DaxibotulinumtoxinA is an injectable acetylcholine release inhibitor and neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity and for the treatment of cervical dystonia in adult patients. DaxibotulinumtoxinA is a 150 kDa botulinum toxin without accessory proteins purified from the bacterium Clostridium botulinum type A. Distant spread of botulinum toxic effects from the site of injection has resulted in symptoms suggestive of systemic botulism (including respiratory compromise and death). In patients who are receiving or have received botulinum toxin products to treat other indications, it is necessary to consider the cumulative dose when using daxibotulinumtoxinA to treat glabellar lines.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: DaxibotulinumtoxinA is NOT interchangeable with other botulinum toxin products. The potency units of daxibotulinumtoxinA are specific to the preparation and assay method utilized; therefore, units of biological activity cannot be compared or converted into units of any other botulinum toxin product assessed with any other specific assay method.
NOTE: In patients who are receiving or have received other botulinum toxin products to treat other indications, it is necessary to consider the cumulative dose when using daxibotulinumtoxinA to treat glabellar lines.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The reconstituted solution is clear to slightly opalescent and colorless. Do not use if the solution is cloudy or discolored or contains flakes or particles.
-Use each vial of reconstituted daxibotulinumtoxinA for 1 session and 1 patient only.
-Administration should be performed by a physician with an understanding of the relevant neuromuscular and orbital anatomy of the involved area and any alterations to the anatomy due to prior surgical procedures or diseases.
Intramuscular Administration
Glabellar lines
Reconstitution/Dilution:
-Reconstitute with preservative-free 0.9% Sodium Chloride Injection.
-Using aseptic technique, withdraw the proper amount of diluent in the appropriate size syringe and slowly inject the diluent into the vial. Discard the daxibotulinumtoxinA vial if a vacuum does not pull the diluent into the vial.
-Reconstitute the 50 unit vial with 0.6 mL to yield a final concentration of 8 units/0.1 mL.
-Reconstitute the 100 unit vial with 1.2 mL to yield a final concentration of 8 units/0.1 mL.
-Gently mix by rotating the vial.
-Storage: Administer within 72 hours after reconstitution. During this time period, store unused reconstituted solution in a refrigerator at 2 to 8 degrees C (36 to 46 degrees F) and protected from light. Do not freeze reconstituted solution. Vials are single-dose only; discard any unused portion.
Administration:
-Draw at least 0.5 mL of the reconstituted toxin into a sterile syringe and expel any air bubbles from the syringe barrel. Replace the needle with a sterile 30- to 33-gauge needle.
-Carefully examine the upper eyelid margin position for separation or weakness of the levator palpebrae superioris muscle. Evaluate the range of upper eyelid excursion while manually immobilizing the frontalis to assess degree of levator function and frontalis compensation.
-Advance the needle through the skin into the underlying muscle while applying finger pressure on the superior medial orbital rim.
-Inject 8 units (0.1 mL) intramuscularly into each of 5 sites [total dose 40 units (0.5 mL)]: 2 injections into medial corrugator and lateral corrugator muscles, respectively and 1 injection into the procerus muscle. Discard any remaining solution.
-To reduce the complication of eyelid ptosis:
--Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes.
-Ensure doses used are accurate and administer in a steady, controlled manner.
-Do not inject toxin closer than 1 centimeter above the superior orbital rim.
-The risk of ptosis may also be mitigated by careful examination for separation or weakness of the levator palpebrae superioris muscles. Evaluate the range of upper eyelid excursion while manually immobilizing the frontalis to assess the degree of levator function and frontalis compensation.
Cervical dystonia
Reconstitution/Dilution:
-Reconstitute with preservative-free 0.9% Sodium Chloride Injection.
-Using aseptic technique, withdraw the proper amount of diluent in the appropriate size syringe and slowly inject the diluent into the vial. Discard the daxibotulinumtoxinA vial if a vacuum does not pull the diluent into the vial.
-Reconstitute the 100 unit vial with 1 mL or 2 mL to yield a final concentration of 10 units/0.1 mL or 5 units/0.1 mL, respectively.
-Gently mix by rotating the vial.
