Project Title
Drugs in Pregnancy (indications &
contraindications)
Project supervisor Dr.Rafiq R. A. Abou-Shaaban
Jan.2001
A research presented by
Student name: Rana Rasheed Al- Hassan
Student No : 9860295
Ajman University for Sciences and Technology
Abu Dhabi Branch
UAE
Research for this project was carried out by me during the period of Hospital
Pharmacy Training-1 no.700315 (academic year 2000-2001)
Signed Date Jan 10th 2000
ACKNOWLEDGMENTS
Sincere gratitude were extended to Dr. Rafeeq Abu Shaaban from the
pharmaceutical department, to the support, encouragement and fruitful
accompaniment through out the training and presentation of this project.
The author is indebted to project supervisor Dr Asim Ahmed, for the
continuous follow up, constructive criticism, and valuable comments.
The author wishes to express special gratitude and thanks to those
contributing in this revolutionary, distinctive and advanced Hospital
Pharmacy training 1; namely Dr.Danna Sallam and the staff of the
New Medical Center Hospital.
Finally the author wishes to express heartfelt thanks to Dr. Abduelmula
in- Charge of the Central training committee for furnishing the entire
Clinical Pharmacy services as far as this term is concerned.
2
INDEX
Description Page No.
Section l Introduction
1.0 The Drug effects on fetus
1.1 Malformation
1.2 Table of FDA categories
Section II
2.0 Hypertension in Pregnancy
2.1 Anti- hypertensives
2.2 adverse effect of anti-hypertensive drugs
2.3 Introduction to Malaria in pregnancy
2.4 Anti- malaria’s
Section III
3.0 Introduction Of Cardiovascular Disorders in pregnancy
3.1 Drugs used
a) Anti- arithmetic’s
Two) Anti- thrombotics
Three) Anti- anginal
Four) Lowering lipid agents
3.2 Introduction Tuberculosis During pregnancy
3.3 Anti- tuberculosis
3.4 Headaches during pregnancy
SectionIV
Antibiotics in pregnancy
4.0 Table
3
4.1 Drugs indicated in pregnancy
Section V
Contraindications of Drugs Used in Pregnancy
5.0 Drugs
5.1 Drugs and classifications
5.2 Risk of drugs
Section VI
Treatment of disease in tables during pregnancy (Indicated)
6.0 Schizophrenia
6.1 Depression
6.2 Bipolar illness
6.3 Panic disorders
6.4 Compulsive disorder
Conclusion
4
Section I:
1.0 Introduction:
Drugs can have harmful effects on the fetus at any time during pregnancy. It is
important to bear this in mind when prescribing for women of childbearing age.
During the 1st trimester drugs may produce congenital malformation (teratogenisis),
and the period of greatest risk is from the 3rd to the 11th week of pregnancy. The term
“congenital malformation” is defined as structural abnormalities of parents origin that
are present at birth and that seriously interfere with viability or physical well being”.
During the 2nd and 3rd trimesters drugs may affect the growth and functional
development of the fetus or have toxic effects on fetal tissues; and drugs given shortly
before term or during labour may have adverse effects on labour or on the neonate
after delivery.
The following list includes drugs, which may have harmful effects in pregnancy and
indicates the trimester of risk. It’s based on human data but information on animal
studies has been included for some newer drugs when it’s omission might be
misleading.
Drugs should be prescribed in pregnancy only if the expected benefit to the mother is
thought to be greater than the risk to the fetus; and all drugs should be avoided if
possible during the 1st trimester. Drugs, which have been extensively used in
pregnancy and appear to be usually safe should be prescribed in preference to new or
untried drugs; and the smallest effective does should be used.
Few drugs have been shown conclusively to be teratogenic in man but no drug is safe
beyond all doubts in early pregnancy. Screening procedures are available where there
is a known risk of certain defects.
5
1.2 FDA Categories of drug safety during pregnancy:
Category Description
A Controlled human studies have
demonstrated no fetal risks; these drugs
are the safest
B Animal studies show no risk to the fetus
and no control human studies have been
conducted, or animal studies show a risk
to the fetus but well – controlled, human
studies do not.
C No adequate animal or human studies
have been conducted, or adverse. Fetal
effects have been shown in animals but
no human data are available.
D Evidence of human fetal risk exists, but
benefits may outweigh in certain
situations (e.g. life-threatening conditions
or serious diseases in which safer drugs
can’t be used or are ineffective)
X Proven fetal risks outweigh any possible
benefit.
6
Section II
2.0 Pregnancy and Hypertension:
Chronic hypertension, defined as hypertension diagnosed before pregnancy or before
20 weeks' gestation complicates from 1 percent to 5 percent of all pregnancies. The
Incidence is expected to rise as the demographic trend towards childbearing at older
Ages continue. Chronic hypertension in pregnancy is associated with:
Serious maternal and fetal complications, including superimposed preeclampsia.
1. Fetal growth retardation.
2. Premature delivery.
3. Placental abruption.
4. Stillbirth.
ACE inhibitors are contraindicated in pregnancy because of possible
teratogenicity.
B- blockers may cause neonatal hypoglycemia and bradycardia and low birth
weights, have been associated with Atenolol. A number of studies have shown that
Labetolol is effective and safe in the control of hypertension in pregnancy.
Thiazides may produce low platelet count and also cause a fall in plasma volume.
Ca++ channel blockers may inhibit labour and some of those agents may be
teratogenic in animals.
MethylDopa has an important role to play in hypertension in pregnancy.
2.1Antihypertensives drugs used in pregnancy:
All thiazide-like drugs cross the placenta, but no teratogenic effects on the fetus have
been observed.
However, transient volume depletion may result in placenta hyperperfusion. Diuretics
should also be avoided by nursing mothers since they appear in the mother’s milk.
