Pizotifen Malate

(BANM, rINNM)
Synonyms: Malato de pizotifeno; Pizotifen Hydrogen Malate; Pizotifène, Malate de; Pizotifeni Malas; Pizotyline Malate.
Cyrillic synonym: Пизотифена Малат.

💊 Chemical information

Chemical formula: C19H21NS,C4H6O5 = 429.5.
CAS — 5189-11-7.
ATC — N02CX01.
ATC Vet — QN02CX01.

Pharmacopoeias.

In Br.

BP 2008

(Pizotifen Malate). A white or slightly yellowish-white, odourless or almost odourless, crystalline powder. Very slightly soluble in water; slightly soluble in alcohol and in chloroform; sparingly soluble in methyl alcohol. Protect from light.

💊 Adverse Effects and Precautions

As for the sedating antihistamines in general. Increased appetite and weight gain may occur with pizotifen. Drowsiness may be troublesome.

Incidence of adverse effects.

Adverse effects were noted in 22 of 47 patients with severe migraine given pizotifen 1 to 2 mg daily.1 These reactions included weight increase (15), muscle pain or cramps (3), heavy or restless legs (3), fluid retention (3), drowsiness (2), more frequent milder headaches (2), facial flushing (1), reduced libido (1), exacerbation of epilepsy (1), and dreaming (2). Adverse effects necessitating withdrawal occurred in 11 patients.
1. Peet KMS. Use of pizotifen in severe migraine: a long-term study. Curr Med Res Opin 1977; 5: 192–9.

💊 Interactions

As for the sedating antihistamines in general.

Antihypertensives.

After a report1 of loss of blood pressure control when treatment with pizotifen was started in a patient receiving debrisoquine the manufacturer suggested that since pizotifen had a similar chemical structure to the tricyclic antidepressants it might antagonise the actions of adrenergic neurone blockers in a similar manner.
1. Bailey RR. Antagonism of debrisoquine sulphate by pizotifen (Sandomigran). N Z Med J 1976; 1: 449.

💊 Pharmacokinetics

Pizotifen is well absorbed from the gastrointestinal tract, peak plasma concentrations occurring about 5 hours after a single oral dose. Over 90% is bound to plasma proteins. Pizotifen undergoes extensive metabolism. Over half of a dose is excreted in the urine, chiefly as metabolites; a significant proportion is excreted in the faeces. The primary metabolite of pizotifen (N-glucuronide conjugate) has a long elimination half-life of about 23 hours. Distribution into milk has been found in animal studies.

💊 Uses and Administration

Pizotifen is a sedating antihistamine that has strong serotonin antagonist and weak antimuscarinic properties. It also antagonises the action of tryptamine. Pizotifen is used, usually as the malate, for the prophylaxis of migraine and for the prevention of headache attacks during cluster periods. It is not effective in treating an acute attack. Doses of pizotifen malate are expressed in terms of the base; pizotifen malate 1.45 mg is equivalent to about 1 mg of pizotifen. The usual adult oral dose is 1.5 mg daily either in three divided doses or as a single dose at night; children aged over 2 years may also be given up to 1.5 mg daily, although the maximum single dose (at night) should not exceed 1 mg. Gradual increase from an initial dose of 500 micrograms may help to avoid undue drowsiness. Doses in adults may vary from 500 micrograms up to a maximum of 4.5 mg daily; not more than 3 mg should be given as a single dose. Pizotifen hydrochloride has also been used in the management of migraine.

Abdominal migraine.

Abdominal migraine is a recurrent disorder seen mainly in children and characterised by episodic midline abdominal pain lasting for up to 72 hours. The pain is severe enough to disrupt normal activities and may be associated with pallor, anorexia, nausea, and vomiting.1,2 Sleep, and sometimes vomiting, terminate the attack. Pizotifen was found to be effective for the prophylaxis of abdominal pain in children with abdominal migraine.3 Prophylactic treatment with propranolol or cyproheptadine may also be of benefit.4
1. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia 2004; 24 (suppl 1): 9–160. Also available at: http://216.25.100.131/ihscommon/guidelines/ pdfs/ihc_II_main_no_print.pdf (accessed 01/10/04
2. Russell G, et al. The child with recurrent abdominal pain: is it abdominal migraine? Br J Hosp Med 2007; 68: M110–M113
3. Symon DNK, Russell G. Double blind placebo controlled trial of pizotifen syrup in the treatment of abdominal migraine. Arch Dis Child 1995; 72: 48–50
4. Worawattanakul M, et al. Abdominal migraine: prophylactic treatment and follow-up. J Pediatr Gastroenterol Nutr 1999; 28: 37–40.

Migraine and cluster headache.

Pizotifen has been widely used for the prophylaxis of migraine but evidence for its efficacy is limited. It has also been tried in the management of cluster headache to prevent headache attacks during a cluster period.
1. Cleland PG, et al. Studies to assess if pizotifen prophylaxis improves migraine beyond the benefit offered by acute sumatriptan therapy alone. Eur Neurol 1997; 38: 31–8
2. Barnes N, Millman G. Do pizotifen or propranolol reduce the frequency of migraine headache? Arch Dis Child 2004; 89: 684–5.

💊 Preparations

BP 2008: Pizotifen Tablets.

Proprietary Preparations

Arg.: Sandomigran; Austral.: Sandomigran; Belg.: Sandomigran; Braz.: Sandomigran; Canad.: Sandomigran; Cz.: Sandomigran; Denm.: Sandomigrin; Fr.: Sanmigran; Ger.: Mosegor†; Gr.: Mosegor†; Hong Kong: Sandomigran; Hung.: Sandomigran†; Indon.: Lysagor; Irl.: Sanomigran; Ital.: Sandomigran; Malaysia: Sandomigran; Neth.: Sandomigran; NZ: Sandomigran; Philipp.: Litec; Mosegor; Pol.: Polomigran; S.Afr.: Sandomigran; Spain: Mosegor; Sandomigran; Swed.: Sandomigrin; Switz.: Mosegor; Thai.: Anorsia; Mosegor; Moselar; Pizomed; Zofen; Turk.: Sandomigran; UK: Sanomigran; Venez.: Sandomiran†. Multi-ingredient: Philipp.: Appetens; Mosegor Vita.
Published November 04, 2018.