Cyproheptadine
JFDA label: Periactin
Mechanism of Action
A potent antihistamine and serotonin antagonist with anticholinergic effects; competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract (Paton 1985).
Indications
Approved
- Allergic conditions
Off-label
- Decreased appetite secondary to chronic disease
- Episodic migraine prevention (pediatrics)
- Serotonin syndrome (adults)
- Spasticity associated with spinal cord damage
- serotonin syndrome (pediatrics)
Contraindications
Source: Lexicomp
- Use in newborn or premature infants or breast-feeding mothers Absolute
- angle-closure glaucoma Absolute
- bladder neck obstruction Absolute
- elderly, debilitated patients Absolute
- hypersensitivity to cyproheptadine or any component of the formulation Absolute
- monoamine oxidase inhibitor therapy Absolute
- pyloroduodenal obstruction Absolute
- stenosing peptic ulcer Absolute
- symptomatic prostatic hypertrophy Absolute
Adverse Reactions
Cardiac disorders (4)
Not Known Extrasystoles · hypotension · palpitations · tachycardia
Nervous system disorders (20)
Not Known Ataxia · chills · confusion · dizziness · drowsiness · euphoria · excitement · fatigue · hallucination · headache · hysteria · insomnia · irritability · nervousness · neuritis · paresthesia · restlessness · sedation · seizure · vertigo
Hepatobiliary disorders (3)
Not Known Hepatic failure · hepatitis · jaundice
Renal and urinary disorders (3)
Not Known Difficulty in micturition · urinary frequency · urinary retention
Blood and lymphatic system disorders (4)
Not Known Agranulocytosis · hemolytic anemia · leukopenia · thrombocytopenia
Immune system disorders (3)
Not Known Anaphylactic shock · angioedema · hypersensitivity reaction
Gastrointestinal disorders (9)
Not Known Abdominal pain · anorexia · cholestasis · constipation · diarrhea · increased appetite · nausea · vomiting · xerostomia
Skin and subcutaneous tissue disorders (4)
Not Known Diaphoresis · skin photosensitivity · skin rash · urticaria
Musculoskeletal and connective tissue disorders (1)
Not Known Tremor
Eye disorders (2)
Not Known Blurred vision · diplopia
Ear and labyrinth disorders (2)
Not Known Labyrinthitis (acute) · tinnitus
Respiratory, thoracic and mediastinal disorders (3)
Not Known Nasal congestion · pharyngitis · thickening of bronchial secretions
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
CNS depression
May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Disease-related concerns:
Cardiovascular disease
Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease).
Increased intraocular pressure
Use with caution in patients with increased intraocular pressure.
Respiratory disease
Use with caution in patients with asthma or other chronic breathing disorders.
Thyroid dysfunction
Use with caution in patients with thyroid dysfunction. Concurrent drug therapy issues:
Drug-drug interactions
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:
Elderly
Antihistamines are more likely to cause dizziness, sedation and hypotension in elderly patients.
Pediatric
Antihistamines may cause excitation in young children.
Pregnancy & Lactation
Pregnancy
Adverse events were observed in some animal reproduction studies. Per the product labeling, an increased risk of congenital abnormalities was not observed following maternal use of cyproheptadine during the first, second, or third trimesters in two studies of pregnant women; however the possibility of harm cannot be ruled out. Although cyproheptadine is approved for the treatment of allergic conditions such as rhinitis and uritcaria, other agents are preferred for use in pregnant women (Scadding 2008; Wallace 2008; Zuberbier 2014). Antihistamines are not recommended for treatment of pruritus associated with intrahepatic cholestasis in pregnancy (Ambros-Rudolph 2011; Kremer 2014).
