Newsletter – January 2015   Chronic  Cough  in  Adults     Written  by:  Brent  Springer  –  ISU  Pharm  D  Candidate  2016  

Idaho Drug Information Center Idaho State University 921 S. 8th Ave, Stop 8092 Pocatello, ID 83209-8092 208-282-4689 [email protected] Rebecca Hoover, PharmD, MBA, Director, [email protected] Ryan Jensen, PharmD Candidate 2016, Founding Editor

  Coughing  is  an  important  defense  mechanism  to  remove   harmful  or  unwanted  material  from  the  upper  respiratory   tract.  A  normal,  relatively  healthy,  cough  should  resolve  in  a   few  weeks,  but  when  it  doesn’t  coughing  can  cause  a  number   of  harmful  complications.  Chronic  cough  is  defined  as  a  cough   lasting  continuously  for  eight  weeks  or  more.  1,2,3  Identifying   the  cause  of  a  chronic  cough  can  be  more  difficult  than  acute   coughs  which  are  often  associated  with  the  common  cold  or   seasonal  allergies.  Since  pharmacists  are  one  of  the  most   readily  accessible  professionals  within  the  health  care  system,   understanding  the  various  causes  of  chronic  cough,  both  drug-­‐ related  and  otherwise  can  help  us  to  assist  patients  and  other   health-­‐care  professionals  to  provide  evidence-­‐based  therapies   for  this  condition.     A  significant  number  of  chronic  coughs  are  attributed  to   multiple  causes  and  a  careful  workup  is  required.  Be  aware   that  a  small  percentage  of  chronic  coughs  are  idiopathic.  3  One   of  the  most  commonly  reported  drug-­‐related  origins  of   chronic  cough  is  ACE  inhibitors  such  as  lisinopril,  although   overall,  cause  of  a  mere  1-­‐3%  of  chronic  cough  cases.  4  ACE   Inhibitors  are  thought  to  sensitize  cough  receptors  through  a   buildup  of  prostaglandins  and  bradykinin.    Oxymetazoline   (Afrin)  has  also  been  associated  with  chronic  cough  but  is  not   mentioned  extensively  in  the  available  literature.  The   following  paragraphs  describe  several  of  the  more  common   non-­‐drug  causes  of  chronic  cough:    


