- The use of either prescribed or over-the-counter medicines or herbal drugs during pregnancy in women is common. Over 90 % of women use at least one medicine during pregnancy and over 70% use at least one prescription medicine.
- However, the use of drugs in pregnancy is complicated by the potential of harmful effects on growing fetus, altered maternal physiology and the difficulties of research in this field. Pharmacokinetic parameters of drugs may be altered during pregnancy. Drugs may pass though placenta to fetus and cause harmful effects.
- Pharmacokinetic parameters may be altered due to increased gastric pH and decreased gastric motility (altered absorption), increased total body water and plasma volume (altered distribution), increased glomerular filtration (increased renal clearance) and altered activity of drug metabolizing enzymes in liver.
- So, any drugs should be approached with caution by pregnant women and their health care providers. Before prescribing, risk of medicine against benefits of treatment on mother and fetus should be accessed.
- According to US FDA, drugs can be classified as following according to use in pregnancy.
| FDA rating | Conditions | Examples |
| A | Controlled human studies show no risk | Folic acid |
| B | No confirmatory evidence of risk in human | Metronidazole |
| C | Risks cannot be ruled out | interferon beta, dimethyl fumarate |
| D | Possible evidence or risk exists | Tetracycline, streptomycin |
| X | Absolutely contraindicated | Thalidomide, alcohol |
Table – Different category of drugs based on their risk in pregnancy
Drug prescribing during pregnancy
Following points should be noted for drug prescribing during pregnancy.
- Treat minor problems without drugs.
- If it is compulsory to prescribe drugs, it should be of known safety during pregnancy.
- Chose a drug which has been in use from long periods than a newly introduced drug.
- The dose of drug should be adjusted. The dose of some drugs should be lowered whereas dose of some drug should be increased.
- Discourage the self- administration of OTC drugs.
Anti-emetics
- Nausea and vomiting during pregnancy are common but are self-limiting. It should be managed with reassurance and non-drug strategies like small frequent meals, raising the head of the bed.
- If symptoms are severe or prolonged, antihistamines- antiemetic like cyclizine, meclizine and promethazine may be prescribed. Metoclopramide is safe and effective in labor and before anesthesia during late pregnancy.
Anti-microbial drugs
- Beta-lactam antibiotics (penicillin and most of cephalosporins) are safest antimicrobials during pregnancy. Nystatin, nitrofurantoin, miconazole and methanamine mandelate are considered safe during pregnancy.
- Aminoglycosides are ototoxic to fetus. Tetracycline damage the fetal teeth and bones. Its high dose is associated with severe hepatotoxicity in mother. Chloramphenicol can cause grey baby syndrome and fetal bone marrow toxicity. Griseofulvin and nalidixic acid are embryotoxic. Use of sulfonamides can cause kernicterus in neonates. Cotrimoxazole is avoided especially during 1st and 3rd
- There is no evidence of teratogenic activity of metronidazole in human, so it is preferred for anaerobic infection. Antiviral agents are generally avoided unless in life-threatening infection in mother.
Analgesics
- Paracetamol is preferred than aspirin for mild analgesic effect. aspirin is not teratogenic, but its high doses can cause serious post-partum hemorrhage, increased gestation time and prolonged labor.
- NSAIDs induce premature closure of ductus arteriosus in the fetus. Hence, they are avoided in pregnancy.
Anti-epileptics
- Convulsion in pregnancy can lead to fetal and maternal morbidity and mortality so adequate seizure control is important. All anti-convulsant are teratogens so before using any anti-epileptics during pregnancy, its benefits and risk should be accessed.
- Phenytoin, a common anticonvulsant drug can cause cleft palate and congenital heart disease. Sodium valproate and carbamazepine are associated with spinal bifida.
- While prescribing any anti-epileptic drugs in pregnancy, they should be prescribed folic acid 5 mg per day throughout pregnancy. The routine injection of vitamin K before delivery and to newborn babies after birth may be helpful to counteract some possible side-effects. Regular plasma concentration monitoring especially for phenytoin is helpful.
CVS drugs
- Hypertension in pregnancy can be controlled by using methyldopa or labetalol. Parenteral hydralazine is useful for lowering BP in pre-eclampsia. Modified release preparation of nifedipine can be used. ACE inhibitors and ARBs (angiotensin receptor blocker) are avoided.
