Skip to main content
MyDeficiencies

Frovatriptan

Selective serotonin (5-HT1B/1D) receptor agonist, "triptan"

Also sold as Frova.

Analyze another medication Medication directory

Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Frovatriptan has no classical nutrient-depletion machinery. Its pharmacokinetic profile (CYP1A2 substrate only, not an inducer or inhibitor of CYP450 or MAO enzymes, mixed renal/fecal elimination, no documented chelation or antacid/mineral interaction, no renal tubular wasting signal) checks negative against all nine mechanism classes screened in this review. Consistent with that, a search of the standard consumer drug-nutrient-depletion references turned up no triptan or frovatriptan entries at all, classical or otherwise. The red and orange tiers are empty, and no classical vitamin or mineral earns even a yellow grade for this drug specifically.

Selective serotonin (5-HT1B/1D) receptor agonist, "triptan" · ATC N02CC07 · also sold as Frova; generic frovatriptan succinate · reviewed October 1, 2026. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Frovatriptan in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden, class-level signal only, supra-pharmacologic, not demonstrated for frovatriptan

Yellow — Low

See study details

No frovatriptan-specific data exist. An in vitro sumatriptan hepatocyte study reported mitochondrial membrane-potential collapse at concentrations far above clinical exposure, a class-pharmacology signal, not evidence of mitochondrial harm from frovatriptan at approved doses.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Null/negative findings: Frovatriptan's own label and postmarketing experience report no hepatotoxicity signal; mild-to-moderate hepatic impairment only doubles systemic exposure, with no stated mitochondrial-injury mechanism tied to that finding.
  • At-risk subgroups: None established for frovatriptan. A theoretical concern would concentrate in severe hepatic impairment, already flagged in the label as a pharmacokinetic caution independent of this finding.
  • Counter-evidence on record: The in vitro concentration tested (millimolar range) vastly exceeds any achievable plasma concentration at approved sumatriptan or frovatriptan doses; this is a cytotoxicity-assay signal, not a clinical observation.

Regulatory status

No mitochondrial-toxicity or hepatic-injury language appears anywhere in the FDA frovatriptan label (Warnings and Precautions or Adverse Reactions).

Population evidence

Khalili Fard J, Hamzeiy H, Sattari M, Eghbal MA (2016). Isolated rat hepatocytes, in vitro, concentration-response design. Sumatriptan LC50 ≈5 mM at 120 minutes; mitochondrial membrane potential (MMP) collapse and reactive oxygen species (ROS) generation reported; protection by L-carnitine and the MPT-pore sealant trifluoperazine cited as supporting a mitochondrial permeability transition (MPT) mechanism. Tier B for sumatriptan; Tier C (class extrapolation) for frovatriptan, frovatriptan was not in the studied cohort.

Mechanism

Named for sumatriptan (ROS-driven MPT pore opening), not established for frovatriptan. The two drugs share the 5-HT1B/1D agonist pharmacophore but are cleared through different enzyme systems, sumatriptan primarily via monoamine oxidase-A, frovatriptan primarily via CYP1A2, so the class-extrapolation cohort test is met only at the receptor-pharmacology level, not the metabolic-pathway level, and mechanistic transfer to frovatriptan is weaker than a same-pathway class member would provide.

Counter-evidence held on record

This is a mechanism-plausibility flag from a different triptan at non-physiological concentrations, not a demonstrated frovatriptan effect. No supplementation or monitoring is recommended on this basis alone.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress, same class-level signal, supra-pharmacologic, not demonstrated for frovatriptan

Yellow — Low

See study details

The same sumatriptan in vitro hepatocyte study that reported mitochondrial change also reported reactive-oxygen generation that was blunted by antioxidants, again a class-level, supra-pharmacologic in vitro signal, not evidence of oxidative stress from frovatriptan.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Null/negative findings: No oxidative-stress or redox-marker signal is reported anywhere in frovatriptan's clinical trial or postmarketing safety data.
  • At-risk subgroups: None established for frovatriptan.
  • Counter-evidence on record: Same supra-pharmacologic concentration limitation as the mitochondrial-burden entry above; this is an in vitro cytoprotection experiment, not a measurement of oxidative stress at clinical doses.

Regulatory status

No oxidative-stress or antioxidant-depletion language appears in the FDA frovatriptan label.

