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Drug intake during Ramadan

Authors:

Abstract

During Ramadan, the ninth month of the Islamic lunar calendar, adult Muslims are required to refrain from taking any food, beverages, or oral drugs, as well as from sexual intercourse, between dawn and sunset. Ramadan can occur in any of the four seasons, and the hours spent fasting vary accordingly from 11 hours to 18 hours a day. Rhythms of life and habits during this fasting period differ from one country to another. In Morocco, two to three meals daily are eaten within a short overnight span during this month. The first meal might be taken immediately after sunset (Iftar) and the second one around three hours later (dinner); the last meal might be taken shortly before dawn (Sohour). Intake of drug doses is therefore not easy, and its adjustment to the life rhythm of Ramadan is often not rational. Aslam et al surveyed 81 patients to determine the alterations they made to their drug regimens during the fasting period of Ramadan.1 They found that 42% of the patients adhered to their usual treatment, and 58% changed their intake pattern. Among the second group, 35 patients stopped their treatments, eight changed the administration schedule, and four took all the daily doses in one intake. Another survey of 325 outpatients in a Kuwaiti hospital found that most of them changed their drug regimens during Ramadan.2 Sixty four per cent of the patients changed their therapeutic scheme during the month; 18% took their daily medicines in a single intake, either before the first meal (sunset) or straight after the last one (before dawn). The authors warned about the high risk of drug interactions in such cases. In fact, a 57 year old woman with heart failure experienced side effects of digitalis after being treated with both a thiazide diuretic and …
Clinical review
Drug intake during Ramadan
N Aadil, I E Houti, S Moussamih
During Ramadan, the ninth month of the Islamic lunar
calendar, adult Muslims are required to refrain from
taking any food, beverages, or oral drugs, as well as
from sexual intercourse, between dawn and sunset.
Ramadan can occur in any of the four seasons, and the
hours spent fasting vary accordingly from 11 hours to
18 hours a day. Rhythms of life and habits during this
fasting period differ from one country to another. In
Morocco, two to three meals daily are eaten within a
short overnight span during this month. The first meal
might be taken immediately after sunset (Iftar) and the
second one around three hours later (dinner); the last
meal might be taken shortly before dawn (Sohour).
Intake of drug doses is therefore not easy, and its
adjustment to the life rhythm of Ramadan is often not
rational.
Aslam et al surveyed 81 patients to determine the
alterations they made to their drug regimens during
the fasting period of Ramadan.1They found that 42%
of the patients adhered to their usual treatment, and
58% changed their intake pattern. Among the second
group, 35 patients stopped their treatments, eight
changed the administration schedule, and four took all
the daily doses in one intake. Another survey of 325
outpatients in a Kuwaiti hospital found that most of
them changed their drug regimens during Ramadan.2
Sixty four per cent of the patients changed their thera-
peutic scheme during the month; 18% took their daily
medicines in a single intake, either before the first meal
(sunset) or straight after the last one (before dawn). The
authors warned about the high risk of drug
interactions in such cases. In fact, a 57 year old woman
with heart failure experienced side effects of digitalis
after being treated with both a thiazide diuretic and a
digitalis compound. According to the authors, the con-
comitant intake of those two drugs induced a drop in
potassium following a diuretic induced decrease in
water retention, which led to an increase in sensitivity
of heart muscle to digitalis.
Wheatly and Shelly reported that two patients with
chronic reversible respiratory disease were admitted to
an intensive care unit two weeks after the start of
Ramadan. Both patients subsequently admitted to not
having taken their treatment, including inhalers,
during daylight hours.3A prospective study evaluated
the changes in frequency of seizures during Ramadan
in 124 patients with idiopathic epilepsy. Seizures
occurred in 27 patients during this month; 20 of them
did not use any antiepileptic drugs from dawn to
sunset. The author concluded that withdrawal of drugs
was the most important cause of recurrence of epilepsy
during Ramadan.4
The main emphasis of the authors of these studies
was that most of the patients did not receive any
particular information about changing their treatment
during Ramadan. In the face of this arbitrary use of
drugs during Ramadan, drug intake needs to be
adapted according to the prescription components
the route of administration, the rhythm and schedule
of administration, and interaction with food intake. In
this paper we review current knowledge on this subject.
Sources
To build up this review, we used our own knowledge,
experience, and previous publications on the subject of
drug intake during Ramadan. We also searched
Medline and consulted several websites.
Route of administration
The compatibility of fasting with the various drug
administration routes and their choice during Ram-
Summary points
Ramadan, a month of fasting, is a daily abstinence
from any food, beverage, or oral drug from dawn
to sunset
Patients with chronic diseases often insist on
fasting even though they are permitted not to by
Islamic rules
Patients with acute diseases would similarly be
allowed to stop fasting and make up for it after
Ramadan
Several studies have shown that patients
arbitrarily change the intake time and dosing of
drugs without taking medical advice
This behaviour could alter the pharmacokinetics
and pharmacodynamics of drugs, especially those
with a narrow therapeutic index, and
consequently their efficacy and tolerance
Extra references are on bmj.com
Laboratory of
Pharmacology and
Toxicology, Faculty
of Medicine and
Pharmacy, 19 Rue
Tarik Bnou Ziad,
Casablanca 20000,
Morocco
N Aadil
assistant professor
I E Houti
assistant professor
S Moussamih
assistant professor
Correspondence to:
N Aadil
aadil_nadia@yahoo.fr
BMJ 2004;329:778–82
778 BMJ VOLUME 329 2 OCTOBER 2004 bmj.com
adan remain a matter for the doctor’s own judgment.
To settle differences in point of view and standardise
the choice of routes, a religious-medical seminar
entitled “An Islamic view of certain contemporary
medical issues” was held in Morocco in June 1997; one
of the main topics discussed was the substances and
actions that nullify fasting. The participants
distinguished Muslim jurists and religion experts,
medical practitioners, pharmacologists, and specialists
in other human sciences
agreed unanimously that the
following administration routes do not nullify fasting5:
xEye and ear drops
xAll substances absorbed into the body through the
skin, such as creams, ointments,and medicated plasters
xInsertion into the vagina of pessaries, medical
ovules, and vaginal washes
xInjections through the skin, muscle, joints, or veins,
with the exception of intravenous feeding
xOxygen and anaesthetic gases
xNitroglycerin tablets placed under the tongue for
the treatment of angina
xMouthwash, gargle, or oral spray, provided nothing
is swallowed into the stomach.