-Storage: Administer within 72 hours after reconstitution. During this time period, store unused reconstituted solution in a refrigerator at 2 to 8 degrees C (36 to 46 degrees F) and protected from light. Do not freeze reconstituted solution. Vials are single-dose only; discard any unused portion.
Postmarketing safety data from other approved botulinum toxins products suggest the potential for toxin effects to be observed beyond the injection site. Symptoms resulting from the distant spread of toxin effects are consistent with the mechanism of botulinum toxin and include asthenia, generalized muscle weakness, effects on vision, dysphagia (2% to 4%), dysphonia, dysarthria, urinary incontinence, and dyspnea. The onset of these adverse events is variable, with symptoms being reported hours to weeks after the injection. In patients receiving botulinum toxin products for unapproved indications, symptoms consistent with the spread of toxin effects have been reported at doses comparable to or lower than the maximum recommended total dose. Toxin-associated dysphagia and dyspnea can be life-threatening. Severe dysphagia may lead to aspiration and may persist for several months. Deaths as a complication of severe dysphagia have been reported. Treatment with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity (respiratory arrest) in patients with respiratory disorders who may have become dependent upon these accessory muscles. Immediate medical attention is required in patients who develop swallowing, speech, or respiratory difficulties.
Ophthalmic symptoms resulting from the distant spread of toxin effects from botulinum toxins include diplopia, blurred vision, and ptosis. In clinical studies, eyelid ptosis was reported in 1% to 2% of people who received daxibotulinumtoxinA compared to 0% of people who received placebo. Xerophthalmia has been reported with the use of botulinum toxins in the treatment of glabellar lines. Ocular problems such as reduced tear production, reduced blinking, and corneal disorders may occur. Consider referring the patient to an ophthalmologist if symptoms of dry eye (e.g., ocular irritation, photophobia, visual impairment) persist; clinicians should be alert that visual impairment may be a symptom of distant spread of toxins.
Serious and/or immediate hypersensitivity reactions have been reported for botulinum toxin products. These reactions include anaphylactoid reactions/anaphylactic shock, serum sickness, urticaria, soft tissue edema, and dyspnea. Discontinue daxibotulinumtoxinA immediately institute appropriate medical therapy if these symptoms occur.
Adverse events involving the cardiovascular system have been reports with the administration of botulinum toxins, including arrhythmia exacerbation and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular disease.
Headache (5% to 9%) and facial paralysis/muscle paralysis (1%), including facial asymmetry have been reported with the use of daxibotulinumtoxinA.
Injection site reaction has been reported in 5% to 9% of patients with the use of daxibotulinumtoxinA. Reactions at the injection site include pain (4%), erythema (2% to 3%), edema (2% to 5%), bruising (1%), hematoma, papule (less than 1%), eyelid ptosis, and pruritus (less than 1%).
Formation of neutralizing antibodies to daxibotulinumtoxinA may reduce the effectiveness of the toxin by inactivating its biological activity. In trials involving 2,786 drug recipients receiving up to 3 treatments with daxibotulinumtoxinA in the phase 3 studies, 12 subjects (0.4%) had preexisting binding antibodies to daxibotulinumtoxinA and 75 subjects (3%) had preexisting binding antibodies to the 35 amino acid peptide excipient RTP004. A total of 20 subjects (0.8%) developed treatment emergent binding antibodies (antibody formation) to daxibotulinumtoxinA and 33 subjects (1.2%) developed treatment emergent binding antibodies to RTP004. No subjects developed neutralizing antibodies to daxibotulinumtoxinA. Detection of the antibodies is highly dependent on the sensitivity and specificity of the assay and may be influenced by assay methodology, sample handling and collection timing, concomitant medications, and underlying diseases.
Muscular weakness or myasthenia (2% to 5%), arthralgia (1% to 2%), and musculoskeletal pain (4%) have been reported during clinical trials for cervical dystonia. Spinal pain (2% to 3%) was also reported.
Nasopharyngitis (2% to 3%), upper respiratory tract infection (2% to 5%) and urinary tract infection (2%) were reported during clinical trials for cervical dystonia.
