Histamine Dihydrochloride

Allergy Skin Testing (Positive Control)

• Skin Prick Method: One drop of a 1 mg/mL or 10 mg/mL solution is applied to the skin, followed by a prick through the drop.
• Intradermal Method: 0.02 mL of a highly diluted solution (e.g., 0.01 mg/mL) may be injected into the dermal layer of the skin.

Therapeutic Use (Oncology Adjunct)

• Dosage is highly specialized and usually involves subcutaneous injections of 0.5 mg twice daily for specific cycles, often in conjunction with other immunotherapies.

Histamine Dihydrochloride is used in children for allergy testing. The procedure is identical to adult skin testing, though the number of test sites may be limited based on the child's size and tolerance. It is not generally approved for therapeutic use in pediatric oncology populations.

Renal Impairment

No specific dose adjustments are typically required for diagnostic skin testing due to minimal systemic absorption. For systemic therapeutic use, caution is advised as metabolites are renally cleared.

Hepatic Impairment

Use with caution in patients with severe hepatic dysfunction, as the liver is a primary site for histamine metabolism.

Elderly Patients

Elderly patients may have reduced skin reactivity; healthcare providers may need to interpret skin test results with caution.

This medication is administered exclusively by healthcare professionals in a clinical setting.

• Preparation: The skin (usually the forearm or back) is cleaned with alcohol.
• Administration: For testing, it is applied via a lancet or specialized skin testing device.
• Observation: The site is monitored for 15–20 minutes to measure the resulting wheal and flare.

As this is typically administered in a clinical setting for diagnostic purposes, missed doses are handled by rescheduling the clinical appointment.

Signs of systemic overdose (rare with skin testing but possible with injection) include:

• Severe headache
• Flushing and heat sensation
• Rapid heart rate (tachycardia)
• Hypotension (low blood pressure)
• Difficulty breathing

In the event of a systemic reaction, emergency medications such as epinephrine must be administered immediately.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

In the context of skin testing, the following are expected and indicate a 'normal' positive reaction:

• Pruritus (Itching): Intense itching at the site of application.
• Erythema (Redness): A localized red 'flare' around the test site.
• Wheal Formation: A raised, pale bump similar to a mosquito bite.

• Localized Pain: A stinging or burning sensation at the application site.
• Extended Redness: Redness that spreads significantly beyond the test area.

• Headache: Systemic absorption can trigger vascular headaches.
• Dizziness: Feeling lightheaded or faint.
• Tachycardia: An abnormally fast heart rate.

> Warning: Stop the procedure and alert medical staff immediately if you experience any of these:

• Anaphylaxis: A severe, life-threatening allergic reaction characterized by swelling of the throat, difficulty breathing, and a sharp drop in blood pressure.
• Severe Bronchospasm: Sudden wheezing or chest tightness, especially in patients with pre-existing asthma.
• Generalized Urticaria: Hives spreading to parts of the body far from the test site.
• Syncope: Fainting or loss of consciousness.

Because Histamine Dihydrochloride is typically used as a one-time diagnostic tool or in short therapeutic cycles, long-term side effects are rare. However, repeated systemic exposure in therapeutic settings may lead to chronic flushing or gastrointestinal upset.

No FDA black box warnings are currently issued for Histamine Dihydrochloride when used as a diagnostic skin test reagent. However, it must always be administered in a facility equipped to treat anaphylaxis.

Report any unusual symptoms to your healthcare provider.

Histamine Dihydrochloride is a potent biological agent. It should only be administered by trained professionals in settings where emergency resuscitation equipment (including oxygen, epinephrine, and IV fluids) is immediately available.

No FDA black box warnings for Histamine Dihydrochloride.

• Asthma and Respiratory Disease: Histamine can cause bronchoconstriction. Patients with unstable asthma or significantly reduced lung function may be at higher risk for respiratory distress.
• Cardiovascular Disease: Because histamine can cause vasodilation and tachycardia, it should be used with extreme caution in patients with severe hypertension, recent myocardial infarction (heart attack), or cardiac arrhythmias.
• Peptic Ulcer Disease: Histamine stimulates gastric acid secretion, which may exacerbate active peptic ulcers.
• Hypersensitivity: While used to test for allergies, the drug itself can rarely cause systemic hypersensitivity reactions.

• Immediate Observation: Patients must be monitored for at least 20–30 minutes following administration for signs of systemic reactions.
• Vitals: In therapeutic settings, blood pressure and heart rate monitoring are required.

Patients who experience dizziness or systemic symptoms after administration should avoid driving or operating heavy machinery until symptoms have completely resolved.

Alcohol can increase the effects of histamine and may worsen flushing or headaches. It is advised to avoid alcohol consumption for 24 hours before and after administration.

For diagnostic use, there is no withdrawal syndrome. For therapeutic use in AML, discontinuation must be managed by an oncologist to avoid compromising the treatment protocol.

