|
Use this link to order from Amazon.com and IARP will
receive a donation.
| |
November Newsletter
& Notes From Nancy
Hello all! It's been a very busy month! In my
note this month, I want to encourage you to start thinking about the upcoming holiday
season. Living with a child suffering from GERD is not an easy task and sometimes
it's easy to get caught up in the negative things we are going through and forget about
those things for which we are thankful. I'm not an avid watcher of Oprah, but her
idea to do a gratitude journal is a good one. I try to write down atleast one thing
I'm thankful for each day. It certainly helps me when I'm having a rough day.
Thanks to all of you who are working hard in your
areas to support parents close to you. I would like to add a page for each of your
active local organizations. I'd love to include photos of activities and would be
happy to have an updated calendar of events, etc. Please let me know if you want one
for your group.
I am wanting to start a mailing list for parents
with older children, if you are interested, please email me. I would also appreciate
suggestions for site content for older children.
Hang in there parents of GERD children--keep your
hopes and spirits up and have a wonderful Thanksgiving Holiday! Feel free to email
me with comments or questions anytime!
Love, Nancy
Founder--International Association of Reflux
Parents
Great Comments From Parents About the GERD WORD! (Thanks!!)
Hello,
I just found your web site and I am so happy to have found it! My daughter was diagnosed
with reflux when she was 6 weeks old and her pediatrician just doesn't seem to care. My
husband and I have struggled with the lack of support and understanding from other
parents, relatives and strangers. It is wonderful to find people in the same boat that we
are! Hayley is now
almost 10 months and she is still spitting up constantly. She is healthy and happy so we
are luckier than a lot of people and babies, but we still need the support that you offer.
Thank you so much!
Kate, Scott and Hayley Davis
Just came across your site and THANK GOD!!!!!!!!! My 7 week old son
was finally just dianosed with Reflux (after I got patronized all over town for being
unable to cope with "just a fussy baby")
1: Janssen and Sepracor Announce Propulsid(R) Metabolite Licensing
Agreement
2: Gastroesophageal reflux disease: is there a familial
predisposition?
3: Something I've not seen before---"Nutritional
Treatment"
4: Medications that should not be taken with Propulsid because
of possible
interaction.
5: Questions that you should always ask when your child is put on
medication.
1: Janssen and Sepracor Announce Propulsid(R) Metabolite Licensing
Agreement
MARLBOROUGH, Mass., July 21 /PRNewswire/ -- Sepracor Inc. (Nasdaq: SEPR) today announced a
licensing agreement with Janssen Pharmaceutica, N.V., a wholly owned subsidiary of Johnson
& Johnson (NYSE: JNJ), relating to (+) norcisapride, an isomer of the active
metabolite of Propulsid(R) (cisapride). Propulsid, marketed by Janssen Pharmaceutica, is
indicated for the symptomatic treatment of patients with nocturnal heartburn due to
gastroesophageal reflux disease (GERD). In 1997, worldwide sales of Propulsid exceeded $1
billion for the first time.
"We are very pleased to be collaborating with Janssen on another ICE compound, which
may provide a platform to expand the Propulsid franchise. The isomer of norcisapride has
the potential for reduced side effects, increased efficacy and less frequent dosing, and
the opportunity for additional indications such as emesis, irritable bowel syndrome, and
bulimia," said Timothy J. Barberich, President and Chief Executive Officer of
Sepracor Inc.
Under the terms of the agreement, Sepracor has exclusively licensed to Janssen all of
Sepracor's worldwide rights to develop and market norcisapride enantiomers. Janssen will
pay Sepracor royalties on product sales beginning upon launch and royalties will escalate
upon achievement of sales volume milestones. Under certain circumstances, Sepracor may
co-promote the product in the pediatric market.
"This agreement with Janssen further validates Sepracor's ICE strategy as a unique
opportunity to potentially improve and extend the life cycle of major pharmaceutical
franchises," said David S. Barlow, President of Pharmaceuticals at Sepracor.
Sepracor is a specialty pharmaceutical company that develops and commercializes
potentially improved versions of widely prescribed drugs. Referred to as Improved Chemical
Entities ("ICE"), Sepracor's ICE(TM) Pharmaceuticals are being developed as
proprietary, single-isomer or active-metabolite versions of these leading drugs. ICE
Pharmaceuticals are designed to offer meaningful improvements in patient outcome through
reduced side effects, increased therapeutic efficacy, improved dosage forms, and in some
cases the opportunity for additional indications.
