Identification

Name
Frovatriptan
Accession Number
DB00998  (APRD00270)
Type
Small Molecule
Groups
Approved, Investigational
Description

Frovatriptan is a triptan drug developed by Vernalis for the treatment of migraine headaches, in particular those associated with menstruation. Frovatriptan causes vasoconstriction of arteries and veins that supply blood to the head.

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Frovatriptan succinate36K05YF32G158930-09-7WHTHWNUUXINXHN-SBSPUUFOSA-N
Frovatriptan succinate monohydrateD28J6W18HY158930-17-7CUETXFMONOSVJA-KLQYNRQASA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FrovaTablet, film coated2.5 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2010-08-182017-11-07Us
FrovaTablet2.5 mgOralEndo Pharmaceuticals2008-01-04Not applicableCanada
FrovaTablet, film coated2.5 mg/1OralStat Rx USA2001-11-08Not applicableUs
FrovaTablet, film coated2.5 mg/1OralUnit Dose Services2001-11-08Not applicableUs
FrovaTablet, film coated2.5 mg/1OralEndo Pharmaceuticals2001-11-08Not applicableUs
Frovatriptan SuccinateTablet, film coated2.5 mg/1OralQualitest2015-10-05Not applicableUs
Teva-frovatriptanTablet2.5 mgOralEndo Pharmaceuticals2015-01-16Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-frovatriptanTablet2.5 mgOralApotex Corporation2014-08-11Not applicableCanada
FrovatriptanTablet, film coated2.5 mg/1OralMylan Pharmaceuticals2016-04-29Not applicableUs
Frovatriptan SuccinateTablet, film coated2.5 mg/1OralGlenmark Pharmaceuticals Inc.,Usa2016-03-11Not applicableUs
International/Other Brands
Allergo filmtabletten / Frovelan / Miguard
Categories
UNII
H82Q2D5WA7
CAS number
158747-02-5
Weight
Average: 243.3043
Monoisotopic: 243.137162181
Chemical Formula
C14H17N3O
InChI Key
XPSQPHWEGNHMSK-SECBINFHSA-N
InChI
InChI=1S/C14H17N3O/c1-16-9-3-5-13-11(7-9)10-6-8(14(15)18)2-4-12(10)17-13/h2,4,6,9,16-17H,3,5,7H2,1H3,(H2,15,18)/t9-/m1/s1
IUPAC Name
(3R)-3-(methylamino)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide
SMILES
CN[[email protected]@H]1CCC2=C(C1)C1=C(N2)C=CC(=C1)C(N)=O

Pharmacology

Indication

For the acute treatment of migraine attacks with or without aura in adults.

Structured Indications
Pharmacodynamics

Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT1B and 5-HT1D receptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT1B/1D receptor agonists. Frovatriptan has no significant effects on GABAA mediated channel activity and has no significant affinity for benzodiazepine binding sites. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. Research has shown that migraine can be caused by the swelling of blood vessels around the brain. Frovatriptan eases the pain associated with migraine by narrowing these blood vessels. Frovatriptan has one of the highest affinities for the 5-HT1B of the second-generation triptan agonists.

Mechanism of action

Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.

TargetActionsOrganism
A5-hydroxytryptamine receptor 1D
agonist
Human
A5-hydroxytryptamine receptor 1B
agonist
Human
Absorption

Frovatriptan is rapidly absorbed from the duodenum, but has low oral bioavailability.

Volume of distribution
  • 4.2 L/kg [males]
  • 3 L/kg [females]
Protein binding

Binding to serum proteins is low (approximately 15%). Reversible binding to blood cells at equilibrium is approximately 60%.

Metabolism

In vitro, cytochrome P450 1A2 appears to be the principal enzyme involved in the metabolism of frovatriptan to several metabolites including hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan, and several other minor metabolites. Desmethyl frovatriptan has lower affinity for 5-HT1B/1D receptors compared to the parent compound. The N-acetyl desmethyl metabolite has no significant affinity for 5-HT receptors. The activity of the other metabolites is unknown.

