Drugs in Pregnancy

1104421 - Clinical Pharmacy IAPregnancy and lactation_2007.ppt

Drug use during

Pregnancy and Lactation

21104421 - Clinical Pharmacy IA

Objectives

• To introduce concepts related to administration of drugs to pregnant women

– To understand how drugs are classified to guide use during pregnancy

– To be able to provide appropriate guidance on drug use during pregnancy

To introduce concepts related to administration of drugs to breastfeeding

women– To understand drug use during breastfeeding– To be able to provide appropriate guidance on

drug use during breastfeeding


Reading

•Chapter - Pregnancy and Lactation Pharmacotherapy Handbook 6th Ed. Barbara G Wells (Editor), Joseph T DiPiro (Editor), Terry L Schwinghammer (Editor), Cindy W Hamilton (Editor)

•Chapter - Pregnancy and Lactation: Therapeutic considerations McCombs J and Cramer MK IN: Pharmacotherapy: a pathophysiological approach. 6th Edition. Ed. Joseph T. Dipiro et al. Elsevier Science Publishing Co. Inc., New York 1999.


Normal pregnancy

• 40 weeks from date of conception– Generally divided into 3 trimesters

• 1:25 babies born in Australia has a birth defect– Underlying risk, not all related to

medication• General health advice

– Smoking– Folic acid supplementation

> Neural tube defects– 0.4/5mg daily before conception and for 12 weeks after

– Diet


Drug use during pregnancy

• Most medicines cross the placenta– Even if cross placenta may not cause

problems

• During first 2 weeks (conception to first missed period) embryo is thought to be resistant to teratogenic effects

• Critical period of development is 17 days-70 days post conception– Exposure during this period can cause

major birth defects


What is a teratogen?

• A chemical which has the capability to produce congenital abnormalities

• Factors influencing teratogenicity of a drug include:– Genotype of mother and fetus– Embryonic stage at exposure– Dose– Specificity of drug


Medications known to be teratogens

• Alcohol• ACE inhibitors• Antithyroid drugs• Benzodiazepines• Carbamazepine• Cocaine• Cyclophosphamide• Danazol• Diethylstilbestrol• Isotretinoin

• Lithium• Methotrexate• Misoprostol• Phenytoin• Tetracyclines• Thalidomide• Valproic acid• Warfarin


Case 1

• Mrs McDonald enters the pharmacy and says that she needs to take regular medication but would like to become pregnant. What effect will it have on the baby?– What do you tell her?– Where will you find the information?


Case 2

• 28yr old women asks the pharmacist for advice on whether she can still take her antiepileptic drug whilst she is pregnant.– What are her options?– Where can you find the information you

need?– What should you tell her?


FDA pregnancy risk classification

• CATEGORY INTERPRETATION A Adequate, well-controlled

studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy.

> Paracetamol



• B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women.ORAnimal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

• Examples• Penicillins, B-lactam antibiotics, macrolides

(erythromycin), Metronidazole, nystatin•



> C Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women.ORNo animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.

> Calcium channel blockers– Potential to cause fetal hypoxia due low maternal BP

> Statin hypolipidaemics– Cholesterol is necessary for fetal development

> Opiod analgesics– May cause fetal respiratory depression or withdrawal

symptoms in newborn> Aspirin

– Avoid in last trimester– Inhibits prostaglandin synthesis



• D Adequate well-controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective.

> Carbamazepine (Tegretol), phenytoin (Dilantin), sodium valproate (Epilim)

> Doxycycline > most anticancer agents> ACE inhibitors (eg.enalapril) and AII antagonists

(e.g.losartan)– Intereferes with renal development in second and third trimester,

resulting in renal dysfunction

> Paroxetine (Paxil)

•



• X Adequate well-controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities or risks. The use of the product is contraindicated in women who are or may become pregnant.

> Isotretinoin (Accutane), tretinoin (Retin-A)> Raloxifene (Evista)> thalidominde> Misoprostol (Cytotec)> Warfarin (Coumadin)


Drug use in pregnancy

• Generally four options1. Stop taking the drug 2. Continue to take the drug3. Change to another less toxic drug4. If available take something to reduce

the likelihood of toxic effects


Stop taking the drug

• Where possible drug use should be avoided during pregnancy

• Stopping a drug may be a possible (or necessary) solution depending on indication for drug– Necessary for most toxic groups of drugs

> Category X– Not recommended for use during pregnancy or when

there is a chance of pregnancy


Continue taking the drug

• May be best option– Consider drug category

> Not OK for category X– Consider whether stabilized on

treatment> Well controlled disease is probably safer

for mother and baby than stopping or changing treatment

– Consider whether other treatment alternatives exist

> Insulin instead of oral hypoglycemics> Non-drug therapies


Change to another drug

• May be possible to choose less toxic drug

> Eg. Heparin therapy in place of warfarin for woman with history of DVT

– Treatment effectiveness (of less toxic drug) may need to be established

> May take significant period of time – Eg. Antiepileptic therapies

• Need to balance benefits and risk


Add a supplement

• If continuing with necessary drug therapy then may need to add supplements to reduce chance of teratogenic effects– Folic acid supplementation– Vit K (prevent haemorrhagic disease of

the newborn)– Both could be used in antiepileptic

agents-some have been implicated in above condition)


Conditions caused or exacerbated by Pregnancy• Nausea and vomiting: -Morning Sickness;

affects about ½ of pregnant women mainly in 1st trimester.