7
Beta-adrenergic antagonists may be used in pregnancy; controlled trials have not
supported initial fears about induction of premature labor, neonatal hyperglycemia or
small newborns. Selective beta-blockers should be preferred to non-selective beta-
blockers.
Alpha-adrenergic antagonists are not recommended, because of missing data. From
the centrally acting agents methyldopa is often used for treatment of hypertension in
pregnancy.
Vasodilators like hydralazine can be used in pregnancy, with caution during the first
trimenon.
Calcium blocking agents should not be given during pregnancy and lactation. If
administered, calcium-blockers of the non-dihydropyridine type should be preferred.
ACE-inhibitors and AT-I-receptor blockers are contraindicated, because they cause
fetal injury and death.
2.2 Adverse Effects of Antihypertensive Agents in pregnancy:
The methodological quality of research evidence addressing adverse effects of
Anti-hypertensive drug therapy in pregnant women is weak. Establishing causation in
Pregnancy with de-challenge/re-challenge tests is not feasible and large clinical trials
Enrolling pregnant women have not been done. Adverse teratogenic effects are
studied
Primarily in animal studies, and adverse effects in pregnant women are most often
Described in case reports. Thus, limited information on the incidence and magnitude
of adverse effect risks is available.
Regardless, several anti-hypertensive agents have been associated with specific
Adverse events:
Angiotensin-converting enzyme (ACE) inhibitors used in the second or third
Trimester have caused renal dysfunction in the fetus, leading to oligohydramnios
And anuria. ACE inhibitors have been associated with pulmonary hypoplasia,
Growth retardation, and a unique hypoplasia of the fetal skull.
Among the beta-blockers, atenolol, especially when started early in pregnancy,
8
Has been associated with fetal growth retardation in several uncontrolled studies
And one small trial. In most studies, the causal nature of the association was
Unclear either because multiple agents were administered simultaneously or
because of inability to separate effects of the mother's underlying pathophysiology
from effects of the drug.
Labetalol has been associated with intrauterine growth retardation in three
Randomized trials of hypertensive disorders other than chronic hypertension.
Other beta-blockers, such as metoprolol, pindolol, and oxprenolol, have not been
associated with intrauterine growth retardation, but available data concerning
these agents, particularly when started early in pregnancy, are scarcer than
For atenolol and labetalol.
2.3 Malaria During pregnancy:
Malaria during pregnancy poses a serious threat to both the mother and fetus. If travel
to an endemic area is unavoidable, chemoprophylaxis with at least chloroquine should
be given. The safety of mefloquine during pregnancy is under study, but limited
experience suggests that it may be safe after the 16th wk of gestation. The safety of
pyrimethamine/sulfadoxine during pregnancy has not been established. Doxycycline
and primaquine should not be used during pregnancy.
Once a person leaves an endemic area, functional resistance lasts only a few months
and protects against only those parasite strains to which the person was exposed.
2.4 Anti-Malarias in pregnancy:
Malaria in a pregnant woman should be promptly and effectively treated. It is
recommended that the total dose of chloroquine be calculated on weight basis, i.e. 25
mg/kg body weight, and given over a period of 3 days. Quinine should be reserved for
resistant cases. In an attempt to counteract any stimulant action of quinine on the
uterus, some obstetricians recommend the concurrent use of a tocolytic agent.
Pyrinethamine + sulphadoxine combination is to be avoided if possible.
9
Section III
3.0 Cardiovascular Disorders in pregnancy:
Cardiovascular disorders during pregnancy, delivery and lactation are not too
frequent, but potentially deleterious. The most common problem is hypertension,
occurring in up to 10% of pregnancies. Three out of four cases of hypertension during
pregnancy are pregnancy-induced. Maternal mortality in eclampsia varies between
0% and 13,9%, the average mortality being 3,1%.
Worldwide 50 000 pregnant women die annually of this disease, mainly due to
cerebral bleeding or acute left hearts failure. Fetal morbility and mortality are also
high, varying from 0,6% - 7,1% in pre-eclampsia to 7,7% - 60% in HELLP-syndrome
(Hemolysis, Elevated Liver enzymes, Low Platelets).
Other cardiovascular problems during pregnancy include cardiomyopathy, heart
failure and arrhythmia.
Problems may also arise from patients with congenital or aquired valve disease or
artificial heart valves when becoming pregnant.
Many commonly used drugs for the treatment of cardiovascular diseases like
ACE-inhibitors, AT-I-blockers, cumarines and statines are contraindicated during
pregnancy, at least during the first 12 weeks, because of their teratogenic effects.
Some drugs may cross the placenta or appear in the mother’s milk and thereby cause
fetal injury or damage to the newborn.
During the session "Drug Therapy of Cardiovascular Problems in Pregnancy" the
treatment options we have to handle cardiovascular problems in pregnancy and
lactation are discussed.
10
3.1 Antiarrhythmics in Pregnancy:
Sodium channel blockers, have no teratogenicity, but should only be administered if
necessary.
Sotalol should not be used in the third trimenon as the blood flow of the placenta may
be reduced, which could lead to early delivery as well as to bradycardia and
respiratory problems in the newborn.
Amiodaron passes the placenta and is contraindicated during pregnancy.
Antithrombotics In Pregnancy :
Low dose aspirin has been used a lot during pregnancy and should be avoided only
during the last trimenon, because of bleeding risk.
Ticlopidine should only be given if absolutely necessary and phenprocoumon is
contraindicated because of teratogenicity.
Heparin and low molecular weight heparins may be used during pregnancy under
careful observation.
Antianginal drugs In Pregnancy:
Organic nitrates can be given during pregnancy and may be very effective in the
treatment of eclampsia. Since there are no data of molsidomine and nicorandil, these
drugs should not be administered.