This news release contains forward-looking statements that involve risks and
uncertainties, including statements with respect to the safety, efficacy and potential
benefits of the company's ICE Pharmaceuticals under development. Among the factors that
could cause actual results to differ materially from those indicated by such
forward-looking statements are: the results of the company's clinical trials with respect
to its products under development; the scope of the company's patent protection with
respect to such product candidates; the availability of sufficient funds to continue
research and development efforts; and certain other factors that may affect future
operating results and are detailed in the company's periodic reports filed with the
Securities and Exchange Commission.
Propulsid is a registered trademark of Johnson & Johnson.
SOURCE Sepracor Inc.
2: Gastroesophageal reflux disease: is there a familial predisposition?
Presented by: Yvonne Romero, MD
Affiliation: Mayo Clinic and Olmstead Medical Group, Rochester MN
This study compared the prevalence of symptoms of gastroesophageal reflux disease (GERD)
among the parents and siblings of patients with reflux esophagitis (RE) to prevalence of
GERD in the parents and siblings of the patient’s spouse. Two separate samples were
examined. The data resources of the Rochester Epidemiology Project were used to identify
all married and non-adopted patients (probands), ages 18 to 80, with endoscopically and/or
pathologically proven RE. A second consecutive group of probands with reflux esophagitis
seen in a sub-specialty esophagus clinic were also evaluated. Data from these two groups
were pooled. Probands and spouses completed a mailed questionnaire and, if needed, were
contacted by telephone follow-up. The analysis adjusted for tobacco and alcohol use, and
body mass index. 32 community and 24 referral probands and their spouses completed surveys
as did 227 of their living relatives.
GERDRelatives of probandsRelatives of spouses (controls)Odds Ratio (adjusted)yes40291.32
(NS)no867295% CI0.61-2.81
The investigators concluded that although GERD symptoms were more prevalent in the first
degree relatives of patients with reflux esophagitis than the spouses, this difference was
not statistically significantly. If a familial predisposition, independent of obesity and
social habits, toward the development of GERD does exists, it is too small an effect to be
identified in a study of over 200 first degree relatives. It should be noted that a
research report was presented at the Digestive Disease Week conference (May 1996) that
showed a strong familial association among relatives of patients with Barrett's esophagus
and esophageal adenocarcinoma.
3: Nutritional Treatment?
Reflux in infants can be associated with failure to thrive and recurrent
respiratory symptoms. It can be caused by Hiatus Hernia, oesophagitis or stricture as well
as sensitivities to foods. Positioning of the baby influences the symptoms. Sitting
upright 60 degrees from horizontal increases reflux. Less reflux occurs in the prone
position then in the supine position.
NUTRITIONAL TREATMENT
•Check for food sensitivities especially milk.
•Keep babies prone in a harness with head elevated at 30 degrees which is more
effective than the horizontal prone position.
•Carob seed powder can be used to thicken feed.
•Sprinkle digestive enzymes over meal (vikase granules).
•Childrens Formula ½ - 1 teaspoon/day in water. •Cytobifid Lactobacillus
capsules - sprinkle over meal. •Mineral Matrix - crushed 1/2 - 1 tablet/day.
•If the child is breast fed, the mothers diet should be investigated for possible
allergens or food intolerances.
The herbs and nutrients mentioned above reflect the major nutritional supplements that may
help the condition. Please do remember however that nutritional supplementation is an
adjunct to medical treatment and in no way replaces medical treatment.
From the Physician's Handbook of Clinical Nutrition
4: Medicines that may interact with cisapride (Propulsid).
It is never possible to know all of the medications that interact with cisapride.
This list is not complete. It was gathered from various sources in the Summer of 1998.
Please have your doctor and pharmacist check for new information.