• Manage by dietary intervention ( dry crackers 15-20 min before arising), small dry meals high in carbs, avoid spicy foods and those with noxius odors.

• Meds have been used including phenothiazines (Prochlorperazine) , meclizine, dimenhydrinate, doxylamine , pyroxidine and ondansetron.


Conditions caused or exacerbated by Pregnancy• Hyperemesis gravidarum : is severe

N/V that could lead to dehydration and malnutrition. Hospitalization is required with proper fluid hydration , antiemetics sedatives and may be parenteral nutrition.


Conditions caused or exacerbated by Pregnancy• Heartburn: Many experience during latter

half of pregnancy. Manage by dietary modification first: smaller more frequent meals, avoiding liquids other than water 3 hours before bedtime, raising the head of the bed with blocks also helps.

• Antacids like magnesium and aluminium-containing products help alleviate the symptoms, calcium carbonate could be used for short periods to prevent rebound effect.


Conditions caused or exacerbated by Pregnancy• Constipation: common problem

resulting from decreased peristalsis. • Manage by adding bulk laxatives like

fibercon and citrucel to diet, increasing fluid intake ( at least 8 glasses/day)

• Avoid mineral oil (parafin oil) in any dosage as it could impair vitamin K absorption in mother leading to low vit, K available for fetus and possible causing hypoprothrombinemia.


Conditions caused or exacerbated by Pregnancy• Hemorrhoids: caused by constipation

and increased venous pressure below the uterus. Correction of constipation, use of stool softeners and sitz baths are helpful. Avoid topical preps containing anesthetics or steroids as absorption could happen. Procto-glyvenol crm. or supp. has been used safely.


Conditions caused or exacerbated by Pregnancy• Coagulation Disorders: Thromboembolic

phenomena are common in pregnancy. Warfarin should be avoided.

• Sub Q heparin and low -molecular-weight heparins (LMWH) are drugs of choice as effect can be reversed by protamine sulfate in case surgery is needed.

• Heparin is assoc. with osteoporosis which may or may not be reversible and it also could cause thrombocytopenia.


Treatment of common conditions

• Allergies– Oral first-generation antihistamines

> Chlorpheniramine (in combination products), dexchlorpheniramine

> Second-generation (non-sedating agents) are (also recommended, eg. Telfast); loratadine (Claratin)

– Avoid in first trimester– Loratadine is the preferred non sedating

antihistamine after the first trimester> Nasal sod. cromolyn is a topical product with safe

profile> Nasal corticosteroids may be used for allergic

rhinitis (Beconase/Allergy, Rhinocort)



• Asthma– Inhaled prn short-acting -agonist (eg. Ventolin) – Inhaled corticosteroids: budesonide (Pulmicort),

beclomethasone (Qvar), fluticasone (Flixotide) safe to use although have differing classification categories

– Inhaled corticosteroid/long-acting -agonist (Seretide)

– Oral B-agonists and theophylline appear to have no negative effect as well.

– Benefit>>risk– Asthma control is extremely important



• Diabetes– Incidence of malformations increases in poorly

controlled diabetes– Insulin is treatment of choice

> For both type 1 and type 2 patients– Goals for self-monitoring of blood glucose is

important– Oral hypoglycemics should be avoided as they

could cause fetal hypoglycemia, they may be tertogenic as well and so should be stopped before conception if possible.

– Gestational diabetes is usually managed first by diet and then insulin.



• Epilepsy– risk of teratogenicity is probably greatest with

sodium valproate, then carbamazepine and then phenytoin & primidone.

> Risk increases with polytherapy> Phenobarbital has been drug of choice in

pregnancy due to vast experience with the drug

– risk of an abnormality is about 2-3 times that of the general population

– medication change not usually recommended> All women taking antiepileptics should take

folic acid 5mg before conception and 12 weeks after



• Hypertension– Generally recommended agents are

older agents> Methyldopa (Aldomet)> Clonidine (Catapres)> Labetolol (Trandate)> Prazosin (Minipress)> Hydralazine (Apresoline)



• Psychotropic agents– Treatment should involve

psychotherapy– Lowest possible dose

> Olanzapine , chlorpromazine (cat C)> Benzodiazepines (Cat C)> Antidepressants

– citalopram, fluvoxamine, sertraline- Cat C mirtazepine.

– tricyclics- Cat C– paroxetine- Cat D

– Benefits may outweigh risk



• Thyroid disorders– Hypothyroidism

> Thyroid replacement therapy– Should continue or be implemented

» Thyroxine– Dose may increase by 25-50%(pregnancy itself

affects dosing)

– Hyperthyroidism> Consider surgery prior to pregnancy> either methimazole or propylthiouracil

(PTU)can be continued through pregnancy using the smallest possible dose

– High doses may cause congenital goitre

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Drugs in Pregnancy

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