Newsletter – January 2015 Gastroesophageal  Reflux  (GERD):  A  segment  of  the  patients  who  experience  chronic   cough  are  diagnosed  with  GERD  and  often  empirically  treated  with  proton-­‐pump  inhibitors   (PPIs).  These  patients  often  do  not  exhibit  any  other  symptoms  of  GERD.  Physicians  may   order  a  24-­‐hour  pH  Study  and/or  endoscopy  procedures  to  verify  this  diagnosis.1,2,5   Upper  Airway  Cough  Syndrome  (Post-­‐Nasal  Drip):  Often  associated  with  frequent   clearing  of  the  throat  due  to  rhinitis,  with  or  without  sinusitis.  Allergic  rhinitis  is  commonly   treated  with  newer  generation  antihistamines,  although  treatment  may  include  therapy   with  mast  cell  stabilizers  and  nasal  corticosteroids.  Non-­‐allergic  rhinitis,  due  to  the   common  cold  and  other  causes,  is  often  treated  with  diphenhydramine/decongestant   combinations.  2  A  number  of  over-­‐the-­‐counter  (OTC)  therapies  are  available.  Pharmacists   may  recommend  an  initial  trial  of  OTC  medications  followed  by  a  provider  referral  if  the   symptoms  persist.   Asthma:  Chronic  cough  is  a  common  symptom  of  asthma  and  with  cough-­‐variant  asthma,  is   the  only  symptom.  Elderly  patients  with  asthma  may  only  present  with  a  chronic  cough.  5  If   asthma  is  suspected,  an  immediate  referral  to  a  provider  is  warranted.  Once  asthma  has   been  diagnosed,  pharmacists  should  be  able  to  provide  patients  with  accurate  information   regarding  drug  therapy  for  this  disease.  All  patients  with  asthma  should  have  a  short-­‐acting   beta  agonist  (SABA)  inhaler  and  should  understand  its  proper  use.  Other  common   therapies  include  long-­‐acting  beta  agonists,  inhaled  corticosteroids,  leukotriene  receptor   antagonists,  and  mast  cell  stabilizers.   Smoking:  Users  of  tobacco  are  three  times  more  likely  to  experience  chronic  cough   compared  to  non-­‐users.  5  Tobacco  smoke  can  reduce  or  even  paralyze  the  action  of  the   mucociliary  escalator  –  the  ciliated  epithelium  of  the  respiratory  tract.  Pharmacists  should   take  every  opportunity  to  encourage  smoking  cessation  and  recommend  evidence-­‐based   therapies  to  assist  patients  with  a  desire  to  quit.  Smoking  is  a  major  cause  of  COPD.   Chronic  Bronchitis/COPD:  Persistent  exposure  to  tobacco  smoke  and/or  other   environmental  irritants  contribute  heavily  to  this  condition.  5,6      Chronic  cough  may  be  an   early  indicator  of  COPD.  Many  of  the  same  drugs  used  in  asthma  are  also  used  to  help   manage  COPD  and  Chronic  Bronchitis.  If  COPD  is  suspected,  provider  referral  is  necessary.   A  1998  study  found  that  asthma,  upper-­‐airway  cough  syndrome,  and  GERD  accounted  for   the  majority  of  chronic  cough  diagnoses.  1  By  thorough  clinical  assessment,  the  underlying   cause  of  chronic  cough  can  be  determined  and  appropriate  therapy  initiated.  Antitussive   therapy,  both  prescription  and  OTC,  may  be  warranted  in  some  cases.6,7  Pharmacists   should  be  able  to  provide  patients  with  accurate  information  to  help  manage  the  various   drug  therapies  available  for  this  distressing  condition.    See  appendix  1  (page  5)  for   recommendations  in  treating  chronic  cough.  






Newsletter – January 2015 Question  of  the  Month:  Do  Fentanyl  transdermal  patches   contain  metal  and  can  they  safely  be  used  during  a  MRI?     Written  By:  Brigham  Wilcox  –  ISU  Pharm  D  Candidate  2015      



Some  Fentanyl  transdermal  patches  may  contain  a  metal  backing  usually  used  to  separate   the  active  ingredient  from  other  portions  of  the  patch,  such  as  adhesive.    The  metal   contained  in  transdermal  patches  is  usually  aluminum  but  could  also  be  titanium  dioxide  or   other  metals.  Due  to  their  ability  to  conduct  electricity,  the  metal  in  the  patch  can  become   very  hot  causing  severe  burns  if  worn  during  an  MRI.  Keep  in  mind  not  all  metal  backing   are  visible  on  the  patches.  The  chart  below  summarizes  the  results  of  our  research  on  this   topic.  Encourage  patients  and  providers  to  disclose  all  transdermal  patch  use  to  the   imaging  lab.      


No  metal  

Contains  Metal  









 ѱ  




















*  -­‐  Have  not  studied  the  fentanyl  transdermal  patch  in  MRI   ѱ-­‐  Printed  ink  contains  minimal  amounts  of  titanium  dioxide,  remainder  of  patch  is  metal   free   †  -­‐  Safe  for  use  in  MRI   ‡  -­‐  May  contain  trace  heavy  metals  that  are  within  USP  limits,  but  safe  in  MRI              