Population evidence

Khalili Fard et al. (2016), same isolated rat hepatocyte experiment as above. ROS generation and hepatocyte membrane lysis (LC50 ≈5 mM) were significantly reduced by taurine, N-acetyl cysteine, quercetin, BHT, and vitamin E. Tier B for sumatriptan; Tier C (class extrapolation) for frovatriptan, which was not in the cohort.

Mechanism

ROS generation tied to the same MPT-pore/mitochondrial pathway described above, for sumatriptan specifically; no frovatriptan-specific oxidative-stress mechanism is established, and frovatriptan's different clearance enzyme (CYP1A2 vs. MAO-A) limits direct transfer.

Counter-evidence held on record

Do not read the antioxidant-protection finding as evidence that frovatriptan users need antioxidant supplementation; the experiment protects isolated hepatocytes from a concentration no patient reaches. See the Overlap map: this entry shares its entire evidentiary basis with Mitochondrial burden above and must not be counted as independent confirmation of it.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

See study details

No frovatriptan-specific or class-level evidence links frovatriptan to copper status, and no circulating consumer claim exists to rebut.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B/C mechanistic or class-level evidence was located, and no circulating consumer claim linking frovatriptan or triptans generally to copper status was found.

Channels tried

PubMed direct search "frovatriptan copper" (completed; result page explicitly stated "No results were found"). General web search for circulating claims (completed; no triptan-specific copper claims found in the consumer drug-nutrient-depletion references reviewed for this dossier, including a U.S. Pharmacist drug-induced nutrient depletion CE article and a Riordan Clinic medication-induced nutrient depletion reference table, neither of which lists any triptan). Europe PMC REST API, Crossref API, and Semantic Scholar API cross-checks were attempted but each returned HTTP 429 (session-level rate limiting) before a result set could be retrieved.

Disclosure

The PubMed-direct and consumer-claim channels produced genuine, completed null results. The three database cross-check channels did not complete due to tooling rate-limits encountered during this specific review (not a confirmed absence from those databases) and should be re-attempted in a future revision before this gap is treated as fully exhausted.

Iron

Not graded — disclosed evidence gap

See study details

No frovatriptan-specific or class-level evidence links frovatriptan to iron status, and no circulating consumer claim exists to rebut.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B/C mechanistic or class-level evidence was located, and no circulating consumer claim linking frovatriptan or triptans generally to iron status was found.

Channels tried

PubMed direct search "frovatriptan iron" (completed; result page explicitly stated "No results were found"). General web search for circulating claims, including a specific search for frovatriptan/triptan iron or anemia case reports (completed; no drug-specific hits beyond generic drug-information pages). Europe PMC REST API, Crossref API, and Semantic Scholar API cross-checks were attempted but each returned HTTP 429 (session-level rate limiting) before a result set could be retrieved.

Disclosure

As with Copper above, the completed channels (PubMed-direct, consumer-claim search) are genuine negatives; the database cross-check channels were blocked by tooling rate limits during this review, not confirmed clean, and should be re-run in a future revision.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Not graded — disclosed evidence gap

See study details

No frovatriptan-specific evidence on gut microbiome composition or function was located, and no circulating consumer claim exists to rebut; the direct database check for this category was less complete than for Copper or Iron.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. ungraded

Limits on what this shows

  • Why no grade: Dual condition applied: no Tier B/C evidence found, and no circulating consumer claim found, but the confirmation of "no evidence" is weaker here than for Copper/Iron because one of the two PubMed attempts returned a bot-verification challenge rather than a clean result page (see below).

Channels tried

General web search "frovatriptan gut microbiome" (completed; returned general gut-microbiome-pharmacology reviews and a non-drug-specific "Frovatriptan, an overview" topic page, with no frovatriptan-specific microbiome finding in any result). PubMed direct search "frovatriptan microbiome" (interrupted: the fetch returned a reCAPTCHA/bot-verification challenge page instead of a search-results page). Europe PMC REST API cross-check attempted but returned HTTP 429 (session-level rate limiting) before completion.

