Serious and life-threatening peripheral ischemia have been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.
Note: Safety: Do not use within 24 hours of triptans or another ergotamine preparation. Screen patients for risk factors for coronary artery disease (CAD); perform a cardiovascular evaluation in patients with CAD risk factors being initiated on dihydroergotamine injection or nasal spray (0.5 mg per spray). Perform cardiovascular evaluation regardless of CAD risk factors in patients initiated on nasal spray (0.725 mg per spray). If evaluation reveals coronary artery vasospasm or myocardial ischemia, do not initiate therapy. If evaluation does not reveal coronary artery or ischemic myocardial disease, administer the first dose in an adequately equipped facility, unless the patient has previously received dihydroergotamine without cardiovascular complications. Obtain an ECG immediately following the first dose in patients with CAD risk factors. Limit use to <10 days per month to avoid medication-overuse headache (AHS [Ailani 2021]).
Cluster headache:
IM/SUBQ: 1 mg as a single dose; may repeat hourly as needed. Maximum: 3 mg per 24 hours, 6 mg/week.
IV: 1 mg as a single dose; may repeat hourly as needed. Maximum: 2 mg per 24 hours; 6 mg/week.
Medication-overuse headache or intractable migraine/status migrainosus (alternative agent) (off-label use):
Note: For medication-overuse headache, use in inpatient setting when patients are unlikely to be successful with discontinuing the overused medication along with rescue therapy and preventive therapy (Garza 2022). Premedicate with metoclopramide for nausea; during therapy, administer metoclopramide as needed for nausea, diphenoxylate with atropine as needed for diarrhea, and benztropine as needed for akathisia or dystonic reactions (Ford 1997; Raskin 1990). Dosing regimens may vary based on institutional protocols.
Intermittent infusion (Raskin protocol): IV: Initial: 0.5 mg; subsequent dosing is titrated based on response and tolerability (range: 0.2 to 1 mg) every 8 hours for up to 7 days. Most patients will be headache free within 3 days. If headache persists without nausea following initial dose, a second dose of 0.5 mg may be given in 1 hour (Ford 1997; Raskin 1986; Raskin 1990).
Continuous infusion (Ford protocol): IV: 3 mg in 1 L of NS at 42 mL/hour for up to 7 days. Most patients will be headache free within 3 days. If significant nausea persists, decrease rate to 21 to 30 mL/hour (Ford 1997).
Migraine, moderate to severe, acute treatment (alternative agent):
Note: Administration early in the course of a migraine attack, at the first sign of pain, may improve response to treatment (AHS [Ailani 2021]).
IM: 1 mg as a single dose; may repeat hourly as needed. Maximum: 3 mg per 24 hours, 6 mg/week.
IV: 1 mg as a single dose; may repeat hourly as needed. Maximum: 2 mg per 24 hours; 6 mg/week.
Intranasal:
0.5 mg per spray: 1 spray (0.5 mg) into each nostril; repeat after 15 minutes (total of 4 sprays per dose). Maximum: 4 sprays (1 dose) per 24 hours; safety of doses >8 sprays (2 doses)/week has not been established (Gallagher 1996; manufacturer's labeling).
0.725 mg per spray: 1 spray (0.725 mg) into each nostril (total of 2 sprays per dose); may repeat as needed after ≥1 hour for a total of 4 sprays (2 doses). Maximum: 4 sprays (2 doses) per 24 hours; 6 sprays (3 doses) per 7 days (Smith 2021; manufacturer's labeling).
SUBQ: 1 mg as a single dose; if symptoms persist, may repeat dose after ≥2 hours. Maximum: 3 mg per 24 hours, 6 mg/week (Winner 1996; manufacturer's labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Severe impairment: Use is contraindicated.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Severe impairment: Use is contraindicated.
(For additional information see "Dihydroergotamine: Pediatric drug information")
Migraine, intractable (>72 hours) (status migrainosus): Limited data available; optimal dose not established:
IV: Premedicate with antiemetic (metoclopramide or prochlorperazine have been used)
Low-dose regimen: Note: Improvement usually seen after 5 doses; some experts recommend administering 1 additional dose after headache subsides. If no improvement noted after 5 doses, discontinue therapy (Linder 1994; O'Brien 2010).
Children 6 to <10 years: 0.1 mg/dose every 6 hours; continue therapy until headache-free up to a maximum of 8 doses per episode (Linder 1994).
Children 10 to 12 years: 0.15 mg/dose every 6 hours; continue therapy until headache-free up to a maximum of 8 doses per episode.
Adolescents ≤16 years: 0.2 mg/dose every 6 hours; continue therapy until headache-free up to a maximum of 8 doses per episode.
