Neurologic Disorders and COVID-19: Difference between revisions

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To go to the COVID-19 project topics list, click '''[[COVID-19 Project Topics|here]]'''.
To go to the COVID-19 project topics list, click '''[[COVID-19 Project Topics|here]]'''.
{{COVID-19}}
{{COVID-19}}
{{CMG}} {{AE}}{{Fs}},{{NE}}, {{RAB}}
{{CMG}}; {{AE}};{{Fs}};{{NE}};{{RAB}}
==Overview==
==Overview==


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==== 1. Statin induced myotoxicity ====
==== 1. Statin induced myotoxicity ====


* Myalgia, myopathies, rhabdomyolysis
*[[Myalgia]], [[myopathies]], [[rhabdomyolysis]]


==== 2. 2nd and 3rd degree atrioventricular block ====
==== 2. 2nd and 3rd degree atrioventricular block ====


* Lopinavir/ Ritonavir (Kaltera) (400 mg/100 mg)
*[[Lopinavir]]/ [[Ritonavir]] (Kaltera) (400 mg/100 mg)


==== 3. Prolong QTc interval ====
==== 3. Prolong QTc interval ====


* Chloroquine/Hydroxychloroquine
*[[Chloroquine]]/[[Hydroxychloroquine]]
*Azithromycin
*[[Azithromycin]]


==== 4. Myelotoxicity ====
==== 4. Myelotoxicity ====


* Ribavirin
*[[Ribavirin]]


==== 5. Prolonged PR interval ====
==== 5. Prolonged PR interval ====


* Atazanavir
*[[Atazanavir]]


==== 6. Myelosuppression ====
==== 6. Myelosuppression ====
==COVID-19 Experimental Treatments with Interaction Potential==
===1. [[Remdesivir]] (GS‐5734)===
=====Pharmacokinetics and Dosing:=====


*Adults ≥40 kg: Daily IV dose over 30 min.


==Complications due to medication interaction==
Day 1: 200 mg, Day 2‐10: 100 mg
====1. Statin induced myotoxicity====
 
*Myalgia, myopathies, rhabdomyolysis


====2. 2nd and 3rd degree atrioventricular block====
*Lopinavir/ Ritonavir (Kaltera) (400 mg/100 mg)
====3. Prolong QTc interval====
*Chloroquine/Hydroxychloroquine
====4. Myelotoxicity====
*Ribavirin
====5. Prolonged PR interval====
*Atazanavir
====6. Myelosuppression====
==COVID-19 Experimental Treatments with Interaction Potential==
===1. Remdesivir (GS‐5734)===
=====Pharmacokinetics and Dosing:=====
*Adults ≥40 kg: Daily IV dose over 30 min. Day 1: 200 mg, Day 2‐10: 100 mg
*Paed <40 kg: Daily IV dose over 30 min.  Day 1: 5 mg/kg, Day 2‐10: 2.5 mg/kg
*Paed <40 kg: Daily IV dose over 30 min.  Day 1: 5 mg/kg, Day 2‐10: 2.5 mg/kg


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=====Interaction Potential:=====
=====Interaction Potential:=====


*Inhibits: CYP3A4, OATP1B1/3, BSEP, MRP4 and NTCP
*Inhibits: [[CYP3A4]][[, OATP1B1/3]], [[BSEP]][[, MRP4]], and [[NTCP]]
*Induces: CYP1A2 and CYP2B6
*Induces: [[CYP1A2]] and [[CYP2B6]]
*Unlikely clinically significant (all in vitro data)
*Unlikely clinically significant (all in vitro data)
*Concurrent use with Hydroxychloroquine- decreases antiviral activity of Remdesivir.
*Concurrent use with [[Hydroxychloroquine|hydroxychloroquine-]] decreases the antiviral activity of [[Remdesivir|remdesivir.]]


