subacute cognitive decline, seizures Signs of elevated intracranial pressure: Dilated pupil(s) Progressive drowsiness Cushing triad (bradycardia, respiratory depression, hypertension) Evaluation Assess airway, breathing, circulation, and disability to initiate supportive care Determine GCS and neurologic deficits (eg, hemiparesis, numbness, speech or vision impairment) Identify exposure to anticoagulant medications (eg, warfarin, DOACs, heparinoids) Obtain emergency imaging (eg, head CT or fast MRI) Laboratory evaluation: Complete blood count, PT, PTT, INR, basic electrolytes, pregnancy test in female of childbearing age Initial serial monitoring: Neurologic examination (hourly) for signs of deterioration Repeat head CT 6 to 8 hours after initial study and for any clinical signs of deterioration Treatment Manage trauma patients according to principles of advanced trauma life support* Perform tracheal intubation for any patient unable to protect their airway, with rapidly deteriorating mental status, or with GCS 8 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 25/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Obtain immediate neurosurgical consultation as indicated by clinical signs or imaging: Hemispheric SDH >10 mm thickness or midline shift >5 mm SDH causing brainstem compression or pupillary abnormalities SDH causing progressive neurologic deterioration (eg, GCS drop 2 points) Reverse anticoagulation (agent specific): Warfarin Reverse with 4-factor PCC and IV vitamin K Dabigatran Reverse with idarucizumab Factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) Reverse with 4-factor PCC or andexanet alfa Heparin (unfractionated) Reverse with protamine sulfate Low molecular weight heparin Reverse with andexanet alfa; protamine sulfate is an alternative Medical management of intracranial pressure: Blood pressure control: Prevent HYPOtension to maintain SBP >100 mmHg: fluid resuscitation with isotonic IV fluids; phenylephrine for refractory symptoms Initial dose 0.5 to 2 mcg/kg per minute IV; maintenance dose 0.25 to 5 mcg/kg per minute Treat HYPERtension: Initial treatment to rapidly reduce SBP to <220 mmHg: nicardipine 5 mg/hour IV, titrate by 2.5 mg/hour every 5 to 15 minutes (maximum dose: 15 mg/hour); alternate: labetalol 20 mg IV bolus, may repeat every 10 minutes Subsequent treatment to reduce SBP to <160 mmHg while monitoring for stability of neurologic status Elevate head of bed >30 degrees Give antipyretics for temperature >38 degrees Celsius (eg, acetaminophen [paracetamol] 325 to 650 mg orally or PR every 4 to 6 hours or 650 mg IV every 4 hours) Repeat imaging (eg, head CT) for signs of new or progressive elevated intracranial pressure: Obtain immediate neurosurgical consultation for surgical indications (refer to above) Osmotic therapy (mannitol or hypertonic saline) or hyperventilation as temporary treatment measures https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 26/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate GCS: Glasgow coma scale; DOAC: direct oral anticoagulant; CT: computed tomography; MRI: magnetic resonance imaging; PT: prothrombin time; PTT: partial thromboplastin time; INR: international normalized ratio; SDH: subdural hematoma; PCC: prothrombin complex concentrate; IV: intravenous; SBP: systolic blood pressure; PR: per rectum. Refer to the UpToDate topics on trauma management in adults. Refer to the UpToDate topics on management of elevated intracranial pressure in adults. Graphic 132691 Version 5.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 27/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Management of acute and symptomatic chronic subdural hematoma SDH: subdural hematoma; CT: computed tomography; EEG: electroencephalogram; MRI: magnetic resonance imaging. For patients with trauma, follow principles of advanced trauma life support. https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 28/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Refer to the UpToDate on reversal of anticoagulation in intracranial hemorrhage for additional details. Glasgow Coma Scale drop 2+ points; worsening of neurologic exam including pupillary abnormalities, cranial nerve palsies, and limb weakness. Includes patients with nontraumatic SDH without cerebral atrophy, coagulopathy, or other risk factors to explain SDH. Refer to the UpToDate topic on the etiology, clinical features, and diagnosis of subdural hematoma in adults for additional details. Graphic 134178 Version 1.