High-dose regimen: Note: Improvement usually seen after 5 doses; some experts recommend administering 1 additional dose after headache subsides. If no improvement after 5 doses, discontinue therapy. Some experts recommend using an initial test dose (half of the appropriate dose for age and weight); if test dose tolerated, remainder of dose administered 30 minutes later (Kabbouche 2009).
Children 6 to 9 years or Children ≥10 years who weigh <25 kg: 0.5 mg/dose every 8 hours; if improvement noted, continue therapy until headache-free up to a maximum of 15 doses per episode (Kabbouche 2009; Kabbouche 2015; Kacperski 2016; O'Brien 2010).
Children ≥10 years weighing >25 kg and Adolescents: 1 mg/dose every 8 hours; if improvement noted, continue therapy until headache-free up to a maximum of 15 doses per episode (Kabbouche 2009; Kabbouche 2015; Kacperski 2016; O'Brien 2010).
Intranasal: Limited data available: Adolescents: 1 spray (0.5 mg) into each nostril (total dose: 1 mg) (Kliegman 2016); adult data suggests that dose should be repeated after 15 minutes for a total of 4 sprays (2 mg); maximum daily dose: 6 sprays (3 mg)/24-hour period; Note: Do not exceed 8 sprays (4 mg)/week.
Contraindicated in severe renal impairment
Dosage reductions are most likely necessary but specific guidelines are not available; contraindicated in severe hepatic dysfunction
Refer to adult dosing; use with caution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Aerosol Solution, Nasal, as mesylate:
Trudhesa: 0.725 mg/actuation (1 mL)
Solution, Injection, as mesylate:
D.H.E. 45: 1 mg/mL (1 mL [DSC]) [contains alcohol, usp]
Generic: 1 mg/mL (1 mL)
Solution, Nasal, as mesylate:
Migranal: 4 mg/mL (1 mL)
Generic: 4 mg/mL (1 mL)
May be product dependent
Migranal nasal solution contains caffeine 10 mg/mL
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as mesylate:
Generic: 1 mg/mL (1 mL)
Solution, Nasal, as mesylate:
Migranal: 4 mg/mL (1 mL)
Trudhesa nasal spray is available exclusively through Trudhesa Direct via Phil and Carepoint Pharmacy. Further information is available at https://www.trudhesahcp.com/how-to-prescribe/.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Trudhesa: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213436s000lbl.pdf#page=22
Intranasal:
0.5 mg per spray: Assemble nasal sprayer immediately prior to use. Lift tab on vial to bend back blue cover; remove the blue cover and metal seal in a circular motion. Keeping the vial upright, remove rubber stopper and set vial aside. Remove plastic cover from bottom of nasal spray pump unit; screw spray pump onto vial until secure. Remove cap from spray unit, hold vial upright with nasal sprayer pointed away from face, and prime by pumping 4 times. Spray once into each nostril. Do not tilt head back or sniff through nose while spraying or immediately after. Wait 15 minutes and spray once again into each nostril. Dispose nasal spray pump with vial; do not reuse.
0.725 mg per spray: Assemble nasal sprayer immediately prior to use. Flip up blue plastic vial cover; use vial cover to peel metal foil from gray rubber stopper in circular motion. Metal foil may come off in 2 or more pieces; remove all metal foil. Remove rubber stopper and set vial aside. Holding nasal spray device upright, remove clear plastic cover from base; push glass vial onto bottom of nasal spray device and screw vial onto spray device until secure. Hold assembled nasal sprayer device upright with sprayer pointed away from face; while pressing finger grips down, prime by pressing glass vial up 4 times. Keeping head straight, spray once into each nostril. Dispose nasal spray pump with vial; do not reuse.
IV:
Continuous infusion (Ford protocol): Administer as a continuous infusion; refer to indication-specific infusion rates in dosing for detailed recommendations (Ford 1997).
Intermittent infusion (Raskin protocol): Administer slowly over 2 to 3 minutes (Raskin 1986; Raskin 1990).
IV: Children ≥6 years and Adolescents: Administer without dilution slowly over 2 to 3 minutes
Intranasal: Adolescents: Prior to administration, the nasal spray applicator must be primed (pumped 4 times); in order to let the drug be absorbed through the skin in the nose, avoid deep inhalation through the nose while spraying or immediately after spraying; do not tilt head back. For best results, treatment should be initiated at the first symptom or sign of an attack; however, nasal spray can be used at any stage of a migraine attack. For further information, consult manufacturer labeling.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Dihydroergotamine may cause teratogenicity, reproductive toxicity and has a structural or toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
Assess risk to determine appropriate containment strategy (USP-NF 2017). NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and (when dosage form allows) closed system transfer devices (CSTDs) for preparation. Double gloves and a protective gown are required during IM, IV or SubQ administration. NIOSH recommends double gloving, a protective gown, and (if liquid that could splash) eye/face protection for administration of a topical product; if there is potential for inhalation, respiratory protection is recommended (NIOSH 2016).