Disclosure

This entry reflects a genuinely attempted, multi-host, multi-phrasing search (general web search plus two database channels) but not a fully confirmed clean result, since the PubMed attempt was blocked by a bot challenge rather than returning a definitive zero-result page. Flagged as the highest-priority of the three ungraded entries for re-check once direct PubMed and Europe PMC access is unblocked.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization, mechanism clarification of the class's intended vasoconstrictive pharmacology, not a nutrient-type deficiency

Yellow — Low

See study details

A human study found a transient reduction in post-exercise muscle oxidative-phosphorylation recovery after subcutaneous sumatriptan, which the study's own authors attributed to vasoconstriction-driven regional hypoxia, not a nutrient or mitochondrial defect. This is a pharmacodynamic/vascular finding, not a deficiency, and frovatriptan itself was not studied.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow · mechanism clarification

Limits on what this shows

  • Null/negative findings: Mitochondrial/oxidative function returned to normal during the recovery period in all subjects studied; the authors described the effect as transient and self-limited, not persistent impairment.
  • At-risk subgroups: None established for frovatriptan.
  • Counter-evidence on record: Frovatriptan reaches a lower, slower-rising peak concentration than subcutaneous sumatriptan (oral Tmax 2-4 hours vs. subcutaneous Tmax ≈15 minutes), making an equivalent transient hemodynamic spike at a comparable magnitude uncertain for frovatriptan specifically.

Regulatory status

The FDA frovatriptan label documents peripheral vascular ischemia and Raynaud's phenomenon as rare class-type adverse events (Warnings and Precautions, section 5.5), consistent with 5-HT1B-mediated vasoconstriction as the drug's own intended pharmacology, not a nutrient pathway. No hemoglobin, hematocrit, or oxygen-carrying-capacity signal appears in the label's adverse-reaction data.

Population evidence

Boska MD, Welch KMA, Schultz L, Nelson JA (2000), Cephalalgia. 18 migraine patients (8 with aura, 10 without), open pre/post design, 6 mg subcutaneous sumatriptan, isometric calf exercise, 31P-MRS. Patients who developed limb/muscle side-effects (10 of 18: heaviness, pressure/tightness, weakness) showed a significant reduction in the initial rate of phosphocreatine recovery versus their own pre-injection baseline (p=0.009), more pronounced in migraine-with-aura patients (p=0.007). Tier B for sumatriptan; Tier C (class extrapolation) for frovatriptan, which was not in the cohort.

Mechanism

The authors explicitly interpreted this as transient regional muscle hypoxia from "minor constriction in arteries or capillaries", the drug's own vasoactive mechanism, not a mitochondrial, ATP-synthesis, or nutrient-related oxygen-carrying defect. Per Hard Rule 2, this entry exists to correctly label that mechanism, not to grade it as a deficiency.

Counter-evidence held on record

This entry exists only to correctly label the triptan class's known vasoconstrictive pharmacodynamics so it is not mistaken for an oxygen-delivery nutrient deficiency. No iron, B12, or oxygen-support supplementation is implied or recommended by this finding.

ATP production, same exercise study, transient and vascular in origin, not demonstrated for frovatriptan

Yellow — Low

See study details

The same 31P-MRS study measured oxidative-phosphorylation (ATP-generating) recovery rate specifically; the reduction was transient and tied to the vasoconstrictive side-effect, not a baseline ATP-synthesis defect, and was never studied for frovatriptan.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow · mechanism clarification

Limits on what this shows

  • Null/negative findings: No reduction in steady-state ATP production was found; only the instantaneous recovery rate immediately after exercise, in the subset with side-effects, was affected, and it normalized during recovery.
  • At-risk subgroups: None established for frovatriptan.
  • Counter-evidence on record: Same pharmacokinetic-exposure caveat as the Oxygen delivery/utilization entry (oral frovatriptan's slower, lower peak vs. subcutaneous sumatriptan).

Regulatory status

No ATP, energy-metabolism, or fatigue-mechanism language appears in the FDA frovatriptan label beyond the generic "fatigue" adverse-reaction listing (5% in trials, cause not attributed to energy metabolism).

Population evidence

Boska et al. (2000), same cohort and protocol as the Oxygen delivery/utilization entry above: 18 migraine patients, 6 mg subcutaneous sumatriptan, 31P-MRS measuring oxidative phosphorylation (Ox Phos), anaerobic glycolysis, and creatine-kinase contributions to ATP production during calf exercise recovery. Tier B for sumatriptan; Tier C (class extrapolation) for frovatriptan, not in the cohort.

Mechanism

Authors attributed the reduced Ox Phos recovery rate to transient regional hypoxia from vasoconstriction rather than a primary defect in mitochondrial ATP-synthesis capacity; steady-state mitochondrial function was preserved.