11
Lipid lowering drugs In Pregnancy :
Nicotinic acid should not be used, unless it is absolutely essential to prevent life-
threatening pancreatitis.
Fibric acids are contraindicated in pregnant and nursing women. Bile acid binding
resins should probably not be administered during pregnancy. Statines have
teratogenic effects in animals and are contraindicated in pregnant women.
3.2 Tuberculosis during Pregnancy
There is no evidence to support an increased risk of tuberculosis disease during
pregnancy, and neither is there evidence that would indicate an increased relapse of
tuberculosis infection provided that pregnant women are treated adequately. The one
exception is in pregnant women with HIV infection and previously infected with
tuberculosis.
It is, however, essential to detect maternal tuberculosis disease early and to treat
adequately if the serious potential risk of tuberculosis disease in the fetus and new
born is to be reduced.
Ante-natal screening should include consideration of the possibility of increased
tuberculosis risk in any mother from a high risk group and appropriate screening
procedures applied using Mantoux testing and CXR where necessary (with suitable
monitoring of the fetus).
Isoniazid preventive therapy should be used in exactly the same context as for a non-
pregnant person, but with careful attention to liver function testing at regular (at least
monthly) intervals.
Treatment of active tuberculosis disease during pregnancy is mandatory. There is no
evidence that standard first line drugs (rifampicin, isoniazid, ethambutol, and
pyrazinamide) represent anything other than a negligible teratogenic risk. Injectable
12
drugs such as streptomycin, capreomycin, and other amino-glycosides have a high
risk of fetal oto-toxicity, and must not be used during pregnancy.
Standard treatment policies should be employed as described elsewhere, and the risk
of drug toxicity evaluated against the risk of fetal and maternal tuberculosis.
Tuberculosis during pregnancy is generally not considered to be an indication for
termination of pregnancy.
In cases of known drug resistance of disease, alternative drugs have much higher risks
of toxicity and the risk of the infection to both mother and fetus has to be evaluated
carefully against the risk of toxic effects and teratogenicity. In this context,
termination of pregnancy may be justifiable.
The use of BCG vaccine is specifically contraindicated during pregnancy due to the
risk of placental transfer of infection to the fetus.
3.3 Antituberculous Drugs In Pregnancy:
Isoniazid, ethambutol and pyrizinamide can be safely used. No serious
teratogenicity has been reported with the use of rifampicin. However, there are a few
reports of bleeding in neonates due to hypoprothrombinemia. It may, therefore, be
advisable to give Vitamin K to the mother near term.
Recommendations for the initial treatment of tuberculosis in pregnant women
include the drugs isoniazid (INH) and rifampin. If resistance to INH seems likely,
ethambutol should also be added. Isoniazid has not been shown to cause birth defects
or other fetal harm in humans. Neither has its use been demonstrated to cause birth
defects in animal studies, although the drug may cause embryo death in rats and
rabbits and can cause lung cancer in specific strains of mice. It is FDA category C.
when INH is prescribed during pregnancy, pyridoxine (Vitamin B6) should be
concurrently taken. Rifampin causes birth defects in rodents. Its effect on the human
fetus, either alone or in combination with other antituberculous drugs, is unknown.
13
Ethambutol is not known to produce adverse effects on the human fetus, although data
is limited, and the drug’s effects when it is used in combination with other
tuberculosis drugs is not known. Streptomycin, another antituberculous agent, should
not be used during pregnancy, since it can cause adverse fetal effects. Other
antituberculous drugs should also be avoided because their effects on the fetus have
not been adequately evaluated.
3.4 Headaches in pregnancy
Headaches are common in pregnancy, especially in the first trimester. Hormonal
changes, dietary changes, and cardiovascular changes are partial factors. For some,
quitting coffee can lead to withdrawal headaches early on. For others, it's stress and
tension headaches. Migraines can be triggered by estrogen, high in pregnancy. If the
headaches are mild, cremedies take precedence, such as increasing rest, neck and
scalp massage, cold packs, stress reduction, etc. For stronger headaches, the patient
needs to be evaluated. The use of any medication, prescription or not, natural or not,
requires an understanding of the risk/benefit ratio. This concept is as follows:
1. What is the risk of using the product, and what is
The benefit of using it?
AND the second part of this is...
2. What is the risk of NOT using the product, and
The benefit of NOT using it.
The choice is made after weighing these factors. Tylenol (acetaminophen) at any
stage in pregnancy, not to exceed the package dosing. Tylenol taken in moderation
has an excellent safety profile, yet Tylenol overdose can be lethal due to liver damage.
Aspirin products, included all the "ofens" (ibuprofen, ketoprofen, etc), are generally
to be avoided during pregnancy. Codeine, Vicodin, etc. are rarely used, but for serious
headaches may occasionally be indicated. Migraine drugs such as IMMITEX should
NOT be used... they constrictblood vessels.
14
Section IV
4.0 Antibiotics Used in Pregnancy
Two factors must be taken into consideration for the selection of an antibiotic in
pregnancy:
Altered pharmacokinetics
There is an increase in volume of distribution, glomerular filtration rate and hepatic
activities especially in late pregnancy with the result that serum concentrations may
be as much as 50% lower compared with the non-pregnant women.
Toxicity to the fetus
Most antibiotics cross the placenta and are present in measurable amounts in foatal
blood. The trimester of pregnancy will also determine the consequences of toxic
effects; e.g. many antibiotics are contra-indicated in the first trimester of pregnancy,
when organ development is occurring.
In general, full adult doses should be used when treating infections in pregnant
women. To compensate for accelerated elimination and reduced plasma levels shorter
dosage intervals or higher doses may be necessary. The B- lactams are regarded as
safe. The main problem is selection of an alternative antibiotic in a patient allergic to
B- lactams. Antibacterial drugs that are contraindicated or that should be used with
caution in pregnancy are shown, e.g. azithromycin, aztreonam, clarithromycin and
meropenem. Some antibiotics, e.g. co-amoxiclav & vanomycin are not recommended
unless essential.