DaxibotulinumtoxinA is contraindicated in patients with known hypersensitivity to any ingredient in the formulation, hypersensitivity to daxibotulinumtoxinA, or hypersensitivity to any botulinum toxin preparations.
DaxibotulinumtoxinA is contraindicated if an infection is present at the proposed injection sites. Use caution when administering daxibotulinumtoxinA to patients with surgical alterations to the facial anatomy, marked facial asymmetry, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, inflammation at the injection site(s), pre-existing eyelid or eyebrow ptosis, when excessive weakness or atrophy is present in the target muscles, or the inability to substantially lessen glabellar lines even by physically spreading them apart.
Postmarketing safety data from other approved botulinum toxins products suggest the potential for toxin effects to be observed beyond the injection site. Symptoms resulting from the distant spread of toxin effects are consistent with the mechanism of botulinum toxin, and include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, swallowing problems, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. The onset of these adverse events is variable, with symptoms being reported hours to weeks after the injection. In patients receiving botulinum toxin products for unapproved indications, symptoms consistent with the spread of toxin effects have been reported at doses comparable to or lower than the maximum recommended total dose. Toxin-associated swallowing and breathing difficulties can be life-threatening, and there have been reports of patient deaths. Instruct patients to seek immediate medical care if swallowing, speech, or respiratory difficulties develop.
Administration of daxibotulinumtoxinA requires an experienced clinician with an understanding of the relevant anatomy of the involved area (neuromuscular and orbital) and any alterations to the anatomy due to prior surgical procedures or diseases. Health care providers should be aware that the potency units of daxibotulinumtoxinA are specific to the preparation and assay method utilized; therefore, units of biological activity cannot be compared or converted into units of any other botulinum toxin product assessed with any other specific assay method. DaxibotulinumtoxinA is only indicated to treat glabellar lines; use of this toxin to treat any condition other than glabellar lines must be avoided. Patients who have received botulinum toxin injections for unapproved indications have experienced severe and sometimes fatal adverse reactions, including excessive weakness, trouble breathing, and aspiration pneumonia.
Use caution when administering daxibotulinumtoxinA to patients with pre-existing cardiac disease. Treatment with botulinum toxins has been associated with the development of cardiovascular adverse events, including cases of arrhythmia and myocardial infarction, some with fatal outcomes.
Administration of botulinum toxins, including daxibotulinumtoxinA, can result in swallowing or breathing difficulties; these adverse reactions may occur within hours to weeks after receipt of the botulinum toxin. Patients with pre-existing dysphagia or respiratory insufficiency may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection, but swallowing and respiratory difficulties may also result from spread of the toxin effects from a distant injection site. Severe dysphagia may lead to aspiration, which is of particular risk when treating patients in whom swallowing or respiratory function is already compromised. Dysphagia may persist for several months. Deaths as a complication of severe dysphagia have been reported. Treatment with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. Immediate medical attention is required in patients who develop swallowing, speech, or respiratory difficulties.
Use daxibotulinumtoxinA cautiously in patients with peripheral neuromuscular disease, amyotrophic lateral sclerosis (ALS), or neuromuscular junctional disorders (e.g., myasthenia gravis, or Lambert-Eaton syndrome) for increased neuromuscular compromised following treatment. These patients may be at increased risk of clinically significant systemic effects including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise from typical doses of daxibotulinumtoxinA.
As with other botulinum toxin products, administer daxibotulinumtoxinA with caution to patients with a history of surgery in the treatment area as this may alter drug distribution within the injected muscles and thus alter the intended effect. Further, ask all patients if they have any planned surgical procedures. Advise patients to tell their other health care practitioners of this therapy prior to any surgeries.
Caution all patients to avoid driving or operating machinery if they experience a loss of strength, muscle weakness, blurred vision, or drooping eyelids as a result of daxibotulinumtoxinA therapy.
