Perampanel

Medically reviewed on Nov 15, 2018

Pronunciation

(per AM pa nel)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Oral:

Fycompa: 0.5 mg/mL (340 mL) [contains sodium benzoate]

Tablet, Oral:

Fycompa: 2 mg, 4 mg, 6 mg, 8 mg

Fycompa: 10 mg, 12 mg [contains fd&c blue #2 aluminum lake]

Brand Names: U.S.

• Fycompa

Pharmacologic Category

• AMPA Glutamate Receptor Antagonist
• Anticonvulsant, Miscellaneous

Pharmacology

The exact mechanism by which perampanel exerts antiseizure activity is not definitively known; it is a noncompetitive antagonist of the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on postsynaptic neurons. Glutamate is a primary excitatory neurotransmitter in the central nervous center causing many neurological disorders from neuronal over excitation.

Absorption

Oral: Rapid and complete; food slows rate of absorption

Metabolism

Extensive via primary oxidation mediated by CYP3A4/5, and to a lesser extent by CYP1A2 and CYP2B6, and sequential glucuronidation

Excretion

Tablet: Feces (48%); urine (22%)

Time to Peak

0.5 to 2.5 hours; delayed ~1 to 3 hours with food

Half-Life Elimination

~105 hours

Protein Binding

~95% to 96%; primarily albumin and alpha₁-acid glycoprotein

Special Populations: Renal Function Impairment

Apparent clearance decreased by 27% in patients with mild renal impairment (CrCl 50 to 80 mL/minute), with a corresponding 37% increase in AUC.

Special Populations: Hepatic Function Impairment

The total (free and protein bound) exposure (AUC_0-inf) of perampanel was 50% greater in mild hepatic impairment and more than doubled (2.55-fold) in moderate hepatic impairment. The AUC_0-inf of free perampanel in mild and moderate hepatic impairment was 1.8-fold and 3.3-fold greater, respectively. The half-life was prolonged in mild impairment (306 vs 125 hours) and moderate impairment (295 vs 139 hours).

Use: Labeled Indications

Partial-onset seizures: Treatment of partial-onset seizures with or without secondarily generalized seizures as adjunct or monotherapy in patients with epilepsy who are ≥4 years of age.

Primary generalized tonic-clonic seizures: Treatment of primary generalized tonic-clonic seizures as adjunct therapy in patients with epilepsy who are ≥12 years of age.

Contraindications

There are no contraindications listed in manufacturer's US labeling.

Canadian labeling: Hypersensitivity to perampanel or any component of the formulation.

Dosing: Adult

Note: Reduce the dosage in patients who experience serious psychiatric or behavioral reactions; discontinue immediately if symptoms are severe or worsening. Tablets and oral suspension may be used interchangeably.

Partial-onset seizures: Oral:

Patients not receiving enzyme-inducing AED regimens: Initial: 2 mg once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Recommended maintenance dose: 8 to 12 mg once daily at bedtime; some patients may respond to 4 mg once daily; 12 mg once daily has resulted in somewhat greater reductions in seizure rates in some patients but with substantial increase in side effects.

Patients receiving enzyme-inducing AED regimens (eg, phenytoin, carbamazepine, oxcarbazepine): Initial: 4 mg once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Maintenance dose has not been established; highest dose used in clinical trials was 12 mg once daily.

Primary generalized tonic-clonic seizures (adjunct): Oral:

Patients not receiving enzyme-inducing AED regimens: Initial: 2 mg once daily at bedtime; may increase dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Recommended maintenance dose: 8 mg once daily at bedtime; if tolerated and further seizure control is needed, may increase up to 12 mg once daily (maximum dose: 12 mg once daily).

Patients receiving enzyme-inducing AED regimens (eg, phenytoin, carbamazepine, oxcarbazepine): Initial 4 mg once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Maintenance dose has not been established; highest dose used in clinical trials was 12 mg once daily.

Dosing: Geriatric

Refer to adult dosing. Increase dose no more frequently than every 2 weeks.