Alcohol
Amantadine (Symmetrel for Parkinson's, viral)
Antiarrythmics (several for heart arrythmias)
Anticholinergics (Cogentin or Bentyl and others for abdominal, intestinal, or muscle
spasms)
Antidepressants (several for depression)
Antidyskinetics (several for Parkinson's and movement disorders)
Antihistamines (several for allergies, especially minimally sedating varieties)
Antipsychotics (several for mental illness)
Antispasmodics (Bentyl and Cogentin for bowel or muscle spasms)
Astemizole (Hismanol for allergies)
Bepridil (Vascor for arrhythmia)
Carbamazepine (Tegretol for seizures, pain)
Clarythromycin (Biaxin for infections)
Cyclobenzaprine (Flexeril for muscle spasms)
Diazapam (Valium for anxiety)
Disopyramide (Norpace for arrythmia)
Erythromycin (Biaxin, Clarithromycin, Crythromycin, E-Mycin, EES, ERYC, Ery-Ped, Ery-Tab,
Erythrocin, Ilosone, Ilotycin, PCE, Pediazole, Zithromax for infections)Flavoxamine (Luvox
for obsessive compulsive disorder)
Flavoxate (Urispas for bladder spasms)
Fluconazole (Diflucan for fungal infection)
Indinavir (Crixivan for HIV)
Ipratropium (Atrovent for asthma)
Itraconazole (Sporanox for fungal infections)
Ketoconazole (Nizoral for yeast, thrush, fungal infections)
Meclizine (Antivert for nausea, motion sickness)
Methylphenidate (Ritalin for attention deficit)
Miconazole (Monistat i.v. for yeast, fungal infections)
Nefazodone (Serzone for depression)
Orphenadrine (Norflex for pain, inflamation)
Oxybutynin (Ditropan for bladder spasms)
Procainamide (Pronestyl for arrythmia)
Promethazine (Phenergan for pain, cough)
Quinidine (Quinidex for arrhythmia)
Ritonavir (Norvir for HIV)
Sotalol (?? For ??)
Sparfloxacin (Zagam for infections)
Terodiline (??? for ??)
Tranquillizers (Librium, Valium, Xanax, etc.)
Troleandomycin (Tao for infections) Medications that may be absorbed differently with
cisapride
Please ask your doctor about closer monitoring for any medications that have very
sensitive dosing. Cisapride may move the medication out of the stomach and into the
intestines quicker and this can alter absorption rates. Doses may need to be adjusted
again if cisapride is discontinued.Warfarin (Coumadin for blood clotting
Dilantin for seizures
Benzodiazapines for anxiety, seizures, sedation
Thyroid hormones to replace missing hormones
5: Questions Parents Should Ask When Meds Are Prescribed For Their Child(and
should probably write down the answers)
What results can be expected from taking this medication?
How long should I wait before reporting if this medication does not help?
How does this medicine work?
What is the exact dose of the medicine?
What time of day should I take this medicine?
Special precautions with this medication in combination with other drugs (prescription or
over-the-counter)?
Can I take this medicine without regard to food or meal times?
Any special instructions concerning how to use this medicine?
How long should I continue to take this medicine?
Which side effects should be reported? Which can be disregarded?
How should I store this medication? Can I save unused portions for future use?
What should I do if I forget to take a dose of this medication?
Send us Email: 
[ Nov. Newsletter ] [ January Newsletter ] [ December Newsletter ]
<Picture>PHYSICIAN ALERT
Consider side-effect profile when prescribing metoclopramide (Reglan)
Physicians should consider, and discuss with patient families, the CNS side effects of
metoclopramide (Reglan) when prescribing this drug. Metoclopramide crosses the blood-brain
barrier and frequently affects the Central Nervous System.
"Side effects occur in 20% -30% of patients treated with effective doses. Side
effects include somnolence, restlessness, and insomnia, but the most troubling are
dystonic and extrapyramidal movements. Tremors, trismus, facial spasms, and oculogyric
crises improve after withdrawal of the drug or administration of intravenous
diphenhydramine 1mg/kg. Tardive dyskinesias may not respond to drug withdrawal."
Pediatric Gastrointestinal Motility Disorders, (Hyman, Di Lorenzo, eds), Chapter 25
(Pharmacotherapy), p. 379.
------------------------------------------------------------------------
Volume 15 Number 2
March 1995
NEUROLOGICAL SIDE EFFECTS ASSOCIATED WITH UNNECESSARY USE OF METOCLOPRAMIDE IN CHILDREN
REPRINTED WITH PERMISSION OF AUTHORS
Abdullah Abdulaziz Al Zaben, MBBS, DCH, FRCPC; Abdullah Solaiman Al Herbish, MBBS, FRCPC,
FAAP
Department of Pediatrics (Dr. Al-Zaben), Riyadh Medical Complex, and Department of
Pediatrics (Dr. Al-Herbish), King Khalid University Hospital, Riyadh. Address reprint
requests and correspondence to Dr. Al-Herbish: P.O. Box 90533, Riyadh 11623, Saudi Arabia.
