Identification

Name
Pizotifen
Accession Number
DB06153
Type
Small Molecule
Groups
Approved
Description

Pizotifen belongs to the class of antamines and is related to Cyproheptadine [1]. It is a potent serotonin and tryptamine antagonist that has been used for migraine prevention for many years. It exhibits weak anticholinergic, antihistamine, and antikinin actions in addition to sedative and appetite-stimulating properties [10]. Some patients receiving pizotifen treatment developed tolerance with the prolonged use of the drug [10]. Numerous studies have revealed the potential antidepressant effects of pizotifen, which are independent of its antimigraine action [5]. While it is suggested that pizotifen may act similarly to the classic tricyclic antidepressants [5], its full mechanism of antidepressant action is not fully elucidated. Pizotifen hydrochloride is an active ingredient in Sandomigran, which is used for the prophylactic management of migraines. Sandomigran is available in a number of countries but is not approved by the FDA nor EMA.

Structure
Thumb
Synonyms
  • Pizotyline
External IDs
BC-105
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SandomigranTablet0.50 mgOralPaladin Labs Inc1975-01-01Not applicableCanada
Sandomigran DSTablet1 mgOralPaladin Labs Inc1980-12-31Not applicableCanada
Categories
UNII
0BY8440V3N
CAS number
15574-96-6
Weight
Average: 295.44
Monoisotopic: 295.139470854
Chemical Formula
C19H21NS
InChI Key
FIADGNVRKBPQEU-UHFFFAOYSA-N
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
IUPAC Name
1-methyl-4-{6-thiatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3(7),4,10,12-pentaen-2-ylidene}piperidine
SMILES
CN1CCC(CC1)=C1C2=C(CCC3=CC=CC=C13)SC=C2

Pharmacology

Indication

Indicated for the prophylactic management of migraines [10].

Associated Conditions
Pharmacodynamics

Various studies have shown pizotifen to be effective in the prophylaxis of migraines in reducing the frequency and severity of vascular headaches [3]. Evidence from studies in vivo and in vitro demonstrate antagonistic actions towards serotonin and histamine. Pizotifen blocks the postsynaptic 5-HT2 receptors, as supported by antagonism of several direct agonists of 5-HT receptors [5]. It is an antagonist at histamine H1 receptors, and is weakly anticholinergic [9]. It also binds to α1- and α2-adrenergic receptors, and dopamine receptors [9]. Pizotifen elicits a minimal effect as an epinephrine or bradykinin antagonist [10]. Pizotifen exhibits weak sedative properties in mouse and monkey studies, as indicated by inhibition of locomotion and potentiation of barbiturates, without changes in cardiac or respiratory rates [10]. In dogs, intravenous administration of pizotifen cause rapid hypotension but was reversed to normal within 30 minutes [10]. Pizotifen was shown to inhibit serotonin uptake in the isolated perfused cat spleen and, in vivo, inhibits serotonin-induced contractions in rat uterus and cat nictiating membrane [2]. In contrast, pizotifen demonstrated a venoconstrictor activity in vivo when orally or intravenously administered to saphenous veins in conscious dogs [4]. Pizotifen has the potential to stimulate the appetite and may cause weight gain upon treatment [2].

In a double-blind clinical study of patients with mild to moderate depression, treatment of pizotifen led to clinical improvement of the depressive symptoms. However, deterioration of the schizophrenic emotional symptoms was also observed in patients with depression and chronic schizophrenia [1]. This indicates that pizotifen may potentially improve the symptoms of patients with depressions in conjunction with migraines [1].

Neuroprotective effect of pizotifen was investigated in vitro in a mouse cell model of Huntington's disease (HD). According to a chemical screen of a mouse HdhQ111/Q111 striatal cell model of HD, treatment of pizotifen was associated with increased ATP levels and decreased activation of caspase-3, leading to enhanced cell viability [6]. Transient activation of ERK signalling pathway lasting for less than 3 hours was also observed. In the R6/2 transgenic mouse model of HD, rotarod performance of the mouse treated with pizotifen was seen, accompanied by an increase in DARPP-32 protein expression and restoration of striatal area [6]. However these effects being reflected in vivo are not established.

Mechanism of action

While the mechanism of action is not fully understood, it is proposed that pizotifen works by inhibiting the peripheral actions of serotonin and histamine in increasing the membrane permeability of cranial vessels and transudation of plasmakinin, while altering pain thresholds in migraines [10]. By blocking 5-HT receptors, pizotifen attenuates the signalling of serotonin in causing cranial vasoconstriction, as well as serotonin-enhanced platelet function and aggregation [7, 9]. There is evidence that it also inhibits the peripheral actions of bradykinin [2]. Pizotifen may inhibit serotonin reuptake by blood platelets, which affects the tonicity and decreases passive distension of extracranial arteries [10]. The effects of pizotifen leading to appetite stimulation may be due to the drug acting at the metabolic level rather than a direct stimulation of the appetite centre [3].

TargetActionsOrganism
UMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
U5-hydroxytryptamine receptor 2A
antagonist
Human
U5-hydroxytryptamine receptor 2B
antagonist
Human
U5-hydroxytryptamine receptor 2C
antagonist
Human
U5-hydroxytryptamine receptor 1A
antagonist
Human
U5-hydroxytryptamine receptor 1B
antagonist
Human
U5-hydroxytryptamine receptor 1D
antagonist
Human
UHistamine H1 receptor
antagonist
Human
UAlpha-1A adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
antagonist
Human
UAlpha-1D adrenergic receptor
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UAlpha-2B adrenergic receptor
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
Absorption

The absorption half-life of pizotifen following oral administration is 0.5 to 0.8 hours in an adult male with nearly complete absorption rate of 80%. Maximum blood levels are reached 5 hours post-administration and the absolute bioavailability is 78% [10].

Volume of distribution

The volume of distribution in an adult male is 833L for pizotifen and 70L for the N-glucuronide conjugate [10].

Protein binding

Plasma protein binding of pizotifen is > 90% [10].

Metabolism

Pizotifen is extensively metabolized in the liver, where it primarily undergoes N-glucuronidation to form the main metabolite, N-glucuronide conjugate [10]. N-glucuronide conjugate accounts for at least 50% of the plasma and 60-70% of the urinary-excreted radioactivity [10].

Route of elimination

About one third of the total orally administered dose is excreted into the feces. Less than 1% of the total dose is excreted in the urine as the unchanged parent drug, and up to 55% of the dose is excreted as its metabolites [10].

Half life

The elimination half-life for pizotifen and N-glucuronide conjugate is about 23 hours [10].

Clearance
Not Available
Toxicity

The oral Lowest published toxic dose (TDLo) is 12.86 mg/kg in man [MSDS]. Oral LD50 ranges from 410 to 1500 mg/kg in rat [MSDS]. Oral LD50 in mouse and rabbit is 880 mg/kg and 700 mg/kg, respectively [10]. The LD50 following intravenous administration in rat was 17 mg/kg [10].

In adults, the symptoms of overdosage include sedation, drowsiness (preceding excitement, convulsions, and postictal depression), dizziness, hypotension, dryness of the mouth, confusion, tachycardia, ataxia, nausea, vomiting, dyspnea, cyanosis, convulsions, coma, respiratory paralysis and CNS depression [10]. Antihistamine toxicity of pizotifen in children may involve excitation, hallucinations, ataxia, incoordination, convulsions, fixed dilated pupils, flushed faces, and fever, leading to coma and cardiorespiratory collapse [10]. The use of activated charcoal is recommended in the management of overdose. For drug recent uptake, induction of emesis or gastric lavage and diuresis should be performed [10]. Supportive measures should be initiated to maintain effective respiration while closely monitoring vital signs. While severe hypotension must be corrected, the use of adrenaline may produce paradoxical effects [10].

