1St Medx-Patch

Drug overview for 1ST MEDX-PATCH (lidocaine/methyl salicylate/capsaicin/menthol):

Generic name: LIDOCAINE/METHYL SALICYLATE/CAPSAICIN/MENTHOL
Drug class: Topical Local Anesthetics
Therapeutic class: Dermatological

Lidocaine, a nonselective voltage-gated sodium channel inhibitor, is an amide-type local anesthetic.

Lidocaine is used topically for the treatment of pain. Various topical lidocaine products are commercially available. Lidocaine 1.8%

and 5% topical systems (i.e., patches) are FDA-labeled for the treatment of pain associated with postherpetic neuralgia (PHN). Lidocaine is also available in various over-the-counter (OTC) topical preparations for the temporary treatment of pain.

DRUG IMAGES

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The following indications for 1ST MEDX-PATCH (lidocaine/methyl salicylate/capsaicin/menthol) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following dosing information is available for 1ST MEDX-PATCH (lidocaine/methyl salicylate/capsaicin/menthol):

Dosing
Administration
Dosing Information
Generic

No enhanced Dosing information available for this drug.

Lidocaine patches are applied topically to intact skin. Applyimmediately after removal from the protective envelope. Patches may be cut into smaller sizes with scissors prior to removal of therelease liner.

Up to 3 patches may be applied at one time as prescribed; application of more than the recommended number of patches or for longer durations than recommended can result in increased blood concentrations of lidocaine, resulting in adverse reactions. Advise patients on proper application of the patches. Clothing may be worn over the area ofapplication.

If irritation or a burning sensation occurs during application, remove the patch(es) and do not reapply until the irritation subsides. Lidocaine 5% (Lidoderm(R)) patches may not stick if they get wet. The manufacturer states to avoid contact with water, such as bathing,swimming or showering.

The manufacturer of Ztlido(R) states that the patches may be used during moderate exercise, such as biking for 30 minutes and may be exposed to water, such as showering, for 10 minutes or immersion for 15 minutes. To dry the topical system after water exposure, gently pat the skin; do not rub the skin or topical system. Do not apply external heat sources, such as heating pads or electric blankets,directly to lidocaine patches, since this may increase plasma lidocaine levels.

The manufacturer of Ztlido(R) states that the patches can beapplied to an administration site after moderate heat exposure, such as15 minutes of heating pad exposure on a medium setting. Topical lidocaine (Lidoderm(R)and generics; Ztildo(R)) patches should be stored at 20-25degreesC with excursions permitted to 15-30degreesC.

No dosing information available.

No generic dosing information available.

The following drug interaction information is available for 1ST MEDX-PATCH (lidocaine/methyl salicylate/capsaicin/menthol):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Slt Anticoagulants (Vit K Antagonists)/Topical Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Multiple processes are involved: 1) Salicylate doses greater than 3 gm daily decrease plasma prothrombin levels. 2) Salicylates may also displace anticoagulants from plasma protein binding sites. 3) Aspirin is an irreversible platelet inhibitor. Salicylates impair platelet function, resulting in prolonged bleeding time. 4) Salicylates may cause gastrointestinal(GI) bleeding due to irritation. CLINICAL EFFECTS: The concurrent use of anticoagulants and salicylates leads to blockade of two distinct coagulation pathways and may increase the risk for bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. When aspirin is required for cardioprotection, a low dose (< 100 mg daily) is recommended to decrease the risk for aspirin-induced GI bleeding. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Topical use of methyl salicylate has been reported to increase the effects of warfarin.(1-7) In a case series on 11 patients who used significant amounts of methyl salicylate (2-4 g of ointment for previous 2 weeks), all had significant increases in INR and positive blood levels of salicylates. Two patients experienced diffuse bruising and one experienced gastrointestinal bleeding.(1) A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of warfarin and diflunisal resulted in a ratio of rate ratios (RR) (95% CI) of 3.85 (1.34-11.03); and warfarin and aspirin ratio of RR 2.13 (1.72-2.64).	ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM
Long-acting Bupivacaine/Local Anesthetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1) CLINICAL EFFECTS: Concurrent or use of local anesthetics with 96 hours of use of long-acting bupivacaine may result in neurologic and cardiovascular toxicity. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also result in methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1) PREDISPOSING FACTORS: Use of additional agents that are associated with methemoglobinemia may further increase the risk of methemoglobinemia.(1) Patients who are at increased risk of developing methemoglobinemia include those with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.(1) PATIENT MANAGEMENT: Avoid the use of other local anesthetics within 96 hours following the administration of long-acting bupivacaine. In patients for whom use is required, monitor for neurologic and cardiovascular effects. Also monitor for methemoglobinemia with use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine.(1,2) Non-liposomal bupivacaine may be administered in the same syringe as bupivacaine liposomal or injected immediately before bupivacaine liposomal as long as the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1) DISCUSSION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposome bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally. Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1)	BUPIVACAINE LIPOSOME, EXPAREL, XARACOLL, ZYNRELEF

Drug Interaction

Drug Names

Slt Anticoagulants (Vit K Antagonists)/Topical Salicylates

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Multiple processes are involved: 1) Salicylate doses greater than 3 gm daily decrease plasma prothrombin levels. 2) Salicylates may also displace anticoagulants from plasma protein binding sites. 3) Aspirin is an irreversible platelet inhibitor.