- Heart diseases are treated as in non-pregnant woman. Digoxin clearance increases during pregnancy. Quinidine is safe at therapeutic concentration and has mild oxytocic effect.
- Vasopressor agents like dopamine and adrenaline stimulate uterine contraction. They are preferred only if mother’s life is at stake.
CNS drugs
- Lithium has teratogenic effect and is avoided. MAO inhibitors are contraindicated. Anti-parkinsonism drugs like benzhexol with phenothiazine should eb avoided during 1st trimester. Benzodiazepines may cause hypotonia, hypothermia and periodic cessation of respiration. They are avoided during 1st trimester and before delivery.
- Phenothiazine, tricyclic antidepressants and SSRIs (Selective Serotonin Reuptake Inhibitors) should be continued with lowest possible dose. Tricyclic antidepressants should be avoided in last few weeks of pregnancy and started after delivery.
Peptic Ulcer
- Dietary modification and non-systemic antacids are preferred. Sucralfate (as it is not absorbed), H2 receptor antagonist and bismuth subsalicylate are safe to use.
- Misoprostol is contraindicated as it causes abortion.
Dyspepsia and constipation
- Dyspepsia is common during 2nd and 3rd Non-drug treatment like small frequent meals and proper posture is preferred. Metoclopramide and non-absorbable antacids are preferred in late pregnancy. H2 receptor blocker are not preferred for non-ulcer dyspepsia.
- Constipation can be controlled by dietary changes like high fiber diet, plenty liquid and mild laxatives. Stimulant laxatives are avoided.
Tuberculosis
- Isoniazid and ethambutol are safe to use during pregnancy. Rifampicin is usually avoided but may be used if 3rd drug is required.
- Streptomycin is contraindicated as it is ototoxic.
Anti-coagulants
- Warfarin is mostly avoided in pregnancy due to risk of bleeding complications. Low molecular weight heparin is preferred anticoagulant during pregnancy as it doesn’t cross placenta.
- However, in patients with artificial heart valves, warfarin is administered despite risk to fetus as heparin cannot produce sufficient anticoagulant action. The prothrombin time should be monitored closely if warfarin is used.
Respiratory problems
- Bronchial asthma is treated with inhaled beta-adrenergic agonists, inhaled glucocorticoids or aminophylline. Concurrent administration of IV salbutamol and corticosteroids is avoided due to risk of fetal death.
- Dry cough can be treated by using diphenhydramine, codeine and dextromethorphan. Allergic rhinitis may be treated locally (with glucocorticoids or decongestants) or systemically (with antihistamines).
Thyroid problems
- Radioactive iodine and stable iodine are contraindicated. Propylthiouracil is preferred than carbimazole or methimazole. It should be used in lowest dose possible.
Hormonal drugs
- Corticosteroids don’t cause serious problem when administered during inhalation or in short courses. Prednisolone is preferred than dexamethasone and betamethasone if glucocorticoid treatment is needed during pregnancy.
- Synthetic progesterone can masculinize the female fetus in large dose.
References
- Daw JR, Hanley GE, Greyson DL, Morgan SG. Prescription drug use during pregnancy in developed countries: a systematic review. Pharmacoepidemiol Drug Saf. 2011; 20(9): 895–902.
- Pariente G, Leibson T, Carls A, Webber TA, Ito S, Koren G. Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review. PLOS Medicine. 2016; 1-36.
- Freyer AM. Drug-prescribing challenges during pregnancy. Obstetrics, Gynaecology & Reproductive Medicine. 2008; 18(7): 180-186.
- Ventura M, Maraschini A, D’Aloja P, Kirchmayer U, lega I, Davoli M et al. Drug prescribing during pregnancy in a central region of Italy, 2008-2012. BMC Public Health. 2018; 623.
- Ward RK, Zamorski MA. Benefits and Risks of Psychiatric Medications During Pregnancy. Am Fam Physician. 2002; 66(4): 629-637.
- https://www.cdc.gov/pregnancy/features/pregnancy-meds-keyfindings.html
- Pharmacology and Pharmacotherapeutics. 24th edition.
- A Textbook of Clinical Pharmacology and Therapeutics.