Usage
Histamine dihydrochloride is used as maintenance therapy in adult patients with acute myeloid leukemia (AML) in first remission, concomitantly treated with interleukin-2 (IL-2). Its efficacy has not been fully demonstrated in patients older than 60. It is also used in skin prick testing to serve as a positive control.
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Pharmacological Classification: Immunomodulator, positive control in allergy testing
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Mechanism of Action: Histamine dihydrochloride improves the immune-enhancing properties of IL-2, potentially inducing immune-mediated killing of leukemic cells. In allergy testing, it serves as a positive control, helping assess the patient’s reactivity to histamine and validate the test’s accuracy.
Alternate Names
- Histamine
- Histamine phosphate
- Ceplene (brand name for AML treatment)
How It Works
Pharmacodynamics
Histamine exerts its effects by binding to histamine receptors (H1, H2, H3, and H4). Histamine dihydrochloride, when used with IL-2 in AML, is thought to enhance the immune response against leukemic cells. As a positive control in skin testing, it induces a localized allergic reaction (wheal and flare) due to H1 receptor stimulation, causing vasodilation and increased vascular permeability.
Pharmacokinetics
- Absorption: After subcutaneous administration, histamine is rapidly absorbed.
- Metabolism: Histamine is rapidly metabolized by diamine oxidase and histamine-N-methyltransferase.
- Elimination: Histamine metabolites are primarily excreted in the urine.
Mode of Action (AML Treatment)
Histamine dihydrochloride enhances the anti-leukemic effects of IL-2. Its precise mechanism is not fully understood, but may involve modulating immune cell function.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation (Allergy Testing)
Histamine binds to H1 receptors in the skin, triggering vasodilation and increased vascular permeability.
Dosage
Standard Dosage
This pertains to the Ceplene brand for AML maintenance therapy and should be administered under the supervision of a physician experienced in managing AML.
Adults:
- 0.5 mL (500 micrograms) subcutaneously twice daily, administered 1 to 3 minutes after a subcutaneous injection of IL-2 (16,400 IU/kg).
- Inject slowly over 5 to 15 minutes.
Children: Not applicable for AML treatment. For allergy skin testing, a tiny amount (e.g., 10 mg/mL) is administered intradermally.
Special Cases: For AML Treatment: Dose modification based on individual patient tolerance. The dose reductions can be temporary or permanent. For elderly patients, dose adjustments are not typically necessary based solely on age but rather on renal or hepatic function. Dosage in renal or hepatic dysfunction needs to be adjusted based on individual patient response. For allergy testing, special consideration should be given to patients with dermatographism, where a lower concentration may be necessary.
Dosage Adjustments Based on tolerance and side effects.
Side Effects
Common Side Effects
- Flushing
- Headache
- Hypotension
- Tachycardia
- Dizziness
- Nausea
- Vomiting
- Injection site reactions
Rare but Serious Side Effects
- Severe allergic reactions
- Seizures (with large overdoses)
- Cardiac events (in patients with pre-existing cardiac conditions)
Long-Term Effects Data not available
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Severe hypotension
- Angina
Contraindications
- Hypersensitivity to histamine
- Significantly compromised cardiac function (e.g., NYHA Class III/IV)
- Patients receiving systemic steroid therapy, clonidine, and H2 blocking agents
- Patients who have received an allogeneic stem cell transplant
- Pregnancy and breastfeeding
- Severe hypertension, hypotension, or vasomotor instability
- Severe cardiac, pulmonary, or renal disease
Drug Interactions
- Antihistamines can counteract the effects of histamine dihydrochloride.
- Medications affecting the cardiovascular system, such as beta-blockers or antihypertensives, may interact with histamine dihydrochloride.
- Consult a comprehensive drug interaction database for a complete list of potential interactions. Many drugs have interactions with histamine, including but not limited to: crizotinib, dabrafenib, dacomitinib, dalfampridine, desipramine, dexchlorpheniramine maleate, disopyramide, dofetilide, dolutegravir, dopamine, doxazosin, dronedarone, famotidine, fedratinib, fexinidazole, flurazepam, formoterol, ganciclovir, choline salicylate, cimetidine, cisplatin, clofarabine, clopidogrel, and codeine.
Pregnancy and Breastfeeding
Histamine dihydrochloride is contraindicated during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Enhances IL-2’s immune-enhancing effects in AML. Serves as a positive control in skin testing by inducing localized allergic reactions.
- Side Effects: Flushing, headache, hypotension, tachycardia, dizziness, nausea, vomiting.
- Contraindications: Hypersensitivity, severe cardiac dysfunction, concomitant use of certain medications, pregnancy, breastfeeding.
- Drug Interactions: Antihistamines, cardiovascular medications.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: AML: 0.5 mL (500 mcg) subcutaneously twice daily after IL-2 injection. Skin testing: Tiny amount intradermally.
- Monitoring Parameters: Blood pressure, heart rate, lung function (initial administration).
Popular Combinations
- IL-2 (for AML treatment).
Precautions
- Monitor blood pressure, heart rate, and lung function during initial administration.
- For skin testing, avoid intravascular injection.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Histamine Dihydrochloride in AML treatment?
A: 0.5 mL (500 mcg) subcutaneously twice daily after IL-2 administration.
Q2: What are the common side effects?
A: Flushing, headache, hypotension, and tachycardia.
Q3: Can Histamine Dihydrochloride be used during pregnancy?
A: No, it is contraindicated during pregnancy and breastfeeding.
Q4: How is Histamine Dihydrochloride administered?
A: By slow subcutaneous injection.
Q5: What is the role of Histamine Dihydrochloride in skin testing?
A: It serves as a positive control, helping assess histamine reactivity.
Q6: What are the contraindications for AML treatment?
A: Hypersensitivity to histamine, severe cardiac dysfunction, specific concomitant medications, and prior allogeneic stem cell transplant.
Q7: Should the dose be adjusted for elderly patients with AML?
A: Dose adjustments are not specifically recommended for elderly patients, but rather, based on renal or hepatic function.
Q8: Are there any drug interactions I should be aware of in patients with AML?
A: Yes, antihistamines can counteract the effects of Histamine Dihydrochloride, and caution should be taken with cardiovascular medications. A comprehensive drug interaction resource should be consulted.
Q9: What monitoring should be done when starting a patient on Histamine Dihydrochloride and IL-2 for AML?
A: Monitor the patient’s blood pressure, heart rate, and lung function, especially during initial doses.