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 29/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Glasgow Coma Scale (GCS) Score Eye opening Spontaneous 4 Response to verbal command 3 Response to pain 2 No eye opening 1 Best verbal response Oriented 5 Confused 4 Inappropriate words 3 Incomprehensible sounds 2 No verbal response 1 Best motor response Obeys commands 6 Localizing response to pain 5 Withdrawal response to pain 4 Flexion to pain 3 Extension to pain 2 No motor response 1 Total The GCS is scored between 3 and 15, 3 being the worst and 15 the best. It is composed of three parameters: best eye response (E), best verbal response (V), and best motor response (M). The components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS score of 9. A score of 13 or higher correlates with mild brain injury, a score of 9 to 12 correlates with moderate injury, and a score of 8 or less represents severe brain injury. Graphic 81854 Version 9.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 30/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Emergency reversal of anticoagulation from warfarin for life-threatening hemorrhage in adults: Suggested approaches based upon available resources A. If 4-factor prothrombin complex concentrate (4F PCC) is available (preferred approach): 1. Give 4F PCC* 1500 to 2000 units IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is not 1.5, give additional 4F PCC (refer to topic or drug reference for details). 2. Give vitamin K 10 mg IV over 10 to 20 minutes. B. If 3-factor prothrombin complex concentrate (3F PCC) is available but 4F PCC is not available: 1. Give 3F PCC* 1500 to 2000 units IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is not 1.5, give additional 3F PCC (refer to topic or drug reference for details). 2. Give Factor VIIa 20 mcg/kg IV OR give FFP 2 units IV by rapid infusion. Factor VIIa may be preferred if volume overload is a concern. 3. Give vitamin K 10 mg IV over 10 to 20 minutes. C. If neither 3F PCC nor 4F PCC is available: 1. Give FFP 2 units IV by rapid infusion. Check INR 15 minutes after completion of infusion. If INR 1.5, administer 2 additional units of FFP IV rapid infusion. Repeat process until INR 1.5. May wish to administer loop diuretic between FFP infusions if volume overload is a concern. 2. Give vitamin K 10 mg IV over 10 to 20 minutes. These products and doses are for use in life-threatening bleeding only. Evidence of life-threatening bleeding and over-anticoagulation with a vitamin K antagonist (eg, warfarin) are required. Anaphylaxis and transfusion reactions can occur. It may be reasonable to thaw 4 units of FFP while awaiting the PT/INR. The transfusion service may substitute other plasma products for FFP (eg, Plasma Frozen Within 24 Hours After Phlebotomy [PF24]); these products are considered clinically interchangeable. PCC will reverse anticoagulation within minutes of administration; FFP administration can take hours due to the volume required; vitamin K effect takes 12 to 24 hours, but administration of vitamin K is needed to counteract the long half-life of warfarin. Subsequent monitoring of the PT/INR is needed to guide further therapy. Refer to topics on warfarin reversal in individual situations for further management. PCC: unactivated prothrombin complex concentrate; 4F PCC: PCC containing coagulation factors II, VII, IX, X, protein S and protein C; 3F PCC: PCC containing factors II, IX, and X and only trace factor VII; FFP: fresh frozen plasma; PT: prothrombin time; INR: international normalized ratio; FEIBA: factor eight inhibitor bypassing agent. Before use, check product label to confirm factor types (3 versus 4 factor) and concentration. Activated complexes and single-factor IX products (ie, FEIBA, AlphaNine, Mononine, Immunine, BeneFix) are NOT used for warfarin reversal. https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 31/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate PCC doses shown are those suggested for initial treatment of emergency conditions. Subsequent treatment is based on INR and patient weight if available. Refer to topic and Lexicomp drug reference included with UpToDate for INR-based dosing. Graphic 89478 Version 10.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 32/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Direct oral anticoagulant reversal agents for life-threatening bleeding (imminent risk of death from bleeding) Reversal agent (all are given Anticoagulant intravenously) Dabigatran (Pradaxa; oral thrombin inhibitor) Idarucizumab (Praxbind). Dose: 5 grams* Oral factor Xa inhibitors: Andexanet alfa (AndexXa). Dosing for the initial bolus and subsequent infusion depend Apixaban (Eliquis) on the dose level of the factor Xa inhibitor and Edoxaban (Lixiana, Savaysa) the interval since it was last taken. Rivaroxaban (Xarelto) OR- 4-factor PCC (Kcentra, Beriplex P/N, Octaplex). Dosing can be done with a fixed dose of 2000 units OR a weight-based dose of 25 to 50 units per kg. Reversal agents carry a risk of life-threatening thrombosis and should only be used under the direction of a specialist with expertise in their use and/or in a patient at imminent risk of death from bleeding. In general, a single dose is given; dosing