Route of elimination

Radiolabeled compounds excreted in urine were unchanged frovatriptan, hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan, together with several other minor metabolites. Less than 10% of frovatriptan was excreted in urine after an oral dose.

Half life

26 hours

Clearance
  • 220 mL/min [male receiving IV dose of 0.8 mg]
  • 130 mL/min [Female receiving IV dose of 0.8 mg]
Toxicity

There is no direct experience of any patient taking an overdose of Frovatriptan. The maximum single dose of frovatriptan given to male and female patients with migraine was 40 mg (16 times the clinical dose) and the maximum single dose given to healthy male subjects was 100 mg (40 times the clinical dose) without significant adverse events.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3---(T;T) / (C;T)T AlleleEffect Directly StudiedPatients with this genotype have an increased likelihood of responding to frovatriptan when treating (condition: cluster headache).Details

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe metabolism of Frovatriptan can be decreased when combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.Experimental
AbirateroneThe serum concentration of Frovatriptan can be increased when it is combined with Abiraterone.Approved
AcepromazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Acepromazine.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Aceprometazine.Approved
AcetophenazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Acetophenazine.Approved
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Frovatriptan.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Amisulpride.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Frovatriptan.Approved
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Frovatriptan.Approved
AmperozideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Amperozide.Experimental
AmphetamineThe serum concentration of Frovatriptan can be increased when it is combined with Amphetamine.Approved, Illicit
AripiprazoleThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Aripiprazole.Approved, Investigational
AsenapineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Asenapine.Approved
AzaperoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Azaperone.Investigational, Vet Approved
AzithromycinThe metabolism of Frovatriptan can be decreased when combined with Azithromycin.Approved
BenmoxinThe metabolism of Frovatriptan can be decreased when combined with Benmoxin.Withdrawn
BenperidolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Benperidol.Investigational
BifeprunoxThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Bifeprunox.Investigational
BortezomibThe metabolism of Frovatriptan can be decreased when combined with Bortezomib.Approved, Investigational
BrexpiprazoleThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Brexpiprazole.Approved
BrofaromineThe serum concentration of Frovatriptan can be increased when it is combined with Brofaromine.Experimental
BromocriptineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Bromocriptine.Approved, Investigational
BromperidolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Bromperidol.Investigational
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Frovatriptan.Approved, Investigational
ButaperazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Butaperazine.Experimental
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Frovatriptan.Approved
CaffeineThe metabolism of Frovatriptan can be decreased when combined with Caffeine.Approved
CariprazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Cariprazine.Approved
CaroxazoneThe metabolism of Frovatriptan can be decreased when combined with Caroxazone.Withdrawn
ChlorproethazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Chlorproethazine.Experimental
ChlorpromazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Chlorpromazine.Approved, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Chlorprothixene.Approved, Investigational, Withdrawn
CitalopramThe risk or severity of adverse effects can be increased when Citalopram is combined with Frovatriptan.Approved
ClomipramineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Clomipramine.Approved, Vet Approved
ClopenthixolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Clopenthixol.Experimental
ClothiapineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Clothiapine.Experimental
ClotrimazoleThe metabolism of Frovatriptan can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Clozapine.Approved
CyamemazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Cyamemazine.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Frovatriptan.Approved
Cyproterone acetateThe serum concentration of Frovatriptan can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DapiprazoleThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Dapiprazole.Approved
DapoxetineThe risk or severity of adverse effects can be increased when Dapoxetine is combined with Frovatriptan.Investigational
DeferasiroxThe serum concentration of Frovatriptan can be increased when it is combined with Deferasirox.Approved, Investigational
DesipramineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Desipramine.Approved
DesvenlafaxineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Desvenlafaxine.Approved
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Frovatriptan.Approved
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Frovatriptan.Approved
DixyrazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Dixyrazine.Experimental
DolasetronDolasetron may increase the serotonergic activities of Frovatriptan.Approved
DosulepinThe metabolism of Frovatriptan can be decreased when combined with Dosulepin.Approved
DoxepinThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Doxepin.Approved
DroperidolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Droperidol.Approved, Vet Approved
DroxidopaFrovatriptan may increase the hypertensive activities of Droxidopa.Approved, Investigational
DuloxetineThe risk or severity of adverse effects can be increased when Duloxetine is combined with Frovatriptan.Approved
EcopipamThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Ecopipam.Investigational