Counter-evidence held on record

See the Overlap map: this entry shares its entire evidentiary basis with Oxygen delivery/utilization above and must not be counted as independent confirmation of it. No CoQ10, B-vitamin, or other ATP-support supplementation is implied or recommended.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Magnesium / riboflavin (B2) / CoQ10 "depletion" by frovatriptan or triptans

    Where it comes from: Popular headache/migraine-nutraceutical content recommends magnesium, riboflavin, and CoQ10 as migraine-prevention supplements (e.g., American Headache Society nutraceutical guidance; a 2025 narrative review of CoQ10 in migraine therapy). Consumer content sometimes conflates "nutrients studied for migraine" with "nutrients this drug depletes."

    Why it fails: These three nutrients are studied as prophylactic nutraceuticals addressing migraine's own disease-intrinsic pathophysiology (proposed neurovascular and energy-metabolism mechanisms of migraine itself), not as substances frovatriptan's pharmacokinetics remove from the body. Frovatriptan's Step 1 pharmacokinetic profile shows no absorption interference, no hepatic enzyme induction or accelerated catabolism, and no renal-wasting mechanism that would plausibly lower levels of any of the three, and no Tier A, B, or C source (frovatriptan-specific or class-level) was found measuring any effect of frovatriptan on magnesium, riboflavin, or CoQ10 status. This is disease-intrinsic nutraceutical research wearing the drug's name, per Hard Rule 2.

  • Frovatriptan "depletes serotonin" or tryptophan

    Where it comes from: General confusion about serotonergic drugs, amplified by the label's own serotonin-syndrome warning when combined with SSRIs, SNRIs, TCAs, or MAO inhibitors, sometimes miscast online as the drug "using up" the body's serotonin.

    Why it fails: Frovatriptan is a 5-HT1B/1D receptor agonist. Its labeled risk when combined with other serotonergic drugs is serotonin excess (serotonin syndrome: agitation, autonomic instability, neuromuscular aberrations, FDA label, Warnings and Precautions 5.7), the opposite direction from depletion. No Tier A or B evidence shows frovatriptan lowering central or peripheral serotonin or tryptophan status; the drug's own labeled receptor pharmacology runs counter to the claim, per the Hard Rule 4/5 direction check.