Administer daxibotulinumtoxinA during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no available data for use in pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. When administered intramuscularly (3, 10, and 30 units/kg) to pregnant rats four times during the period of organogenesis (on gestation days 7, 10, 13, and 16) it caused maternal toxicity, reduced fetal skeletal ossification, and reduced fetal body weight at the highest dose (approximately 40 times the maximum recommended human dose [MRHD]). No embryofetal developmental toxicity was noted at doses up to 10 units/kg (15 times the MRHD). Intramuscular administration (0.02, 0.1, 0.48, or 2.4 units/kg) of 13 doses to pregnant rabbits during the period of organogenesis resulted in maternal lethality at 2.4 units/kg/day and a significant reduction in maternal body weight at 0.48 units/kg/day. No embryofetal developmental toxicity was noted at doses up to 0.48 units/kg/day, which is approximately equivalent to the MRHD.
There are no data regarding the presence of daxibotulinumtoxinA in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested or administered drug, health care providers are encouraged to report the adverse effect to the FDA.
DaxibotulinumtoxinA is not interchangeable with other preparations of botulinum toxin products.
For temporary improvement in the appearance of moderate to severe glabellar lines (facial wrinkles) associated with corrugators and/or procerus muscle activity:
Intramuscular dosage:
Adults: 40 units IM administered in 5 equal aliquots of 8 units each: 2 injections in each corrugator muscle and 1 injection in the procerus muscle. Do not administer more frequently than every 3 months.
For the treatment of cervical dystonia:
Intramuscular dosage:
Adults: 125 Units to 250 Units given intramuscularly as a divided dose among affected muscles. In patients previously treated with another botulinum toxin, their past dose, response to treatment, duration of effect, and adverse event history should be taken into consideration when determining the initial dose. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.
Maximum Dosage Limits:
-Adults
Glabellar lines
40 units IM per treatment session; sessions should be no more than every 3 months.
Cervical dystonia
250 units IM per single treatment; no more frequently than every 3 months.
-Geriatric
Glabellar lines
40 units IM per treatment session; sessions should be no more than every 3 months.
Cervical dystonia
250 units IM per single treatment; no more frequently than every 3 months.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Amikacin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Anticholinergics: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Atracurium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Atropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Atropine; Difenoxin: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Baclofen: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Belladonna; Opium: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Benztropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Budesonide; Glycopyrrolate; Formoterol: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Capreomycin: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin.
Capsaicin; Metaxalone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Carisoprodol: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Chlordiazepoxide; Clidinium: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Chlorzoxazone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Cisatracurium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Colistimethate, Colistin, Polymyxin E: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Colistin: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Cyclobenzaprine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Dantrolene: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Dicyclomine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Diphenoxylate; Atropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Flavoxate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Gentamicin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Glycopyrrolate; Formoterol: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Homatropine; Hydrocodone: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Hyoscyamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Indacaterol; Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Metaxalone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Methscopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Neomycin: (Minor) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. However, neomycin oral and topical products are not well absorbed systemically; interactions are not expected.
Neostigmine; Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Neuromuscular blockers: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Orphenadrine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Oxybutynin: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Pancuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Paromomycin: (Minor) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. However, paromomycin is not well absorbed following oral administration; interactions are not expected.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Propantheline: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Rocuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Scopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Skeletal Muscle Relaxants: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Solifenacin: (Moderate) Systemic anticholinergic effects (e.g., blurred vision) may be potentiated if antimuscarinics are administered after administration of botulinum toxins.
Streptomycin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Succinylcholine: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Tobramycin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Trihexyphenidyl: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Trospium: (Moderate) Systemic anticholinergic effects (e.g., blurred vision) may be potentiated if antimuscarinics are administered after administration of botulinum toxins.
Vecuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent. It blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine. When injected into skeletal muscle, daxibotulinumtoxinA is internalized into the nerve terminal, translocates into the neuronal cytosol where it cleaves SNAP25, a protein necessary for synaptic vesicle membrane docking and subsequent release of acetylcholine which produces a dose dependent decrease of muscle function. Recovery of activity is gradual and results from the degradation of neurotoxin light chain in the neurons with a contribution from the formation of axonal sprouts. Muscle reinnervation occurs, leading to a slow reversal of the pharmacological effects of daxibotulinumtoxinA.
DaxibotulinumtoxinA is administered by local intramuscular injection.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intramuscular Route
Using currently available analytical technology, it is not possible to detect daxibotulinumtoxinA in the peripheral blood following intramuscular injection at the recommended dose.