===2. Lopinavir/ Ritonavir (Kaltera) (400 mg/100 mg)===
===2. [[Lopinavir and Ritonavir|Lopinavir/ Ritonavir (Kaltera)]] (400 mg/100 mg)===
=====Pharmacokinetics and Dosing:=====
=====Pharmacokinetics and Dosing:=====


*400mg/100mg twice daily for 14 days
*400mg/100mg twice daily for 14 days
*Crushing tablet ↓ absorption ≅ 45%133. Use oral liquid (42.4% alcohol and 15.3% propylene glycol)
*Crushing tablet ↓ absorption ≅ 45%133.
*Use compatible feeding tubes (PVC or silicone) Avoid metronidazole and disulfiram
*Use oral liquid (42.4% alcohol and 15.3% propylene glycol)
*Absorbed in jejunum: NG ok; NJ may ↓ effect
*Use compatible feeding tubes (PVC or silicone)
*Avoid [[Metronidazole|metronidazole a]]<nowiki/>nd [[disulfiram]]
*Absorbed in jejunum: [[Nasogastric tube|NG]] ok; NJ may ↓ effect


=====ClinicalTrials.gov Identifier:=====
=====ClinicalTrials.gov Identifier:=====
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=====Interaction Potential:=====
=====Interaction Potential:=====


*Lopinovir extensively metabolised by CYP3A
*[[Lopinavir|Lopinavi]]<nowiki/>r extensively metabolized by [[CYP3A]]
*Inhibitor of: CYP3A4 (potent), P‐gp, BCPR, OATP1B1
*Inhibitor of [[CYP3A4]] (potent), [[P‐gp]], [[BCPR]], and [[OATP1B1]]
**''can increase concentration of drugs metabolised or substrates of these pathways''
**''can increase concentration of drugs metabolized or substrates of these pathways''


*Inducer of: CYP2C9, CYP2C19, glucuronidation
*Inducer of [[CYP2C9]], [[CYP2C19,]] and [[glucuronidation]]


*Can prolong PR interval.
*Can [[PR interval|prolong PR interval.]]
*Rare reports of 2nd and 3rd degree atrioventricular block in patients with underlying risk factors
*Rare reports of [[Second degree AV block|2nd and 3rd-degree atrioventricular block]] in patients with underlying risk factors


===3. Chloroquine/Hydroxychloroquine===
===3. [[Chloroquine|Chloroquin]]<nowiki/>[[Chloroquine|e]]/[[Hydroxychloroquine]]===
=====Pharmacokinetics and Dosing:=====
=====Pharmacokinetics and Dosing:=====


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=====Interaction Potential:=====
=====Interaction Potential:=====


*Metabolised by: CYP2C8, CYP3A4, CYP2D6
*Metabolised by [[CYP2C8]], [[CYP3A4]], [[CYP2D6]]
*Inhibited by: CYP2D6 and P‐gp
*Inhibited by CYP2D6 and P‐gp
*Can prolong QTc interval, consider ECG monitoring where appropriate
*Can [[QT-interval prolongation|prolong QTc interval]], consider [[The electrocardiogram|ECG]] monitoring where appropriate
*Concurrent use of HCQS with antibiotic Azithromycin causes Chest pain, Congestive Heart Failure.
*Concurrent use of [[Hydroxychloroquine|HCQS]] with antibiotic [[azithromycin]] causes [[chest pain]], [[congestive heart failure]].
*Antacids decrease the absorption of Hydroxychloroquine.
*[[Antacids]] decrease the absorption of [[hydroxychloroquine]].
*Neostigmine, Pyridostigmine antagonise the action of Hydroxychloroquine.
*[[Neostigmine]], [[pyridostigmine]] antagonize the action of [[Hydroxychloroquine|hydroxychloroquin]]<nowiki/>e.