How the body handles this medication

Metabolism
CYP1A2 is the principal metabolizing enzyme; frovatriptan is not an inhibitor or inducer of cytochrome P450 enzymes or monoamine oxidase.FDA label, 2018 revision, section 12.3
Elimination route
Mixed, not predominantly renal: 32% of a dose recovered in urine, 62% in feces; renal clearance accounts for roughly 40-45% of total clearance.FDA label, 2018 revision, section 12.3
Absorption
Oral bioavailability ~20% (male), ~30% (female); food delays but does not reduce overall bioavailability; no chelation, antacid, or mineral-binding interaction is documented.FDA label, 2018 revision, section 12.3
Renal impairment
Single-dose pharmacokinetics in renally impaired patients were not different from subjects with normal renal function; no dosage adjustment specified.FDA label, 2018 revision, section 12.3
Hepatic impairment
AUC approximately doubles in mild-to-moderate impairment (no adjustment needed); more than doubles in severe impairment, where caution is advised.FDA label, 2018 revision, sections 8.6 and 12.3
Half-life and exposure
Terminal half-life ~26 hours in both sexes; systemic exposure is roughly 2-fold higher in females than males, and 1.5-2x higher in elderly patients than younger adults.FDA label, 2018 revision, sections 8.5 and 12.3
All references used above
  1. FROVA (frovatriptan succinate) tablets, full prescribing information, 2018 revision (021006s022) — U.S. FDA-approved regulatory label. Sections 5, 6, 8, 12 used for pharmacokinetic basis, warnings, adverse reactions, and special-population data.
  2. DailyMed listing, FROVA / frovatriptan succinate tablet, film coated — Used to cross-confirm label identity, NDC, and generic-manufacturer landscape.
  3. WHO Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index, code N02CC07 — Confirms ATC code N02CC07 = frovatriptan; class N02CC, selective serotonin (5HT1) agonists; DDD 2.5 mg oral.
  4. Boska MD, Welch KMA, Schultz L, Nelson JA. Effects of the anti-migraine drug sumatriptan on muscle energy metabolism: relationship to side-effects. Cephalalgia. 2000. — Human, n=18 migraine patients, open pre/post design, 6 mg subcutaneous sumatriptan, 31P-MRS of calf muscle during isometric exercise and recovery. DOI 10.1046/j.1468-2982.2000.00009.x.Cohort studied sumatriptan only; frovatriptan was not included. Used as Tier C class extrapolation (Oxygen delivery/utilization and ATP production entries) only.
  5. Khalili Fard J, Hamzeiy H, Sattari M, Eghbal MA. Protective roles of N-acetyl cysteine and/or taurine against sumatriptan-induced hepatotoxicity. 2016. — In vitro, isolated rat hepatocytes, concentration-response cytotoxicity assay. Journal of record not independently confirmed beyond a secondary ResearchGate listing accessed for this review; full citation details (journal name, volume, pages) could not be verified before this entry's database channels became rate-limited.Cohort studied sumatriptan only, in vitro; frovatriptan was not included. Used as Tier C class extrapolation (Mitochondrial burden and Oxidative stress entries) only. A follow-up fetch to confirm the parent journal returned HTTP 429 (rate limited) and was not completed.
  6. PubMed search listing, term "frovatriptan mitochondria" — Direct drug-specific search attempt, completed. Result: 0 results ("No results were found").
  7. PubMed search listing, term "frovatriptan copper" — Direct drug-specific search attempt, completed. Result: 0 results ("No results were found").
  8. PubMed search listing, term "frovatriptan iron" — Direct drug-specific search attempt, completed. Result: 0 results ("No results were found").
  9. PubMed search listing, term "frovatriptan oxidative stress" / "frovatriptan antioxidant" — Direct drug-specific search attempts. Could not be completed: repeated HTTP 500 server errors, then HTTP 429 session-level rate limiting at the fetch proxy.Access blocked during this review; genuinely attempted with two phrasings, not completed. Flagged for re-check.
  10. PubMed search listing, term "frovatriptan microbiome" — Direct drug-specific search attempt. Returned a reCAPTCHA/bot-verification challenge page instead of search results.Access blocked by bot-verification during this review, not completed. Flagged as highest-priority re-check (see Gut microbiome risk entry).
  11. PubMed search listing, terms "frovatriptan hematocrit" / "frovatriptan hemoglobin" — Direct drug-specific search attempts, two phrasings.Access blocked during this review by HTTP 429 session-level rate limiting at the fetch proxy before any result page loaded; not completed.
  12. Europe PMC REST API (www.ebi.ac.uk/europepmc/webservices/rest/search), multiple queries for frovatriptan plus mitochondria/oxidative stress/copper/iron/microbiome/ATP — Cross-database check attempted as a second channel per Step 4's thoroughness requirement.Access blocked throughout this review by HTTP 429 at the fetch proxy; no query on this host returned usable results.
  13. Crossref API (api.crossref.org/works), query for frovatriptan plus the seven physiological categories — Cross-database check attempted as a third channel.Access blocked by HTTP 429 at the fetch proxy; not completed.
  14. Semantic Scholar Graph API (api.semanticscholar.org), query for frovatriptan plus mitochondrial/oxidative stress terms — Cross-database check attempted as a fourth channel.Access blocked by HTTP 429 at the fetch proxy; not completed.
  15. NCBI E-utilities esearch (eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi) — Attempted as a structured alternative to the PubMed HTML search listing.Disallowed by the fetch tool's robots.txt handling for this host; not used.
  16. U.S. Pharmacist. Drug-Induced Nutrient Depletions: What Pharmacists Need to Know. — Reviewed for circulating consumer drug-nutrient-depletion claims (Step 6 audit). Covers corticosteroids, anticonvulsants, beta blockers, statins, metformin, oral contraceptives, PPIs, and diuretics; contains no triptan or migraine-medication entry.
  17. Riordan Clinic. Medication-Induced Nutrient Depletion (reference table). — Reviewed for circulating consumer drug-nutrient-depletion claims (Step 6 audit). Contains no triptan, frovatriptan, sumatriptan, or serotonin-receptor-agonist entry.
  18. American Headache Society. Incorporating Nutraceuticals for Migraine Prevention. — Sourced for the disease-intrinsic migraine-nutraceutical context (magnesium, riboflavin, CoQ10) used in the Fails Verification entry; this is migraine-prevention nutraceutical guidance, not a frovatriptan-depletion claim.
  19. Evaluating the Role of Coenzyme Q10 in Migraine Therapy, A Narrative Review. Nutrients (MDPI), 2025. — Same purpose as above: disease-intrinsic CoQ10-migraine nutraceutical context, not a frovatriptan-depletion claim.