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Frovatriptan.Approved, Investigational
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Ergoloid mesylate.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Ergonovine.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Frovatriptan.Approved
EscitalopramThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Escitalopram.Approved, Investigational
FencamfamineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Fencamfamine.Approved, Illicit, Withdrawn
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Frovatriptan.Approved, Illicit, Investigational, Vet Approved
FluanisoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Fluanisone.Experimental
FluoxetineThe risk or severity of adverse effects can be increased when Fluoxetine is combined with Frovatriptan.Approved, Vet Approved
FlupentixolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Fluphenazine.Approved
FluspirileneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Fluspirilene.Approved, Investigational
FluvoxamineThe metabolism of Frovatriptan can be decreased when combined with Fluvoxamine.Approved, Investigational
FurazolidoneThe metabolism of Frovatriptan can be decreased when combined with Furazolidone.Approved, Investigational, Vet Approved
GranisetronGranisetron may increase the serotonergic activities of Frovatriptan.Approved, Investigational
HaloperidolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Haloperidol.Approved
HarmalineThe serum concentration of Frovatriptan can be increased when it is combined with Harmaline.Experimental
HydracarbazineThe metabolism of Frovatriptan can be decreased when combined with Hydracarbazine.Experimental
IloperidoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Iloperidone.Approved
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Frovatriptan.Approved
IproclozideThe metabolism of Frovatriptan can be decreased when combined with Iproclozide.Withdrawn
IproniazidThe metabolism of Frovatriptan can be decreased when combined with Iproniazid.Withdrawn
IsocarboxazidThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Isocarboxazid.Approved
LevomilnacipranThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Levomilnacipran.Approved
LidocaineThe metabolism of Frovatriptan can be decreased when combined with Lidocaine.Approved, Vet Approved
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Frovatriptan.Approved, Investigational
LithiumThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Lithium.Approved
LobeglitazoneThe metabolism of Frovatriptan can be decreased when combined with Lobeglitazone.Approved, Investigational
LorcaserinThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Lorcaserin.Approved
LoxapineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Loxapine.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Lurasidone.Approved
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Frovatriptan.Approved
MebanazineThe metabolism of Frovatriptan can be decreased when combined with Mebanazine.Withdrawn
MelperoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Melperone.Approved, Investigational
MesoridazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Mesoridazine.Approved, Investigational
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Frovatriptan.Approved
MethotrimeprazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Methotrimeprazine.Approved
Methylene blueThe metabolism of Frovatriptan can be decreased when combined with Methylene blue.Approved, Investigational
MethylergometrineMethylergometrine may increase the vasoconstricting activities of Frovatriptan.Approved
MetoclopramideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Metoclopramide.Approved, Investigational
MexiletineThe metabolism of Frovatriptan can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Frovatriptan can be decreased when combined with Midostaurin.Approved
MilnacipranThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Milnacipran.Approved
MinaprineThe metabolism of Frovatriptan can be decreased when combined with Minaprine.Approved
MirtazapineThe risk or severity of adverse effects can be increased when Mirtazapine is combined with Frovatriptan.Approved
MoclobemideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Moclobemide.Approved
MolindoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Molindone.Approved
MoperoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Moperone.Experimental
MosapramineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Mosapramine.Experimental
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Frovatriptan.Approved, Investigational
NefazodoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Nefazodone.Approved, Withdrawn
NevirapineThe metabolism of Frovatriptan can be decreased when combined with Nevirapine.Approved
NialamideThe metabolism of Frovatriptan can be decreased when combined with Nialamide.Withdrawn
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Frovatriptan.Approved
OctamoxinThe metabolism of Frovatriptan can be decreased when combined with Octamoxin.Withdrawn
OlanzapineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Olanzapine.Approved, Investigational
OndansetronOndansetron may increase the serotonergic activities of Frovatriptan.Approved
OsanetantThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Osanetant.Investigational
OsimertinibThe serum concentration of Frovatriptan can be decreased when it is combined with Osimertinib.Approved
OxypertineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Oxypertine.Experimental
PaliperidoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Paliperidone.Approved
PalonosetronPalonosetron may increase the serotonergic activities of Frovatriptan.Approved, Investigational
PargylineThe metabolism of Frovatriptan can be decreased when combined with Pargyline.Approved
ParoxetineThe risk or severity of adverse effects can be increased when Paroxetine is combined with Frovatriptan.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Frovatriptan can be increased when it is combined with Peginterferon alfa-2b.Approved
PenfluridolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Penfluridol.Experimental
PerazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Perazine.Investigational
PerospironeThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Perospirone.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Perphenazine.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Frovatriptan.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Frovatriptan.Approved
PheniprazineThe metabolism of Frovatriptan can be decreased when combined with Pheniprazine.Withdrawn
PhenoxypropazineThe metabolism of Frovatriptan can be decreased when combined with Phenoxypropazine.Withdrawn
PimozideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Pimozide.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Pipamperone.Approved, Investigational
PipotiazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Pipotiazine.Approved, Investigational
PirlindoleThe metabolism of Frovatriptan can be decreased when combined with Pirlindole.Approved
PivhydrazineThe metabolism of Frovatriptan can be decreased when combined with Pivhydrazine.Withdrawn
ProcarbazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Procarbazine.Approved
ProchlorperazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Prochlorperazine.Approved, Vet Approved
PromazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Promazine.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Promethazine.Approved
PropericiazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Propericiazine.Approved
ProthipendylThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Prothipendyl.Investigational
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Frovatriptan.Approved
QuetiapineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Quetiapine.Approved
RacloprideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Raclopride.Investigational
RasagilineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Rasagiline.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Remoxipride.Approved, Withdrawn
ReserpineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Reserpine.Approved, Investigational
RisperidoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Risperidone.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Ritanserin.Investigational
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Frovatriptan.Approved
RopiniroleThe metabolism of Frovatriptan can be decreased when combined with Ropinirole.Approved, Investigational
SafrazineThe metabolism of Frovatriptan can be decreased when combined with Safrazine.Withdrawn
SelegilineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Selegiline.Approved, Investigational, Vet Approved
SertindoleThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Sertindole.Approved, Investigational, Withdrawn
SertralineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Sertraline.Approved
SimeprevirThe metabolism of Frovatriptan can be decreased when combined with Simeprevir.Approved
SulpirideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Sulpiride.Approved, Investigational
SultoprideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Sultopride.Experimental
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Frovatriptan.Approved, Investigational
TapentadolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Tapentadol.Approved
Tedizolid PhosphateTedizolid Phosphate may increase the serotonergic activities of Frovatriptan.Approved
Tenofovir disoproxilThe metabolism of Frovatriptan can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Frovatriptan can be decreased when it is combined with Teriflunomide.Approved
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Tetrahydropalmatine.Investigational
TheophyllineThe metabolism of Frovatriptan can be decreased when combined with Theophylline.Approved
ThiopropazateThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Thiopropazate.Experimental
ThioproperazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Thioproperazine.Approved
ThioridazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Thioridazine.Approved, Withdrawn
ThiothixeneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Thiothixene.Approved
TiaprideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Tiapride.Approved, Investigational
TiclopidineThe metabolism of Frovatriptan can be decreased when combined with Ticlopidine.Approved
ToloxatoneThe metabolism of Frovatriptan can be decreased when combined with Toloxatone.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Frovatriptan.Approved, Investigational
Trans-2-PhenylcyclopropylamineThe metabolism of Frovatriptan can be decreased when combined with Trans-2-Phenylcyclopropylamine.Experimental
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Frovatriptan.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Frovatriptan.Approved, Investigational
TrifluoperazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Trifluoperazine.Approved
TrifluperidolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Trifluperidol.Experimental
TriflupromazineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Triflupromazine.Approved, Vet Approved
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Frovatriptan.Approved
TropisetronTropisetron may increase the serotonergic activities of Frovatriptan.Approved, Investigational
VenlafaxineThe risk or severity of adverse effects can be increased when Venlafaxine is combined with Frovatriptan.Approved
VeraliprideThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Veralipride.Experimental
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Frovatriptan.Approved
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Frovatriptan.Approved
ZiprasidoneThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Ziprasidone.Approved
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Frovatriptan.Approved, Investigational
ZotepineThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Zotepine.Approved, Investigational
ZucapsaicinThe metabolism of Frovatriptan can be decreased when combined with Zucapsaicin.Approved
ZuclopenthixolThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Zuclopenthixol.Approved, Investigational
Food Interactions
  • Food does not affect amount of absorption but delays maximal levels by about 1 hour.
  • Take without regard to meals.