===4. Interferon beta===
===4. [[Interferon beta]]===
=====Pharmacokinetics and Dosing:=====
=====Pharmacokinetics and Dosing:=====
=====ClinicalTrials.gov Identifier:=====
=====ClinicalTrials.gov Identifier:=====
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=====Interaction Potential:=====
=====Interaction Potential:=====


*Interferons have been reported to reduce CYP450 drug metabolism
*[[Interferons]] have been reported to reduce [[Cytochrome P450|CYP450]] drug metabolism
*Care with narrow therapeutic index drugs dependent on CYP450 clearance
*Care with narrow [[therapeutic index]] drugs dependent on [[Cytochrome P450|CYP450]] clearance


===5. Ribavirin===
===5. [[Ribavirin]]===
=====Pharmacokinetics and Dosing:=====
=====Pharmacokinetics and Dosing:=====


*Do not crush – known teratogen.
*Do not crush – known [[teratogen]].
*Contact hospital pharmacy for solution compounded from capsules or (SAS) product availability
*Contact hospital pharmacy for solution compounded from capsules or (SAS) product availability


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=====Interaction Potential:=====
=====Interaction Potential:=====


*Not metabolised by CYP450 unlikely to contribute to CYP interactions.
*Not metabolized by [[Cytochrome P450|CYP450]] unlikely to contribute to [[CYP|CYP interactions]].
*Inhibits inosine monophosphate dehydrogenase:
*Inhibits [[IMP dehydrogenase|inosine monophosphate dehydrogenase:]]
*Can interfere with azathioprine metabolism possibly leading to accumulation of 6‐methylthioinosine monophosphate (6‐MTIMP), which has been associated with myelotoxicity
*Can interfere with [[azathioprine]] metabolism possibly leading to accumulation of [[6‐methylthioinosine monophosphate]] [[6-MTIMP|(6‐MTIMP]]), which has been associated with [[myelotoxicity]]


===6. Favipiravir===
===6. [[Favipiravir covid-19|Favipiravir]]===
=====Pharmacokinetics and Dosing:=====
=====Pharmacokinetics and Dosing:=====
=====Chinese Clinical Trials Registry ID:=====
=====Chinese Clinical Trials Registry ID:=====
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=====Interaction Potential:=====
=====Interaction Potential:=====


*Metabolised by: Aldehyde Oxidase in the cytosol of the Liver.
*Metabolised by [[aldehyde oxidase]] in the cytosol of the liver.
*Inhibits:
*Inhibits:
**CYP2C8 ''(strong)''
**[[CYP2C8]] ''(str[[OAT1,|ong)]]''
**OAT1, OAT3 (mod)
**[[OAT1,]] OAT3 (mod)
**CYP1A2 ''(weak)'' , CYP2C9 ''(weak)'' , CYP2C19 ''(weak)'' , CYP2CD6 ''(weak)'' , CYP2E1 ''(weak)'' , CYP3A4 ''(weak)''
**[[CYP 1A2|CYP1A2 ''('']]''weak)'' , [[CYP2C9]] ''(weak)'' , [[CYP2C19]] ''(weak)'' , [[CYP2CD6]] ''(weak)'' , [[CYP2E1]] ''(weak)'' , [[CYP3A4]] ''(weak)''
**Aldehyde Oxidase Inhibitors increase the conc of Favipiravir. The drugs include Selective Estrogen Receptor Modulators(SERMs), H2 receptor antagonists like Cimetidine, Calcium channel blockers, Anti arrythmic drugs like Propafenone, Tricyclic antidepressants.
**[[Aldehyde oxidase|Aldehyde oxidas]]<nowiki/>e Inhibitors increase the concentration of [[Favipiravir covid-19|favipiravir.]] The drugs include [[selective estrogen receptor modulator]]<nowiki/>s([[SERM]]<nowiki/>s), H2 receptor antagonists like [[cimetidine]], [[calcium channel blocker]]<nowiki/>s, [[Anti-arrhythmic medications|anti-arrythmic drugs]] like [[propafenone]], [[Tricyclic antidepressant|tricyclic antidepressants]].<ref name="ObachHuynh2004">{{cite journal|last1=Obach|first1=R. Scott|last2=Huynh|first2=Phuong|last3=Allen|first3=Mary C.|last4=Beedham|first4=Christine|title=Human Liver Aldehyde Oxidase: Inhibition by 239 Drugs|journal=The Journal of Clinical Pharmacology|volume=44|issue=1|year=2004|pages=7–19|issn=00912700|doi=10.1177/0091270003260336}}</ref>