A majority of participants added:
xNose drops, nose sprays, and inhalers
xAnal injections
xSurgery involving general anaesthesia, if the patient
decided to fast.
Dosing schedule
Dosing schedules have to be altered during Ramadan.
In fact, drug doses can be taken only between sunset
and dawn, and the time span between them is shorter
than outside Ramadan. Two different types of dosage
schedule are commonly used during Ramadan.
Single daily dose
The easiest situation is that of patients who have a
usual evening dose. Their therapeutic scheme remains
unchanged during Ramadan, as it does not interfere
with fasting. When the usual intake is in the morning
or during the day, the doctor must be careful when
delaying the intake to the evening that this will not
alter the efficacy of treatment or the tolerance of the
drug.
The efficacy and toxicity of many drugs can vary
depending on the time of administration in relation to
the circadian rhythms of biochemical, physiological,
and behavioural processes. Thus, circadian time has to
be taken into account as an important factor influenc-
ing a drug’s pharmacokinetics or its effects or side
effects. Table 1 summarises the results of some
chronopharmacokinetic and pharmacodynamic stud-
ies for selected drugs.w1-w12
Few studies have investigated this subject in
relation to Ramadan. A comparative study of the phar-
macokinetics of theophylline before and during Ram-
adan in healthy volunteers showed a significant
decrease in the amount of drug absorbed for the 8 pm
intake (two hours after Iftar) compared with the 4 am
intake (immediately after Sohour).6This result was
mainly explained by the changes in the circadian vari-
ations of the gastric pH and by the modifications of
rhythms and quality of meals during Ramadan.7
A similar study on the pharmacokinetics of
valproic acid in healthy volunteers showed a significant
influence of the alterations to life rhythm and adminis-
tration schedule on the pharmacokinetic parameters
of this drug. In addition to the delayed absorption
phase for the 8 pm intake during Ramadan, the main
impairment was a significant decrease in the plasma
elimination half life for the 5 am intake compared with
the same intake time outside Ramadan.8As this
parameter determines the administration schedule, it
would be relevant to monitor the use of this antiepilep-
tic drug during Ramadan.
Studies on antihypertensive drugs have not shown
any significant effect on their efficacy from either the
Ramadan life rhythm or the changes in administration
schedule.910These studies were done in patients with
high blood pressure and treated by once daily prepara-
tions, before and during Ramadan. All patients in these
studies continued their drugs during Ramadan. The
results of ambulatory blood pressure monitoring in the
first study did not show any significant differences
between the periods before Ramadan and during
Ramadan in systolic pressure, diastolic pressure, 24
hour pressure, diurnal pressure, or nocturnal pres-
sure.9However, the authors observed that during the
month of Ramadan the peak of the awakening is
delayed by two hours and the nocturnal trough is
delayed by one hour. The administration schedules in
this study were not the same in the two time periods.
The patients took their drugs at 8 am outside Ramadan
and at the break of fasting (7-8 pm) during Ramadan.
Perk et al reported similar results of 24 hour blood
pressure monitoring before Ramadan and during the
last week of Ramadan in 70 hypertensive patients, all of
whom continued their once daily antihypertensive
drugs during Ramadan.10 No significant differences
Table 1 Selected drugs with circadian variation in pharmacokinetics and
pharmacodynamics
Drug Variation
Propranolol Absorbed more rapidly after morning dosage than after night dosage.w1 However, chronokinetics
cannot explain circadian changes in effects. Circadian variation in sympathetic tone and vascular
reactivity is mainly responsible for circadian changes in effects of propranololw2
Nifedipine Pharmacokinetics of immediate release but not sustained release preparation depends on time
of day. Immediate release nifedipine had higher Cmax (peak concentration) and shorter tmax (time
to peak concentration) after morning dosing than after evening dosing, and bioavailability in the
evening was reduced by about 40%w3
Digoxin Time to reach maximum plasma concentration was significantly shorter after 8 am dosing (54
min) than after 8 pm dosing (96 min)w4
Diltiazem Diltiazem HCl extended release tablets administered in the evening (10 pm) had 17% and 22%
greater bioavailability than morning administration (7 am or 8 am) under single dose and steady
state conditions, respectivelyw5
Enalapril Subchronic treatment at 7 am significantly reduced blood pressure during the day but was less
effective at night. Subchronic dosing at 7 pm significantly decreased night time blood pressure
followed by a slow increase during the day, with no effect on elevated afternoon valuesw6
TheophyllineIntake of a timed release formulation of theophylline at 3 pm achieved therapeutic drug
concentrations during the night and avoided toxic concentrations during the day.w7 A new
asymmetric dosage regimen of sustained release formulation of theophylline glycerinate (one
tablet in the morning and four tablets in the evening) produced a steady and effective
concentration of theophylline in plasma for the whole day, especially in the eveningw8
Inhaled
steroids
Optimal once daily dosing of inhaled steroid is between 3 pm and 5 30 pmw9
Prednisone Oral prednisone has been shown to be much more effective in improving several features of
nocturnal asthma when administered at 3 pm rather than at 8 amw10
Cimetidine Administration of H2antagonists at bedtime is more effective than administration in the
morning. Nocturnal administration not only reduces acid secretion more effectively but also
promotes ulcer healing and reduces ulcer recurrencew11
Ibuprofen After administration of ibuprofen press coated formulation, both the rate and extent of
absorption were lower when dosing took place at 8 am than when dosing took place at 10 pm.
The difference between morning and evening dosing of the immediate release formulation was
minimalw12
Clinical review
779BMJ VOLUME 329 2 OCTOBER 2004 bmj.com
were found between mean blood pressure or blood
pressure load before and during Ramadan. The
authors of both studies concluded that in patients with
essential hypertension without complications, fasting
during the month of Ramadan can be safely
undertaken with continuation of previous drug
treatment.