> Important: Discuss all your medical conditions with your healthcare provider before starting Histamine Dihydrochloride.

• H1-Antihistamines (e.g., Diphenhydramine, Loratadine): These drugs directly block the receptors Histamine Dihydrochloride targets. Using them will cause a 'false negative' in skin tests, rendering the diagnostic procedure useless.

• Tricyclic Antidepressants (TCAs) (e.g., Amitriptyline): These medications possess potent antihistamine properties and can suppress skin test reactivity for several days or weeks.
• Beta-Blockers (e.g., Propranolol): Patients on beta-blockers may be resistant to the effects of epinephrine if an accidental systemic reaction occurs during the test.

• H2-Receptor Antagonists (e.g., Famotidine): While primarily affecting stomach acid, they can partially reduce the flare response in skin testing.
• Topical Corticosteroids: If applied to the test site, these can suppress the inflammatory response and lead to inaccurate results.

• High-Histamine Foods: Consuming foods high in histamine (aged cheeses, red wine, fermented foods) immediately before testing may theoretically increase the baseline sensitivity of the patient, though this is rarely clinically significant for skin tests.

• Quercetin: This supplement has natural antihistamine properties and may interfere with skin test results.
• Vitamin C: High doses of Vitamin C may have a mild antihistamine effect and should be disclosed to the provider.

Histamine Dihydrochloride is used to create a lab result (the skin test). Its presence in the system does not typically interfere with standard blood chemistry or hematology panels, other than potentially causing a transient increase in white blood cell activity in the localized area.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

• History of Severe Systemic Allergic Reaction to Histamine: If a patient has previously experienced anaphylaxis specifically to histamine dihydrochloride.
• Active Peptic Ulcer: Due to the risk of stimulating excessive gastric acid.
• Severe Uncontrolled Asthma: Risk of inducing a life-threatening asthma attack.

• Pregnancy: Risk-benefit must be weighed, as systemic reactions could cause uterine contractions or fetal distress.
• Recent Myocardial Infarction: The cardiovascular stress of a systemic reaction could be dangerous.
• Dermatographism: A condition where the skin overreacts to any touch; this makes interpreting a histamine 'positive control' difficult or impossible.

There is no significant cross-sensitivity with other common drugs, as histamine is an endogenous (naturally occurring in the body) substance. However, patients sensitive to preservatives in the solution (like phenol) should be identified.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Histamine Dihydrochloride.

Category C. There are no adequate and well-controlled studies in pregnant women. Histamine Dihydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Systemic histamine can theoretically stimulate uterine contractions.

It is unknown if Histamine Dihydrochloride is excreted in human milk. Because many drugs are excreted in milk and because of the potential for serious adverse reactions in nursing infants, caution should be exercised. However, for diagnostic skin testing, the systemic dose is virtually zero.

Approved for use as a diagnostic control in children. Safety and effectiveness for therapeutic (oncology) use in children have not been established.

Clinical studies have shown that skin reactivity to histamine may decrease with age. Providers may need to use a higher concentration (10 mg/mL instead of 1 mg/mL) to achieve a valid positive control in patients over 65.

No specific dose adjustment is required for diagnostic use. In systemic therapeutic use, the rate of metabolite clearance may be reduced, necessitating closer monitoring for side effects.

Since the liver metabolizes histamine via the HNMT pathway, patients with severe hepatic impairment should be monitored for prolonged systemic effects if the drug is injected.

> Important: Special populations require individualized medical assessment.

Histamine Dihydrochloride is a direct-acting agonist at H1 and H2 receptors.

• H1 Receptors: Activation on vascular endothelial cells causes the release of nitric oxide, leading to vasodilation and increased capillary permeability (the wheal). It also stimulates sensory nerve endings (the itch and flare).
• H2 Receptors: Activation on gastric parietal cells increases acid secretion and contributes to vascular effects.

• Onset of Action: 1–2 minutes for skin reaction.
• Peak Effect: 15–20 minutes.
• Duration: 30–60 minutes for the visible skin reaction.

| Parameter | Value |

|---|---|

| Bioavailability | 100% (Subcutaneous); Negligible (Epicutaneous) |

| Protein Binding | Low |

| Half-life | 2–5 minutes |

| Tmax | ~15 minutes (Subcutaneous) |

| Metabolism | Hepatic/Tissue (DAO and HNMT enzymes) |

| Excretion | Renal (>90% as metabolites) |

• Molecular Formula: C5H9N3 · 2HCl
• Molecular Weight: 184.07 g/mol
• Solubility: Highly soluble in water.
• Structure: An imidazole ring connected to an ethylamine chain, provided as a dihydrochloride salt for stability.

Histamine Dihydrochloride is classified as a diagnostic biological and a histamine agonist. It is the gold standard positive control for allergy testing.