References

Synthesis Reference

Samir Naik, Anthony Crasto, Narendra Joshi, Sachin Srivastava, "Amorphous frovatriptan succinate and process for the preparation thereof." U.S. Patent US20070299123, issued December 27, 2007.

US20070299123
General References
  1. Markus F, Mikko K: Frovatriptan review. Expert Opin Pharmacother. 2007 Dec;8(17):3029-33. [PubMed:18001261]
  2. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616]
  3. Balbisi EA: Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. Ther Clin Risk Manag. 2006 Sep;2(3):303-8. [PubMed:18360605]
  4. Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705. [PubMed:15311727]
  5. Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65. [PubMed:15342617]
  6. Jhee SS, Shiovitz T, Crawford AW, Cutler NR: Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a comparative review. Clin Pharmacokinet. 2001;40(3):189-205. [PubMed:11327198]
External Links
Human Metabolome Database
HMDB15133
KEGG Drug
D07997
PubChem Compound
77992
PubChem Substance
46506288
ChemSpider
70378
BindingDB
50073689
ChEBI
134991
ChEMBL
CHEMBL1279
Therapeutic Targets Database
DAP000063
PharmGKB
PA164754891
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Frovatriptan
ATC Codes
N02CC07 — Frovatriptan
AHFS Codes
  • 28:32.28 — Selective Serotonin Agonists
FDA label
Download (871 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentAnalgesic Overuse Headache / Medication Overuse Headache1
3CompletedPreventionMenstrually Associated Migraine1
3CompletedTreatmentMigraines2
4CompletedPreventionMigraines1
4CompletedTreatmentMenstrual Migraine (MM) Headaches1
Not AvailableCompletedTreatmentHaemorrhage / Migraines / Spotting1
Not AvailableCompletedTreatmentMigraines1