As pizotifen has the potential to cause tachycardia, an ECG should be performed and attention directed at the QRS and QT intervals [10]. Excitatory states or convulsions induced by pizotifen may be treated with short-acting barbiturates or benzodiazepines. However analeptics should be avoided [10].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Pizotifen.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Pizotifen.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Pizotifen.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Pizotifen.Experimental, Illicit
4-MethoxyamphetaminePizotifen may decrease the vasoconstricting activities of 4-Methoxyamphetamine.Experimental, Illicit
7-NitroindazoleThe risk or severity of adverse effects can be increased when Pizotifen is combined with 7-Nitroindazole.Experimental
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the anticholinergic activities of Pizotifen.Experimental
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
AcepromazineAcepromazine may increase the antihypertensive activities of Pizotifen.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Aceprometazine.Approved
AdipiplonThe risk or severity of adverse effects can be increased when Pizotifen is combined with Adipiplon.Investigational
AdrafinilPizotifen may decrease the vasoconstricting activities of Adrafinil.Withdrawn
AgmatineThe therapeutic efficacy of Agmatine can be decreased when used in combination with Pizotifen.Experimental, Investigational
AgomelatineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Agomelatine.Approved, Investigational
AlaproclateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Alaproclate.Experimental
AlfaxaloneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Alfaxalone.Vet Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Pizotifen.Approved, Illicit
AlfuzosinAlfuzosin may increase the antihypertensive activities of Pizotifen.Approved, Investigational
AllopregnanoloneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Allopregnanolone.Investigational
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Alphacetylmethadol.Experimental, Illicit
AlphaprodineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Alphaprodine.Illicit
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Pizotifen.Approved, Illicit, Investigational
AlprenololAlprenolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Withdrawn
AmibegronPizotifen may decrease the vasoconstricting activities of Amibegron.Investigational
AmikacinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Amikacin.Approved, Investigational, Vet Approved
AmiodaroneThe risk or severity of hypotension can be increased when Pizotifen is combined with Amiodarone.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Amisulpride.Approved, Investigational
AmitrazPizotifen may decrease the vasoconstricting activities of Amitraz.Vet Approved
AmitriptylineAmitriptyline may increase the antihypertensive activities of Pizotifen.Approved
AmlodipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Amlodipine.Approved
AmobarbitalThe risk or severity of adverse effects can be increased when Amobarbital is combined with Pizotifen.Approved, Illicit
AmoxapineAmoxapine may increase the antihypertensive activities of Pizotifen.Approved
AmperozideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Amperozide.Experimental
AmphetamineAmphetamine may increase the anticholinergic activities of Pizotifen.Approved, Illicit, Investigational
AmrinoneThe risk or severity of hypotension can be increased when Pizotifen is combined with Amrinone.Approved
AnisodaminePizotifen may decrease the vasoconstricting activities of Anisodamine.Investigational
ApomorphinePizotifen may decrease the vasoconstricting activities of Apomorphine.Approved, Investigational
ApraclonidinePizotifen may decrease the vasoconstricting activities of Apraclonidine.Approved
AranidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Aranidipine.Approved, Investigational
ArbutaminePizotifen may decrease the vasoconstricting activities of Arbutamine.Approved
ArformoterolPizotifen may decrease the vasoconstricting activities of Arformoterol.Approved, Investigational
AripiprazoleAripiprazole may increase the antihypertensive activities of Pizotifen.Approved, Investigational
ArotinololArotinolol may increase the orthostatic hypotensive activities of Pizotifen.Investigational
ArticaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Articaine.Approved
AsenapineAsenapine may increase the antihypertensive activities of Pizotifen.Approved
AtenololAtenolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
AtropineThe risk or severity of adverse effects can be increased when Atropine is combined with Pizotifen.Approved, Vet Approved
AvanafilAvanafil may increase the hypotensive activities of Pizotifen.Approved
AzaperoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Azaperone.Investigational, Vet Approved
AzelastinePizotifen may increase the central nervous system depressant (CNS depressant) activities of Azelastine.Approved
AzelnidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Azelnidipine.Approved, Investigational
AzimilideThe risk or severity of hypotension can be increased when Pizotifen is combined with Azimilide.Investigational
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Pizotifen.Approved
BambuterolPizotifen may decrease the vasoconstricting activities of Bambuterol.Approved, Investigational
BarbitalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Barbital.Illicit
BarnidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Barnidipine.Approved
BefunololBefunolol may increase the orthostatic hypotensive activities of Pizotifen.Experimental
BencyclaneThe risk or severity of hypotension can be increased when Pizotifen is combined with Bencyclane.Experimental
BenidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Benidipine.Approved, Investigational
BenmoxinBenmoxin may increase the anticholinergic activities of Pizotifen.Withdrawn
BenperidolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Benperidol.Approved, Investigational
BenzatropineThe risk or severity of adverse effects can be increased when Benzatropine is combined with Pizotifen.Approved
BenzphetamineThe risk or severity of serotonin syndrome can be increased when Pizotifen is combined with Benzphetamine.Approved, Illicit
Benzyl alcoholThe risk or severity of adverse effects can be increased when Pizotifen is combined with Benzyl alcohol.Approved
Benzylpenicilloyl PolylysinePizotifen may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BepridilThe risk or severity of hypotension can be increased when Pizotifen is combined with Bepridil.Approved, Withdrawn
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Pizotifen.Approved, Investigational
BetaxololBetaxolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
BevantololBevantolol may increase the antihypertensive activities of Pizotifen.Approved
BioallethrinThe risk or severity of hypotension can be increased when Pizotifen is combined with Bioallethrin.Approved, Experimental
BisacodylThe therapeutic efficacy of Bisacodyl can be decreased when used in combination with Pizotifen.Approved
BisoprololBisoprolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
BitolterolPizotifen may decrease the vasoconstricting activities of Bitolterol.Withdrawn
BopindololBopindolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
BrexpiprazolePizotifen may increase the antihypertensive activities of Brexpiprazole.Approved, Investigational
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved
BrofaromineBrofaromine may increase the anticholinergic activities of Pizotifen.Experimental
BromazepamThe risk or severity of adverse effects can be increased when Bromazepam is combined with Pizotifen.Approved, Illicit, Investigational
BromisovalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Bromisoval.Experimental
BromocriptinePizotifen may decrease the vasoconstricting activities of Bromocriptine.Approved, Investigational
BromperidolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Bromperidol.Approved, Investigational
BrompheniramineThe risk or severity of adverse effects can be increased when Brompheniramine is combined with Pizotifen.Approved
BrotizolamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Brotizolam.Approved, Investigational, Withdrawn
BucindololBucindolol may increase the antihypertensive activities of Pizotifen.Investigational
BufuralolBufuralol may increase the orthostatic hypotensive activities of Pizotifen.Experimental, Investigational
BunazosinBunazosin may increase the antihypertensive activities of Pizotifen.Investigational
BupivacaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Bupivacaine.Approved, Investigational
BupranololBupranolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
BuprenorphinePizotifen may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BupropionThe risk or severity of adverse effects can be increased when Pizotifen is combined with Bupropion.Approved
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Pizotifen.Approved, Investigational
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Pizotifen.Approved, Illicit
ButacaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Butacaine.Vet Approved
ButalbitalThe risk or severity of adverse effects can be increased when Butalbital is combined with Pizotifen.Approved, Illicit
ButambenThe risk or severity of adverse effects can be increased when Pizotifen is combined with Butamben.Approved, Withdrawn
ButethalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Butethal.Approved, Illicit
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Pizotifen.Approved, Illicit, Vet Approved
CanertinibThe risk or severity of adverse effects can be increased when Pizotifen is combined with Canertinib.Investigational
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Pizotifen.Approved, Investigational
CarbinoxamineThe risk or severity of adverse effects can be increased when Carbinoxamine is combined with Pizotifen.Approved
CarboxyamidotriazoleThe risk or severity of hypotension can be increased when Pizotifen is combined with Carboxyamidotriazole.Investigational
CarfentanilThe risk or severity of adverse effects can be increased when Pizotifen is combined with Carfentanil.Illicit, Investigational, Vet Approved
CarisoprodolThe risk or severity of adverse effects can be increased when Carisoprodol is combined with Pizotifen.Approved
CaroverineThe risk or severity of hypotension can be increased when Pizotifen is combined with Caroverine.Experimental
CaroxazoneCaroxazone may increase the anticholinergic activities of Pizotifen.Withdrawn
CarteololCarteolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
CarvedilolCarvedilol may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Pizotifen.Approved, Investigational
CeliprololCeliprolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
CetirizineThe risk or severity of adverse effects can be increased when Cetirizine is combined with Pizotifen.Approved