Saour et al evaluated, over a period of five years,
the efficacy and tolerance of a long acting oral
anticoagulant in two groups of patients.11 During this
period, the 106 patients in the first group made the
Ramadan fast, whereas the 183 patients in the second
group did not fast. All the patients in the first group
took their drugs at night rather than during the day.
The incidence of thromboembolic events and
haemorrhagic complications did not differ signifi-
cantly between the two groups. The authors
concluded that Ramadan fasting has no adverse
effects on the efficacy and safety of long term oral
anticoagulant treatment.
Two or more daily doses
During Ramadan, accurate distribution of drugs
prescribed twice a day is difficult to achieve between
the break from fasting and the beginning of fasting.
Refraining from fasting according to the Islamic rules
could be a wiser prescription. Nonetheless, patients
with two doses could take the first one at the break of
fasting and the second one before the beginning of
fasting, in which case the dosing time and the time
span between the doses are both altered. These altera-
tions could affect the drug’s plasma concentration pro-
file and, therefore, its efficacy and tolerance. This is
even more relevant for drugs with a narrow therapeu-
tic index as the risk of toxicity is higher.
In fact, Daghfous et al reported an influence of
fasting on the pharmacokinetics and side effects of a
sustained release preparation of theophylline taken
twice a day.12 The study included 12 patients with cur-
rent stable asthma and was done in two stages
the
first stage was during Ramadan, and the second stage
was four weeks after the end of Ramadan. In both
periods, the patients received two oral doses of
theophylline, one just before dawn (3 am) and the sec-
ond at sunset (7 pm) for five days. Outside Ramadan,
only four out of 12 patients reported adverse events of
minor nausea. During the fast of Ramadan, eight out
of 12 patients reported adverse effects of abdominal
pain and nausea. Six of them had also vomiting;
fasting was then interrupted. In these patients, the
blood theophylline concentrations were moderately,
but not significantly, higher than in the patients with-
out marked gastrointestinal problems. The authors
concluded that a longer acting preparation taken in a
single daily dose, preferably at the end of the night,
would be a solution for asthmatic patients during
Ramadan.
In the event of therapeutic problems during Ram-
adan, the number of doses should be reduced by using,
when available, slow release formulations or chrono-
therapeutic formulations. Verapamil hydrochloride
(Verelan PM, Covera-HS),13 propranolol CR (Innopran
XL),14 diltiazem hydrochloride (graded release
diltiazem),15 and tulobuterol (tulobuterol transdermal
therapeutic system),16 are some of the new chrono-
therapeutic formulations available. Otherwise, a drug
with a longer elimination half life should be used. Such
drugs will have a longer duration of action and can
therefore be taken at longer intervals, such as once a
day. This is the case with non-steroidal anti-
inflammatory drugs that are used for joint disease such
as arthritis: ibuprofen (half life 2-3 hours), flurbiprofen
(3-4 hours), naproxen (12-15 hours), and piroxicam
(26-38 hours) are some examples. Patients who are
prescribed drugs such as ibuprofen or flurbiprofen
need to take doses three or four times a day to
maintain a concentration of the drug in the body
tissues sufficient to provide adequate pain relief. These
drugs could be replaced by a single daily dose of
piroxicam, which is more suitable for the fasting
patient.17
Interaction with food intake
Generally, drug-food interactions may result in
reduced, delayed,or increased systemic availability of a
drug (table 2).w13-w26 The degree of interaction, and
whether it positively or negatively affects drug
absorption, depends on several factors, including the
physical and chemical nature of the drug, the
formulation, the type of meal, and the time interval
between eating and dosing. The last two factors could
have an enhanced effect during the month of
Ramadan, as the rhythm and composition of meals
are modified. In Morocco, an average of three meals
are served between sunset and dawn. The first one is
taken immediately after sunset and contains an
important amount of fat and carbohydrates; the
second one, containing mainly animal proteins, is
taken three to four hours later. The last meal is taken
between 30 minutes and one hour before sunrise and
is a breakfast-like meal. Thus particular care should be
taken when using drugs that have to be administered
on an empty stomach, such as furosemide, rifampicin,
and erythromycin.
The quality of the food eaten during the fast break-
ing meal could also have an influence on the
absorption of some drugs. Beverages such as tea,
coffee, and orange juice can increase gastric acidity,
which increases the absorption of weak acids such as
salicylates, dipyridamole, sulfamides, and some antibi-
otics and hypnotics; the action of pethidine, amitriptyl-
ine, and antihistamines may be inhibited. The high
concentration of fat and carbohydrates at this meal
could alter the bioavailability of drugs, but this
alteration depends on the formulation used. For exam-
ple, the intake of free acid phenytoin, as Hydantol
powder, with a high fat meal increased its bioavailabil-
ity,18 whereas the intake of an extended release pheny-
Fasting from dawn to dusk during Ramadan could cause problems
with drug dosage regimens for Muslim patients
Clinical review
780 BMJ VOLUME 329 2 OCTOBER 2004 bmj.com
toin sodium formulation (Phenytek) with a high fat
meal decreased its bioavailability.19
The clinical impact of such interactions depends on
the narrowness of the drug’s therapeutic index. An
alteration in bioavailability as a result of these interac-
tions could have a substantial effect on the plasma con-
centration of a drug, particularly a drug with a narrow
therapeutic index, leading to reduced efficacy or
increased side effects.
Conclusion
Extensive misuse of prescribed drugs during Ramadan
may lead to therapeutic failures. The lack of survey
data on this subject impairs effective evaluation of the
problem. This lack of information is a problem for
doctors, as they cannot give unbiased advise. Further
studies should be carried out to provide more
guidelines about the ways in which the administration
of drugs should be modified. In the meantime, doctors
and scientists in the Muslim world should be
encouraged to follow up their patients with chronic
diseases during Ramadan, in order to establish optimal
dosage regimens.