may be repeated in rare situations in which the oral anticoagulant persists for longer in the circulation, such as severe kidney dysfunction. Andexanet dosing is as follows: If the patient took rivaroxaban >10 mg, apixaban >5 mg, or dose unknown within the previous 8 hours: Andexanet 800 mg bolus at 30 mg/minute followed by 960 mg infusion at 8 mg/minute for up to 120 minutes. OR- If the patient took rivaroxaban 10 mg or apixaban 5 mg, or if 8 hours have elapsed since the last dose of a factor Xa inhibitor: Andexanet 400 mg bolus at 30 mg/minute followed by 480 mg infusion at 4 mg/minute for up to 120 minutes. Refer to UpToDate topics on treatment of bleeding in patients receiving a DOAC or perioperative management of patients receiving a DOAC for additional information on administration, risks, and alternative therapies. DOAC: direct oral anticoagulant; PCC: prothrombin complex concentrate; FEIBA: factor eight inhibitor bypassing activity. If idarucizumab is unavailable, an activated PCC (FEIBA, 50 to 80 units per kg intravenously) may be a reasonable alternative. Graphic 112299 Version 9.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 33/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Traumatic subdural hematoma (SDH) CT scan showing a left acute SDH (arrow). SDHs are typically crescent shaped. In this case the SDH is causing significant mass effect and shift of midline structures to the right. CT: computed tomography. Reproduced with permission from: J Claude Hemphill III, MD and Nicholas Phan, MD, FRCSC. Graphic 68102 Version 5.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 34/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Uncal herniation from subdural hematoma Noncontrast head CT shows a large right holohemispheric subdural hematoma on axial (A) and coronal (B) images. Mass effect from hematoma causes a right-to-left midline shift (line) and subfalcine herniation (arrowhead). Axial image through the temporal lobes (C) shows uncal herniation with compression of the cerebral peduncles (arrow). CT: computed tomography. https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 35/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Courtesy of Glenn A Tung, MD, FACR. Graphic 132682 Version 1.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 36/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Symptoms of transient ischemic attacks and the vascular territories involved ICA/MCA VA/BA PCA SVD Visual abnormalities Transient ++++ monocular blindness Hemianopia + +++ Blindness ++ ++ Motor abnormalities Hemiparesis + + ++ Quadriparesis ++++ Single part weakness Face + ++ + Arm/hand +++ + Thigh/leg/foot ++ + + Crossed weakness* ++++ Limb ++ ++ ataxia/weakness Gait ataxia +++ + Sensory abnormalities Hemisensory + ++ ++ Single part sensory Face + ++ + ++ Arm/hand ++ ++ + Thigh/leg/foot + + + + Crossed sensory* ++++ Cognitive abnormalities Aphasia ++++ + Amnesia + +++ Alexia +++ +++ https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 37/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Abulia ++ + + Brainstem and cranial nerve symptoms Dizziness/vertigo + +++ Diplopia ++++ Dysarthria + ++ ++ Dysphagia ++ ++ Tinnitus/hearing loss ++++ ICA: internal carotid arteries; MCA: middle cerebral arteries; VA: vertebral arteries; BA: basilar artery; PCA: posterior cerebral arteries; SVD: small vessel disease. Crossed weakness or crossed sensory refers to one side of the cranial structures and the opposite side limbs and trunk. Graphic 71676 Version 5.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 38/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Pharmacologic properties of antiseizure medications Enzyme or Metabolism and Protein binding Half-lif transporter clearance (%) adults (h induction/inhibition* 20 Brivaracetam Metabolized Inhibits epoxide 9 primarily by CYP- hydroxylase independent hydrolysis (60%) and CYP2C19 (30%) Dose adjustment is needed in hepatic impairment Cannabidiol Hepatic (primarily) and gut by CYP2C19, CYP3A4, UGT1A7, UGT1A9, and UGT2B7 to Inhibits BCRP/ABCG2, BSEP/ABCB11, CYP2C19 (moderate) >94 56 to 61 May increase serum concentration of clobazam and the active metabolite(s) of clobazam active metabolite 7- OH-CBD and then to inactive metabolite 7-COOH-CBD Dose adjustment is needed in moderate to severe hepatic impairment Carbamazepine >90% metabolized by CYPs 3A4 (major) Potent and broad- spectrum inducer of CYP, 75 25 to 65 (init enzyme-ind and 1A2/2C8 (minor) to active (epoxide) UGT-glucuronidation, and P-gp naive patien 8 to 22 (afte and inactive weeks due t induction) metabolites Dose adjustment is needed in severe renal impairment; use is not recommended in moderate or severe hepatic impairment Cenobamate Primarily May increase serum 60 50 to 60 hou metabolized by glucuronidation via concentrations of