Chloral hydrateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Chloral hydrate.Approved, Illicit, Investigational, Vet Approved
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Chlordiazepoxide is combined with Pizotifen.Approved, Illicit, Investigational
ChlormezanoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Chlormezanone.Approved, Investigational, Withdrawn
ChloroprocaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Chloroprocaine.Approved
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Pizotifen.Approved
ChlorphentermineChlorphentermine may decrease the sedative activities of Pizotifen.Illicit, Withdrawn
ChlorpromazineChlorpromazine may increase the antihypertensive activities of Pizotifen.Approved, Investigational, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Chlorprothixene.Approved, Investigational, Withdrawn
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Chlorzoxazone is combined with Pizotifen.Approved
CilnidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Cilnidipine.Approved, Investigational
CinchocaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Cinchocaine.Approved, Vet Approved
CinnarizineThe risk or severity of hypotension can be increased when Pizotifen is combined with Cinnarizine.Approved, Investigational
CirazolinePizotifen may decrease the vasoconstricting activities of Cirazoline.Experimental
CitalopramThe risk or severity of adverse effects can be increased when Pizotifen is combined with Citalopram.Approved
ClemastineThe risk or severity of adverse effects can be increased when Clemastine is combined with Pizotifen.Approved, Investigational
ClenbuterolPizotifen may decrease the vasoconstricting activities of Clenbuterol.Approved, Investigational, Vet Approved
ClevidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Clevidipine.Approved, Investigational
ClidiniumThe risk or severity of adverse effects can be increased when Clidinium is combined with Pizotifen.Approved
ClindamycinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Clindamycin.Approved, Vet Approved
ClobazamThe risk or severity of adverse effects can be increased when Clobazam is combined with Pizotifen.Approved, Illicit
clomethiazoleThe risk or severity of adverse effects can be increased when Pizotifen is combined with clomethiazole.Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Pizotifen.Approved, Investigational, Vet Approved
ClonazepamThe risk or severity of adverse effects can be increased when Clonazepam is combined with Pizotifen.Approved, Illicit
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Pizotifen.Approved
ClopenthixolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Clopenthixol.Experimental
CloranololCloranolol may increase the orthostatic hypotensive activities of Pizotifen.Experimental
ClorazepateThe risk or severity of adverse effects can be increased when Clorazepate is combined with Pizotifen.Approved, Illicit
ClothiapineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Clothiapine.Experimental
ClozapineClozapine may increase the antihypertensive activities of Pizotifen.Approved
CocaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Cocaine.Approved, Illicit
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Pizotifen.Approved, Illicit
CyclandelateThe risk or severity of hypotension can be increased when Pizotifen is combined with Cyclandelate.Approved
CyclizineThe risk or severity of adverse effects can be increased when Cyclizine is combined with Pizotifen.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Pizotifen.Approved
CyclopropaneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Cyclopropane.Experimental
CyclosporineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Cyclosporine.Approved, Investigational, Vet Approved
CyproheptadineThe risk or severity of adverse effects can be increased when Cyproheptadine is combined with Pizotifen.Approved
DantroleneThe risk or severity of adverse effects can be increased when Dantrolene is combined with Pizotifen.Approved, Investigational
DapiprazoleDapiprazole may increase the antihypertensive activities of Pizotifen.Approved
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Pizotifen.Investigational
DarodipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Darodipine.Experimental
DeramciclaneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Deramciclane.Investigational
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Pizotifen.Approved
DesipramineDesipramine may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
DesloratadineThe risk or severity of adverse effects can be increased when Desloratadine is combined with Pizotifen.Approved, Investigational
DesvenlafaxineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Desvenlafaxine.Approved, Investigational
DetomidineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Detomidine.Vet Approved
DexbrompheniramineThe risk or severity of adverse effects can be increased when Dexbrompheniramine is combined with Pizotifen.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dexmedetomidine.Approved, Vet Approved
DexniguldipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Dexniguldipine.Experimental
DextroamphetaminePizotifen may increase the antihypertensive activities of Dextroamphetamine.Approved, Illicit
DextromethorphanThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dextromethorphan.Approved
DextromoramideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dextromoramide.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dextropropoxyphene.Approved, Illicit, Investigational, Withdrawn
DexverapamilThe risk or severity of hypotension can be increased when Pizotifen is combined with Dexverapamil.Experimental
DezocineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dezocine.Approved, Investigational
DiazepamThe risk or severity of adverse effects can be increased when Diazepam is combined with Pizotifen.Approved, Illicit, Investigational, Vet Approved
Diethyl etherThe risk or severity of adverse effects can be increased when Pizotifen is combined with Diethyl ether.Experimental
DiethylpropionDiethylpropion may decrease the sedative and stimulatory activities of Pizotifen.Approved, Illicit
DifenoxinThe risk or severity of adverse effects can be increased when Difenoxin is combined with Pizotifen.Approved, Illicit
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Pizotifen.Approved, Illicit
DihydroergotaminePizotifen may decrease the vasoconstricting activities of Dihydroergotamine.Approved, Investigational
DihydroetorphineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dihydroetorphine.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dihydromorphine.Experimental, Illicit
DiltiazemThe risk or severity of hypotension can be increased when Pizotifen is combined with Diltiazem.Approved, Investigational
DimenhydrinateThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Pizotifen.Approved
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Pizotifen.Approved, Investigational
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Pizotifen.Approved, Illicit
DipivefrinPizotifen may decrease the vasoconstricting activities of Dipivefrin.Approved
DipyridamoleDipyridamole may increase the hypotensive activities of Pizotifen.Approved
DixyrazineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dixyrazine.Experimental
DL-MethylephedrinePizotifen may decrease the vasoconstricting activities of DL-Methylephedrine.Approved
DobutaminePizotifen may decrease the vasoconstricting activities of Dobutamine.Approved
DocusateThe therapeutic efficacy of Docusate can be decreased when used in combination with Pizotifen.Approved
DopexaminePizotifen may decrease the vasoconstricting activities of Dopexamine.Approved, Investigational
DoramectinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Doramectin.Vet Approved
DotarizineThe risk or severity of hypotension can be increased when Pizotifen is combined with Dotarizine.Investigational
DoxazosinDoxazosin may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Pizotifen.Approved
DoxepinDoxepin may increase the antihypertensive activities of Pizotifen.Approved, Investigational
DoxofyllinePizotifen may decrease the vasoconstricting activities of Doxofylline.Approved, Investigational
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when Pizotifen is combined with DPDPE.Experimental
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved, Illicit
DronedaroneDronedarone may increase the antihypertensive activities of Pizotifen.Approved
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved, Vet Approved
DrotebanolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Drotebanol.Experimental, Illicit
DroxidopaPizotifen may decrease the vasoconstricting activities of Droxidopa.Approved, Investigational
DuloxetineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Duloxetine.Approved
DyclonineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Dyclonine.Approved
EcgonineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ecgonine.Experimental, Illicit
EcopipamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ecopipam.Investigational
EfavirenzThe risk or severity of adverse effects can be increased when Efavirenz is combined with Pizotifen.Approved, Investigational
EfonidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Efonidipine.Approved, Investigational
EltanoloneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Eltanolone.Investigational
EmopamilThe risk or severity of hypotension can be increased when Pizotifen is combined with Emopamil.Experimental
EnfluraneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Enflurane.Approved, Investigational, Vet Approved
EntacaponeThe risk or severity of adverse effects can be increased when Entacapone is combined with Pizotifen.Approved, Investigational
EpanololEpanolol may increase the orthostatic hypotensive activities of Pizotifen.Experimental
EperisoneThe risk or severity of hypotension can be increased when Pizotifen is combined with Eperisone.Approved, Investigational
EphedraPizotifen may decrease the vasoconstricting activities of Ephedra.Approved, Nutraceutical, Withdrawn
EphedrinePizotifen may decrease the vasoconstricting activities of Ephedrine.Approved
EpinastinePizotifen may decrease the vasoconstricting activities of Epinastine.Approved, Investigational
EpinephrinePizotifen may increase the antihypertensive activities of Epinephrine.Approved, Vet Approved
ErgonovinePizotifen may decrease the vasoconstricting activities of Ergonovine.Approved
ErgotaminePizotifen may decrease the vasoconstricting activities of Ergotamine.Approved
EsatenololEsatenolol may increase the orthostatic hypotensive activities of Pizotifen.Experimental
EscitalopramEscitalopram may increase the antihypertensive activities of Pizotifen.Approved, Investigational
EsmololEsmolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
EstazolamThe risk or severity of adverse effects can be increased when Estazolam is combined with Pizotifen.Approved, Illicit
EszopicloneThe risk or severity of adverse effects can be increased when Eszopiclone is combined with Pizotifen.Approved, Investigational