According to the data that are available, patients
arbitrarily modify the times of doses, the number of
doses, the time span between doses, and even the total
daily dosage of drugs during the month of Ramadan,
often without seeking any medical advice. Recommen-
dations are not easy to make as the reliability of the
available results remains questionable. In fact, most of
the studies carried out during Ramadan were
retrospective, and small samples were often used.
Other methodological errors were also seen, such as
incomplete descriptions of the therapeutic schemes
observed before and during Ramadan. In order to
make an objective comparison of the results obtained
before and during the month of Ramadan, the admin-
istered doses, the number of daily doses, and the
administration times need to be shown for the two
periods studied. For patients with chronic diseases, the
new dosage regimen to be used during Ramadan
needs to be established beforehand. Patients must also
be informed about when they should take their drugs
(before, during, or after food intake), particularly when
they are treated with drugs of which the absorption
could be impaired by food intake.
The best reference period for comparison with
Ramadan would be the period before Ramadan rather
than that immediately afterwards. Ramadan is charac-
terised by repeated fasting and altered life habits that
last four weeks, and its influence on chronobiological
parameters can last beyond the end of the month of
Ramadan.
The choice of drugs to be studied during Ramadan
could be determined by surveys evaluating the
therapeutic problems encountered during this month
of fasting. Focus should be on drugs for chronic
diseases, and especially on those with a narrow
therapeutic index. Wide dissemination of research
results, as well as achievement of consensus on relevant
clinical and therapeutic issues, would allow health pro-
fessionals throughout the Muslim world, and in
countries with an important Muslim population, to
provide accurate and standardised advice on the
appropriate use of drugs during the holy month of
Ramadan.
Contributors: NA had the original idea for the article. All three
authors contributed to the literature search. NA and IEH wrote
the review.NA is the guarantor.
Funding: None.
Competing interests: None declared.
Table 2 Commonly encountered drug-food interactions and recommendations (outside Ramadan)
Drug Interaction Recommendation
Levothyroxine Intake with food may decrease absorption.w13 High fibre diets have been shown to
decrease levothyroxine absorption.w14 Levothyroxine absorption is increased when
it is taken on an empty stomachw15
Thyroid hormones should be taken an hour before eating, at the same time
every dayw14
Digoxin High fibre foods, such as whole wheat products, raw vegetables, bran cereal, and
fruits, inhibit absorption of digoxin and decrease its effectw16
To avoid this problem, patients should take digoxin one hour before food or
two hours after eatingw17
Verapamil/felodipine Ingestion of grapefruit juice has been shown to increase absorption of
verapamilw17 and felodipinew18
In order to prevent side effects of these drugs, patients who are taking
verapamil or felodipine, or similar drugs such as amlodipine and nifedipine,
should avoid grapefruit and its juicew17 w18
Propranolol High protein foods may interfere with propranolol metabolism by increasing blood
concentrations and activity of propranololw19
Lithium Foods that alkalinise the urine may increase elimination of lithium from the body,
potentially decreasing its actionsw17
Theophylline A diet low in carbohydrates and high in protein, as well as charcoal grilled beef,
increases elimination of theophylline, resulting in poor control of asthma and
other conditions. Therefore, a high carbohydrate, low protein diet will halt
elimination of theophylline, leading to optimal therapeutic effectw20
Food can have different effects depending on the dose form. Sustained
release forms of theophylline should be taken on an empty stomach. Liquid
and non-sustained release theophylline products are best taken on an empty
stomach, but they may be taken with food if stomach upset occursw20
Loratadine Food slows the absorption of loratadine and also increases the total amount
absorbedw21
Loratadine should be taken on an empty stomachw21
Fexofenadine Ingestion of grapefruit juice, orange juice, or apple juice along with fexofenadine
decreases its blood concentrationsw22
Carbamazepine Grapefruit juice increases the bioavailability of carbamazepine by inhibiting
CYP3A4 enzymes in gut wall and liverw23
Diazepam Substantial increase of absorption with grapefruit juicew24
Bisphosphonates Food substantially reduces the bioavailability of oral alendronate.w25
Taking alendronate either 60 or 30 minutes before a standardised breakfast reduced
bioavailability by 40% relative to a two hour wait. Black coffee or orange juice alone,
when taken with the drug, also reduced bioavailability (approximately 60%)w26
A practical dosing recommendation is that patients should take the drugs
with water after an overnight fast and at least 30 minutes before any other
food or beverage
Additional educational resource
Islam Set (www.islamset.com)
Includes responses to
questions on a variety of Islam related science subjects
Clinical review
781BMJ VOLUME 329 2 OCTOBER 2004 bmj.com
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patients. J Clin Hosp Pharm 1986;11:321-5.
2 Aslam M, Assad A. Drug regimens and fasting during Ramadan: a survey
in Kuwait. Public Health 1986;100:49-53.
3 Wheatly RS, Shelly MP. Stopping bronchodilator treatmentis dangerous.
BMJ 1993;307:801.
4 Etemadyfar M. Effect of Ramadan on frequency of seizures. Abstract
book, Congress on Health and Ramadan, October 2001. Tehran: Iranian
Journal of Endocrinology and Metabolism, 2001:32.
5 Recommendations of the 9th Fiqh-Medical seminar “An Islamic View of
Certain Contemporary Medical Issues,” Casablanca, Morocco,14-17 June
1997 (www.islamset.com/search/index.html).
6 Gay JP, Cherrah Y, Aadil N, Hassar M, Brazier JL, Ollagnier M. Influence
of Ramadan on the pharmacokinetics of a SR preparation of
theophylline and cortisol cycle. J Interdiscipl Cycle Res 1990;21:190-2.
7 Iraki L, Bogdan A, Hakkou F, Amrani N, Abkari A, Touitou Y. Ramadan
diet restrictions modify the circadian time structure in humans: a study
on plasma gastrin, insulin, glucose, and calcium and on gastric pH. J Clin
Endocrinol Metab 1997;82:1261-73.
8 Aadil N, Fassi-Fihri A, Houti I, Benaji B, Ouhakki M, Kotbi S, et al. Influ-
ence of Ramadan on the pharmacokinetics of a single oral dose of valp-
roic acid administered at two different times. Methods Find Exp Clin
Pharmacol 2000;22:109-14.