15
Drug Trimester Adverse Drug effect
Aminoglycoside 2,3 Auditory or vestibular
nerve damage
Chloramphenicol 3 Neonatal “Grey
syndrome”
Imipenem Caution Toxicity in animal studies
Metronidazole 1,2,3 Avoid in 1st,high doses in
2nd & 3rd may be
mutagenic
Nitrofuranation 3 May produce neonatal
haemolysis if used at term
4- Quinolones 1,2,3 Arthropathy
Rifampicin 1,3 1st teratogenic in animal
studies,3rd neonatal
haemolysis &
methaemoglobinaemia
Sulphonamides 3 neonatal haemolysis &
methaemoglobinaemia
Tinidazole 1 Avoid
Trimethoprim 1 Possible teratogenic risk
Co- trimoxazole 1,3 As sulphonamides
Tetracyclines 1,2,3 Effects on skeletal
developments, dental
discoloration.
Bacterial infections in pregnant women are of special concern because of the
possible adverse effects of the infection, and the compromise of maternal health,
onfetal health and well being. An important concern is the risk to the fetus from
antibacterial therapy given to the mother.
16
Essentially all antibiotics cross the placenta, thereby exposing the fetus to their
effects. Moreover, there are only a limited number of studies that assess the safety and
efficacy of antibiotic therapy during pregnancy. In balancing the risks of treatment
against the risks to the fetus from disease in the mother, it is generally agreed that
protection of maternal health confers the greatest likelihood of a healthy outcome in
the newborn child. Infections of the urinary tract are the most common bacterial
infections that women experience during pregnancy. Bodily changes attributable to
Pregnancy increases the likelihood that an expectant mother will experience bacterial
growth in her urine. Perhaps seven percent of pregnant women experience such
bacterial growth without symptoms. Approximately thirty-three percent of these
prospective mothers will develop a serious infection of the kidney called
pyelonephritis. Women who display bacteria in their urine during pregnancy should
be treated with antibiotics. Pregnant women can also develop pneumonia, sexually
transmitted diseases, and other bacterially produced illnesses that are frequent in the
Non-pregnant population, as well as infections that are unique to pregnancy or the
postpartum period. For example, infection within the pregnant uterus can develop, and
may cause harm or death to the growing fetus.
During the postnatal period, mothers may contract infections of the uterine lining or
the nipples. Infections in the mother following delivery are the most common cause of
maternal mortality in the U.S. Nursing moms can pass medications to their children in
breast milk. For these women, antibiotic selection during the postnatal period is
particularly important.
Just as in the general population, infections that are likely to be of viral origin do
not respond to antibiotics, and ordinarily should not be treated with them. Examples
of such "self-limited" diseases include acute bronchitis or tracheobronchitis, sore
throats that are not caused by Group A Streptococcus bacteria (i.e., those sore throats
that are not considered to be "Strep Throat"), and head colds.
Anti-Fungal In Pregnancy:
Nystatin, micanazol and amphotericin are considered to be safe. There is some
Evidence of teratogenicity in animals with the use of ketoconazole and griseofulvin
but the significance of this in humans is uncertain.
17
Anti-Amoebic Agents In Pregnancy:
Metronidazole is safe in recommended doses. No fetal malformations have
Been reported. Diloxanide (for trophozoites in the gut) should be avoided since its
safety status is unclear.
4.1 Some Antibiotics in Pregnancy:
Penicillin’s In Pregnancy:
Penicillin’s, as a group is generally believed to be the antibiotics that are safest to
use during pregnancy. These drugs have been prescribed extensively in pregnant
women, without evidence that they are harmful to the fetus. Examples of this class of
antibiotic are penicillin G, penicillin V, ampicillin, amoxicillin, dicloxacillin, and
oxacillin. In addition, "extended spectrum" penicillins have been developed in recent
years that are active against an increased range of bacterial organisms. Because of the
resistance of some bacteria to penicillin, a number of newer agents that prevent or
limit bacterial resistance have also been created. One commonly used
example of such a drug is called Augmentin, which combines amoxicillin with a
chemical called clavulanic acid. The newer penicillins appear to be safe for use during
pregnancy as well.
Obviously, expectant and lactating mothers are susceptible to the possible side effects
of any antibiotic, two common examples of which are allergic reactions and diarrhea.
Cephalosporins In Pregnancy:
The Cephalosporins are chemically related to the penicillins, and are among the
most frequently prescribed antibiotics during pregnancy. They are FDA category B,
and most are believed to be safe for use during pregnancy. Some common examples
of Cephalosporins are cephalexin (Keflex), cefaclor (Ceclor), and cefixime (Suprax).
18
Macrolides In Pregnancy :
This class of antimicrobials includes erythromycin, azithromycin
(Zithromax) and clarithromycin (Biaxin). Erythromycin is considered to be safe for
use during pregnancy. It does not readily cross the placenta. This is a disadvantage in
the treatment of infections in which the fetus should also be treated. Both
azithromycin and clarithromycin have a broader spectrum of activity and fewer
gastrointestinal side effects than erythromycin. Erythromycin and azithromycin are
FDA category B drugs. Biaxin appears to have adversely affected pregnancy outcome
in some animal studies, but it has no known detrimental effects on human
pregnancies.
Sulfonamides In Pregnancy :
These drugs are the oldest class of antibiotics. The best known sulfonamide is
trimethoprim-sulfamethoxazole. It is marketed under the trade names Bactrim and
Septra. Bactrim is actually a combination of a sulfamethoxazole, a sulfonamide, and
trimethoprim, a drug, which belongs to another antibiotic class. Among its many uses,
Bactrim is frequently prescribed for urinary tract and respiratory tract infections.