*Low risk QT prolongation
* Low-risk [[QT prolongation]]


===7. Atazanavir===
===7. [[Atazanavir]]===
=====Pharmacokinetics and Dosing:=====
=====Pharmacokinetics and Dosing:=====


*Requires pH <4. Avoid antacids 2 h before and 1 hour after.
*Requires pH <4.  
*Avoid [[antacids]] 2 h before and 1 hour after.
*Food ↑ bioavailability
*Food ↑ bioavailability
*Absorbed in jejunum: NG ok; NJ may ↓ effect
*Absorbed in jejunum: [[Nasogastric intubation|NG]] ok; NJ may ↓ effect


=====ClinicalTrials.gov Identifier:=====
=====ClinicalTrials.gov Identifier:=====
=====Interaction Potential:=====
=====Interaction Potential:=====


*Metabolised by: CYP3A4 (extensively)
*Metabolised by: [[CYP3A4]] (extensively)
*Inhibits: CYP3A4, UGT1A1, OATP1B1 (strong), CYP2C8 (weak)
*Inhibits: [[CYP3A4]], [[UGT1A1]], [[OATP1B1]] (strong), [[CYP2C8]] (weak)
*Absorption depends on low pH; drugs increasing pH will decrease atazanavir concentration
*Absorption depends on [[low pH]]; drugs increasing pH will decrease [[atazanavir]] concentration
*Dose related prolongation in PR interval.
*Dose-related [[PR interval|prolongation in PR interval]].
*Care with drugs increasing QT interval or in patients with pre‐existing risk factors.
*Care with drugs increasing [[QT interval]] or in patients with pre‐existing risk factors.


===8. Nitazoxanide (prodrug) (active metabolite: tizoxanide)===
===8. [[Nitazoxanide]] (prodrug) (active metabolite: [[tizoxanide]])===
=====Pharmacokinetics and Dosing:=====
=====Pharmacokinetics and Dosing:=====


*May be dispersible or crushed– check brand
*Maybe dispersible or crushed– check the brand
*Take with food ‐ increases bioavailability by 50%.
*Take with food ‐ increases bioavailability by 50%.


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=====Interaction Potential:=====
=====Interaction Potential:=====


*Nil effects on CYP450 enzymes
*Nil effects on [[CYP450]] enzymes
*Tizoxanide highly protein bound (>99.9%)
*[[Tizoxanide]] highly [[protein-bound]] (>99.9%)
*Will compete for binding sites; monitor drugs highly protein bound with a narrow therapeutic index (such as  warfarin)
*Will compete for binding sites; monitor drugs highly protein-bound with a narrow [[therapeutic index]] (such as  warfarin)


===9. Tocilizumab (IL‐6 monoclonal antibody)===
===9. [[Tocilizumab]] [[(IL‐6 monoclonal antibody]])===
====Pharmacokinetics and Dosing:====
====Pharmacokinetics and Dosing:====
=====ClinicalTrials.gov Identifier:=====
=====ClinicalTrials.gov Identifier:=====
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*Nil significant drug interactions.
*Nil significant drug interactions.
*COVID‐19 increases IL‐6 expression. Tocilizumab reduces IL‐6 expression. IL‐6 increases CYP3A4, CYP26C19, CYP2C9, CYP1A2. When tocilizumab is used to treat COVID‐19, the effect on drugs effected by these CYP enzymes is unknown.
*COVID‐19 increases IL‐6 expression. [[Tocilizumab]] reduces IL‐6 expression. IL‐6 increases [[CYP 3A4|CYP3A4,]] [[CYP26C19]], [[CYP2C9]], [[CYP1A2]]. When [[tocilizumab]] is used to treat COVID‐19, the effect on drugs affected by these [[CYP]] enzymes is unknown.


=== 10. Dexamthasone ===
=== 10. [[Dexamethasone|Dexamthasone]]===


==== Pharmacokinetics and Dosing: ====
==== Pharmacokinetics and Dosing: ====


* Oral or Intravenous- 6mg/day for 10 days
* Oral or [[Intravenous]]- 6mg/day for 10 days
* Given in patients who are mechanically ventilated.
* Given in patients who are [[Mechanical ventilation|mechanically ventilated.]]


