cyproheptadine

Cyproheptadine is a medication used to prevent and treat allergic reactions including sneezing, runny nose, watery eyes, swelling, itching, rashes and hives. Cyproheptadine is also used to prevent migraines and to manage severe life-threatening allergic reactions (anaphylaxis). Cyproheptadine is a first generation antihistamine that easily crosses the blood-brain barrier, causing drowsiness as a side effect, which the second generation antihistamines do not cause.

Cyproheptadine blocks the activity of histamine, a natural compound in the body that causes allergy symptoms. Histamine is released by mast cells and basophils, types of immune cells, in response to allergen exposure. Cyproheptadine binds to histamine H1 receptors in blood vessels, respiratory tract and gastrointestinal tract, preventing their stimulation by histamine and the resultant allergic reaction.

Cyproheptadine also binds to serotonin 5-HT2 receptors and blocks serotonin from stimulating them. Serotonin is an important chemical neurotransmitter in the brain that regulates many functions including sleep, appetite and memory by activating different sets of receptors on the nerve cells (neurons). Serotonin plays a role in migraine by stimulating 5-HT receptors, which causes constriction of blood vessels in the brain, and cyproheptadine prevents this activity.

Serotonin reduces appetite and blocking its effect in the appetite center in the hypothalamus may help stimulate appetite. Cyproheptadine inhibits another neurotransmitter acetylcholine which causes muscle contractions, and may help relieve bronchospasms in severe allergic reactions. Cyproheptadine may also block calcium channels in the neurons, inhibiting the action potential for transmission of pain signals.

Cyproheptadine is approved to treat both adults and children with allergic conditions that include:

• Perennial and seasonal allergic rhinitis
• Vasomotor rhinitis
• Allergic conjunctivitis due to inhalant allergens and foods
• Hives (urticaria)
• Urticaria from exposure to cold
• Swelling of tissue under the skin and mucous membranes (angioedema)
• Allergic reactions to blood or plasma
• Skin welts from mild scratching (dermatographism)
• Adjunctive therapy for anaphylactic reactions, following treatment with epinephrine and other standard emergency measures

Off-label uses include:

Adult:

• Migraine prevention
• Spasticity associated with spinal cord
• Decreased appetite secondary to chronic disease
• Drug-induced sexual dysfunction
• Serotonin syndrome

Pediatric:

• Prevention of migraine
• Anorexia nervosa (off-label)

• Do not use cyproheptadine to treat:
  • Newborn or premature infants
  • Nursing mothers
  • Patients with hypersensitivity to cyproheptadine or any other drugs of similar chemical structure
  • Patients on monoamine oxidase inhibitor treatment
  • Elderly debilitated patients
• Do not use cyproheptadine to treat patients with:
  • Angle-closure glaucoma
  • Stenosing peptic ulcer
  • Symptomatic prostate enlargement (prostatic hypertrophy)
  • Bladder neck obstruction
  • Obstruction between the stomach and the intestine (pyloroduodenal obstruction)
• Use with particular caution in young children; overdose may cause hallucinations, central nervous system (CNS) depression, convulsions, respiratory and cardiac arrest, and death
• Avoid use with other CNS depressants including alcohol; may have additive effects
• Antihistamines including cyproheptadine are more likely to cause dizziness, sedation, and low blood pressure (hypotension) in elderly patients; use with caution
• Use with caution in patients with cardiovascular disease, including high blood pressure (hypertension) and other heart disease
• Use with caution in patients with:
  • Increased intraocular pressure
  • History of asthma or other chronic breathing disorders
  • Thyroid dysfunction

Common side effects of cyproheptadine include:

• Temporary sedation and sleepiness
• Confusion
• Restlessness
• Excitation
• Nervousness
• Irritability
• Euphoria
• Hallucinations
• Hysteria
• Insomnia
• Disturbed coordination
• Dizziness
• Feeling faint
• Abnormal skin sensations (paresthesias)
• Nerve inflammation (neuritis)
• Tremor
• Convulsions
• Rash
• Swelling (edema)
• Hives (urticaria)
• Light sensitivity (photosensitivity)
• Excessive sweating 
• Low blood pressure (hypotension)
• Palpitations
• Rapid heart rate (tachycardia)
• Extra heartbeats (extrasystoles)
• Anaphylactic shock
• Dryness of nose and throat
• Thickening of bronchial secretions
• Tightness of chest
• Wheezing
• Nasal stuffiness
• Acute inner ear infection that affects balance (labyrinthitis)
• Ringing in ears (tinnitus)
• Vertigo
• Blurred vision
• Double vision (diplopia)
• Fatigue
• Chills
• Headache
• Blood disorders including:
  • Anemia due to rapid destruction of red blood cells (hemolytic anemia)
  • Low count of leukocyte immune cells (leukopenia)
  • Low count of granulocyte immune cells (agranulocytosis)
  • Low platelet count (thrombocytopenia)
• Dryness of mouth
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Upper abdominal pain (epigastric distress)
• Loss of appetite (anorexia)
• Increase in appetite and weight gain
• Impaired bile flow (cholestasis)
• Liver inflammation (hepatitis)
• Abnormal liver function
• Jaundice
• Liver failure
• Frequent urination
• Difficulty in urination
• Urinary retention
• Early menstrual periods