Newsletter – January 2015      

OTC  Sodium  Phosphate  Warning   Written  by:  Alicia  Romero  –  Pharm  D  




  On  January  8,  2014  the  FDA  issued  a  safety  warning   regarding  OTC  sodium  phosphate  and  sodium   biphosphate  products  used  for  the  treatment  of   constipation  (ie.  Fleet®  and  corresponding   generics).  This  warning  was  for  both  oral  products   and  enemas.    When  these  products  were  taken  in   larger  doses  than  recommended  or  more  frequent   than  one  dose  per  day,  serious  electrolyte   disturbances  have  occurred.  Electrolyte  imbalances   can  lead  to  severe  dehydration,  acute  renal  injury,   other  organ  damage  including  the  heart,  and  even   death.    Of  the  54  reports  submitted  to  the  FDA   regarding  electrolyte  imbalance,  13  resulted  in  death   showing  that  although  rare,  these  electrolyte   imbalances  should  not  be  taken  lightly.  This  serious   adverse  event  occurs,  on  average,  1-­‐2  days  after   incorrect  product  usage.     If  patients  purchase  or  seek  counseling  on  this   product,  be  sure  to  identify  any  risk  factors  that  may   exclude  them  from  safely  using  OTC  sodium   phosphate  products.  These  risk  factors  include   dehydration,  heart  or  kidney  problems,  bowel   inflammation  or  obstruction,  and  current   medications  that  may  influence  electrolyte  balance   such  as  ACE  inhibitors,  ARB’s,  diuretics  or  NSAIDS.  It   is  typically  a  safe  practice  to  avoid  recommending   these  products  for  children.    Proper  usage   instructions  need  to  be  a  priority  due  to  these   serious  adverse  events  in  the  FDA  warning.    





Newsletter – January 2015 Appendix  1:  Recommendations  for  the  Treatment  of  Chronic  Cough     General  Recommendations  for  the  Treatment  of  Chronic  Cough     Implement  non-­‐pharmacological  treatment  plus  acid   Gastroesophageal  Reflux  (GERD)  6,8   suppression  therapy.    Non-­‐pharmacological  treatments     include:  diet  restrictions,  raising  head  while  sleeping,  and   weight  reduction.    Acid  suppression  is  usually  a  PPI.     Some  PPI  options  include  omeprazole  20-­‐40mg,   lansoprozole  30mg,  and  pantoprazole  40mg  usually  taken   once  daily  before  a  meal.    If  cough  is  resistant,  more  studies   may  be  performed  and  in  certain  situations  patients  may   benefit  from  the  addition  of  a  prokinetic  drug  (ie.   Metoclopramide  10mg  up  to  four  times  daily  before  meals   and  bedtime)     Treatment  of  what  was  formerly  known  as  post-­‐nasal  drip   6,8   Upper  Airway  Cough  Syndrome   should  initially  be  a  first  generation  antihistamine  and/or  a   (Post-­‐Nasal  Drip)   decongestant.    Diphenhydramine  25-­‐50  mg  before  bedtime     would  be  a  great  first  choice.    Decongestants  pose  some   risks  if  used  long  term.    Nasal  decongestants,  such  as   Afrin®,  should  only  be  used  for  a  few  days,  while  oral   pseudoephedrine  should  be  used  with  caution  in  patients   with  cardiovascular  risks.       Chronic  cough  as  a  result  of  asthma  is  best  treated  in  the   Asthma  6,8   same  way  as  asthma  without  a  cough.    Patients  should     ideally  be  prescribed  a  rescue  bronchodilator  such  as   Albuterol  and  should  also  have  an  inhaled  corticosteroid  for   maintenance  (ie.  Low  dose  fluticasone  inhaled  twice  daily)     The  best  recommendation  is  smoking  cessation.    Avoiding   6,8 Smoking     other  irritants  may  help,  but  around  90%  of  those  who  quit     smoking  experience  relieve  of  chronic  cough.       If  the  determined  cause  of  chronic  cough  is  linked  to   Rhinitis  6,8   rhinitis,  topical  corticosteroids  (ie.  fluticasone  nasal  spray)     are  first  line  therapy.    Other  options  include  topical   ipratropium  (40  mcg  BID)  or  a  1st  generation  antihistamine.       Wait  and  observe.       Post-­‐infection  6           Antitussive  agents  have  not  been  proven  to  be  highly   ANTITUSSIVE/PROTUSSIVE   effective  in  chronic  cough.    In  some  select  cases  they  may  be   8   THERAPY   chosen.    Some  options  include  codeine,  dextromethorphan,   and  diphenhydramine.      Estimated  minimal  effective  doses   are  as  follows:  codeine  20  mg,  dextromethorphan  20  mg,   and  25  mg  diphenhydramine.    Codeine,  although  considered   more  effective  by  some,  has  high  patient  variability  and  has   a  high  incidence  of  nausea.       Protussive  therapy  for  chronic  cough  has  not  shown  any   merit  and  lacks  evidence  of  efficacy.    (ie.  Guaifenesin)          