Incidence of side effects of metoclopramide is 20%.1 Neurological symptoms such as
oculogyric crisis and involuntary contractions of the eye muscles leading to upward
conjugate gaze occur in about 1% of patients.2 Children and young adults are more prone to
develop these symptoms, even after a single dose.3,4 Despite the fact that these effects
disappear spontaneously and completely after discontinuation of this treatment, they
create unnecessary anxiety for the patient, parents and health care personnel. This
problem would not have emerged without the uncontrolled, and most of the time unnecessary,
prescription of metoclopramide to young children. In this study, over a one-year period,
we analyzed the clinical data of 24 children who presented with these manifestations after
being prescribed metoclopramide for an acute illness.
Material and Methods
Clinical data and hospital course of children presenting over a one-year period (starting
July 1991) to the emergency room of the Pediatric Department of the Riyadh Medical Complex
with neurological symptoms due to metoclopramide (primperan or plasil) were analyzed. The
number of admissions to this emergency unit was 30 to 50 children per day with various
acute pediatric problems. Age, weight, indicating symptoms for prescribing metoclopramide,
dose given, frequency and route of administration were all recorded. The specific
neurological symptom and/or sign, e.g., oculogyric crisis defined as involuntary
contractions of the eye muscles resulting in upward conjugate gaze, dystonia, drowsiness,
etc. was elicited at presentation and its course thereafter was followed. Some children
were given diazepam to abort or lessen these symptoms and the rest resolved spontaneously.
Results
Twenty-four children presented with clinical data fulfilling the criteria. They represent
zero to one case of 30 to 50 admissions per day during the period of the study with
estimated prevalence of 0.6% among total admissions. Nine were males and 15 were females.
Metoclopramide was prescribed as plasil in 11 and as primperan in 13 children. Most of
these children were young; 10 were below six months of age, three between six and 12
months of age, nine were between one and six years and two were above six years of age
(Table 1). The dose ranged from one to 10 mg given three to four times daily.
Suppositories were prescribed in five cases and oral preparation (drops or syrup) in the
rest. Indicating symptoms were vomiting in 19 cases, cough in 17 cases and wheezing in two
cases. The drug was taken accidentally in one case and was mistakenly prescribed as an
antipyretic in another case (Table 2). All 24 children presented with neurological
symptoms and/or signs. Nineteen children showed the typical oculogyric crises. Dystonia
manifested in 13; lethargy in two, sleepiness in one and drowsiness in two. One child was
ataxic; four showed tonic-clonic movements described as seizures (Table 3). The duration
of symptoms ranged from 0.5 to 72 hours (mean 10). Diazepam 0.3 mg/kg/dose intravenously
was used once in 13 children. All children were admitted and observed in the hospital.
Discussion
Metoclopramide, a dopamine receptor antagonist that possesses central antiemetic and
peripheral gastrointestinal motility effects, is widely used.1,4 It has been used in the
pediatric age group for various indications, e.g., gastroesophageal reflux,4,5
chemotherapy-induced emesis,6 ureterolithiasis,7 surgery-induced emesis,8 and many other
indications. Its use as an antiemetic for acute illness, e.g., gastroenteritis, is rarely
if at all indicated. On the contrary, it may mask helpful symptoms and signs in the
evolving acute illness. Furthermore, the value of metoclopramide, even for the
above-mentioned indications, is recently debated.6-10 Despite all of this, metoclopramide
remains a popular antiemetic, used widely in developing countries as it is readily
accessible to patients and physicians. The estimated prevalence of neurological side
effects in our study of 0.6% represents only the tip of the iceberg, as we feel that mild
symptomatology may be overlooked by patients and parents.
Neurological deficits are more hazardous in young children, especially infants and
neonates, where it can precipitate apnea and death.11 Unfortunately, our study showed a
predominance of the use of metoclopramide in young infants (less than six months). All of
our patients presented with acute illness without prior indication of an antiemetic. The
most common neurological sequela of metoclopramide was oculogyric crisis (19 out of 24 or
79%). This percentage certainly reflects a high frequency when compared to other
neurological sequelae. In addition, dystonia was the second highest precipitating symptom
in the emergency room. Extrapyramidal symptoms were reported in 1% to 5% of metoclopramide
users.2,12 Obviously these symptoms are frightening to the patient and the parents. Less
frequent symptoms such as ataxia, aphasia, and decreased level of consciousness are also
worrisome. The presence of these symptoms in young children and infants may predispose to
even more respiratory compromise, namely apnea, in addition to the previously reported
symptoms of restlessness, anxiety and sudden death.2,9,11 Most of our patients received
doses of
------------------------------------------------------------------------
TABLE 1. Number of children according to age.