Dosing: Pediatric

Note: Reduce the dosage in patients who experience serious psychiatric or behavioral reactions; discontinue immediately if symptoms are severe or worsening. Tablets and oral suspension may be used interchangeably.

Partial-onset seizures: Children ≥4 years and Adolescents: Refer to adult dosing.

Primary generalized tonic-clonic seizures (adjunct): Children ≥12 years and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl 30 to 49 mL/minute: No dosage adjustment necessary; monitor closely and consider slower titration based on response and tolerability.

CrCl <30 mL/minute: Use not recommended (has not been studied).

Hemodialysis: Use not recommended (has not been studied).

Dosing: Hepatic Impairment

Mild impairment (Child-Pugh class A): Initial 2 mg once daily; may increase daily dose by 2 mg once daily no more frequently than every 2 weeks based on response and tolerability. Maximum: 6 mg once daily

Moderate impairment (Child-Pugh class B): Initial 2 mg once daily; may increase daily dose by 2 mg once daily no more frequently than every 2 weeks based on response and tolerability. Maximum: 4 mg once daily

Severe impairment (Child-Pugh class C): Use not recommended (has not been studied)

Administration

Tablets: Administer at bedtime without regard to food.

Oral suspension: Shake well before every administration. Use a calibrated measuring device to measure dose (a household teaspoon or tablespoon is not an adequate measuring device). Insert the provided adapter firmly into the neck of the bottle prior to use; adapter should remain in place for the duration of use. Insert the dosing syringe into the adapter and withdraw the dose from the inverted bottle. The cap should be replaced after each use; the cap fits properly when the adapter is in place.

Storage

Tablets: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Oral suspension: Do not store above 30°C (86°F). Do not freeze. Use within 90 days after first opening the bottle.

Drug Interactions

Alcohol (Ethyl): Perampanel may enhance the CNS depressant effect of Alcohol (Ethyl). Alcohol may also worsen the negative behavioral and psychiatric effects of Perampanel. Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used with carbamazepine. Patients receiving this combination should be followed closely for response, especially with any changes to carbamazepine therapy. Consider therapy modification

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: Perampanel may enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosphenytoin: May decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used with phenytoin/fosphenytoin. Patients receiving this combination should be followed closely for response, especially with any changes to phenytoin/fosphenytoin therapy. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

OXcarbazepine: Perampanel may increase the serum concentration of OXcarbazepine. OXcarbazepine may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used with oxcarbazepine. Patients receiving this combination should be followed closely for response, especially with any changes to oxcarbazepine therapy. Consider therapy modification

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Phenytoin: May decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used with phenytoin/fosphenytoin. Patients receiving this combination should be followed closely for response, especially with any changes to phenytoin/fosphenytoin therapy. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Progestins (Contraceptive): Perampanel may decrease the serum concentration of Progestins (Contraceptive). Management: Patients should use an alternative, nonhormonal-based form of contraception both during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

Many adverse effects are dose-related. Frequency not always defined.

Cardiovascular: Peripheral edema (2%)

Central nervous system: Dizziness (16% to ≤47%), vertigo (3% to ≤47%), hostility (≤12% to ≤20%), aggressive behavior (2% to ≤20%), drowsiness (9% to 18%), abnormal gait (4% to 16%), fatigue (8% to 15%), headache (12% to 13%), irritability (2% to 12%), falling (5% to 10%), ataxia (≤8%), equilibrium disturbance (3% to 5%), anxiety (2% to 5%), dysarthria (1% to 4%), hypoesthesia (3%), hypersomnia (1% to 3%), anger (1% to 3%), memory impaired (2%), paresthesia (2%), confusion (1% to 2%), euphoria (≤2%), mood changes (1% to 2%), agitation, altered mental status, delusion, disorientation, emotional lability, homicidal ideation, paranoia, psychiatric disturbance (worsening)

Dermatologic: Skin rash (4%)