Sulfonamides should not be used during the last trimester of pregnancy, or during
nursing, because they can produce jaundice in the newborn. Trimethoprim interferes
with folate metabolism, at least in bacteria. Since inadequate folate intake is
associated with birth defects in humans, trimethoprim and Bactrim probably should be
avoided during pregnancy.
Aminoglycosides In Pregnancy :
Examples of this class of drug include gentamycin, the most commonly
prescribed aminoglycoside during pregnancy, tobramycin, and streptomycin. Known
side effects in those taking the drug includes kidney and hearing injury. However,
gentamycin has not been shown to cause birth defects, or damage kidneys or hearing
19
in the fetus. Gentamycin is an FDA category C drug, and may be used when its
benefits outweigh the risks of its use. Examples of such situations include certain
pelvic, heart valve, or kidney infections.
Tetracycline’s In Pregnancy :
Tetracycline’s are FDA drug category D, and should not be used during
pregnancy unless no other alternatives are available. Tetracycline’s cross the placenta,
and will deposit in fetal teeth causing discoloration if they are given after the fifth
month of pregnancy. Tetracylines may also cause other, more serious, birth
abnormalities. Some representative examples of tetracylines are
tracycline, doxycycline Vibramycin), and minocycline (Minocin). Tetracycline use
has been associated with liver damage in pregnant women.
Floroquinolones In Pregnancy :
This class of antimicrobials includes drugs such as ciprofloxacin (Cipro),
norfloxacin (Noroxin), and ofloxacin (Floxin). They are FDA category C.
Floroquinolones should be avoided during pregnancy and breast feeding because of
concerns about possible detrimental effects on cartilage and joint development in the
developing fetus and infant.
Nitrofurantoin (Macrobid, Macrodantin) In Pregnancy :
This drug is mainly used during pregnancy to treat urinary tract infections. It has
not been shown to cause harmful effects on the human fetus. Nor has it caused
adverse effects on the fetus in animal studies. However the drug’s safety in pregnant
women has not been established. Moreover, nitrofurantoin should not be used in
women at term.
20
Vancomycin In Pregnancy :
Vancomycin has several clearly defined uses in pregnancy. Among these are
infections caused by Staphylococcus Aureus bacteria, commonly known as "staph
infections," that are resistant to other drugs; certain heart valve infections; and
intestinal infections with toxic strains of the bacterium Clostridium Difficile.
Vancomycin is typically administered intravenously since its oral absorption is poor,
but when the antibiotic is used to treat intestinal infections, it is taken by mouth.
Vancomycin can cause hearing and kidney damage in recipients of the drug, but is not
known to cause fetal harm.
Clindamycin (Cleocin) In Pregnancy :
It is indicated for a number of infections during pregnancy, including certain pelvic
infections. It is also used to treat postpartum uterine infections. Clindamycin is not
known to cause fetal harm.
Spectinomycin In Pregnancy :
Spectinomycin is related to the aminoglycoside antibiotics. Is not known to cause
fetal harm. It can be an effective alternative for the treatment of gonorrhea infections
pregnant women who are allergic to penicillin and cephalosporin drugs.
Metronidazole (Flagyl) In Pregnancy :
Metronidazole is used to treat trichomonas vaginal infections, which can be the
cause of significant vaginal irritation. It has not been demonstrated to be harmful to
human fetuses. Metronidazole does cause cancer in rodent studies. However, this
effect has not been demonstrated in other animal models. The drug should not be
prescribed during the first trimester of pregnancy, and should only be used if clearly
needed.
21
Section V
5.0 contraindicated Drugs in Pregnancy
Accutane:
Isotretinoin may increase the level of blood fats, sometimes to risky levels.
Occasionally it may affect the liver. That's why regular blood tests are necessary
When you are taking isotretinoin; these tests must be done when you have fasted
For 12 hours (no breakfast), so that the blood fat determinations are reliable. A
Baseline blood chemistry test is established before patients start isotretinoin.
The most damaging side effect of isotretinoin is serious birth defects if taken during
pregnancy.
It is critically important for women not to take isotretinoin while pregnant, and not to
become pregnant while taking it. Women who are, or expect to be, sexually active
while taking isotretinoin must use an effective method of birth control. This usually
means oral contraceptive pills and one other additional method of birth control such
as condoms for the male partner. A woman who does get pregnant while on
isotretinoin must be prepared to have an abortion and must state this in writing before
many physicians will prescribe isotretinoin for her.
A women who has taken Accutane should not get pregnant until one month after
stopping the medication. After that time, it's safe to become pregnant. Because the
birth defects caused by isotretinoin are so serious, it's important not to share the
pills with others.
We don't know whether isotretinoin taken by men can cause birth defects, so it's
best not to get a woman pregnant while taking isotretinoin. If she is not using birth
control, the man should use a condom.
22
There are a few reports of patients having decreased night vision after using
Accutane. One patient still had problems six months after the drug was stopped. If
you experience trouble with your vision while on Accutane, call the office right
away. Some people develop headaches while on Accutane.
Accutane rarely causes depression and thoughts of suicide. If this were to
occur stop the medicine immediately.
5.1 Some Other Drugs & Classification in Pregnancy:
Amitriptyline and Perphenazine
Classification: Antidepressant
Uses: Depression with moderate to severe anxiety and/or agitation. Depression and
anxiety in clients with chronic physical disease. Also schizophrenic clients with
symptoms of depression.
Contraindications in Pregnancy:
Use during pregnancy. CNS depression due to drugs. In presence of bone marrow
depression. Concomitant use with MAO inhibitors. During acute recovery phase from
MI. Use in children.
Triazolam:
Class: Hypnotic
Triazolam is a benzodiazepine with a very short elimination half-life (about 3 hours).