Cluster headaches (injection): Acute treatment of cluster headaches.
Migraine, moderate to severe, acute treatment (nasal spray; injection): Acute treatment of migraine headaches with or without aura (AHS [Ailani 2021]; Worthington 2013).
Limitations of use: Not intended for the prophylactic therapy of migraine or for the management of hemiplegic migraine or migraine with brainstem aura (basilar migraine).
Medication-overuse headache or intractable migraine/status migrainosus; Orthostatic hypotension; Pelvic congestion with pain
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for nasal spray in adults unless otherwise indicated.
>10%:
Local: Local irritation (30% to 52%; including altered sense of smell, burning sensation of the nose, dry nose, epistaxis, nasal cavity pain, nasal congestion, nasal discomfort, nasal mucosa irritation, nasal sore, nasopharyngitis, otalgia, rhinorrhea, sinus discomfort, sinusitis)
Respiratory: Rhinitis (26%)
1% to 10%:
Endocrine & metabolic: Hot flash (1%)
Gastrointestinal: Diarrhea (injection, intranasal: ≤2%), dysgeusia (8%), nausea (10%), vomiting (4%)
Local: Application-site reaction (6%)
Nervous system: Asthenia (1%), dizziness (injection, intranasal: ≤4%), drowsiness (3%), paresthesia (injection, intranasal: ≤2%)
Neuromuscular & skeletal: Stiffness (1%)
Respiratory: Pharyngitis (3%)
Frequency not defined:
Cardiovascular: Hypotension
Hypersensitivity: Facial edema, hypersensitivity reaction
Nervous system: Depression
Postmarketing (any formulation):
Cardiovascular: Acute myocardial infarction, coronary artery vasospasm, flushing, hypertension, ischemic heart disease, peripheral ischemia, vasospasm, ventricular fibrillation, ventricular tachycardia
Dermatologic: Diaphoresis, skin rash
Gastrointestinal: Colonic ischemia
Genitourinary: Retroperitoneal fibrosis (prolonged use)
Nervous system: Anxiety, cerebral hemorrhage, cerebrovascular accident, headache, subarachnoid hemorrhage
Respiratory: Dyspnea, fibrothorax (prolonged use)
Hypersensitivity to dihydroergotamine, ergot alkaloids, or any component of the formulation; uncontrolled hypertension, ischemic heart disease, angina pectoris, history of MI, silent ischemia, or coronary artery vasospasm including Prinzmetal angina; peripheral vascular disease; sepsis; severe hepatic or renal dysfunction; following vascular surgery; avoid use within 24 hours of 5-hydroxytryptamine-1 (5-HT1) receptor agonists (triptans), other serotonin agonists, or ergotamine-containing or ergot-like agents; concurrent use of peripheral and central vasoconstrictors; concurrent use of potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); pregnancy, breastfeeding.
Injection, nasal spray (0.5 mg per spray): Additional contraindications: Hemiplegic migraine or migraine with brainstem aura (basilar migraine).
Concerns related to adverse effects:
• Cardiac valvular fibrosis: Dihydroergotamine has been associated with cardiac valvular fibrosis; usually associated with long-term, frequent use or in combination with other medications associated with cardiac valvular fibrosis.
• Cardiovascular effects: Adverse cardiac events, including acute myocardial infarction, life-threatening disturbance of cardiac rhythm, and death have been rarely reported following use of dihydroergotamine. May cause vasospastic reactions associated with symptoms of muscle pains, numbness, coldness, pallor, and cyanosis of the digits; myocardial, colonic, and peripheral vascular ischemia have been reported. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. Evaluate patients who experience signs or symptoms suggestive of angina following administration for the presence of coronary artery disease (CAD) or a predisposition to variant angina before receiving additional doses. Similarly, evaluate patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud syndrome. Discontinue therapy if patients develop symptoms of vasoconstriction. Significant hypertension has been reported (rarely) in patient with and without a history of hypertension.
• Cerebrovascular events: Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred (in some cases resulted in fatalities) following use of dihydroergotamine. Discontinue therapy if a cerebrovascular event is suspected.
• Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use.
Disease-related concerns:
• Cardiovascular disease: Screen patients for risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, postmenopausal patients, males who are >40 years of age) prior to initiation of therapy; perform a cardiovascular evaluation in patients with CAD risk factors being initiated on dihydroergotamine injection or 0.5 mg/spray nasal spray. Perform cardiovascular evaluation regardless of CAD risk factors in patients initiated on 0.725 mg/spray nasal spray. If evaluation reveals coronary artery vasospasm or myocardial ischemia, do not initiate therapy. If evaluation does not reveal coronary artery disease, ischemic myocardial disease, or other significant cardiovascular disease, administer the first dose in an adequately equipped facility unless the patient has previously received dihydroergotamine without cardiovascular complications. ECG monitoring is recommended in patients with CAD risk factors.