EtafedrinePizotifen may decrease the vasoconstricting activities of Etafedrine.Approved
EthanolPizotifen may increase the central nervous system depressant (CNS depressant) activities of Ethanol.Approved
EthchlorvynolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ethchlorvynol.Approved, Illicit, Withdrawn
EthosuximideThe risk or severity of hypotension can be increased when Pizotifen is combined with Ethosuximide.Approved
EthotoinThe risk or severity of adverse effects can be increased when Ethotoin is combined with Pizotifen.Approved
Ethyl carbamateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ethyl carbamate.Withdrawn
Ethyl chlorideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ethyl chloride.Approved, Experimental, Investigational
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ethyl loflazepate.Approved, Illicit
EthylmorphineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ethylmorphine.Approved, Illicit
EtidocaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Etidocaine.Approved
EtifoxineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Etifoxine.Investigational, Withdrawn
EtilefrinePizotifen may decrease the vasoconstricting activities of Etilefrine.Withdrawn
EtizolamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Etizolam.Approved
EtomidateThe therapeutic efficacy of Etomidate can be decreased when used in combination with Pizotifen.Approved
EtoperidoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Etoperidone.Withdrawn
EtorphineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Etorphine.Illicit, Vet Approved
EzogabineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Pizotifen.Approved, Investigational
FelbamateThe risk or severity of adverse effects can be increased when Felbamate is combined with Pizotifen.Approved
FelodipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Felodipine.Approved, Investigational
FencamfamineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Fencamfamine.Approved, Illicit, Withdrawn
FendilineThe risk or severity of hypotension can be increased when Pizotifen is combined with Fendiline.Withdrawn
FenoterolPizotifen may decrease the vasoconstricting activities of Fenoterol.Approved, Investigational
FentanylThe risk or severity of serotonin syndrome can be increased when Fentanyl is combined with Pizotifen.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe risk or severity of adverse effects can be increased when Fexofenadine is combined with Pizotifen.Approved, Investigational
Fish oilThe risk or severity of hypotension can be increased when Pizotifen is combined with Fish oil.Approved, Nutraceutical
FlibanserinThe risk or severity of adverse effects can be increased when Flibanserin is combined with Pizotifen.Approved, Investigational
FluanisoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Fluanisone.Experimental
FludiazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Fludiazepam.Approved, Illicit
FlunarizineThe risk or severity of hypotension can be increased when Pizotifen is combined with Flunarizine.Approved
FlunitrazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Flunitrazepam.Approved, Illicit
FluoxetineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Fluoxetine.Approved, Vet Approved
FlupentixolFlupentixol may increase the antihypertensive activities of Pizotifen.Approved, Investigational, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Pizotifen.Approved
FlurazepamThe risk or severity of adverse effects can be increased when Flurazepam is combined with Pizotifen.Approved, Illicit, Investigational
FluspirileneThe risk or severity of hypotension can be increased when Pizotifen is combined with Fluspirilene.Approved, Investigational
Fluticasone propionateThe risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Pizotifen.Approved
FluvoxamineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Fluvoxamine.Approved, Investigational
FormoterolPizotifen may decrease the vasoconstricting activities of Formoterol.Approved, Investigational
FosphenytoinThe risk or severity of adverse effects can be increased when Fosphenytoin is combined with Pizotifen.Approved, Investigational
FospropofolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Fospropofol.Approved, Illicit, Investigational
FostamatinibFostamatinib may increase the hypotensive activities of Pizotifen.Approved, Investigational
FurazolidoneFurazolidone may increase the anticholinergic activities of Pizotifen.Approved, Investigational, Vet Approved
GabapentinThe risk or severity of hypotension can be increased when Pizotifen is combined with Gabapentin.Approved, Investigational
Gabapentin EnacarbilThe risk or severity of adverse effects can be increased when Pizotifen is combined with Gabapentin Enacarbil.Approved, Investigational
GallopamilThe risk or severity of hypotension can be increased when Pizotifen is combined with Gallopamil.Investigational
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Gamma Hydroxybutyric Acid is combined with Pizotifen.Approved, Illicit, Investigational
GepefrineGepefrine may decrease the sedative activities of Pizotifen.Experimental
GepironeThe risk or severity of adverse effects can be increased when Pizotifen is combined with Gepirone.Investigational
GlutethimideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Glutethimide.Approved, Illicit
GlycerinThe therapeutic efficacy of Glycerin can be decreased when used in combination with Pizotifen.Approved, Investigational
GuanabenzPizotifen may decrease the vasoconstricting activities of Guanabenz.Approved, Investigational
GuanfacineThe therapeutic efficacy of Guanfacine can be decreased when used in combination with Pizotifen.Approved, Investigational
HalazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Halazepam.Approved, Illicit, Withdrawn
HaloperidolThe risk or severity of adverse effects can be increased when Haloperidol is combined with Pizotifen.Approved
HalothaneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Halothane.Approved, Vet Approved
HarmalineHarmaline may increase the anticholinergic activities of Pizotifen.Experimental
HeroinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Heroin.Approved, Illicit, Investigational
HexobarbitalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Hexobarbital.Approved
HexoprenalinePizotifen may decrease the vasoconstricting activities of Hexoprenaline.Approved, Withdrawn
HigenaminePizotifen may decrease the vasoconstricting activities of Higenamine.Investigational
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Pizotifen.Approved, Investigational
HydracarbazineHydracarbazine may increase the anticholinergic activities of Pizotifen.Experimental
HydrochlorothiazideThe serum concentration of Hydrochlorothiazide can be increased when it is combined with Pizotifen.Approved, Vet Approved
HydrocodonePizotifen may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.Approved, Illicit
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Pizotifen.Approved, Illicit
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Pizotifen.Approved
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved
HyoscyamineThe risk or severity of adverse effects can be increased when Hyoscyamine is combined with Pizotifen.Approved
IloperidoneIloperidone may increase the antihypertensive activities of Pizotifen.Approved
ImipramineImipramine may increase the antihypertensive activities of Pizotifen.Approved
IndacaterolPizotifen may decrease the vasoconstricting activities of Indacaterol.Approved
IndalpineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Indalpine.Investigational, Withdrawn
IndenololIndenolol may increase the orthostatic hypotensive activities of Pizotifen.Withdrawn
IndiplonThe risk or severity of adverse effects can be increased when Pizotifen is combined with Indiplon.Investigational
IndoraminIndoramin may increase the antihypertensive activities of Pizotifen.Withdrawn
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Pizotifen.Approved
IpratropiumThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ipratropium.Approved
IproclozideIproclozide may increase the anticholinergic activities of Pizotifen.Withdrawn
IproniazidIproniazid may increase the anticholinergic activities of Pizotifen.Withdrawn
IsocarboxazidIsocarboxazid may increase the anticholinergic activities of Pizotifen.Approved
IsoetarinePizotifen may decrease the vasoconstricting activities of Isoetarine.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Pizotifen.Approved, Vet Approved
IsometheptenePizotifen may decrease the vasoconstricting activities of Isometheptene.Approved
IsoprenalinePizotifen may decrease the vasoconstricting activities of Isoprenaline.Approved, Investigational
IsoxsuprinePizotifen may decrease the vasoconstricting activities of Isoxsuprine.Approved, Withdrawn
IsradipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Isradipine.Approved, Investigational
KetamineThe risk or severity of adverse effects can be increased when Ketamine is combined with Pizotifen.Approved, Vet Approved
KetazolamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ketazolam.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ketobemidone.Approved, Investigational
LabetalolLabetalol may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Pizotifen.Approved
LacidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Lacidipine.Approved, Investigational
LactuloseThe therapeutic efficacy of Lactulose can be decreased when used in combination with Pizotifen.Approved
LamotrigineThe risk or severity of hypotension can be increased when Pizotifen is combined with Lamotrigine.Approved, Investigational
LandiololLandiolol may increase the orthostatic hypotensive activities of Pizotifen.Investigational
LercanidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Lercanidipine.Approved, Investigational
LevetiracetamThe risk or severity of hypotension can be increased when Pizotifen is combined with Levetiracetam.Approved, Investigational
LevobetaxololLevobetaxolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
LevobupivacaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Levobupivacaine.Approved, Investigational
LevocabastineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Levocabastine.Approved, Investigational
LevocetirizineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Levocetirizine.Approved
LevodopaThe risk or severity of adverse effects can be increased when Levodopa is combined with Pizotifen.Approved
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Levomethadyl Acetate.Approved, Investigational
LevomilnacipranThe risk or severity of adverse effects can be increased when Pizotifen is combined with Levomilnacipran.Approved, Investigational
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Pizotifen.Approved
LevosalbutamolPizotifen may decrease the vasoconstricting activities of Levosalbutamol.Approved, Investigational
LidoflazineThe risk or severity of hypotension can be increased when Pizotifen is combined with Lidoflazine.Experimental