clobazam, phenobarbital, https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 39/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate UGT2B7 and to a phenytoin, and CYP2C19 lesser extent by substrates UGT2B4, and by oxidation via May decrease serum concentrations of carbamazepine, CYP2E1, CYP2A6, CYP2B6, and to a lamotrigine, and CYP2B6 and CYP3A substrates lesser extent by CYP2C19 and CYP3A4/5 Dose adjustment is needed for hepatic impairment; not recommended for patients with severe hepatic impairment or end-stage renal disease Clobazam >90% metabolized by CYPs 3A4, 2C19, 2B6 and non-CYP transformations to active (N- Inhibits CYP2D6 (weak) 80 to 90 (clobazam, parent drug) 36 to 42 (clo parent drug 70 (N- 71 to 82 (N- desmethylclobazam, active metabolite) desmethylcl active metab desmethylclobazam) and inactive metabolites Active metabolite is primarily metabolized by CYP2C19 Dose adjustment is needed in hepatic impairment Eslicarbazepine Prodrug; <33% of active form Induces CYP3A4 (moderate) <40 13 to 20 (pro in renal undergoes UGT- insufficiency Inhibits CYP2C19 (weak) glucuronidation (including <5% metabolized to oxcarbazepine); 66% is excreted renally as unchanged drug Dose adjustment is needed for renal impairment; not https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 40/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate recommended in patients with severe hepatic impairment Ethosuximide ~80% metabolized by CYP3A4 (major) None <5 40 to 60 and non-CYP transformations to inactive metabolites Felbamate 50% metabolized by CYPs 3A4, 2E1 Increases conversion of carbamazepine to active 25 13 to 22 (pro in renal (minor); ~50% epoxide metabolite; insufficiency renally excreted as unchanged drug mechanism not established Dose adjustment is needed in renal impairment Inhibits CYP2C19 (weak) Gabapentin >95% renally None <5 5 to 7 (prolo excreted as unchanged drug (ie, does not undergo hepatic metabolism) renal insuffi >130 hours anuria) Dose adjustment is needed in renal impairment Lacosamide 40% renally excreted as unchanged drug; 30% metabolized by non-CYP transformations None <15 13 (including methylation) to inactive metabolite Dose adjustment is needed in hepatic and renal impairment Lamotrigine >90% metabolized by UGT- May induce its own metabolism by UGT- 55 12 to 62 glucuronidation and other non-CYP glucuronidation (minor) transformations to inactive metabolites https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 41/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Dose adjustment is needed in moderate to severe renal or hepatic impairment Levetiracetam >65% renally None <10 6 to 8 excreted as unchanged drug; 24% metabolized by non-CYP transformation (including amidase hydrolysis) to inactive metabolites Dose adjustment is needed in renal impairment Oxcarbazepine Prodrug; 70% of Induces CYP3A4 (weak) 40 9 (active me active (MHD) form undergoes UGT- glucuronidation; 30% is renally excreted as unchanged active drug and UGT-glucuronidation but does not induce its own metabolism prolonged in insufficiency Dose adjustment is needed in severe renal impairment Perampanel >70% metabolized Appears to induce 95 105 by CYPs 3A4, 3A5 and non-CYP transformations to metabolism of progestin- containing hormonal contraceptives inactive metabolites Dose adjustment is needed in mild or moderate hepatic impairment Phenobarbital 75% metabolized by Potent and broad- 55 75 to 110 CYPs 2C19, 2C9 (minor) and spectrum inducer of CYP and UGT-glucuronidation glucosidase hydrolysis and 2E1 (minor) to inactive metabolites; 25% https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 42/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate excreted renally as unchanged drug Dose adjustment is needed in severe renal or hepatic impairment Phenytoin >90% metabolized Potent and broad- 90 to 95 9 to >42 (do by CYPs 2C9, 2C19, 3A4 (minor) and spectrum inducer of CYP and UGT-glucuronidation dependent) non-CYP transformations to inactive metabolites; clearance is dose dependent, saturable, and may be subject to genetic polymorphism Dose adjustment is needed in severe renal or hepatic insufficiency; monitoring of free (unbound) concentrations also suggested Pregabalin >95% excreted None <5 6 renally as unchanged drug Dose adjustment is needed in renal impairment Primidone 75% metabolized by CYPs 2C19, 2C9 Potent and broad- spectrum inducer of CYP 0 to 20 10 to 15 (pa 29 to 100 (ac (minor) and 2E1 metabolite) (minor) to active intermediates; ~25% excreted renally as unchanged drug Dose adjustment is needed in moderate and severe renal or hepatic impairment; https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 43/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate close monitoring of plasma levels suggested Rufinamide >90% metabolized by non-CYP Induces CYP3A4 (weak) 35 6 to 10 transformations (hydrolysis) to inactive metabolites