Endocrine & metabolic: Weight gain (4% to 9%), hyponatremia (2%)

Gastrointestinal: Vomiting (4% to 9%), nausea (6% to 8%), abdominal pain (5%), constipation (3%)

Genitourinary: Urinary tract infection (4%)

Hematologic & oncologic: Bruise (2% to 6%)

Neuromuscular & skeletal: Back pain (5%), sprain (4%), myalgia (3%), arthralgia (2% to 3%), limb pain (2% to 3%), musculoskeletal pain (2%), weakness (2%)

Ophthalmic: Blurred vision (3% to 4%), diplopia (3%)

Respiratory: Cough (4%), upper respiratory tract infection (4%), oropharyngeal pain (2%)

Miscellaneous: Head trauma (3%), laceration (2%), limb injury (1% to 2%)

<1%, postmarketing, and/or case reports: Acute psychosis, delirium, DRESS syndrome, hallucination, increased serum triglycerides, suicidal ideation

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: Dizziness, fatigue (including lethargy and weakness), gait disturbances (including abnormal coordination, ataxia, and balance disorder), and somnolence may occur during therapy; patients should be cautioned about performing tasks that require alertness (eg, operating machinery, driving).

• Multiorgan hypersensitivity reactions: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including perampanel. Symptoms may include fever, rash, lymphadenopathy, eosinophilia, and/or facial swelling, in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems. Early symptoms of hypersensitivity reactions (eg, fever, lymphadenopathy) may occur without rash; discontinuation and conversion to alternate therapy may be required.

• Neuropsychiatric disorders: [US Boxed Warning]: Dose-related serious or life-threatening neuropsychiatric events (including aggression, anger, homicidal ideation and threats, hostility, and irritability) have been reported most often occurring in first 6 weeks of therapy in patients with or without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression; monitor patients closely especially during dosage adjustments and when receiving higher doses. Adjust dose or immediately discontinue use if severe or worsening symptoms occur; permanently discontinue for persistent severe or worsening psychiatric symptoms or behaviors. Inform patients and caregivers to contact their healthcare provider immediately if they experience any atypical behavioral and/or mood changes while taking perampanel or after discontinuing perampanel. Concurrent use with alcohol has been associated with significantly worsened mood and increased anger; patients should avoid the use of alcohol during therapy.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.

Disease-related concerns:

• Hepatic impairment: Not recommended for use in patients with severe impairment; dosage adjustment recommended for mild to moderate hepatic impairment.

• Renal impairment: Not recommended for use in patients with severe impairment or on hemodialysis; use caution in patients with moderate impairment and consider slower titration.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use caution in elderly patients due to increased risk of dizziness, gait or coordination disturbances, somnolence, fatigue-related events, and falls; proceed slowly with dosing titration in patients ≥65 years of age.

• Fall risk: Use with extreme caution in patients who are at risk of falls; use has been associated with falls and traumatic injury (including head injuries and bone fracture).

Dosage forms specific issues:

• Lactose: Formulation may contain lactose.

Other warnings/precautions:

• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually (≥1 week) to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Monitoring Parameters

Seizure frequency/duration; suicidality (eg, suicidal thoughts, depression, behavioral changes) during therapy and for at least 1 month after discontinuation; weight

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies at doses equivalent to the human dose (based on BSA). Contraceptives containing levonorgestrel may be less effective; additional nonhormonal forms of contraception are recommended during perampanel therapy and for 1 month after discontinuation of therapy.

Patients exposed to perampanel during pregnancy are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, nausea, vomiting, abdominal pain, bruising, fatigue, loss of strength and energy, back pain, or weight gain. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), thoughts of homicide, shortness of breath, excessive weight gain, swelling of arms or legs, angina, urinary retention, change in amount of urine passed, irritability, agitation, mood changes, panic attacks, fury, anger, confusion, swollen glands, hallucinations, memory impairment, change in balance, severe dizziness, seizures, passing out, or abnormal gait (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

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