LisdexamfetaminePizotifen may increase the antihypertensive activities of Lisdexamfetamine.Approved, Investigational
Lithium cationThe risk or severity of adverse effects can be increased when Pizotifen is combined with Lithium.Experimental
LofentanilThe risk or severity of adverse effects can be increased when Pizotifen is combined with Lofentanil.Illicit
LofexidineThe therapeutic efficacy of Pizotifen can be increased when used in combination with Lofexidine.Approved, Investigational
LomerizineThe risk or severity of hypotension can be increased when Pizotifen is combined with Lomerizine.Experimental
LoperamideThe risk or severity of hypotension can be increased when Pizotifen is combined with Loperamide.Approved
LoprazolamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Loprazolam.Experimental
LoratadineThe risk or severity of adverse effects can be increased when Loratadine is combined with Pizotifen.Approved, Investigational
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Pizotifen.Approved
LormetazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Lormetazepam.Approved
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Pizotifen.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Lurasidone is combined with Pizotifen.Approved, Investigational
Magnesium carbonateThe therapeutic efficacy of Magnesium carbonate can be decreased when used in combination with Pizotifen.Approved, Investigational
Magnesium citrateThe therapeutic efficacy of Magnesium citrate can be decreased when used in combination with Pizotifen.Approved
Magnesium hydroxideThe therapeutic efficacy of Magnesium hydroxide can be decreased when used in combination with Pizotifen.Approved, Investigational
Magnesium sulfateThe therapeutic efficacy of Pizotifen can be increased when used in combination with Magnesium sulfate.Approved, Investigational, Vet Approved
Magnesium TrisilicateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Magnesium Trisilicate.Approved
ManidipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Manidipine.Approved, Investigational
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Pizotifen.Approved, Investigational
MebanazineMebanazine may increase the anticholinergic activities of Pizotifen.Withdrawn
MebicarThe risk or severity of adverse effects can be increased when Pizotifen is combined with Mebicar.Experimental
MeclizineThe risk or severity of adverse effects can be increased when Meclizine is combined with Pizotifen.Approved
MedazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Medazepam.Experimental
MedetomidineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Medetomidine.Vet Approved
MelatoninThe risk or severity of adverse effects can be increased when Pizotifen is combined with Melatonin.Approved, Nutraceutical, Vet Approved
MelperoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Melperone.Approved, Investigational
MentholThe risk or severity of hypotension can be increased when Pizotifen is combined with Menthol.Approved
MephedroneMephedrone may decrease the sedative activities of Pizotifen.Investigational
MephenterminePizotifen may decrease the vasoconstricting activities of Mephentermine.Approved
MepindololMepindolol may increase the orthostatic hypotensive activities of Pizotifen.Experimental
MepivacaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Mepivacaine.Approved, Vet Approved
MeprobamateThe risk or severity of adverse effects can be increased when Meprobamate is combined with Pizotifen.Approved, Illicit
MeptazinolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Meptazinol.Experimental
MesoridazineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Mesoridazine.Approved, Investigational
MetaraminolPizotifen may decrease the vasoconstricting activities of Metaraminol.Approved, Investigational
MetaxaloneThe risk or severity of adverse effects can be increased when Metaxalone is combined with Pizotifen.Approved
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Pizotifen.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Methadyl Acetate.Approved, Illicit
MethamphetaminePizotifen may decrease the vasoconstricting activities of Methamphetamine.Approved, Illicit
MethapyrileneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Methapyrilene.Withdrawn
MethaqualoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Methaqualone.Illicit, Withdrawn
MethocarbamolThe risk or severity of adverse effects can be increased when Methocarbamol is combined with Pizotifen.Approved, Vet Approved
MethohexitalThe risk or severity of adverse effects can be increased when Methohexital is combined with Pizotifen.Approved
MethotrimeprazinePizotifen may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.Approved, Investigational
MethoxaminePizotifen may decrease the vasoconstricting activities of Methoxamine.Approved, Investigational
MethoxyfluraneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Methoxyflurane.Approved, Investigational, Vet Approved
MethoxyphenaminePizotifen may decrease the vasoconstricting activities of Methoxyphenamine.Experimental
MethsuximideThe risk or severity of hypotension can be increased when Pizotifen is combined with Methsuximide.Approved
MethyldopaPizotifen may decrease the vasoconstricting activities of Methyldopa.Approved
MethylecgonineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Methylecgonine.Experimental
Methylene blueMethylene blue may increase the anticholinergic activities of Pizotifen.Approved, Investigational
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Methylphenobarbital.Approved
MetoclopramideThe therapeutic efficacy of Pizotifen can be decreased when used in combination with Metoclopramide.Approved, Investigational
MetoprololMetoprolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
MibefradilThe risk or severity of hypotension can be increased when Pizotifen is combined with Mibefradil.Investigational, Withdrawn
MidazolamThe risk or severity of adverse effects can be increased when Midazolam is combined with Pizotifen.Approved, Illicit
MidodrinePizotifen may decrease the vasoconstricting activities of Midodrine.Approved
MidomafetamineMidomafetamine may decrease the sedative activities of Pizotifen.Experimental, Illicit, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Pizotifen is combined with Milnacipran.Approved, Investigational
MinaprineMinaprine may increase the anticholinergic activities of Pizotifen.Approved
Mineral oilThe therapeutic efficacy of Mineral oil can be decreased when used in combination with Pizotifen.Approved, Vet Approved
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved, Investigational
MirabegronPizotifen may decrease the vasoconstricting activities of Mirabegron.Approved
MirodenafilMirodenafil may increase the hypotensive activities of Pizotifen.Investigational
MirtazapinePizotifen may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.Approved
MMDAMMDA may decrease the sedative activities of Pizotifen.Experimental, Illicit
MoclobemideMoclobemide may increase the anticholinergic activities of Pizotifen.Approved, Investigational
MolindoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Molindone.Approved
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Pizotifen.Approved, Investigational
MoxonidinePizotifen may decrease the vasoconstricting activities of Moxonidine.Approved, Investigational
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved, Investigational
NadololNadolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
NaftopidilThe risk or severity of hypotension can be increased when Pizotifen is combined with Naftopidil.Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Pizotifen.Approved
NaphazolineThe therapeutic efficacy of Naphazoline can be decreased when used in combination with Pizotifen.Approved
NebivololNebivolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
NefazodoneNefazodone may increase the antihypertensive activities of Pizotifen.Approved, Withdrawn
NeomycinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Neomycin.Approved, Vet Approved
NialamideNialamide may increase the anticholinergic activities of Pizotifen.Withdrawn
NicardipineNicardipine may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Pizotifen.Approved, Investigational
NicergolineNicergoline may increase the antihypertensive activities of Pizotifen.Approved, Investigational
NifedipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Nifedipine.Approved
NiguldipineNiguldipine may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Pizotifen.Experimental
NiludipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Niludipine.Experimental
NilvadipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Nilvadipine.Approved, Investigational
NimesulideThe risk or severity of hypotension can be increased when Pizotifen is combined with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Nimodipine.Approved, Investigational
NisoldipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Nisoldipine.Approved
NitrazepamThe risk or severity of adverse effects can be increased when Nitrazepam is combined with Pizotifen.Approved
NitrendipineThe risk or severity of hypotension can be increased when Pizotifen is combined with Nitrendipine.Approved, Investigational
Nitrous oxideThe risk or severity of adverse effects can be increased when Nitrous oxide is combined with Pizotifen.Approved, Vet Approved
NordazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Nordazepam.Approved
NorepinephrinePizotifen may decrease the vasoconstricting activities of Norepinephrine.Approved
NorfenefrinePizotifen may decrease the vasoconstricting activities of Norfenefrine.Experimental
NorfluraneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Norflurane.Approved, Investigational
NormethadoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Normethadone.Approved, Illicit
NortriptylineNortriptyline may increase the antihypertensive activities of Pizotifen.Approved
NylidrinThe therapeutic efficacy of Nylidrin can be decreased when used in combination with Pizotifen.Approved
OctamoxinOctamoxin may increase the anticholinergic activities of Pizotifen.Withdrawn
OctopaminePizotifen may decrease the vasoconstricting activities of Octopamine.Experimental
OlanzapineOlanzapine may increase the antihypertensive activities of Pizotifen.Approved, Investigational
OlodaterolPizotifen may decrease the vasoconstricting activities of Olodaterol.Approved
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Pizotifen.Approved
OndansetronThe risk or severity of serotonin syndrome can be increased when Ondansetron is combined with Pizotifen.Approved
OpiumThe risk or severity of adverse effects can be increased when Pizotifen is combined with Opium.Approved, Illicit
OrciprenalinePizotifen may decrease the vasoconstricting activities of Orciprenaline.Approved
OrphenadrinePizotifen may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.Approved
OsanetantThe risk or severity of adverse effects can be increased when Pizotifen is combined with Osanetant.Investigational