===== Clinical Trial: =====
===== Clinical Trial: =====
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===== Interaction Potential: =====
===== Interaction Potential: =====


* Interacts with many drugs like Oral Contraceptive Pills, Digoxin, Blood thinners ( Clopidogrel, Warfarin, Dabigatran )<br />
* Interacts with many drugs like [[oral contraceptive pills]], [[digoxin]], [[blood thinners]] ( [[clopidogrel]], [[Warfarin|warfarin,]] [[dabigatran]] )
 
=== 11. [[Ivermectin]]: ===
 
* It is not FDA approved for use in SARS-CoV2
 
==== Pharmacokinetics: ====
 
* Metabolised by [[Microsome|liver microsomes]] by [[Cytochrome P450|Cyt P450-3A4]]
 
==== Research Trial: ====
 
* A study by a National Breast Cancer Foundation Fellowship, Australia (ECF-17-007) for KMW and an National Health and Medical Research Council (NHMRC), Australia Senior Prinicple Research Fellow (SPRF) (APP1103050) for DAJ, found Ivermectin to be effective in treating SARs-CoV2.<ref name="pmid32251768">{{cite journal| author=Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM| title=The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. | journal=Antiviral Res | year= 2020 | volume= 178 | issue=  | pages= 104787 | pmid=32251768 | doi=10.1016/j.antiviral.2020.104787 | pmc=7129059 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32251768  }}</ref><ref name="Rizzo2020">{{cite journal|last1=Rizzo|first1=Emanuele|title=Ivermectin, antiviral properties and COVID-19: a possible new mechanism of action|journal=Naunyn-Schmiedeberg's Archives of Pharmacology|volume=393|issue=7|year=2020|pages=1153–1156|issn=0028-1298|doi=10.1007/s00210-020-01902-5}}</ref><br />
 
==== Interactions: ====
 
*[[Ivermectin]] increases the side effects of [[blood thinners]].
 
*[[Grapefruit juice]] increases the concentration of [[Ivermectin|ivermectin.]]
*Avoid or limit [[alcohol]] use in patients taking [[ivermectin]].
 
==References==
==References==
<references />
{{Reflist|2}}
 
{{WH}}
{{WS}}

Latest revision as of 02:28, 11 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ;Fahimeh Shojaei, M.D.;Niloofarsadaat Eshaghhosseiny, MD[2];Rinky Agnes Botleroo, M.B.B.S.

Overview

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Complications in the Central Nervous System

Cerebrovascular Accident/Stroke

  • Hemorrhagic
  • Ischaemic

Acute Encephalitis

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Epileptic Seizures

Encephalopathy

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Complications in the Peripheral Nervous system

Guillain-Barre syndrome

Anosmia

Acute Myelitis

Miller Fischer Sydrome

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Complications due to medication interaction

1. Statin induced myotoxicity

2. 2nd and 3rd degree atrioventricular block

3. Prolong QTc interval

4. Myelotoxicity

5. Prolonged PR interval

6. Myelosuppression

COVID-19 Experimental Treatments with Interaction Potential

1. Remdesivir (GS‐5734)

Pharmacokinetics and Dosing:
  • Adults ≥40 kg: Daily IV dose over 30 min.

Day 1: 200 mg, Day 2‐10: 100 mg

  • Paed <40 kg: Daily IV dose over 30 min. Day 1: 5 mg/kg, Day 2‐10: 2.5 mg/kg
ClinicalTrials.gov Identifier:
  • NCT04302766
  • NCT04292899
Interaction Potential:

