Ketamine 15% | Baclofen 2% | Bupivacaine 1% | Cyclobenzaprine 2% | Diclofenac 3% | Gabapentin 6%

Route: Topical. Apply a small measured amount (typically 0.5–1 mL or as prescribed) to the painful area and gently massage until absorbed. Apply 2–4 times daily as directed by the prescriber. Wash hands immediately after application. Avoid contact with eyes and mucous membranes. Do not apply to open wounds, rashes, or large body-surface areas without prescriber-specific direction.

Dosing is entirely prescriber-determined:

• Application quantity, frequency (typically 2–4 times daily), treatment area, and duration are all prescribed specifically.
• The high ketamine concentration (15%) and inclusion of bupivacaine indicate this formulation is reserved for more severe pain presentations requiring close prescriber supervision.
• All dosing parameters are determined by the prescribing clinician based on patient-specific pain assessment.

• Ketamine 15%: Non-competitive NMDA receptor antagonist; at 15% concentration provides greater occupancy of peripheral and dorsal horn NMDA receptors, reducing central sensitization, wind-up, and allodynia.
• Baclofen 2%: GABA-B receptor agonist; receptor binding causes K⁺ channel opening (neuronal hyperpolarization) and voltage-gated Ca²⁺ channel inhibition at presynaptic terminals, reducing glutamate, CGRP, and substance P release from primary afferent nociceptors; also reduces alpha-motor neuron excitability at the spinal cord level, relieving spasm.
• Bupivacaine 1%: Long-acting amide local anesthetic binding to the inner pore of voltage-gated Na⁺ channels in a state-dependent manner with slower on/off kinetics than lidocaine, providing prolonged inhibition of action potential propagation in nociceptive nerve fibers.
• Cyclobenzaprine 2%: Reduces tonic somatic motor efferent activity via brainstem mechanisms; may modulate descending noradrenergic inhibitory pain pathways.
• Diclofenac 3%: COX-1 and COX-2 inhibition reduces prostaglandin synthesis (PGE2, PGI2) at the application site, lowering peripheral nociceptor sensitization threshold and attenuating neurogenic inflammation.
• Gabapentin 6%: Binds alpha-2-delta subunit of presynaptic Cav2.2 (N-type) and Cav2.1 (P/Q-type) voltage-gated calcium channels; reduces Ca²⁺ influx and glutamate/substance P release from peripheral and central nociceptors; reduces ectopic discharge in injured nerves, attenuating neuropathic pain.

This six-ingredient formulation is intended for prescriber-directed management of severe or treatment-refractory neuropathic pain conditions (complex regional pain syndrome [CRPS], postherpetic neuralgia, diabetic neuropathy), spasm-associated musculoskeletal pain, and mixed nociceptive-neuropathic pain syndromes. The addition of baclofen and substitution of bupivacaine for lidocaine (compared to simpler formulations) provides broader GABA-B inhibitory pathway coverage and extended local anesthesia duration.

Monitoring: Pain scale response at 4–8 weeks; skin tolerance (contact dermatitis, irritation); cardiovascular status in patients with conduction abnormalities (bupivacaine has greater cardiac toxicity potential than lidocaine with systemic absorption); renal and hepatic function with extended use.

Contraindications:

• Known hypersensitivity to any component (particularly bupivacaine/other amide anesthetics or NSAIDs).
• NSAID-exacerbated respiratory disease (diclofenac component).
• Application to large surface areas in patients with significant hepatic or renal impairment.

Warnings & Precautions:

• Bupivacaine: greater cardiac toxicity risk than lidocaine with systemic absorption from large areas, broken skin, or occlusion — apply only to prescribed limited area.
• Ketamine 15%: higher concentration increases systemic absorption risk compared to lower-concentration formulations — strictly limit application area per prescriber direction.
• Baclofen: topical systemic absorption is generally low; concurrent oral baclofen should be disclosed to prescriber to avoid additive CNS effects with significant systemic absorption.
• Avoid in pregnancy (multiple components carry pregnancy safety concerns).

Drug Interactions:

• Topical application to limited areas: clinically significant systemic drug interactions are unlikely but disclose all concurrent medications.
• CNS depressants: theoretical additive CNS effects with significant systemic absorption of cyclobenzaprine or baclofen.
• Class I antiarrhythmics: additive cardiac conduction effects if significant bupivacaine absorption occurs.

Common Side Effects: Local skin reactions (erythema, burning, pruritus) at application site. Rarely: systemic effects with inadvertent excessive application or large-area use.

Store at room temperature (15°C–25°C). Keep tightly sealed and protected from light and heat. Do not freeze. Use within the beyond-use date assigned by Genesis Compounding.

Why does this formula include baclofen in addition to other muscle relaxants?

Baclofen acts through a distinct mechanism — GABA-B receptor agonism reducing presynaptic excitatory neurotransmitter release — complementary to cyclobenzaprine's central tonic motor inhibition. Together, they provide broader coverage of spinal inhibitory signaling and descending pain modulation pathways.

Why is bupivacaine used instead of lidocaine?

Bupivacaine has longer dissociation kinetics from sodium channels, providing more sustained local analgesia between applications, beneficial for patients with persistent severe pain.

Is 15% ketamine safe topically?

At doses applied to a limited prescribed skin area, systemic absorption is expected to be minimal and psychoactive effects should not occur. Prescribers specify both application area and volume. Report any unusual cognitive or cardiovascular symptoms immediately.

Is this FDA-approved?

No. This is a patient-specific, prescriber-directed 503A compounded preparation from Genesis Compounding, not FDA-approved as a compounded drug.

How does this differ from the five-ingredient ketamine cream?

This formulation adds baclofen (GABA-B agonist for presynaptic inhibitory coverage) and uses the longer-acting bupivacaine instead of lidocaine, with a higher ketamine concentration (15%), providing a more intensive multi-mechanism approach for severe or refractory pain presentations.