Contraindications in Pregnancy:
In-patients with known hypersensitivity to this drug or other benzodiazepines.
Triazolam is contraindicated in patients who in the past manifested paradoxical
reactions to alcohol and/or sedative medications, and in subjects with a history of
substance or alcohol abuse.
23
Pregnancy:
Triazolam is contraindicated in pregnant women. Benzodiazepines may cause fetal
damage when administered during pregnancy. During the first trimester of pregnancy,
several studies have suggested an increased risk of congenital malformations
associated with the use of benzodiazepines. During the last weeks of pregnancy,
ingestion of therapeutic doses of a benzodiazepine hypnotic has resulted in neonatal
CNS depression due to transplacental distribution. If triazolam is prescribed to
Women of childbearing potential, the patient should be warned of the potential risk to
a fetus and advised to consult her physician regarding the discontinuation of the drug
if she intends to become pregnant.
Triazolam is contraindicated in patients who have myasthenia gravis or a history of
uncorrected narrow-angle glaucoma.
5.2 Benefits and Risks of Drug Treatment in Pregnancy:
Because of the potential for teratogenesis and other adverse events in the fetus or
newborn, varying degrees of concern exist when any drug is prescribed during
pregnancy. Avoidance of pregnancy and avoidance of drug therapy during pregnancy
are commonly suggested strategies to prevent fetal drug exposure. However, these
strategies are often not possible. It frequently becomes necessary to contemplate
pharmacotherapy following counseling of a pregnant woman who has a serious
psychiatric illness, because the benefit of appropriate psychoactive drug treatment has
been clearly established.
Drug treatment is indicated if psychotherapy is inadequate or inappropriate for the
patient's severity of illness. Once a decision to offer pharmacotherapy is made,
important factors in drug selection for the mother include efficacy of the drugs
available, the anticipated response of the individual patient, and the overall toxicity
profile of the drug for the mother and fetus.
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Section VI
6.0 Treatment of Schizophrenia during Pregnancy:
Generic Name Trade Name
Risperidone Risperdal
Fluphenazine Prolixin
Haloperidol Haldol
Pimozide Orap
Thiothixene Navane
Trifluoroperazine Stealzine
Perphenazine Trilafon
Molindone Moban
Loxapine Loxitane
Prochlorperazine Compazine
Triflupromazine Vesprin
Chlorprothixene Taractan
Messoridazine Serentil
Clozaril Clozapine
Chlorpromazine Thorazine
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Remarks
Neonatal effects: Signs at delivery associated with exposure to the low-potency
group include tachycardia, gastrointestinal dysfunction, sedation, and hypotension.
Depending on the extent of exposure, these reactions seldom persist for more than a
few days. Extrapyramidal signs that are associated with large maternal doses of
high-potency antipsychotics include hyperactivity, hyperactive deep tendon reflexes,
motor restlessness, and abnormal movements. These may persist for several months.
Additional signs reflecting extrapyramidal activity include tremors, posturing and
flapping of the hands, increased muscle tone, unusually vigorous rooting and
sucking, arching of the back, and shrill crying. Teratogenic effects: Haloperidol,
perphenazine, thiothixene and trifluoperazine do not have a known teratogenic
action based on either animal data or limited surveillance data in humans. The lower
potency agents, particularly chlorpromazine, have been cited as being teratogenic by
some authors; however, surveillance data do not support this finding for
chlorpromazine, prochlorperazine, triflupromazine or thioridazine. Most
antipsychotic agents are not known to cause structural birth defects. Studies in
animals suggest that neurobehavioral abnormalities occur. Studies in humans found
no evidence of behavioral, emotional, or cognitive abnormalities, but some
confounding variables were not controlled. Guidelines: Despite the potential for
drug-induced extrapyramidal reactions (usually self-limited) in the neonate, high-
potency antipsychotic agents (ie, fluphenazine, haloperidol, perphenazine,
thiothixene, and trifluoperazine) are preferred to minimize maternal anticholinergic,
hypotensive, and antihistaminergic effects. data on the chlorprothixene, clozapine,
loxapine, mesoridazine, molindone, olanzapine, pimozide, and risperidone are too
limited to provide a recommendation. Long-action (depot) preparations of the high-
potency group (fluphenzine Enanthate, fluphenazine decanoate, and haloperidol
decanoate) should be avoided in order to limit the duration of any possible toxic
effect in the neonate. Withdrawal does not seem to be a serious problem with any of
these agents in the mother or fetus.
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6.1 Treatment of Major Depression during Pregnancy
Drug class Generic name Trade name
Tricyclic Amitriptyline Elavil
antidepressants Endep Amoxapine
Asendin Clomipramine
Anafranil Desipramine
Norpramin Pertofrane
Doxepin Sinequan
Imipramine Janimine
Tofranil Maprotiline
Ludiomil Nortriptyline
Aventyl Pamelor
Protriptyline Vivactil
Selective Trimipramine Surmontil
serotonin reuptake Fluoxetine Prozac
inhibitors Fluvoxamine Luvox
Paroxetine Paxil
Sertraline Zoloft
Venlafaxine Effexor
Bupropion Wellbutrin
Atypical
Mirtazapine Remeron
antidepressants
Nafazodone Serzone
Trazodone Desyrel
Isocarboxazid Marplan
Phenelzine Nardil
Monoamine Tranylcypromine Parnate
oxidase inhibitors
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Remarks
Neonatal Effects: Signs in neonates exposed in utero to desipramine, Imipramine,
and nortriptyline include periodic apnea, cyanosis, tachypnea, irritability, seizures,
feeding difficulties, heart failure, tachycardia, myoclonus, respiratory distress, and
urinary retention. Teratogenicity: Tricyclics and fluoxetine do not have a known
teratogenic effect in humans. Miscarriages do not seem to be increased by fluoxetine.