OtiloniumThe risk or severity of hypotension can be increased when Pizotifen is combined with Otilonium.Experimental, Investigational
OxazepamThe risk or severity of adverse effects can be increased when Oxazepam is combined with Pizotifen.Approved
OxprenololOxprenolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
OxybuprocaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Oxybuprocaine.Approved, Investigational
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Pizotifen.Approved, Illicit, Investigational
OxyfedrinePizotifen may decrease the vasoconstricting activities of Oxyfedrine.Experimental
OxymetazolineThe therapeutic efficacy of Oxymetazoline can be decreased when used in combination with Pizotifen.Approved, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Pizotifen.Approved, Investigational, Vet Approved
PaliperidonePaliperidone may increase the antihypertensive activities of Pizotifen.Approved
ParaldehydePizotifen may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.Approved, Investigational
PargylinePargyline may increase the anticholinergic activities of Pizotifen.Approved
ParomomycinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Paromomycin.Approved, Investigational
ParoxetineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Paroxetine.Approved, Investigational
PenbutololPenbutolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
PenfluridolThe risk or severity of hypotension can be increased when Pizotifen is combined with Penfluridol.Experimental
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Pizotifen.Approved, Vet Approved
PentobarbitalThe risk or severity of adverse effects can be increased when Pentobarbital is combined with Pizotifen.Approved, Investigational, Vet Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Pizotifen.Approved, Investigational
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved
PerazineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Perazine.Approved, Investigational
PergolidePizotifen may decrease the vasoconstricting activities of Pergolide.Approved, Investigational, Vet Approved, Withdrawn
PerospironeThe risk or severity of adverse effects can be increased when Pizotifen is combined with Perospirone.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Pizotifen.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Pizotifen.Approved
PhenazocineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Phenazocine.Experimental
PhendimetrazinePizotifen may decrease the vasoconstricting activities of Phendimetrazine.Approved, Illicit
PhenelzinePhenelzine may increase the anticholinergic activities of Pizotifen.Approved
PhenibutThe risk or severity of adverse effects can be increased when Pizotifen is combined with Phenibut.Experimental
PheniprazinePheniprazine may increase the anticholinergic activities of Pizotifen.Withdrawn
PhenobarbitalThe risk or severity of adverse effects can be increased when Phenobarbital is combined with Pizotifen.Approved, Investigational
PhenoperidineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Phenoperidine.Experimental
PhenoxybenzaminePhenoxybenzamine may increase the antihypertensive activities of Pizotifen.Approved
PhenoxyethanolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Phenoxyethanol.Approved
PhenoxypropazinePhenoxypropazine may increase the anticholinergic activities of Pizotifen.Withdrawn
PhenterminePhentermine may decrease the sedative activities of Pizotifen.Approved, Illicit
PhentolaminePhentolamine may increase the antihypertensive activities of Pizotifen.Approved
PhenylephrineThe therapeutic efficacy of Phenylephrine can be decreased when used in combination with Pizotifen.Approved
PhenylpropanolaminePizotifen may decrease the vasoconstricting activities of Phenylpropanolamine.Approved, Vet Approved, Withdrawn
PhenytoinThe risk or severity of adverse effects can be increased when Phenytoin is combined with Pizotifen.Approved, Vet Approved
PimozideThe risk or severity of adverse effects can be increased when Pimozide is combined with Pizotifen.Approved
PinaveriumThe risk or severity of hypotension can be increased when Pizotifen is combined with Pinaverium.Approved
PindololPindolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
PipamperoneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Pipamperone.Approved, Investigational
PipotiazineThe risk or severity of adverse effects can be increased when Pipotiazine is combined with Pizotifen.Approved, Investigational
PirbuterolPizotifen may decrease the vasoconstricting activities of Pirbuterol.Approved
PiritramideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Piritramide.Approved, Investigational
PirlindolePirlindole may increase the anticholinergic activities of Pizotifen.Approved
PivhydrazinePivhydrazine may increase the anticholinergic activities of Pizotifen.Withdrawn
Platelet Activating FactorPlatelet Activating Factor may increase the orthostatic hypotensive activities of Pizotifen.Experimental
Polymyxin B SulfateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Polymyxin B Sulfate.Approved, Vet Approved
PomalidomideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Pomalidomide.Approved
Potassium ChlorideThe risk or severity of gastrointestinal ulceration can be increased when Pizotifen is combined with Potassium Chloride.Approved, Withdrawn
PractololPractolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
PramipexolePizotifen may increase the sedative activities of Pramipexole.Approved, Investigational
PrazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Prazepam.Approved, Illicit
PrazosinPrazosin may increase the antihypertensive activities of Pizotifen.Approved
PregabalinThe therapeutic efficacy of Pizotifen can be increased when used in combination with Pregabalin.Approved, Illicit, Investigational
PrenalterolPizotifen may decrease the vasoconstricting activities of Prenalterol.Experimental
PrenylamineThe risk or severity of hypotension can be increased when Pizotifen is combined with Prenylamine.Withdrawn
PrilocaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Prilocaine.Approved
PrimidoneThe risk or severity of adverse effects can be increased when Primidone is combined with Pizotifen.Approved, Vet Approved
ProcaineProcaine may increase the anticholinergic activities of Pizotifen.Approved, Investigational, Vet Approved
ProcarbazineProcarbazine may increase the anticholinergic activities of Pizotifen.Approved, Investigational
ProcaterolPizotifen may decrease the vasoconstricting activities of Procaterol.Approved, Investigational
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Pizotifen.Approved, Vet Approved
PromazinePromazine may increase the antihypertensive activities of Pizotifen.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Pizotifen.Approved, Investigational
PropafenonePropafenone may increase the orthostatic hypotensive activities of Pizotifen.Approved
PropanididThe risk or severity of adverse effects can be increased when Pizotifen is combined with Propanidid.Experimental
ProparacaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Proparacaine.Approved, Vet Approved
PropericiazinePizotifen may increase the antihypertensive activities of Propericiazine.Approved, Investigational
PropiomazinePropiomazine may increase the antihypertensive activities of Pizotifen.Approved
PropiverinePizotifen may increase the antihypertensive activities of Propiverine.Approved, Investigational
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Pizotifen.Approved, Investigational, Vet Approved
PropoxycaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Propoxycaine.Approved
PropranololPropranolol may increase the orthostatic hypotensive activities of Pizotifen.Approved, Investigational
ProtokylolPizotifen may decrease the vasoconstricting activities of Protokylol.Approved, Vet Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Pizotifen.Approved
ProxibarbalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Proxibarbal.Experimental
PSD502The risk or severity of adverse effects can be increased when Pizotifen is combined with PSD502.Investigational
PseudoephedrinePseudoephedrine may decrease the sedative and stimulatory activities of Pizotifen.Approved
PyrantelThe risk or severity of adverse effects can be increased when Pizotifen is combined with Pyrantel.Approved, Vet Approved
QuazepamThe risk or severity of adverse effects can be increased when Quazepam is combined with Pizotifen.Approved, Illicit
QuetiapineQuetiapine may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Pizotifen.Approved
QuinidineQuinidine may increase the antihypertensive activities of Pizotifen.Approved, Investigational
QuinisocaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Quinisocaine.Experimental
RacepinephrinePizotifen may increase the antihypertensive activities of Racepinephrine.Approved
RacloprideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Raclopride.Investigational
RactopaminePizotifen may decrease the vasoconstricting activities of Ractopamine.Vet Approved
RamelteonThe risk or severity of adverse effects can be increased when Ramelteon is combined with Pizotifen.Approved, Investigational
RasagilineRasagiline may increase the anticholinergic activities of Pizotifen.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Pizotifen.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Remoxipride.Approved, Withdrawn
ReproterolPizotifen may decrease the vasoconstricting activities of Reproterol.Investigational
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Pizotifen.Approved, Investigational
RilmenidinePizotifen may decrease the vasoconstricting activities of Rilmenidine.Approved, Investigational
RimiterolPizotifen may decrease the vasoconstricting activities of Rimiterol.Experimental
RisperidoneRisperidone may increase the antihypertensive activities of Pizotifen.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ritanserin.Investigational
RitobegronPizotifen may decrease the vasoconstricting activities of Ritobegron.Investigational
RitodrinePizotifen may decrease the vasoconstricting activities of Ritodrine.Approved, Investigational
RizatriptanThe risk or severity of adverse effects can be increased when Pizotifen is combined with Rizatriptan.Approved
RomifidineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Romifidine.Vet Approved
RopinirolePizotifen may increase the sedative activities of Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Ropivacaine.Approved
RotigotinePizotifen may increase the sedative activities of Rotigotine.Approved
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Pizotifen.Approved
SafrazineSafrazine may increase the anticholinergic activities of Pizotifen.Withdrawn
SalbutamolThe therapeutic efficacy of Salbutamol can be decreased when used in combination with Pizotifen.Approved, Vet Approved
SalmeterolThe therapeutic efficacy of Salmeterol can be decreased when used in combination with Pizotifen.Approved
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Pizotifen.Approved, Investigational
