Overview

Zucapsaicin, the cis-isomer of capsaicin, is a topical analgesic used to treat osteoarthritis of the knee and other neuropathic pain. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1, that reduces pain and improves articular functions. Zucapsaicin has also been evaluated for the management of several conditions manifested by chronic nerve pain. These conditions include herpes simplex (HSV) infections, cluster headaches, migraine, and osteoarthritis of the knee. Zucapsaicin was approved by the Health Canada in 2010 as topical cream marketed under the brand name Zuacta but currently not FDA-approved.

Indication

Indicated to be used in conjunction with oral COX-2 inhibitors or NSAIDs for the relief of severe pain in adult patients with osteoarthritis of the knee, not controlled with oral COX-2 inhibitors or NSAIDs alone, for a duration of no more than three months.

Associated Conditions

Severe Pain

Research Report

Published: Oct 29, 2025

A Comprehensive Monograph on Zucapsaicin (DB09120): Pharmacology, Clinical Development, and Therapeutic Profile

Executive Summary & Drug Profile Overview

Synopsis of Zucapsaicin

Zucapsaicin is a synthetically derived small molecule developed as a topical analgesic for the management of pain associated with osteoarthritis and various neuropathic conditions. Chemically, it is the (Z)- or cis-isomer of capsaicin, the naturally occurring pungent compound in chili peppers. Its development was predicated on the hypothesis that this specific stereoisomer could retain the analgesic efficacy of capsaicin while offering a superior local tolerability profile, thereby addressing the primary limitation of its trans-isomer counterpart.[1]

The primary mechanism of action of zucapsaicin is its function as a potent and selective agonist of the Transient Receptor Potential Vanilloid 1 (TRPV1) channel.[4] TRPV1 is a non-selective cation channel predominantly expressed on the peripheral terminals of nociceptive sensory neurons. Zucapsaicin's interaction with this receptor is biphasic: an initial activation phase causes neuronal depolarization, leading to the sensation of burning and warmth at the application site. This is followed by a prolonged period of desensitization, where the neuron becomes refractory to further stimuli, resulting in a durable, localized analgesic effect. This "defunctionalization" of nociceptors is further augmented by the depletion of pronociceptive neuropeptides, such as Substance P and Calcitonin Gene-Related Peptide (CGRP), from nerve terminals.[4]

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Clinical Trials

Title	Posted	Study ID	Phase	Status	Sponsor
Civamide Nasal Solution for the Treatment of Dry Eye	2014/04/16	NCT02116244	Phase 2	Completed	Winston Laboratories
Civamide Nasal Solution for Postherpetic Neuralgia of the Trigeminal Nerve	2013/06/25	NCT01886313	Phase 2	Terminated	Winston Laboratories
Civamide Nasal Solution for Cluster Headache	2011/04/25	NCT01341548	Phase 3	Not yet recruiting	Winston Laboratories
Evaluating the Safety and Efficacy Civamide in Osteoarthritis (OA) of the Knee(s)	2009/10/15	NCT00995306	Phase 3	Completed	Winston Laboratories
Evaluation of Civamide Patch in Treatment of Postherpetic Neuralgia and Post-Incisional Neuralgia	2009/02/18	NCT00845923	Phase 2	Completed	Winston Laboratories
Oral Civamide Safety, Tolerability First in Human Study	2008/12/04	NCT00802217	Phase 1	Terminated	Winston Laboratories
Civamide Patch Safety, Tolerability and PK Study	2008/09/25	NCT00758433	Phase 1	Completed	Winston Laboratories
Civamide in OA of the Knee(s)	2004/02/18	NCT00077935	Phase 3	Completed	Winston Laboratories
Intranasal Civamide for Episodic Cluster Headache	2003/09/16	NCT00069082	Phase 3	Completed	Winston Laboratories
A Phase III Study of Civamide Nasal Solution (Zucapsaicin) for the Treatment of Episodic Cluster Headache	2002/04/12	NCT00033839	Phase 3	Completed	Winston Laboratories

FDA Drug Approvals

Approved Product	Manufacturer	NDC Code	Route	Strength	Effective Date
No FDA approvals found for this drug.

EMA Drug Approvals

Approved Product	Authorization Holder	Status	Issued Date
No EMA approvals found for this drug.

HSA Drug Approvals

Approved Product	Manufacturer	Approval Number	Dosage Form	Strength	Approval Date
No HSA approvals found for this drug.

NMPA Drug Approvals

Approved Product	Company	Approval Number	Drug Type	Dosage Form	Approval Date
No NMPA approvals found for this drug.

PPB Drug Approvals

Approved Product	Registration No.	Company	Licence No.	Strength	Registration Date
No PPB approvals found for this drug.

TGA Drug Approvals

Approved Product	ARTG ID	Sponsor	Registration Type	Status	Registration Date
No TGA approvals found for this drug.

Health Canada Drug Approvals

Approved Product	Company	DIN	Dosage Form	Strength	Market Date
ZUACTA	sanofi-aventis canada inc	02354772	Cream - Topical	0.075 % / W/W	8/24/2011

CIMA AEMPS Drug Approvals

Approved Product	Company	Registration Number	Pharmaceutical Form	Prescription Type	Status
No CIMA AEMPS (Spain) approvals found for this drug.

Philippines FDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Philippines FDA approvals found for this drug.

Saudi SFDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Saudi SFDA approvals found for this drug.

Malaysia NPRA Drug Approvals

Approved Product	Company	Registration Number	Dosage Form	Strength	Approval Date
No Malaysia NPRA approvals found for this drug.

UK EMC Drug Information

Medicine Name	MA Holder	MA Number	Pharmaceutical Form	Active Ingredient	Authorization Date
No UK EMC drug information found for this drug.

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