9 Habbal R, Azzouzi L, Adnan K, Tahiri A, Chraibi N. Variations of blood
pressure during the month of Ramadan. Arch Mal Coeur Vaiss
1998;91:995-8.
10 Perk G, Ghanem J, Aamar S, Ben-Ishay D, Bursztyn M. The effect of the
fast of Ramadan on ambulatory blood pressure in treated hypertensives.
J Hum Hypertens 2001;15:723-5.
11 Saour JN, Sick JO, Khan M, Mamo I. Does Ramadan fasting complicate
anticoagulant therapy? Ann Saudi Med 1989;9:538-40.
12 Daghfous J, Beji M, Louzir B, Loueslati H, Lakhal M, Belkahia C. Fasting
in Ramadan, the asthmatics and sustained release theophylline. Ann
Saudi Med 1994;14:523.
13 Smith DH. Pharmacology of cardiovascular chronotherapeutic agents.
Am J Hypertens 2001;14:296-301s.
14 Sica D, Frishman WH, Manowitz N. Pharmacokinetics of propranolol
after single and multiple dosing with sustained release propranolol or
propranolol CR (innopran XL), a new chronotherapeutic formulation.
Heart Dis 2003;5:176-81.
15 Glasser SP, Neutel JM, Gana TJ, Alber t KS. Efficacy and safety of once
daily graded-release diltiazem formulation in essential hypertension. Am
J Hypertens 2003;16:51-8.
16 Horiguchi T, Kondo R, Myazaki J, Torigoe H, Tachikawa S. Clinical evalu-
ation of tulobuterol patch in patients with mild or moderate persistent
bronchial asthma
effects of long-term treatment on airway inflamma-
tion and hypersensitivity. Nihon Kokyuki Gakkai Zasshi 2004;42:132-7.
17 Aslam M, Wilson JV. Medicines, health and the fast of Ramadan. J R Soc
Health 1992;112:135-6.
18 Hamaguchi T, Shinkuma D, Irie T, Yamanaka Y, Morita Y, Ivanoto B, et al.
Effect of high-fat meal on the bioavailability of phenytoin in a commer-
cial powder with a large particle size. Int J Clin Pharmacol Ther Toxicol
1993;31:326-30.
19 Wilder BJ, Leppik I, Hietpas TJ, Cloyd JC, Randinitis EJ, Cook J. Effect of
food on absorption of Dilantin Kapseals and Mylan extended-release
phenytoin sodium capsules. Neurology 2001;57:571-3.
(Accepted 28 July 2004)
Interactive case report
A 35 year old woman with diabetic nephropathy who wants a baby
This case was described on 18 and 25 September (BMJ 2004;329:
674, 729). Debate on the management of the patient continues on
bmj.com (http://bmj.com/cgi/eletters/329/7467/675). On 14
October we will publish the outcome of the case together with
commentaries on the issues raised by the management and
online discussion from the patient and relevant experts.
The practicable paradox—the five minute emergency
At our surgery, each doctor offers four slots of five minutes each
at the end of the morning for “genuine emergencies.” The other
day I found myself whingeing to a colleague about the banal
nature of complaints that patients often bring to these
appointments. On one particular day the first patient wanted a
sick note, the second had run out of paracetamol, another wanted
to chase a physiotherapy referral that hadn’t come through, and
the last was a chap with an itchy bum. Each consultation ended
with some gentle patient education. Admittedly, a small part of
me was thankful that these weren’t hugely taxing appointments,
but I was mostly annoyed that these slots should have been
reserved for more deserving emergencies.
Then it struck me that I couldn’t actually name more than a
handful of things that would actually qualify as GP emergencies
that could be dealt with in a five minute slot. In fact, what is a GP
emergency? If your arm is hanging off after an accident, then you
need to get to casualty pretty quickly. The “morning after” pill can
be bought over the counter or is available free of charge at
community clinics. The advent of the new local NHS walk-in
centre should be able to see to sore throats and earaches, and
repeat medication should be asked for in advance. So what is a
reasonable five minute emergency? Indeed, is there such a thing?
Suspected appendicitis would be reasonable; so would cellulitis or
a mother sick with worry over her feverish toddler. All of these
seem reasonable to me.
The trouble is that most real emergencies hardly ever take five
minutes to sort out. One evening, during my “duty doctor” five
minute slots, I saw a pregnant woman who was bleeding heavily, a
feverish 6 week old baby with poor feeding, a woman who was
actively suicidal, and then a woman with slurred speech and
incontinence. The time taken to make an assessment of each
patient, to document everything, to arrange admission, and then to
write a referral letter was in the order of 20 minutes. I sometimes
find it incredible that my predecessors were used to routine
appointments of six minutes. Perhaps I’m expecting too much. The
five minutes that are allocated are effectively nominal. I can’t recall
many clinics, in hospital or the community, that run to time.
After all of my pontificating and efforts at patient education, I
am sure of only one thing
that, with recent changes in our
profession, medical law, and the way that people’s health
expectations have changed in the past few decades, I for one
cannot clearly define the realms of what constitutes a genuine five
minute emergency in general practice. So can I honestly expect
my patients to?
Ayan S Panja general practitioner, The Medici Practice, Luton
(ayanpanja@hotmail.com)
We welcome articles up to 600 words on topics such as
A memorable patient, A paper that changed my practice, My most
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relative if an identifiable patient is referred to. We also welcome
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Clinical review
782 BMJ VOLUME 329 2 OCTOBER 2004 bmj.com
... The duration of fasting varies, ranging from 10 to 18 hours, depending on the season and geographical location. 1 Some individuals who wish to fast as a religious obligation may also have chronic diseases or illnesses that necessitate regular treatment. In such cases, adjusting the timing of medication becomes imperative. ...
... 12 In another study, it was found that the common practice in the use of medication during Ramadan was to take a single dose a day or two doses between Iftar and Suhoor. 1 In a study conducted by Pehlivan et al. during ...