SecobarbitalThe risk or severity of adverse effects can be increased when Secobarbital is combined with Pizotifen.Approved, Vet Approved
SelegilineSelegiline may increase the anticholinergic activities of Pizotifen.Approved, Investigational, Vet Approved
SeletracetamThe risk or severity of hypotension can be increased when Pizotifen is combined with Seletracetam.Investigational
SepranoloneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Sepranolone.Investigational
SertindoleThe risk or severity of adverse effects can be increased when Pizotifen is combined with Sertindole.Approved, Investigational, Withdrawn
SertralineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Sertraline.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Pizotifen.Approved, Vet Approved
SildenafilSildenafil may increase the hypotensive activities of Pizotifen.Approved, Investigational
SilodosinSilodosin may increase the antihypertensive activities of Pizotifen.Approved
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved
Sodium phosphate, monobasicThe therapeutic efficacy of Sodium phosphate, monobasic can be decreased when used in combination with Pizotifen.Approved
SolabegronPizotifen may decrease the vasoconstricting activities of Solabegron.Investigational
SotalolSotalol may increase the orthostatic hypotensive activities of Pizotifen.Approved
StiripentolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Stiripentol.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Pizotifen.Approved, Investigational
SulpirideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Sulpiride.Approved, Investigational
SultoprideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Sultopride.Experimental
SumatriptanThe risk or severity of adverse effects can be increased when Pizotifen is combined with Sumatriptan.Approved, Investigational
SuvorexantPizotifen may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.Approved, Investigational
SynephrinePizotifen may decrease the vasoconstricting activities of Synephrine.Experimental
TadalafilTadalafil may increase the hypotensive activities of Pizotifen.Approved, Investigational
TalinololTalinolol may increase the orthostatic hypotensive activities of Pizotifen.Investigational
TamsulosinTamsulosin may increase the antihypertensive activities of Pizotifen.Approved, Investigational
TandospironeThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tandospirone.Investigational
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Pizotifen.Approved
TasimelteonThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tasimelteon.Approved, Investigational
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Pizotifen.Approved, Investigational
TerazosinTerazosin may increase the antihypertensive activities of Pizotifen.Approved
TerbutalineTerbutaline may increase the orthostatic hypotensive activities of Pizotifen.Approved
TerodilineThe risk or severity of hypotension can be increased when Pizotifen is combined with Terodiline.Experimental
TertatololTertatolol may increase the orthostatic hypotensive activities of Pizotifen.Experimental
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Pizotifen.Approved, Investigational
TetracaineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tetracaine.Approved, Vet Approved
TetracyclineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tetracycline.Approved, Vet Approved
TetrahydropalmatineThe risk or severity of hypotension can be increased when Pizotifen is combined with Tetrahydropalmatine.Investigational
TetrandrineThe risk or severity of hypotension can be increased when Pizotifen is combined with Tetrandrine.Experimental
TetrodotoxinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tetrodotoxin.Investigational
TetryzolinePizotifen may decrease the vasoconstricting activities of Tetryzoline.Approved
ThalidomidePizotifen may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.Approved, Investigational, Withdrawn
TheophyllineTheophylline may increase the hypotensive activities of Pizotifen.Approved
ThiamylalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Thiamylal.Approved, Vet Approved
ThiopentalThe risk or severity of adverse effects can be increased when Pizotifen is combined with Thiopental.Approved, Vet Approved
ThioproperazineThioproperazine may increase the antihypertensive activities of Pizotifen.Approved
ThioridazineThioridazine may increase the antihypertensive activities of Pizotifen.Approved, Withdrawn
ThiothixeneThe risk or severity of adverse effects can be increased when Thiothixene is combined with Pizotifen.Approved
TiagabineThe risk or severity of adverse effects can be increased when Tiagabine is combined with Pizotifen.Approved, Investigational
TiaprideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tiapride.Approved, Investigational
TiletamineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tiletamine.Vet Approved
TilidineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tilidine.Experimental
TimololTimolol may increase the orthostatic hypotensive activities of Pizotifen.Approved
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Pizotifen.Approved, Investigational
TolazolineTolazoline may increase the antihypertensive activities of Pizotifen.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Pizotifen.Approved, Withdrawn
Tolfenamic AcidThe risk or severity of hypotension can be increased when Pizotifen is combined with Tolfenamic Acid.Approved, Investigational
ToloxatoneToloxatone may increase the anticholinergic activities of Pizotifen.Approved
TopiramateThe risk or severity of hyperthermia and oligohydrosis can be increased when Pizotifen is combined with Topiramate.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Pizotifen.Approved, Investigational
TranilastThe risk or severity of hypotension can be increased when Pizotifen is combined with Tranilast.Approved, Investigational
TranylcypromineTranylcypromine may increase the anticholinergic activities of Pizotifen.Approved, Investigational
TrazodoneTrazodone may increase the antihypertensive activities of Pizotifen.Approved, Investigational
TretoquinolPizotifen may decrease the vasoconstricting activities of Tretoquinol.Experimental
TriazolamThe risk or severity of adverse effects can be increased when Triazolam is combined with Pizotifen.Approved, Investigational
Tricaine methanesulfonateThe risk or severity of adverse effects can be increased when Pizotifen is combined with Tricaine methanesulfonate.Vet Approved
TrichloroethyleneThe risk or severity of adverse effects can be increased when Pizotifen is combined with Trichloroethylene.Approved
TrifluoperazineTrifluoperazine may increase the antihypertensive activities of Pizotifen.Approved, Investigational
TrifluperidolThe risk or severity of adverse effects can be increased when Pizotifen is combined with Trifluperidol.Experimental
TriflupromazineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Triflupromazine.Approved, Vet Approved
TrimazosinTrimazosin may increase the antihypertensive activities of Pizotifen.Experimental
TrimebutineThe risk or severity of hypotension can be increased when Pizotifen is combined with Trimebutine.Approved
TrimethadioneThe risk or severity of hypotension can be increased when Pizotifen is combined with Trimethadione.Approved
TrimipramineTrimipramine may increase the antihypertensive activities of Pizotifen.Approved
TriprolidineThe risk or severity of adverse effects can be increased when Triprolidine is combined with Pizotifen.Approved
TrospiumThe risk or severity of adverse effects can be increased when Trospium is combined with Pizotifen.Approved
TulobuterolPizotifen may decrease the vasoconstricting activities of Tulobuterol.Investigational
UdenafilUdenafil may increase the hypotensive activities of Pizotifen.Approved, Investigational
UrapidilUrapidil may increase the antihypertensive activities of Pizotifen.Investigational
Valproic AcidThe risk or severity of adverse effects can be increased when Pizotifen is combined with Valproic Acid.Approved, Investigational
VancomycinThe risk or severity of adverse effects can be increased when Pizotifen is combined with Vancomycin.Approved
VardenafilVardenafil may increase the hypotensive activities of Pizotifen.Approved
VecuroniumThe risk or severity of adverse effects can be increased when Pizotifen is combined with Vecuronium.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Pizotifen.Approved
VenlafaxineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Venlafaxine.Approved
VeraliprideThe risk or severity of adverse effects can be increased when Pizotifen is combined with Veralipride.Experimental
VerapamilVerapamil may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Pizotifen.Approved
VigabatrinThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Pizotifen.Approved
VilanterolPizotifen may decrease the vasoconstricting activities of Vilanterol.Approved
VinpocetineThe risk or severity of hypotension can be increased when Pizotifen is combined with Vinpocetine.Investigational
Vinyl etherThe risk or severity of adverse effects can be increased when Pizotifen is combined with Vinyl ether.Experimental
VortioxetineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Vortioxetine.Approved, Investigational
WIN 55212-2The risk or severity of Tachycardia and drowsiness can be increased when Pizotifen is combined with WIN 55212-2.Experimental
XamoterolPizotifen may decrease the vasoconstricting activities of Xamoterol.Experimental
XenonThe risk or severity of adverse effects can be increased when Pizotifen is combined with Xenon.Experimental
XylazineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Xylazine.Vet Approved
XylometazolinePizotifen may decrease the vasoconstricting activities of Xylometazoline.Approved, Investigational
ZaleplonThe risk or severity of adverse effects can be increased when Zaleplon is combined with Pizotifen.Approved, Illicit, Investigational
ZiconotideThe risk or severity of hypotension can be increased when Pizotifen is combined with Ziconotide.Approved
ZimelidineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Zimelidine.Withdrawn
ZiprasidoneZiprasidone may increase the antihypertensive activities of Pizotifen.Approved
ZolazepamThe risk or severity of adverse effects can be increased when Pizotifen is combined with Zolazepam.Vet Approved
ZolmitriptanThe risk or severity of adverse effects can be increased when Pizotifen is combined with Zolmitriptan.Approved, Investigational
ZolpidemPizotifen may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.Approved
ZonisamideThe risk or severity of hypotension can be increased when Pizotifen is combined with Zonisamide.Approved, Investigational
ZopicloneThe risk or severity of adverse effects can be increased when Zopiclone is combined with Pizotifen.Approved
ZotepineThe risk or severity of adverse effects can be increased when Pizotifen is combined with Zotepine.Approved, Investigational, Withdrawn
ZuclopenthixolZuclopenthixol may increase the antihypertensive activities of Pizotifen.Approved, Investigational
Food Interactions
  • Take without regard to meals.