Insufficient human data exist to ascertain the teratogenicity of bupropion, monoamine
oxidase inhibitors, paroxetine, sertraline, or venlafaxine. Neurobehavioral
abnormalities in animals have been cited. Guidelines: Because they have the least
sedative action and adverse gastrointestinal, cardiac, and hypotensive maternal side
effects, the tricyclic antidepressants, nortriptyline and desipramine, are preferred
during pregnancy. Reliable pharmacokinetic data exist to indicate a relationship
between plasma concentrations and clinical response with use of these agents;
therefore, plasma levels should be monitored to minimize overexposure in-patients.
Because physiologic alterations in renal function and total body water occur during
pregnancy that may affect the steady state concentrations achieved with these agents,
it is advisable to monitor maternalantidepressant plasma concentrations once per
trimester to minimize underexposure. The change in dose can be complex depending
on the trimester(s) of exposure. For example, in order to maintain therapeutic serum
levels within the therapeutic range, particularly in the third trimester, the dose of
tricyclic antidepressant must be increased 1.6 times the mean dose required when the
patients are not pregnant. Although data are limited, fluoxetine does not seem to pose
a high risk to the developing fetus in the first trimester. It can be considered an
acceptable alternative to desipramine and nortriptyline. If fluoxetine exposure
continues after 25 weeks of gestation, or begins after 25 weeks' gestation, a higher
risk for low birth weight has been noted. Although this reduction is related, in part, to
reduced maternal weight gain; others have questioned this finding. If possible,
maprotiline and the monoamine oxidase inhibitors should be avoided for reasons cited
in the text. Limited data suggest that fluvoxamine, paroxetine, and sertraline do not
seem to increase the teratogenic risk. Data are too limited to provide a
recommendation for bupropion, mirtazapine, nefazodone, trazodone, and venlafaxine.
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6.2 Treatment of Bipolar Disorder during Pregnancy
Drug Class Generic Name Trade Name
Mood stabilizing drugs Carbamazepine Tegretol
Lithium carbonate Eskalith
Lithane Lithobid
Lithonate Lithotabs
Lithium citrate Cibalith-S
Valproic acid Depakene
Divalproex sodium Depakote
Remarks
Fetal and neonatal effects: The use of lithium during the second and third trimesters
occasionally causes fetal thyroid goiter. Exposure of the mother to toxic amounts of
lithium has caused in the fetus and newborn: cyanosis, hypotonia, bradycardia, atrial
flutter, hepatomegaly, T-wave inversion, cardiomegaly, gastrointestinal bleeding,
diabetes insipidus, seizures, and shock. Most of these adverse reactions are self-
limiting and resolve within 1 to 2 weeks after birth. Teratogenic effects: Lithium is
reported to produce congenital cardiovascular malformations (especially Ebstein's
anomaly) in the fetus when used in the first trimester. A recent reevaluation of this
risk based on cohort and case control studies concludes that Ebstein's anomaly is rare
and the risk is much lower than originally reported. Animal studiescited by Kerns1
suggest that neurobehavioral abnormalities may be produced by lithium. The only
study in humans could not confirm this increased risk; however, the design has been
questioned. The fetal hydantoin syndrome consisting of facial
dysmorphism, cleft lip and palate, cardiac defects, digital hypoplasia, and nail
dysplasia was initially ascribed to the use of phenytoin during pregnancy. It is now
recognized to occur with carbamazepine and valproic acid as well. NTDs also are
associated with carbamazepine and valproic acid Carbamazepine can cause a transient
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and reversible deficiency in vitamin K-dependent clotting factors in the neonate that
may lead to intracerebral hemorrhage. This effect can be minimized by prescribing 10
to 20 mg of vitamin K orally at 36 weeks of gestation until delivery. Valproic acid has
been associated with intrauterine growth retardation, hyperbilirubinemia,
hepatotoxicity, skeletal dysplasia, and fetal/newborn distress. Guidelines: Lithium has
been the major antimanic agent used in bipolar disorder. Unfortunately, the use of
lithium is ineffective or poorly tolerated in at least one third of patients, and it has the
narrowest therapeutic index of any agent routinely prescribed in psychiatric practice.
Alternatively, a high-potency antipsychotic agent can be added or substituted if
needed. Even though recent data suggest that the risk of Ebstein's anomaly from first
trimester use of lithium is very low, cardiac ultrasonography is recommended at 18 to
20 weeks of gestation. Serum lithium concentrations should be monitored monthly in
early pregnancy and weekly near delivery; however, lithium should be reinstituted
promptly after delivery to overcome postpartum depression. Avoidance of sodium
depletion and avoidance of a low salt diet are recommended to prevent lithium
toxicity. Women taking carbamazepine or valproic acid are at higher risk for spina
bifida than the general population. There is no recommendation at the present time for
higher risk women consuming carbamazepine and valproic acid who are planning a
pregnancy. They may consult with their physician about using 4mg of folic acid when
they are planning to start a pregnancy. MSAFP screening for neural tube defects
before the 20th week of gestation with targeted sonography is advised to screen for
NTDs followed by amniocentesis for any elevated a-fetoprotein values.