Salicylates impair platelet function, resulting in prolonged bleeding time. 4) Salicylates may cause gastrointestinal(GI) bleeding due to irritation.

CLINICAL EFFECTS: The concurrent use of anticoagulants and salicylates leads to blockade of two distinct coagulation pathways and may increase the risk for bleeding.

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. When aspirin is required for cardioprotection, a low dose (< 100 mg daily) is recommended to decrease the risk for aspirin-induced GI bleeding. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms.

When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: Topical use of methyl salicylate has been reported to increase the effects of warfarin.(1-7) In a case series on 11 patients who used significant amounts of methyl salicylate (2-4 g of ointment for previous 2 weeks), all had significant increases in INR and positive blood levels of salicylates. Two patients experienced diffuse bruising and one experienced gastrointestinal bleeding.(1)

A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of warfarin and diflunisal resulted in a ratio of rate ratios (RR) (95% CI) of 3.85 (1.34-11.03); and warfarin and aspirin ratio of RR 2.13

(1.72-2.64).

ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM

Long-acting Bupivacaine/Local Anesthetics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1)

CLINICAL EFFECTS: Concurrent or use of local anesthetics with 96 hours of use of long-acting bupivacaine may result in neurologic and cardiovascular toxicity. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also result in methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1)

PREDISPOSING FACTORS: Use of additional agents that are associated with methemoglobinemia may further increase the risk of methemoglobinemia.(1) Patients who are at increased risk of developing methemoglobinemia include those with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.(1)

PATIENT MANAGEMENT: Avoid the use of other local anesthetics within 96 hours following the administration of long-acting bupivacaine. In patients for whom use is required, monitor for neurologic and cardiovascular effects. Also monitor for methemoglobinemia with use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine.(1,2)

Non-liposomal bupivacaine may be administered in the same syringe as bupivacaine liposomal or injected immediately before bupivacaine liposomal as long as the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1)

DISCUSSION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposome bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1)

Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally. Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1)

BUPIVACAINE LIPOSOME, EXPAREL, XARACOLL, ZYNRELEF

There are 0 moderate interactions.

The following contraindication information is available for 1ST MEDX-PATCH (lidocaine/methyl salicylate/capsaicin/menthol):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*Known history of sensitivity to local anesthetic of the amide type, or to any other component of the product.

There are 2 contraindications. Absolute contraindication.

Contraindication List
Large open wound
Methemoglobinemia

There are 6 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Burns
Glucose-6-phosphate dehydrogenase (g6Pd) deficiency
Heart block
Hemolytic anemia from pyruvate kinase and g6PD deficiencies
Sepsis
Shock

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Disease of liver
Respiratory depression
Seizure disorder

The following adverse reaction information is available for 1ST MEDX-PATCH (lidocaine/methyl salicylate/capsaicin/menthol):

Overview
Severe
Less Severe

Adverse reaction overview.

Common adverse effects of lidocaine 1.8 and 5% patches include mild and transient application site reactions (e.g., blisters, bruising, burning sensation, depigmentation,dermatitis, discoloration, edema, erythema, exfoliation, irritation, papules, petechia,pruritus, vesicles). Systemic adverse reactions following topical use of lidoderm patch are unlikely due to minimal drug absorption.

There are 24 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Acidosis Anaphylaxis Angioedema Bradycardia Bronchospastic pulmonary disease Burns Cardiac arrest CNS depression Dyspnea Excitement Facial edema Heart block Hypersensitivity drug reaction Hypertension Hypotension Hypoxia Periorbital edema Pharyngeal edema Severe burns Skin ulcer Superficial skin ulcer Syncope Throat constriction Urticaria

There are 17 less severe adverse reactions.

More Frequent	Less Frequent
Blistering skin Contact dermatitis Stinging of skin Treatment site sequelae	Acute pain at drug application site Dry skin Erythema Pruritus of skin Skin irritation Stinging of skin

Rare/Very Rare
Cough Dysgeusia Headache disorder Ocular pain Pruritus of skin Reduced sensation of skin Stinging of skin

The following precautions are available for 1ST MEDX-PATCH (lidocaine/methyl salicylate/capsaicin/menthol):

Pediatric
Pregnant
Lactation
Geriatric

Safety and effectiveness in pediatric patients have not been established.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Lidocaine 5% patch has not been studied in pregnancy. The limited human data with the 1.8% patch are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

Animal reproductionstudies found that subcutaneous administration of the drug at doses higher than recommended human doses during the period of organogenesis resulted in lower fetal weights. Some manufacturers recommend that lidocaine patches should be used during pregnancy only if clearly needed. Lidoderm patches have not been studied and are contraindicated in labor and delivery. If lidocaine patches are used concomitantly with other productscontaining lidocaine, total doses contributed by all formulations must be considered.

Lidocaine is excreted into humanmilk in low concentrations following topical application. Caution should be exercised whenlidocaine is administered to a nursing woman, especially when administered with other local anesthetics.

Clinical studies of lidocaine 1.8% patch did not include sufficient number of patients >=65 years of age to determine whether they respond differently from younger patients. No differences in response have been identified in other clinical experience.