Contents

Pizotifen

Drug used to reduce frequency of headaches

Pizotifen

Clinical data
Trade names	Sandomigran
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B1
Routes of administration	Oral
ATC code	N02CX01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	78%
Protein binding	91%
Metabolism	Glucuronidation (main route). N-glucuronide accounts for >50% of plasma and 60–70% of urinary excreted drug
Elimination half-life	23 hours
Excretion	18% feces, 55% urine (both as metabolites)
Identifiers
IUPAC name 4-(1-methyl-4-piperidylidine)-9,10-dihydro -4H-benzo-[4,5]cyclohepta[1,2]-thiophene
CAS Number	15574-96-6 N
PubChem CID	27400
IUPHAR/BPS	93
ChemSpider	25497 Y
UNII	0BY8440V3N
KEGG	D05523 Y
ChEMBL	ChEMBL294951 Y
CompTox Dashboard (EPA)	DTXSID6023490
ECHA InfoCard	100.036.014
Chemical and physical data
Formula	C19H21NS
Molar mass	295.44 g·mol−1
3D model (JSmol)	Interactive image
SMILES s1c3c(cc1)C(\c2c(cccc2)CC3)=C4/CCN(C)CC4
InChI InChI=1S/C19H21NS/c1-20-11-8-15(9-12-20)19-16-5-3-2-4-14(16)6-7-18-17(19)10-13-21-18/h2-5,10,13H,6-9,11-12H2,1H3 Y Key:FIADGNVRKBPQEU-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventive to reduce the frequency of recurrent migraine headaches.^[1]

The main medical use for pizotifen is for the prevention of migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid, cyproheptadine and amitriptyline. While pizotifen is effective in adults,^[2] evidence of efficacy in children is limited,^[3] and its use is limited by side effects, principally drowsiness and weight gain, and it is usually not the first choice medicine for preventing migraines, instead being used as an alternative when other drugs have failed to be effective.^[4] It is not effective in relieving migraine attacks once in progress. Pizotifen has also been reported as highly effective in a severe case of erythromelalgia, a rare neurovascular disease that is sometimes refractory to the other drugs named above.^[5]

Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxietyorsocial phobia.^[6][7] Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndromeorMDMA overdose^[8] in a similar manner to the closely related antihistamine/antiserotonin medication cyproheptadine.

Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain.^[9] Occasionally it may cause nausea, headaches, or dizziness. In rare cases, anxiety, aggression and depression may also occur.

Caution is required in patients having closed angle glaucoma and in patients with a predisposition to urinary retention as the medication exhibits a relatively small anticholinergic effect. Dose adjustment is required in people who have chronic kidney disease. Liver injury has also been reported. Pizotifen treatment should be discontinued if there is any clinical evidence of liver dysfunction during treatment. Caution is advised in patients having a history of epilepsy. Withdrawal symptoms like depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder and weight decrease have been reported following abrupt cessation of pizotifen.^[10] Pizotifen is contraindicated in patients who suffer from hypersensitivity to any of its components, also Pizotifen is contraindicated in gastric outlet obstruction, pregnancy, angle-closure glaucoma and difficulty urinating.^[11]

Pizotifen is a serotonin antagonist acting mainly at the 5-HT_2A and 5HT_2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity.^[12]

• Benzocycloheptene
• Cyproheptadine
• Ketotifen

• Sandomigran drug data sheet