Newsletter – January 2015   References    


Chronic  Cough  in  Adults   1. From  a  Prospective  Study  of  Chronic  Cough,  Nicholas  A.  Smyrnios,  Richard  S.  Irwin,  Frederick  J.  Curley,   Cynthia  L.  French.  Archives  of  Internal  Medicine,  1998  June  8;  158:  1222-­‐1228     2. How  should  one  investigate  a  chronic  cough?,  Ryu  P.H.  Tofts,  Gustave  Ferrer,  Eduardo  Olivera.   Cleveland  Clinic  One  Minute  Consult,  2011  February;  78(2):  84-­‐89,­‐chronic-­‐cough-­‐2-­‐2011,  Accessed   August  26,  2014     3. Cough:  an  unmet  clinical  need,  Peter  V.  Dicpinigaitis,  British  Journal  of  Pharmacology,  2011;  163:  116-­‐ 124,,  Accessed  August  28,  2014     4. Irwin  RS,  Boulet  LP,  Cloutier  MM,  et  al.  Managing  cough  asa  defense  mechanism  and  as  a  symptom.  A   consensus  panel  report  of  the  American  College  of  Chest  Physicians.  Chest.  1998  Aug;114(2  Suppl   Managing):133S-­‐181S.     5. Chronic  Cough  1:  Prevalence,  pathogenesis,  and  causes  of  chronic  cough,  Kian  Fan  Chung,  Ian  D.   Pavord,  Lancet,  2008  April  19;  371:  1364-­‐74     6. Chronic  Cough  2:  Management  of  chronic  cough,  Kian  Fan  Chung,  Ian  D.  Pavord,  Lancet,  2008  April  19;   371:  1375-­‐84     7. Cough  management:  a  practical  approach,  De  Blasio  et  al.  Cough,  2011;  7(7),,  Accessed  August  27,  2014     8. Irwin  RS,  Baumann  MH,  Bolser  DC,  et  al.  American  College  of  Chest  Physicians  (ACCP).  Diagnosis  and   management  of  cough  executive  summary:  ACCP  evidence-­‐based  clinical  practice  guidelines.  Chest.   2006  Jan;129(1  Suppl):1S-­‐23S.     9. Image  (page  1:  left-­‐hand  side)  courtesy  of  iStockphoto/drbimages       Question  of  the  Month:  Do  Fentanyl  transdermal  patches  contain  metal  and  can  they  safely  be  used   during  a  MRI?   1. U.S.  Food  and  Drug  Administration.  2011.  Risk  of  burns  during  MRI  scans  from  transdermal  drug   patches  with  metallic  backings.  Retrieved  from     2. Alhammad  A,  Durand  C,  Willett  KC.  Practical  considerations  for  optimal  transdermal  drug  delivery.   American  Journal  of  Health-­‐System  pharmacy.  2012;69(2):116-­‐124.     3. Wilcox,  B.  Personal  interview/correspondence.    Drug  information  Specialists  of  JANSSEN,  MYLAN,   SANDOZ,  ACTAVIS,  APOTEX,  MALLINKRODT,  PAR,  AND  UPSHER-­‐SMITH.  2014      

  OTC  Sodium  Phosphate  Warning   1. U.S.  Food  and  Drug  Administration.  2014.  Sodium  Phosphate  Over-­‐the-­‐Counter  Products:  Drug  Safety   Communication  -­‐  Possible  Harm  From  Exceeding  Recommended  Dose.  Retrieved  from     2. Image  (page  4:  left-­‐hand  side)  courtesy  of  

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