References

General References
  1. Standal JE: Pizotifen as an antidepressant. Acta Psychiatr Scand. 1977 Oct;56(4):276-9. [PubMed:335788]
  2. Peet KM: Use of pizotifen in severe migraine: a long-term study. Curr Med Res Opin. 1977;5(2):192-9. doi: 10.1185/03007997709110164 . [PubMed:340139]
  3. Carroll JD, Maclay WP: Pizotifen (BC 105) in migraine prophylaxis. Curr Med Res Opin. 1975;3(2):68-71. doi: 10.1185/03007997509113649 . [PubMed:1095308]
  4. Muller-Schweinitzer E: Pizotifen, an antimigraine drug with venoconstrictor activity in vivo. J Cardiovasc Pharmacol. 1986 Jul-Aug;8(4):805-10. [PubMed:2427822]
  5. Przegalinski E, Baran L, Palider W, Siwanowicz J: The central action of pizotifen. Psychopharmacology (Berl). 1979 Apr 25;62(3):295-300. [PubMed:111296]
  6. Sarantos MR, Papanikolaou T, Ellerby LM, Hughes RE: Pizotifen Activates ERK and Provides Neuroprotection in vitro and in vivo in Models of Huntington's Disease. J Huntingtons Dis. 2012;1(2):195-210. doi: 10.3233/JHD-120033. [PubMed:23393546]
  7. Lin OA, Karim ZA, Vemana HP, Espinosa EV, Khasawneh FT: The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function. PLoS One. 2014 Jan 23;9(1):e87026. doi: 10.1371/journal.pone.0087026. eCollection 2014. [PubMed:24466319]
  8. Peroutka SJ, Banghart SB, Allen GS: Calcium channel antagonism by pizotifen. J Neurol Neurosurg Psychiatry. 1985 Apr;48(4):381-3. [PubMed:2582093]
  9. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
  10. Paladin Labs - Product Monograph: SANDOMIGRAN (Pizotifen hydrogen malate 0.5 mg and 1 mg tablets) [Link]
External Links
PubChem Compound
27400
PubChem Substance
347827758
ChemSpider
25497
BindingDB
82088
ChEBI
50212
ChEMBL
CHEMBL294951
Wikipedia
Pizotifen
ATC Codes
N02CX01 — Pizotifen
AHFS Codes
  • 28:32.92 — Antimigraine Agents, Miscellaneous
MSDS
Download (340 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral0.50 mg
TabletOral1 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPartly miscibleMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.00706 mg/mLALOGPS
logP4.7ALOGPS
logP4.49ChemAxon
logS-4.6ALOGPS
pKa (Strongest Basic)7.98ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity101.1 m3·mol-1ChemAxon
Polarizability34.36 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cycloheptathiophenes. These are polycyclic compounds containing a thiophene ring fused to a 7 member carbocyclic moiety. Thiophene is 5-membered ring consisting of four carbon atoms and one sulfur atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Cycloheptathiophenes
Sub Class
Not Available
Direct Parent
Cycloheptathiophenes
Alternative Parents
Piperidines / Benzenoids / Thiophenes / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Cycloheptathiophene / Benzenoid / Piperidine / Heteroaromatic compound / Thiophene / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzocycloheptathiophene (CHEBI:50212)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Eltze M, Mutschler E, Lambrecht G: Affinity profiles of pizotifen, ketotifen and other tricyclic antimuscarinics at muscarinic receptor subtypes M1, M2 and M3. Eur J Pharmacol. 1992 Feb 18;211(3):283-93. [PubMed:1377628]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Richards MH: Effects of cyproheptadine and pizotifen on central muscarinic receptors. Eur J Pharmacol. 1991 Apr 3;195(3):403-5. [PubMed:1868883]
  2. Eltze M, Mutschler E, Lambrecht G: Affinity profiles of pizotifen, ketotifen and other tricyclic antimuscarinics at muscarinic receptor subtypes M1, M2 and M3. Eur J Pharmacol. 1992 Feb 18;211(3):283-93. [PubMed:1377628]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Eltze M, Mutschler E, Lambrecht G: Affinity profiles of pizotifen, ketotifen and other tricyclic antimuscarinics at muscarinic receptor subtypes M1, M2 and M3. Eur J Pharmacol. 1992 Feb 18;211(3):283-93. [PubMed:1377628]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Przegalinski E, Baran L, Palider W, Siwanowicz J: The central action of pizotifen. Psychopharmacology (Berl). 1979 Apr 25;62(3):295-300. [PubMed:111296]
  2. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Przegalinski E, Baran L, Palider W, Siwanowicz J: The central action of pizotifen. Psychopharmacology (Berl). 1979 Apr 25;62(3):295-300. [PubMed:111296]
  2. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Mylecharane EJ: 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52. [PubMed:2045831]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Specific Function
Glucuronosyltransferase activity
Gene Name
UGT2B10
Uniprot ID
P36537
Uniprot Name
UDP-glucuronosyltransferase 2B10
Molecular Weight
60773.485 Da
References
  1. Kato Y, Izukawa T, Oda S, Fukami T, Finel M, Yokoi T, Nakajima M: Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97. doi: 10.1124/dmd.113.051565. Epub 2013 Apr 23. [PubMed:23611809]

Drug created on January 21, 2008 05:21 / Updated on August 14, 2018 04:32