... Thus, it becomes inconvenient for patients to follow the regular schedule of medication intake; especially that is taken on an empty stomach or given frequently during the day. In a clinical review of medication intake during Ramadan, a large misuse of medications was found that subsequently led to increasing the rate of treatment failure (Aadil et al., 2004, AlAbdan et al., 2022. Two studies have shown that the majority of patients in Ramadan change their dosing schedule (Leiper et al., 2003, Ali et al., 2007, Amin and Abdelmageed 2020, Mahanani et al., 2021. ...
... The third section measured the pharmacists'/pharmacy technicians' biopharmaceutics knowledge (total number of questions = 34) on administration routes of medication or medical procedures that nullify fasting in Ramadan: (i) topical, local, or inhalational administration routes (n = 9), (ii) enteral (n = 9), (iii) parenteral (n = 3), and medical procedures (n = 13). The questions related to pharmacy personnel consultation practice and knowledge were selected and developed after an extensive review of the literature (Aadil et al., 2004, Mohamed Ibrahim 2015. Adequate answers for the knowledge questions were obtained after extensive reading and searching of the official website of the Fatwa Department of the Hashemite Kingdom of Jordan. ...
Article
Full-text available
Background: In Ramadan, most of the dosing schedules for the patients are changed, and to ensure patient compliance to medications and to healthy life among patients, appropriate guidelines and educations are needed. This can be achieved by pharmacy personnel in all clinical settings who are recognized as biopharmaceutical experts and integral educators of medications. Aims: This study aimed to identify the perspective knowledge of pharmacy personnel about effect of medication route and medical procedure on nullifying fasting in Ramadan and to determine the predictors of this knowledge. Methods: A cross-sectional study was conducted in Jordan during March-April 2022. An internet-based self-administrated questionnaire on knowledge, and views was distributed using social media groups to the pharmacy personnel among different geographical areas in Jordan. A descriptive and univariate analysis were performed. Binary logistic regression was conducted to determine the predictors of knowledge including all variables with p
... The typical fasting day can last up to 18 hours, which can be problematic as patients may elect to forgo their medicine, skip doses, or combine multiple doses without medical advice from their physician [53]. As stated in a clinical review by Aadil et al. [54], one or two daily doses are the most common drug regimens used during Ramadan and are typically much easier to follow than medications with multiple doses. However, physicians must keep in mind that Ramadan fasting can alter the circadian rhythm and lead to variations in gastric pH, which may affect the bioavailability of certain drugs [55]. ...
... Relatedly, the content of meals may also affect the absorption of various medications. Foods high in fiber can impede the absorption of levothyroxine and digoxin, while beverages that increase gastric acidity help aid in the absorption of medications that contain weak acids [54]. Physicians should consider these changes in medication dosing and bioavailability and offer recommendations to improve drug dosing and help patients comply with their treatments during Ramadan fasting. ...
Article
Full-text available
Intermittent fasting is an increasingly popular dieting technique with many well-studied benefits, such as permitting weight loss in obese patients, lowering low-density lipoprotein cholesterol (LDL-C) levels and triglyceride levels, and optimizing circadian rhythms. A special type of intermittent fasting occurs during Ramadan, when Muslims worldwide fast daily from dawn to sunset for a month. Ramadan fasting has demonstrated several health benefits, including improving the gut microbiome, modifying gut hormone levels, and lowering proinflammatory markers such as cytokines and blood lipids. Although fasting has many health benefits, fasting during Ramadan may aggravate chronic medical conditions. We aim to review the literature devoted to Ramadan fasting and its effects on Muslim patients with gastrointestinal (GI) disorders, such as Inflammatory bowel disease (IBD), peptic ulcer disease (PUD), upper GI bleeding (UGIB), gastroesophageal reflux disease (GERD), and liver conditions. We will discuss recommendations for diet and medication compliance during Ramadan in the recommended pre-Ramadan counseling sessions. In this study, we used PubMed to research journals using the key terms "Ramadan," "intermittent fasting," and "gastrointestinal diseases." The current literature studying the impact of Ramadan on gastrointestinal disorders shows that patients with IBD have a minimal risk of disease exacerbation, although older men with ulcerative colitis (UC) were more prone to exacerbation during fasting. Patients with duodenal ulcers were at a higher risk of hemorrhage after Ramadan fasting. Although with mixed results, studies show patients with liver disease demonstrated improvements in liver enzymes, cholesterol, and bilirubin after Ramadan. Physicians should offer pre-Ramadan counseling to educate patients on the risks of fasting and encourage shared decision-making. To facilitate more definitive discussions between the physician and a Muslim patient, clinicians should seek a deeper understanding of how Ramadan fasting affects certain health conditions and offer accommodations, such as diet and medication adjustments.
... 8 During Ramadan, T2DM patients, may experience health issues due to changes in meal times, food patterns, medication use, and lifestyle changes. [9][10][11] Many Muslim patients with T2DM fast during Ramadan. The Diabetes and Ramadan International Alliance (DAR) and The International Diabetes Federation (IDF) have developed comprehensive guidelines for diabetes patients aiming to fast during Ramadan. ...
Article
Full-text available
Background: During Ramadan fasting there are changes in meal frequency, eating pattern, rhythm in life, the sleep cycle, and daily activity. Most people with uncomplicated type 2 DM (T2DM) fast during Ramadan in Bangladesh. Objective: To assess the knowledge, attitude, and practices of people of Bangladesh with T2DM about Ramadan fasting. Methods: The survey enrolled 3835 adult people with T2DM (age 49.4±11.8 years; mean±SD; 57.4% female) through 17 endocrine outpatient centers in Bangladesh. Patient enrolment started one month before Ramadan in 2021. The survey questionnaire comprised 25 questions that addressed the characteristics of study subjects, their knowledge and attitude towards fasting, their lifestyle, and usual practices to control blood glucose during Ramadan. Result: About 83.3% of participants intend to fast. Most were aware of the necessity of pre & post-Ramadan health checkups (48% and 77% respectively). The participants were aware of risks during fasting like hypoglycemia (58.6%), dehydration (64.6%) & uncontrolled DM (74.0%). Near seventy percent answered that they could control diabetes by themselves, and similar proportion did follow the doctor's advice of medication adjustment. The necessity of glucose monitoring was known by 47% while 49% knew what to do if hypoglycemia occurs. However, 36.9% believed finger pricking would break the fast; and 18% said they would not break the fast despite hypoglycemia. Conclusion: Most Bangladeshi adults with T2DM fast during Ramadan, and their knowledge, attitude, and practices are good, but still, some have myths, particularly about monitoring of blood glucose by finger pricking & breaking fast due to hypoglycemia during Ramadan fasting.