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6.3 Treatment and Prevention of Panic Disorder during Pregnancy
Drug Class Generic Name Trade Name
Benzodiazepine agonists Alprazolam Xanax
Clonazepam Klonopin
Diazepam Valium
Lorazepam Ativan
Treatment and prevention
Neonatal effects: The major neonatal side effects of benzodiazepines include
sedation and dependence with withdrawal signs. A benzodiazepine-induced "floppy
infant syndrome" characterized by muscular hypotonia, low Apgar scores,
hypothermia, impaired response to cold, and neurologic depression can occur at the
time of delivery in benzodiazepine-dependent neonates, even with the lower doses
used to treat anxiety disorders. Withdrawal signs include hypertonia, hyperreflexia,
restlessness, irritability, seizures, and abnormal sleep patterns, inconsolable crying,
tremors or jerking of the extremities, bradycardia, cyanosis, chewing movements, and
abdominal distention. These signs can appear shortly after delivery to 3 weeks after
birth and last up to several months depending on the degree of dependence and the
pharmacokinetic profile of the benzodiazepine. Diazepam has a long-acting
metabolite, dimethyldiazepam, whose mean elimination half-life is 73 (30-100) hours
in adults. Of the benzodiazepines with no or weakly active, short-lived metabolites,
clonazepam has the longest mean elimination half-life of 23 (18-50) hours in adults.
Prevention only:
selective serotonin reuptake inhibitor Fluoxetine (Prozac)
Tricyclic antidepresssant , Imipramine
Monoamine oxidase inhibitor ,Phenelzine ( Nardil)
Teratogenic effects: Tricyclics and fluoxetine do not have known teratogenic
effects in the human. Insufficient human data exist to ascertain the teratogenicity of
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monamine oxidase inhibitors. The belief that diazepam causes congenital
malformations, especially cleft lip/palate, is controversial. No congenital defects in
humans have been attributed to lorazepam or alprazolam. The data based on the
conclusion for alprazolam have been contested, but the authors state that the risk for
oral cleft remains small. A limited surveillance study revealed 3 major birth defects
in 19 pregnant women exposed to clonazepam80; therefore, targeted sonography for
anomaly screening is recommended at 18 to 20 weeks of gestation. Animal studies
have suggested that neurobehavioral teratogenicity occur with some of the
benzodiazepines. In humans, the findings were mixed no motor or cognitive deficits
were observed in children at 8 months of age, and no effects on IQ were observed at
4 years of age. Conversely, delayed motor development and mental retardation were
reported in 7 of 8 children with in utero exposure to various benzodiazepines.
Guidelines: From the viewpoint of the fetus, fluoxetine is recommended for
preventive therapy for panic disorder during pregnancy. When a benzodiazepine is
indicated for treatment of an acute panic disorder in the pregnant patient, alprazolam
or lorazepam is preferred during pregnancy to longer-acting diazepam and
clonazepam. No birth defects have been linked to alprazolam, lorazepam, or
fluoxetine. Lorazepam is preferred over alprazolam for preventive therapy, because it
has a somewhat longer duration of action, it lacks active metabolites, and it does not
seem to be associated with an immediate and as severe a withdrawal syndrome in the
neonate compared with alprazolam. However, withdrawal reactions may be more
severe but less protracted compared with the longer acting benzodiazepines,
clonazepam, and diazepam.
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6.4 Treatment of Obsessive-Compulsive Disorder During Pregnancy
Drug Class Generic Name Trade Name
Antiobsessional agents Clomipramine Anafranil
Fluoxetine Prozac
Fluvoxamine Luvox
Sertraline Zoloft
Remarks
Neonatal effects: Larger doses of clomipramine than those required for treatment of
depression are needed for the treatment of obsessive-compulsive disorder. This
possibility increases the potential for enhancing the typical side effects exhibited by
the tricyclics. A withdrawal syndrome has been reported. This was manifested by
lethargy, cyanosis, tachypnea, and respiratory acidosis within a few hours, jitteriness
and tremors by the end of the first day, followed by intermittent hypotonia, tachypnea,
and feeding problems. Full resolution of signs required 2 weeks. No long-term
sequelae were noted at 5 months of age. Teratogenic effects: No congenital
malformations have been reported for clomipramine or fluoxetine. Neurobehavioral
teratogenicity studies in humans have not been conducted. Insufficient data exist to
ascertain the human teratogenicity of the other selective serotonin reuptake inhibitors.
Guidelines: When behavioral therapy is inadequate and drug treatment is indicated,
fluoxetine is recommended for the treatment of obsessive-compulsive disorder during
pregnancy. Although the data are more limited, fluvoxamine, paroxetine, and
sertraline are acceptable alternatives that seem to lack teratogenic effects.
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CONCLUSION:
Patient Counseling in Pregnancy therapy:
If you used a medication before learning that you were pregnant, or need drug
therapy for a chronic health condition...Not every medication poses a risk to your
unborn baby. However, some do. Talk to your doctor.
Discuss the relative risks and benefits of any prescribed drug therapy and do NOT
take over-the-counter drugs or naturopathic remedies without first consulting your
physician.
If you experimented with certain illegal drugs before learning that you were
pregnant...Don't panic. Talk to your doctor and work with him or her to
understand the risk to your unborn child. And decide not to use illegal drugs
again. If you're struggling with a habit that you can't seem to break, get help.
Motherisk can refer you to several programs.
If you look forward to that afternoon cigarette break... Smoking is the leading
preventable cause of low birth weight in babies. Underweight babies are
vulnerable to numerous health problems. So avoid smoking and try not to be a
passive smoker of someone else's cigarette, cigar or pipe. If smoking is a habit, try
to quit or at the very least, cut back. It will help you and your baby.
After counseling of the pregnant woman, severe psychiatric illness may compel drug
treatment. To minimize the risk of fetal and neonatal toxicity, including an abstinence
syndrome, the physician should prescribe the lowest dosage that provides adequate
control of the woman's illness. The neonate must be monitored for evidence of
persistent drug effect or development of an abstinence syndrome. The Committee
encourages long-term research on prospective studies of structural malformations and
neurobehavioral teratogenicity.
References:
British National Formulary (BNF); Pages: 633, BNF 39 March 2000
The Merck Manual; Pages: 2022, Merck Of Medicinal Information
Applied Therapeutics; Pages: 1541
Internet yahoo search
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