Age (years) Number of cases
0-0.5 10
0.5-1 3
1-6 9
>6 2
Total 24
------------------------------------------------------------------------
TABLE 2. Indicating symptoms of prescribing metoclopramide.
Symptom No. of
children
Vomiting 19
Cough 7
Wheezing 2
Accidental 1
Error 1
------------------------------------------------------------------------
TABLE 3. The presenting neurological symptoms in the children presented.
Presenting manifestation No. of
children
Oculogyric crises 19
Dystonia 13
Tonic-clonic seizures 4
Drowsiness 2
Lethargy 2
Aphasia 2
Sleepiness 1
Ataxia 1
------------------------------------------------------------------------
the drug that were more than the recommended therapeutic dose of 0.15 mg/kg/dose6 or 0.7
mg/kg/day.9 However, even with standard therapeutic doses, neurological side effects were
reported.4
The absorption of metoclopramide is rapid throughout the gastrointestinal tract with
variable peak plasma levels according to the route of administration.13 In our patients,
there was no statistical difference between oral and rectal routes, either in terms of
duration of symptoms or severity of symptoms.
Most of these symptoms resolve spontaneously. Some do require treatment with 1 mg/kg of
intravenous diphenhydramine. Fifty-four percent (54%) of our patients were given diazepam,
which abolished symptoms immediately.
In conclusion, we feel that antiemetic agents such as metoclopramide are overused in
children without scientific basis. We recommend that the existing practice of uncontrolled
prescription of these agents should decline. We emphasize the role of senior pediatricians
in publicizing this among their junior colleagues in various institutions.
Acknowledgment
The authors would like to thank Ms. Vangie S. Walz for typing the manuscript.
References
1. McCallum RW, Albibi R. Metoclopramide: pharmacology and clinical application. Ann
Intern Med 1983;98:86-95.
2. McCallum RW. Review of current status of prokinetic agents in gastroenterology. Am J
Gastroenterol 1985;80:1008-16.
3. M.E.P.P.O. The Middle East Drug Compendium, 26th ed. Healthcare Publications 1993;M12,
M13, S134, S135.
4. Harrington RA, Hamilton CW, Brogden RN, Linkewich JA, Romankiewicz JA, Heel RC.
Metoclopramide: an update review of its pharmacological properties and clinical use. Drugs
1983;25:451-94.
5. DiPalma JR. Metoclopramide: a dopamine receptor antagonist. Am Fam Physician
1990;41:919-24.
6. Hainsworth JD. Development of serotonin antagonists for the control of
chemotherapy-induced emesis. Semin Surg Oncol 1993;9:279-84.
7. Muller FF, Naesh O, Svare E, Jensen A, Glyngdal P. Metoclopramide (primperan) in the
treatment of ureterolithiasis: a prospective double blind study of metoclopramide compared
with morphatropin on ureteral colic. Urol Int 1990;45:112-3.
8. Lin DM, Furst SR, Rodarte A. A double-blind comparison of metoclopramide and droperidol
for prevention of emesis following strabismus surgery. Anesthesiol 1992;76:357-61.
9. Machida HM, Forbes DA, Gall DG, Sott RB. Metoclopramide in gastroesophageal reflux of
infancy. J Pediatr 1988;112:483-7.
10. Sledge GW JR, Einhorn L, Nagy C, House K. Phase III double blind comparison of
intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving
multiple day cisplatin-based chemotherapy. Cancer 1991;70:2524-8.
11. Pollera CF, Cognetli F, Nardi M, Mozza D. Sudden death after acute dystonic reaction
to high dose metoclopramide [letter]. Lancet 1984;2:460-1.
12. Bryson JC. Clinical safety of ondansetron. Semin Oncol 1992;92:(suppl 15):26-32.
13. Baterman DN. Clinical pharmacokinetics of metoclopramide. Clin Pharmacokinet
1983;8:523-9.
Links to our Previous Newsletters:
October
September
August
Send us Email: GERDWORD
[ Home ] [ Nov. Newsletter ] [ January Newsletter ] [ December Newsletter ]
| |
|