Lactation
Use while breast-feeding is contraindicated by the manufacturer. It is not known if cyproheptadine is excreted into breast milk. Premature infants and newborns have a higher risk of intolerance to antihistamines. In general, if a nursing infant is exposed to a first generation antihistamine via breast milk, they should be monitored for irritability or drowsiness. When treatment is needed in breast-feeding women, second generation antihistamines are preferred (Butler 2014). Antihistamines may d
Chemistry & Properties
| Formula | C21H21N |
|---|---|
| Molecular weight | 287.41 g/mol |
| IUPAC name | 1-methyl-4-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenylidene)piperidine |
| CAS | 129-03-3 |
| PubChem CID | 2913 |
| InChIKey | JJCFRYNCJDLXIK-UHFFFAOYSA-N |
| logP | 4.7 (XLogP 4.7) |
| Polar surface area | 3.24 Ų |
| H-bond acceptors / donors | 1 / 0 |
| Drug-likeness (QED) | 0.58 |
| Lipinski violations | 0 |
SMILES
CN1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | Yes |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Substrate | — |
| CYP2B6 | Substrate | — |
| CYP2C19 | Substrate | — |
| CYP2D6 | Inhibitor | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 30)
| Target | Action | Affinity |
|---|---|---|
| HISTAMINE H1 (HRH1) | Binding | pKi 10.2 |
| H1 receptor (HRH1) | Antagonist | pKi 10.2 |
| H1 | Binding | pKi 9.0 |
| 5-HT2B (HTR2B) | Binding | pKi 8.7 |
| 5-HT2A (HTR2A) | Binding | pKi 8.5 |
| H2 | Binding | pKi 8.3 |
| 5-HT2C (HTR2C) | Binding | pKi 8.2 |
| Cholinergic, muscarinic M5 (CHRM5) | Binding | pKi 8.1 |
| DOPAMINE D3 (DRD3) | Binding | pKi 8.1 |
| Cholinergic, muscarinic M2 (CHRM2) | Binding | pKi 7.9 |
| Cholinergic, muscarinic M3 (CHRM3) | Binding | pKi 7.9 |
| Cholinergic, muscarinic M4 (CHRM4) | Binding | pKi 7.9 |
| Cholinergic, muscarinic M1 (CHRM1) | Binding | pKi 7.8 |
| α1B-adrenoceptor (ADRA1B) | Antagonist | pKi 7.6 |
| DOPAMINE D1 (DRD1) | Binding | pKi 7.5 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Dextropropoxyphene | major | |
| Potassium chloride | major | |
| Potassium citrate | major | |
| Sodium oxybate | major | |
| Topiramate | major | |
| Zonisamide | major | |
| Acetylcholine | moderate | |
| Aclidinium | moderate | |
| Acrivastine | moderate | |
| Alfentanil | moderate | |
| Alimemazine | moderate | |
| Alprazolam | moderate | |
| Amantadine | moderate | |
| Amitriptyline | moderate | |
| Amobarbital | moderate | |
| Amoxapine | moderate | |
| Apomorphine | moderate | |
| Apraclonidine | moderate | |
| Aripiprazole | moderate | |
| Asenapine | moderate | |
| Atropine | moderate | |
| Azatadine | moderate | |
| Azelastine (nasal) | moderate | |
| Baclofen | moderate | |
| Belladonna | moderate | |
| Benzatropine | moderate | |
| Benzhydrocodone | moderate | |
| Biperiden | moderate | |
| Botulinum Toxin Type B | moderate | |
| Botulinum toxin type A | moderate | |
| Brexanolone | moderate | |
| Brexpiprazole | moderate | |
| Brimonidine (ophthalmic) | moderate | |
| Brimonidine (topical) | moderate | |
| Brivaracetam | moderate | |
| Bromocriptine | moderate | |
| Brompheniramine | moderate | |
| Buprenorphine | moderate | |
| Buspirone | moderate | |
| Butabarbital | moderate |
Showing 40 of 100+.
Registered Products (1)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Periactin | Tablet 4 mg | 20 tab | Adatco Drug Store | 1.100 |