Version July 2025
Cold sore/fever blister: Topical: Apply single dose to cold sore with applicator; may repeat up to 3 times daily.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Cold sore/fever blister: Topical: Children >2 years and Adolescents: Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no adverse reactions listed in the manufacturer's labeling. See individual agents.
OTC labeling: When used for self-medication, do not use if you have hypersensitivity to benzalkonium chloride, benzocaine, other ester-type local anesthetics, or any component of the formulation; for ophthalmic use or for teething; use over a large area of body or >3 times daily; children <2 years of age; longer than 1 week unless directed by health care provider.
Concerns related to adverse effects:
• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).
Other warnings/precautions:
• Self-medication (OTC use): When used for self-medication, notify health care provider if condition worsens or does not improve within 7 days.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Liquid, Oral:
Orajel Cold Sore: Benzalkonium chloride 0.13% and benzocaine 5% (4s) [contains isopropyl alcohol]
No
Topical: Prior to administration, clean lotions, ointments, or cosmetics from the lip using only warm water and a washcloth. Saturate the applicator with solution and apply to the cold sore. Allow a few moments for the lip to numb, then massage the solution (using the applicator) into the cold sore by rubbing firmly without damaging the skin. Avoid brushing with toothpaste or drinking fruit juices or soft drinks for at least one hour after application.
Topical: Children ≥2 years and Adolescents: Prior to administration, clean lip area with warm water and washcloth; remove any residual lotions, ointments, or cosmetics. Saturate the applicator with solution and apply to the cold sore. Allow a few moments for the lip to numb, then massage the solution (using the applicator) into the cold sore by rubbing firmly without damaging the skin. Avoid brushing with toothpaste or drinking fruit juices or soft drinks for at least 1 hour after application. A residual fine white powder at the application site may appear at the application site and is normal; it is unabsorbed benzocaine.
Cold sore/fever blister: Topical treatment of cold sores or fever blisters
KIDs List: Benzocaine, when used in pediatric patients <2 years of age for teething or pharyngitis, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of methemoglobinemia (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Articaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor
Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Methemoglobinemia Associated Agents: May increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Nitric Oxide: May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Prilocaine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor
Primaquine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Primaquine. Specifically, the risk for methemoglobinemia may be increased. Management: Avoid concomitant use of primaquine and other drugs that are associated with methemoglobinemia when possible. If combined, monitor methemoglobin levels closely. Risk D: Consider Therapy Modification
ROPivacaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Sodium Nitrite: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Fruit juices and soft drinks may deactivate the active ingredient. Management: Avoid drinking fruit juices and soft drinks for at least 1 hour after application.
Benzalkonium chloride is an antiseptic and disinfectant; benzocaine is an ester local anesthetic that blocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction
