to store ZTLIDO inside the sealed envelope out of the reach of children, pets, and others and to apply immediately after removal from the envelope. to fold used ZTLIDO so that the adhesive side sticks to itself and to safely discard used ZTLIDO or pieces of cut ZTLIDO where children and pets cannot get to them . to never apply external heat sources, such as heating pads or electric blankets, directly to ZTLIDO, because plasma lidocaine levels are increased.

ZTLIDO can be applied, however, to the administration site after moderate heat exposure, such as 15 minutes of heating pad exposure on a medium setting . that clothing may be worn over the area of application. that ZTLIDO may be used during moderate exercise, such as biking for 30 minutes. that ZTLIDO may be exposed to water, such as showering for 10 minutes or immersion for 15 minutes. to dry the topical system, after water exposure, by gently patting the skin, not by rubbing the skin or topical system. that ZTLIDO topical systems that have lifted at the edges may be reattached by pressing firmly on the edges and that fully detached topical systems may be reapplied as originally directed. that if a ZTLIDO topical system comes off completely and will not stick to patient's skin, to remove and properly dispose of the used ZTLIDO and to apply a new ZTLIDO topical system for a total duration of 12 hours of used and new topical system together. that if irritation or a burning sensation occurs during application, to remove ZTLIDO and to not reapply until the irritation subsides .

Treatment of Post-Herpetic Neuralgia Advise patients to apply

ZTLIDO to intact skin to cover the most painful area and to apply the prescribed number of topical systems (maximum of 3), only once for up to 12 hours within a 24-hour period (12 hours on and 12 hours off) . In patients who are debilitated or have impaired elimination, smaller areas of treatment are recommended. Achieve this by cutting ZTLIDO with scissors into a smaller size prior to removing the release liner.

• The following serious adverse reactions are described elsewhere in the labeling: Excessive Dosing/Overexposure to Lidocaine Methemoglobinemia Application Site Reactions Hypersensitivity Reactions Eye Irritation The following adverse reactions from voluntary reports or clinical studies have been reported with lidocaine. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Skin and subcutaneous tissues: blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erosions, erythema, exfoliation, flushing, irritation, papules, petechia, pruritus, vesicles, and abnormal sensation.
• Immune system: angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, shock, and urticaria.
• Central Nervous System: lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, somnolence, respiratory depression and arrest.
• Cardiovascular: bradycardia, hypotension, and cardiovascular collapse leading to arrest.
• Other: asthenia, disorientation, headache, hyperesthesia, hypoesthesia, metallic taste, nausea, pain exacerbated, paresthesia, taste alteration, and vomiting. Common adverse reactions are application site reactions such as irritation, erythema, and pruritus. To report SUSPECTED ADVERSE REACTIONS, contact Scilex Pharmaceuticals Inc. at 1-866-SCILEX3 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drugs That May Cause Methemoglobinemia

When Used with ZTLIDO Patients who are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicyclic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

Antiarrhythmic Drugs

When ZTLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine), the toxic effects are additive and potentially synergistic. Consider risk/benefit during concomitant use.

Local Anesthetics

When ZTLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. Consider the amount of drug absorbed from all formulations when local anesthetic agents are administered concomitantly.

Pregnancy Risk Summary The limited human data with lidocaine in pregnant woman are not sufficient to inform drug-associated risk for major birth defects and miscarriage. The use of lidocaine for labor neuraxial analgesia has not been associated with an increased incidence of adverse fetal effects either during delivery or during the neonatal period (see Data ). Should ZTLIDO be used concomitantly with other products containing lidocaine, consider total drug doses contributed by all formulations. In a published animal reproduction study, pregnant rats administered lidocaine by continuous subcutaneous infusion at a dose approximately 45 times the maximum recommended daily dose (MRDD) of 108 mg in ZTLIDO during the period of organogenesis resulted in lower fetal body weights.

In a published animal reproduction study, pregnant rats administered lidocaine, containing 1:100,000 epinephrine, injected into the masseter muscle of the jaw or into the gum of the lower jaw at 0.5 times the MRDD on Gestation Day 11 resulted in developmental delays in neonates (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Human Data In 22 parturient women given 1.5% lidocaine epidural anesthesia, there were no effects on neonatal behavior, using the early neonatal neurobehavioral scale (ENNS). Neuraxial analgesia also did not affect fetal heart rate, beat-to-beat variability, or uterine activity. Animal Data Reproductive studies with lidocaine have been performed in rats at doses up to 30 mg/kg (2.7 times the maximum recommended daily dose of 108 mg from ZTLIDO on a mg/m 2 basis) subcutaneously and have revealed no evidence of harm to the fetus due to lidocaine. In a published study, lidocaine administered to pregnant rats by continuous subcutaneous infusion during the period of organogenesis at 100, 250, and 500 mg/kg/day, did not produce any structural abnormalities, but did result in lower fetal weights at 500 mg/kg/day dose (approximately 45 times the MRDD on a mg/m 2 basis) in the absence of maternal toxicity.

In a published study, lidocaine containing 1:100,000 epinephrine at a dose of 6 mg/kg (approximately 0.5 times the MRDD on a mg/m 2 basis) injected into the masseter muscle of the jaw or into the gum of the lower jaw of pregnant Long-Evans hooded rats on Gestation Day 11 resulted in developmental delays in the neonates. 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 these animal data is uncertain.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product. ZTLIDO is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product.

Lidocaine overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of lidocaine overdose, check drug blood concentration. The management of overdose includes close monitoring, supportive care, and symptomatic treatment.

Dialysis is of negligible value in the treatment of acute overdose with lidocaine. In the absence of massive topical overdose or oral ingestion, evaluation of symptoms of toxicity should include consideration of other etiologies for the clinical effects, or overdosage from other sources of lidocaine or other local anesthetics.