... Dua jenis jadwal dosis yang berbeda biasanya digunakan selama bulan Ramadhan. Bila asupan biasa adalah pagi atau siang hari, dokter harus berhati-hati saat menunda asupan hingga malam hari agar tidak mengubah kemanjuran pengobatan atau toleransi obat (Aadil et al., 2015). ...
Article
Full-text available
The holy Ramadan season offers the best chance to maintain a healthy lifestyle because a Muslim can control his eating habits by fasting. Fasting during Ramadan is healthy for a variety of conditions, including those that affect pregnant women, people with diabetes, kidney disease, high cholesterol, obesity, hypertension, the hormone cortisol, the immune system, people who have peptic ulcers, and people who have cancer. This community service aims to educate people about drug use during Ramadan and drug use that does not break fasting. The program's results highlight that patients comprehend facts about drug use and the kinds of medications that don't break the fast during Ramadan.
Article
Although Muslims are a growing population within many non-Muslim countries, there are insufficient Muslim clinicians to care for them. Studies have shown that non-Muslim clinicians have limited knowledge and understanding of Islamic practices affecting health, which may lead to disparities in the quality of healthcare delivery and outcomes when caring for Muslim patients. Muslims come from many different cultures and ethnicities and have variations in their beliefs and practices. This literature review provides some insights which may strengthen therapeutic bonds between non-Muslim clinicians and their Muslim patients resulting in improved holistic, patient-centered care in the areas of cancer screening, mental health, nutrition, and pharmacotherapy. Additionally, this review informs clinicians about the Islamic perspective on childbirth, end of life issues, travel for Islamic pilgrimage, and fasting during the month of Ramadan. Literature was sourced by a comprehensive search in PubMed, Scopus, and CINAHL along with hand screening of citations. Title and abstract screening followed by full-text screening excluded studies including less than 30% Muslim participants, protocols, or reporting results deemed irrelevant to primary care. 115 papers were selected for inclusion in the literature review. These were grouped into the themes of general spirituality, which were discussed in the Introduction, and Islam and health, Social etiquette, Cancer screening, Diet, Medications and their alternatives, Ramadan, Hajj, Mental health, Organ donation and transplants, and End of life. Summarizing the findings of the review, we conclude that health inequities affecting Muslim patients can be addressed at least in part by improved cultural competency in non-Muslim clinicians, as well as further research into this area.
Chapter
Fasting during the month of Ramadan, the ninth month of the lunar calendar, is one of the five pillars of Islam. It represents a model of intermittent daily cycle of fasting/refeeding and is characterized by abstention from food, drink, smoking, and medications from sunset to predawn. The duration of fasting varies from 12 to 20 h according to geographic location and season. Meals are allowed from sunset to predawn. Ramadan fasting is observed in healthy subjects and those with comorbidities. Ramadan fasting may be associated with fatigue, dehydration, volume contraction, disrupted sleep patterns, and impaired renal function. Further, in the diabetic hypertensive subject, fasting may predispose to additional adverse health outcomes including altered blood pressure and glycemic control, hypoglycemic/hyperglycemic episodes, ketoacidosis, hypotension, and hyperosmolar hyperglycemic syndrome. However, in most subjects except those with chronic kidney disease grade 3/5, fasting is safe and associated with improvement in metabolic systemic and renal functional variables. Management of the diabetic hypertensive subject requires continuation of the prefasting antihypertensive and antidiabetic therapeutic regimen. However, the use of antidiabetic drugs may be associated with risk of hypoglycemic episodes. Use of antidiabetic agents with a low risk of hypoglycemia is advisable although other classes of glucose lowering actions may be prescribed. The class of SGLT2 inhibitors affords additional cardiorenal and metabolic protection.
Chapter
Full-text available
Data obtained from observational studies have shown that patients with untreated hypertension display an increased incidence of type 2 diabetes mellitus compared with the normotensive state. They have also shown that this phenomenon is made worse when thiazide diuretics or beta-blockers are administered chronically. Pathophysiological mechanisms recognize in inflammation and impaired insulin sensitivity the principal factors responsible for the new-onset diabetes in hypertensive subjects in particular when affected by concomitant presence of obesity, metabolic syndrome, and heart failure. Patients at high cardiovascular risk needing far a primary and/or secondary prevention with statins have also shown that the use of these drugs are associated with development of new-onset diabetes or worsening of glycemic profile. This could be attributed to the pathophysiological mechanisms of statins that induce an impaired insulin sensitivity and an inflammatory status. This paper will review the above data and discuss their clinical implications for protection of patients from hypertension or dyslipidemia based on current treatment of these conditions.
Chapter
The major cause of morbidity and mortality in diabetes is cardiovascular disease due to microvascular and macrovascular disease. Macrovascular disease in diabetes is typically associated with atherosclerosis and calcification leading to heart disease and stroke. Microvascular disease leads to retinopathy, nephropathy and neuropathy. Clinically this manifests as reduced vision and blindness, kidney dysfunction and peripheral neuropathy—major complications of diabetes. Vascular effects in diabetes are exacerbated by hypertension and other comorbidities, such as obesity and dyslipidaemia. Accordingly, diabetes and hypertension are closely interlinked due to similar risk factors such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidaemia and obesity. Pathophysiological processes that cause diabetes-associated vasculopathy include hyperglycaemia and insulin resistance. Molecular mechanisms that underlie microvascular and macrovascular disease include oxidative stress, inflammation, activation of the immune system, miRNAs and advanced glycation end products (AGEs). This chapter discusses the vasculopathy in diabetes and discusses the pathophysiology and molecular mechanisms of vascular complications associated with diabetes.