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 4 mg

Oral solution

• 2 mg/5 mL

Adult:

Hypersensitivity reaction

• 4 mg orally every 8 hours initially; maintenance: 4-20 mg/day, up to 32 mg/day divided every 8 hours in some patients; not to exceed 0.5 mg/kg/day

Spasticity associated with spinal cord (off-label)

• 2-4 mg orally every 8 hours initially; not to exceed 24 mg/day

Migraine headache prophylaxis (off-label)

• 2 mg orally every 12 hours with or without propanol

Decreased appetite secondary to chronic disease (off-label)

• 2 mg orally every 6 hours for one week; THEN 4 mg every 6 hours

Drug-induced sexual dysfunction (off-label)

• 4-12 mg orally 1-2 hours before anticipated coitus or 1-16 mg/day

Serotonin syndrome (off-label)

• 12 mg initially orally, followed by 2 mg every 2 hours or 4-8 mg orally every 6 hours as needed to control symptoms

Dosing Modifications

• Nonanticholinergic antihistamines should be considered first when treating allergic reactions (Beers Criteria)
• Advanced age is associated with reduced clearance and greater risk of confusion, dry mouth, constipation, and other anticholinergic effects and toxicity; use lower end of dosage range (4 mg orally every 12 hours) for elderly patients, or administer less frequently
• Renal impairment: Elimination is reduced in renal insufficiency; administer lower doses, and monitor closely

Pediatric:

Hypersensitivity Reaction

• Children younger than 2 years old: Safety and efficacy not established
• Children 2-6 years old: 2 mg orally every 8-12 hours; not to exceed 12 mg/day
• Children 7-14 years old: 4 mg orally every 8-12 hours; not to exceed 16 mg/day
• Alternatively, total daily dose of 0.25 mg/kg or 8 mg/m²

Migraine

Prophylaxis

• Children younger than 3 years: Safety and efficacy not established
• Children older than 3 years and adolescents: 0.2-0.4 mg/kg/day orally divided twice daily; not to exceed 0.5 mg/kg/day

Loss of appetite (including anorexia nervosa; off-label)

Stimulation of appetite

• Children younger than 13 years: Safety and efficacy not established
• Children older than 13 years: 2 mg orally every 6 hours initially; increased to up to 8 mg every 6 hours over 3 weeks

Dosing Modifications

• Renal impairment: Elimination is reduced in renal insufficiency; administer lower doses, and monitor closely

• Cyproheptadine overdose effects may vary from central nervous system (CNS) depression to stimulation, especially in pediatric patients. It may also cause symptoms such as dry mouth, fixed, dilated pupils, flushing, and gastrointestinal symptoms.
• Induced vomiting and gastric lavage may be performed followed by activated charcoal treatment to eliminate unabsorbed drug in the stomach. CNS symptoms are treated with symptomatic and supportive care.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe Interactions of cyproheptadine include:
  • isocarboxazid
  • linezolid
  • methylene blue
  • metyrapone
  • phenelzine
  • procarbazine
  • rasagiline
  • safinamide
  • selegiline
  • tedizolid
• Serious Interactions of cyproheptadine include:
  • calcium/magnesium/potassium/sodium oxybates
  • eluxadoline
  • metoclopramide intranasal
  • pitolisant
  • sodium oxybate
  • Cyproheptadine has moderate interactions with at least 220 different drugs.
• Mild Interactions of cyproheptadine include:
  • ashwagandha
  • brimonidine
  • eucalyptus
  • nettle
  • sage
  • Siberian ginseng

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information.

Check with your doctor or health care provider if you have any questions about the medication.

• Cyproheptadine use may be acceptable during pregnancy; studies have not revealed impairment to fertility or fetal harm.
• It is not known if cyproheptadine is excreted in breast milk; do not use while breastfeeding because many drugs are excreted in milk

• Take cyproheptadine exactly as prescribed; seek medical help immediately in case of overdose
• Keep cyproheptadine safely out of reach of children
• Cyproheptadine may affect mental alertness and physical ability; do not engage in activities such as driving or operating heavy machinery
• Do not drink alcohol or take alcohol-containing drugs while on cyproheptadine therapy