Stiripentol Metabolized Inhibits CYP3A4, 99 4.5 to 13 primarily in the liver by CYP450 enzymes CYP2C19, CYP3A4, CYP2C19, P-gp, and BCRP and glucuronidation Tiagabine >90% metabolized None 95 7 to 9 by CYP3A4 and non- CYP transformations to inactive metabolites 2 to 5 (with inducing an medications Topiramate >65% excreted renally as unchanged drug; None 9 to 17 12 to 24 <30% metabolized by non-CYP transformations to inactive metabolites; extent of metabolism is increased ~50% in patients receiving enzyme-inducing antiseizure medications Dose adjustment is needed in moderate and severe renal or hepatic impairment Valproate >95% undergoes None 80 to 95 7 to 16 complex transformations including CYPs 2C9, 2C19, 2A6, UGT- glucuronidation and other non-CYP transformation https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 44/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Dose adjustment is needed in hepatic impairment Vigabatrin >90% excreted renally as None 0 5 to 13 (unre duration of unchanged drug Dose adjustment is needed in renal impairment Zonisamide >65% metabolized None 50 63 by CYPs 3A4, 2C19 (minor) and non- CYP transformations Dose adjustment and/or slower titration is needed in mild renal impairment or hepatic impairment; not recommended in patients with moderate or severe renal impairment CYP: cytochrome P450; MHD: monohydroxy derivative active form of oxcarbazepine; P-gp: membrane P-glycoprotein multidrug resistance transporter; UGT-glucuronidation: metabolism by uridine 5'diphosphate-glucuronyltransferases. The inhibitors and inducers of CYP or UGT drug metabolism and P-gp transporters listed in this table can alter serum concentrations of drugs that are dependent upon these enzymes or transporters for elimination, activation, or bioavailability. Classifications are based on US Food and Drug Administration guidance [4, 5]. Other sources may use a different classification system resulting in some agents being classified differently. Specific interactions should be assessed using a drug interaction program such as Lexicomp interactions included within UpToDate. Highly protein-bound antiseizure medications exhibit altered pharmacokinetics, including greater therapeutic and toxic effects and drug interactions, when given in usual doses to patients with low serum albumin or protein-binding affinity (eg, due to nephrotic syndrome or acidosis). Dose alteration is needed and monitoring of unbound (free) antiseizure medication serum concentrations is suggested. Refer to UpToDate topic for additional information. Inhibitors of epoxide hydroxylase (eg, brivaracetam) can decrease metabolism of phenytoin and active metabolite of carbamazepine; refer to UpToDate topic. Data from: Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. Additional data from: https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 45/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate 1. Bazil CW. Antiepileptic drugs in the 21st century. CNS Spectr 2001; 6:756. 2. Lacerda G, Krummel T, Sabourdy C, et al. Optimizing therapy of seizures in patients with renal or hepatic dysfunction. Neurology 2006; 67:S28. 3. Anderson GD, Hakimian S. Pharmacokinetic of antiepileptic drugs in patients with hepatic or renal impairment. Clin Pharmacokinet 2014; 53:29. 4. US Food and Drug Administration. Clinical drug interaction studies Cytochrome P450 enzyme- and transporter- mediated drug interactions guidance for industry, January 2020. Available at: https://www.fda.gov/regulatory- information/search-fda-guidance-documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and- transporter-mediated-drug-interactions (Accessed on June 5, 2020). 5. US Food & Drug Administration. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug- interactions-table-substrates-inhibitors-and-inducers (Accessed on June 12, 2019). Graphic 60182 Version 35.0 https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 46/47 7/5/23, 12:02 PM Subdural hematoma in adults: Management and prognosis - UpToDate Contributor Disclosures William McBride, MD No relevant financial relationship(s) with ineligible companies to disclose. Jos Biller, MD, FACP, FAAN, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Alejandro A Rabinstein, MD Grant/Research/Clinical Trial Support: Chiesi [Small investigator- initiated project]. Consultant/Advisory Boards: AstraZeneca [Secondary stroke prevention]; Brainomix [AI for stroke diagnostics]; Novo Nordisk [Stroke risk]; Shionogi [Stroke neuroprotection]. Other Financial Interest: Boston Scientific [Adverse event adjudication committee member for stroke risk reduction device in patients with atrial fibrillation]. All of the relevant financial relationships listed have been mitigated. Richard P Goddeau, Jr, DO, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/subdural-hematoma-in-adults-management-and-prognosis/print 47/47