Article
Full-text available
The rule of Ramadan (1 month of food and water intakes restricted to night hours) is followed by the majority of the Moslem fraction of the human population, but the possible consequences of this long-lasting modification of food intake schedule on public health have not yet been extensively documented. Therefore, a group of healthy control subjects and a group of healed duodenal ulcer patients were studied before (controls), during (both groups), and after (both groups) the month of Ramadan. The time-restricted food and water intakes were associated with variations of gastric pH, plasma gastrin, insulin, glucose, and calcium documented on a circadian basis. All of the studied biological variables, except insulin, underwent changes in their 24-h mean concentration (e.g. decrease in gastric pH, increase in plasma gastrin), some of which were still present 1 month after the end of Ramadan. The circadian patterns of all the studied variables were altered during the month of Ramadan. Some differences between the group of healthy control subjects and the group of healed duodenal ulcer patients may suggest a greater susceptibility of the latter to the modifications of feeding and sleeping schedule, which could possibly be a risk factor for the disease.
Article
Between 1981 and 1985, a total of 289 patients were seen at our anticoagulation clinic. Two hundred and forty-seven received long-term oral anticoagulation therapy because of a cardiac condition, 42 for deep vein thrombosis with or without pulmonary embolism. While on treatment, 106 patients fasted 309 Ramadan months and 183 patients elected not to fast during 594 Ramadan months. The incidence of thromboembolic events and hemorrhagic complications in the two groups was compared and no statistically significant differences were found. We conclude that Ramadan fasting, or any other form of short-term fasting, has no adverse effects on the efficacy and safety of long-term oral anticoagulation.
Article
This paper reports the results of a survey of 325 out-patients in the hospitals of Kuwait concerning the Moslem practice of fasting during the hours of daylight in the month of Ramadan and the consequences on the drug regimen of patients. More than 60% of patients were found to change the way in which they took their medicines at this time. Particularly in elderly patients this could lead to potentially serious drug interactions and toxic side-effects. The report recommends a greater awareness amongst the prescribers of the problems which can occur in this way, and better counselling of patients so that they understand the potential hazards of non-compliance and the importance of the prescribed regimen for their treatment.
Article
The effects of fasting on the drug regimens of 81 Asian Moslem patients during the religious month of Ramadan have been examined. Twenty-two male and 15 female patients were found to change their drug dosage pattern while fasting: 35 missed doses; 8 took their tablets at different times and 4 patients took all their medication as one single daily dose after breaking fast in the evening. The consequences of these changes are discussed and ways in which the problems which arise may be overcome are examined.
Article
We report four female patients with nodular goiter (in two of the four due to Hashimoto's thyroiditis) and one male patient with frank hypothyroidism due to Hashimoto's thyroiditis in whom TSH-suppressive or replacement L-T4 therapy failed to suppress or, respectively, normalize serum TSH. As is typical in our country, our patients took L-T4 15-20 min before a light breakfast. Gastrointestinal or other diseases and drugs known to interfere with the intestinal absorption of L-T4 were not the cause of this failure. The gastrointestinal absorption test of L-T4 (1000 micrograms) was performed in four patients; in three patients it revealed peculiar abnormalities in that (i) the absorption peak was > 70% but occurred at 4 hr vs an average of 2 hr in 12 euthyroid controls (EC) and 3 hr in the 10 primary hypothyroid controls (HC); (ii) 50% of the maximal absorption occurred at 110 min vs 45 min in EC and 50 min in HC; (iii) the maximal increment in T4 absorption was between 90 and 120 min (+111%) vs between 30 and 60 min in EC (+312%) and HC (+354%). In sum, only the first part of the absorption curve of T4 was shifted to the right (in three of the four women) and this shift was more pronounced and extended to the second part of the curve in the fourth patient; in this last patient absorption peak was 44% at 180 min. Based on these results, we obtained full suppression or normalization of TSH by postponing breakfast for at least 60 min after T4 ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Clinical studies were performed to examine the oral bioavailability of alendronate (4-amino-1-hydroxy-butylidene-1,1-bisphosphonate monosodium). All studies, with the exception of one performed in men, involved postmenopausal women. Short-term (24 to 36 hours) urinary recovery of alendronate after an intravenous dose of 125 to 250 micrograms averaged about 40% in both men and women. In women, oral bioavailability of alendronate was independent of dose (5 to 80 mg) and averaged (90% confidence interval) 0.76% (0.58, 0.98) when taken with water in the fasting state, followed by a meal 2 hours later. Bioavailability was similar in men [0.59%, (0.43, 0.81)]. Taking alendronate either 60 or 30 minutes before a standardized breakfast reduced bioavailability by 40% relative to the 2-hour wait. Taking alendronate either concurrently with or 2 hours after breakfast drastically (> 85%) impaired availability. Black coffee or orange juice alone, when taken with the drug, also reduced bioavailability (approximately 60%). Increasing gastric pH, by infusion of ranitidine, was associated with a doubling of alendronate bioavailability. A practical dosing recommendation, derived from these findings and reflective of the long-term nature of therapy for a disease such as osteoporosis, is that patients take the drug with water after an overnight fast and at least 30 minutes before any other food or beverage.
The effect of a high-fat meal on the bioavailability of free acid phenytoin (DPH) from Hydantol powder with a large particle size (mean particle size, 190 microns) was investigated in four healthy male subjects. The drug was administered as a single oral 5 mg/kg dose of free acid DPH in the fasting state, with a low-fat meal, or with a high-fat meal using a crossover study design. Seven blood samples were collected over a 34-h period following drug administration, and the drug plasma concentrations were determined by GLC. In comparison with the fasting state results, the mean area under the plasma concentration-time curve up to infinity after administration (AUC0-infinity) and the peak plasma concentration (Cmax) of DPH from Hydantol powder significantly increased about 2-fold with the intake of the high-fat meal and about 1.5-fold with the intake of the low-fat meal. The elimination rate constant was not significantly different among the three treatments. The increased bioavailability with the high-fat meal probably resulted from accelerated dissolution of the poorly soluble Hydantol powder due to the stimulation of bile flow or delay of the gastric emptying time caused by the fat intake.