2. Lopinavir/ Ritonavir (Kaltera) (400 mg/100 mg)

Pharmacokinetics and Dosing:
  • 400mg/100mg twice daily for 14 days
  • Crushing tablet ↓ absorption ≅ 45%133.
  • Use oral liquid (42.4% alcohol and 15.3% propylene glycol)
  • Use compatible feeding tubes (PVC or silicone)
  • Avoid metronidazole and disulfiram
  • Absorbed in jejunum: NG ok; NJ may ↓ effect
ClinicalTrials.gov Identifier:
  • NCT04276688
Chinese Clinical Trials Registry ID:
  • ChiCTR2000029539
EU Clinical Trials Register ID:
  • 2020‐000936‐23
Interaction Potential:

3. Chloroquine/Hydroxychloroquine

Pharmacokinetics and Dosing:
  • 200 mg three times a day for 10 days
ClinicalTrials.gov Identifier:
  • NCT04261517
Chinese Clinical Trials Registry ID:
  • ChiCTR2000029609
Interaction Potential:

4. Interferon beta

Pharmacokinetics and Dosing:
ClinicalTrials.gov Identifier:
  • NCT04276688
Interaction Potential:

5. Ribavirin

Pharmacokinetics and Dosing:
  • Do not crush – known teratogen.
  • Contact hospital pharmacy for solution compounded from capsules or (SAS) product availability
ClinicalTrials.gov Identifier:
  • NCT04276688
Interaction Potential:

6. Favipiravir

Pharmacokinetics and Dosing:
Chinese Clinical Trials Registry ID:
  • ChiCTR2000029600 (favipiravir plus interferon‐α)
  • ChiCTR2000029544 (favipiravir plus baloxavir marboxil)
Interaction Potential:

7. Atazanavir

Pharmacokinetics and Dosing:
  • Requires pH <4.
  • Avoid antacids 2 h before and 1 hour after.
  • Food ↑ bioavailability
  • Absorbed in jejunum: NG ok; NJ may ↓ effect
ClinicalTrials.gov Identifier:
Interaction Potential:

8. Nitazoxanide (prodrug) (active metabolite: tizoxanide)

Pharmacokinetics and Dosing:
  • Maybe dispersible or crushed– check the brand
  • Take with food ‐ increases bioavailability by 50%.
ClinicalTrials.gov Identifier:
Interaction Potential:

9. Tocilizumab (IL‐6 monoclonal antibody)

Pharmacokinetics and Dosing:

ClinicalTrials.gov Identifier:
  • NCT04310228
  • NCT04306705
Interaction Potential:
  • Nil significant drug interactions.
  • COVID‐19 increases IL‐6 expression. Tocilizumab reduces IL‐6 expression. IL‐6 increases CYP3A4, CYP26C19, CYP2C9, CYP1A2. When tocilizumab is used to treat COVID‐19, the effect on drugs affected by these CYP enzymes is unknown.

10. Dexamthasone

Pharmacokinetics and Dosing:

Clinical Trial:
  • Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial
Interaction Potential:

11. Ivermectin:

  • It is not FDA approved for use in SARS-CoV2

Pharmacokinetics:

Research Trial:

  • A study by a National Breast Cancer Foundation Fellowship, Australia (ECF-17-007) for KMW and an National Health and Medical Research Council (NHMRC), Australia Senior Prinicple Research Fellow (SPRF) (APP1103050) for DAJ, found Ivermectin to be effective in treating SARs-CoV2.[2][3]

Interactions:

References

  1. ↑ Obach, R. Scott; Huynh, Phuong; Allen, Mary C.; Beedham, Christine (2004). "Human Liver Aldehyde Oxidase: Inhibition by 239 Drugs". The Journal of Clinical Pharmacology. 44 (1): 7–19. doi:10.1177/0091270003260336. ISSN 0091-2700.
  2. ↑ Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Res. 178: 104787. doi:10.1016/j.antiviral.2020.104787. PMC 7129059 Check |pmc= value (help). PMID 32251768 Check |pmid= value (help).
  3. ↑ Rizzo, Emanuele (2020). "Ivermectin, antiviral properties and COVID-19: a possible new mechanism of action". Naunyn-Schmiedeberg's Archives of Pharmacology. 393 (7): 1153–1156. doi:10.1007/s00210-020-01902-5. ISSN 0028-1298.

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