Pharmacoeconomics

Manufacturers
  • Endo pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
TabletOral2.5 mg
Tablet, film coatedOral2.5 mg/1
Prices
Unit descriptionCostUnit
Frova 9 2.5 mg tablet Box262.31USD box
Frova 2.5 mg tablet33.73USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5962501No1993-12-162013-12-16Us
CA2113726No2008-02-192012-06-17Canada
CA2152630No2005-07-262013-12-16Canada
US5464864No1995-11-072015-11-07Us
US5827871No1995-10-272015-10-27Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
logP0.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.123 mg/mLALOGPS
logP1.2ALOGPS
logP1.08ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)14.54ChemAxon
pKa (Strongest Basic)10.42ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area70.91 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71.84 m3·mol-1ChemAxon
Polarizability27.55 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9934
Blood Brain Barrier+0.986
Caco-2 permeable-0.5794
P-glycoprotein substrateSubstrate0.602
P-glycoprotein inhibitor INon-inhibitor0.8862
P-glycoprotein inhibitor IINon-inhibitor0.7244
Renal organic cation transporterNon-inhibitor0.6147
CYP450 2C9 substrateNon-substrate0.7785
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateInhibitor0.6997
CYP450 2C9 inhibitorNon-inhibitor0.8842
CYP450 2D6 inhibitorNon-inhibitor0.8614
CYP450 2C19 inhibitorNon-inhibitor0.6656
CYP450 3A4 inhibitorNon-inhibitor0.5316
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5744
Ames testNon AMES toxic0.7623
CarcinogenicityNon-carcinogens0.9456
BiodegradationNot ready biodegradable0.9406
Rat acute toxicity1.9582 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9878
hERG inhibition (predictor II)Inhibitor0.6428
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Carbazoles
Alternative Parents
Indolecarboxamides and derivatives / 3-alkylindoles / Aralkylamines / Benzenoids / Pyrroles / Heteroaromatic compounds / Primary carboxylic acid amides / Amino acids and derivatives / Dialkylamines / Azacyclic compounds
show 4 more
Substituents
Carbazole / Indolecarboxamide derivative / Indolecarboxylic acid derivative / 3-alkylindole / Indole / Aralkylamine / Benzenoid / Heteroaromatic compound / Pyrrole / Amino acid or derivatives
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616]
  3. Comer MB: Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan. Headache. 2002 Apr;42 Suppl 2:S47-53. [PubMed:12028320]
  4. Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. [PubMed:11152011]
  5. Deleu D, Hanssens Y: Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000 Jul;40(7):687-700. [PubMed:10883409]
  6. Jahnichen S, Radtke OA, Pertz HH: Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jul;370(1):54-63. Epub 2004 Jun 8. [PubMed:15185063]
  7. Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705. [PubMed:15311727]
  8. Parsons AA, Raval P, Smith S, Tilford N, King FD, Kaumann AJ, Hunter J: Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries. J Cardiovasc Pharmacol. 1998 Aug;32(2):220-4. [PubMed:9700983]
  9. Balbisi EA: Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. Ther Clin Risk Manag. 2006 Sep;2(3):303-8. [PubMed:18360605]
  10. Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65. [PubMed:15342617]
  11. Buchan P, Wade A, Ward C, Oliver SD, Stewart AJ, Freestone S: Frovatriptan: a review of drug-drug interactions. Headache. 2002 Apr;42 Suppl 2:S63-73. [PubMed:12028322]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705. [PubMed:15311727]
  3. Comer MB: Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan. Headache. 2002 Apr;42 Suppl 2:S47-53. [PubMed:12028320]
  4. Parsons AA, Raval P, Smith S, Tilford N, King FD, Kaumann AJ, Hunter J: Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries. J Cardiovasc Pharmacol. 1998 Aug;32(2):220-4. [PubMed:9700983]
  5. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616]
  6. Dodick DW, Sandrini G, Williams P: Use of the sustained pain-free plus no adverse events endpoint in clinical trials of triptans in acute migraine. CNS Drugs. 2007;21(1):73-82. [PubMed:17190530]
  7. Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. [PubMed:11152011]
  8. Deleu D, Hanssens Y: Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000 Jul;40(7):687-700. [PubMed:10883409]
  9. Markus F, Mikko K: Frovatriptan review. Expert Opin Pharmacother. 2007 Dec;8(17):3029-33. [PubMed:18001261]
  10. Balbisi EA: Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. Ther Clin Risk Manag. 2006 Sep;2(3):303-8. [PubMed:18360605]
  11. Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65. [PubMed:15342617]
  12. Buchan P, Wade A, Ward C, Oliver SD, Stewart AJ, Freestone S: Frovatriptan: a review of drug-drug interactions. Headache. 2002 Apr;42 Suppl 2:S63-73. [PubMed:12028322]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616]
  2. Buchan P, Keywood C, Wade A, Ward C: Clinical pharmacokinetics of frovatriptan. Headache. 2002 Apr;42 Suppl 2:S54-62. [PubMed:12028321]
  3. Buchan P, Wade A, Ward C, Oliver SD, Stewart AJ, Freestone S: Frovatriptan: a review of drug-drug interactions. Headache. 2002 Apr;42 Suppl 2:S63-73. [PubMed:12028322]
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 22, 2017 12:41