Dosage form specific issues:
• Nasal spray: Local irritation to nose and throat (usually transient and mild to moderate in severity) can occur; long-term consequences on nasal or respiratory mucosa have not been extensively evaluated (Smith 2021; manufacturer's labeling).
Other warnings and precautions:
• Appropriate use: Exacerbation of headache may occur with the overuse (≥10 days per month) of acute migraine drugs; may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Patients may require detoxification and treatment of withdrawal symptoms.
May cause nausea; in pediatric patients, antiemetic prophylaxis (prochlorperazine or metoclopramide) 30 minutes prior to initial dihydroergotamine dose has been used (O'Brien 2010).
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-/Beta-Agonists: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination
Alpha1-Agonists: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may enhance the vasoconstricting effect of Alpha1-Agonists. Risk X: Avoid combination
Aprepitant: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Bromocriptine: Ergot Derivatives may enhance the adverse/toxic effect of Bromocriptine. Risk X: Avoid combination
Chloroprocaine (Systemic): May enhance the hypertensive effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Delavirdine: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Erythromycin (Systemic): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fosamprenavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Lenacapavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Letermovir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Lisuride: May enhance the adverse/toxic effect of Ergot Derivatives. Risk X: Avoid combination
Lorcaserin (Withdrawn From US Market): May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin (Withdrawn From US Market) may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Risk X: Avoid combination
Methysergide: Ergot Derivatives may enhance the vasoconstricting effect of Methysergide. Risk X: Avoid combination
Nefazodone: May enhance the serotonergic effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Nitroglycerin: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may diminish the vasodilatory effect of Nitroglycerin. Nitroglycerin may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Management: Avoid the use of ergot derivatives in patients receiving nitroglycerin for angina (or in any angina patient) if possible. If combined, monitor for decreased effects of nitroglycerin and increased adverse effects of the ergot derivative (eg, ergotism). Risk D: Consider therapy modification
Pergolide: May enhance the adverse/toxic effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Reboxetine: May enhance the hypertensive effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Roxithromycin: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Serotonergic Agents (High Risk): Ergot Derivatives may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Tipranavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Dihydroergotamine is oxytocic and should not be used during pregnancy.
Ergot derivatives inhibit prolactin and it is known that ergotamine is excreted in breast milk (vomiting, diarrhea, weak pulse, and unstable BP have been reported in breastfeeding infants). It is not known if dihydroergotamine would also cause these effects; however, it is likely that it is excreted in human breast milk. Do not use in patients who are breastfeeding.
Injection, nasal spray (0.5 mg per spray): Cardiovascular evaluation in patients with coronary artery disease (CAD) risk factors (prior to initiation); ECG (immediately following first dose in patients with CAD risk factors).
Nasal spray (0.725 mg per spray): Cardiovascular evaluation (prior to initiation); ECG (immediately following first dose in patients with CAD risk factors).
Efficacy in migraine is attributed to the activation of 5-HT1D receptors located on intracranial blood vessels resulting in vasoconstriction and/or activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system resulting in the inhibition of pro-inflammatory neuropeptide release. Dihydroergotamine binds with high affinity to serotonin 5-HT1Dα, 5-HT1Dβ, 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α1 receptors, and dopamine D2L and D3 receptors. Dihydroergotamine also possesses oxytocic properties.
Distribution: Vd: ~800 L.
Protein binding: 93%.
Metabolism: Extensively hepatic (one active metabolite, 8'-β-hydroxydihydroergotamine).
Bioavailability: IM, IV: 100%; Intranasal: 40% (Saper 2006).
Half-life elimination: IM, IV, Intranasal (0.5 mg per spray): ~9 to 10 hours; Intranasal (0.725 mg per spray): 12 hours.
Time to peak, serum: IM: 24 minutes; IV: 1 to 2 minutes; Intranasal: 30 to 60 minutes (Saper 2006; manufacturer’s labeling); SUBQ 15 to 45 minutes (Schran 1985).
Excretion: Primarily feces; urine (6% to 7% as unchanged drug).
Aerosol solution (Trudhesa Nasal)
0.725 mg/ACT (per mL): $267.75
Solution (Dihydroergotamine Mesylate Injection)
1 mg/mL (per mL): $82.88 - $199.33
Solution (Dihydroergotamine Mesylate Nasal)
4 mg/mL (per mL): $65.99 - $514.03
Solution (Migranal Nasal)
4 mg/mL (per mL): $573.44
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