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Anticoagulants. (Drugs, Pregnancy, and Lactation).

Many of the agents below have been recently approved, and for most there are no human pregnancy exposure data. But since they are often used in life-threatening situations, the maternal benefits usually far outweigh any potential fetal harm. Maternal hemorrhage and the resulting potential for fetal risk are the primary concerns when anticoagulants are used during pregnancy.

* Antithrombin III (Thrombate). This agent is indicated for patients with hereditary antithrombin III deficiency or thromboembolism and is rated pregnancy risk category B. It has also been studied as a treatment for preeclampsia, but its efficacy for this indication has not been proven. It has a high molecular weight, so it's not expected to cross the placenta. Reproductive studies in rats and rabbits at doses up to four times the human dose reveal no evidence of impaired fertility or fetal harm. Because it is prepared from pooled units of human plasma, the potential for maternal and fetal infection with an unknown infectious agent cannot be excluded.

* Thrombolytic agents. All of these agents are given intravenously. Alteplase (Activase), reteplase (Retavase), and tenecteplase (TNKase), produced with recombinant DNA technology are not teratogenic in experimental animals and are all rated C. No animal reproductive data are available for drotrecogin alfa (activated), marketed as Xigris and rated C, a genetically engineered version of activated protein C. This agent has anticoagulant and profibrinolytic effects and was approved last year for treating sepsis.

Alteplase (tissue plasminogen activator) has a very high molecular weight so it probably does not cross the placenta. It is not teratogenic in rats and rabbits, but is embryocidal in rabbits. The few reports of its use in human pregnancy, including a report of a woman with a thrombosed mitral valve prosthesis, have nor described adverse effects attributable to the drug in fetuses or newborn infants. Reteplase, which also has a high molecular weight, treats acute MI and is not teratogenic in animals but was an abortifacient in rats and rabbits.

No problems have been found in animal reproductive studies of tenecteplase, another tissue plasminogen activator similar to alteplase when single doses were used.

* Thrombolytic enzymes. The three agents in this category are anistreplase (Eminase) and streptokinase (Streptase), both rated C, and urokinase (Abbokinase). Urokinase is rated B because it is the only one of the three that has been studied in animals. At doses up to 1,000 times the human dose, no adverse fetal effects were seen in rats and mice. Several human reports indicate that it does not appear to be harmful to the fetus, although only one case early in pregnancy has been reported.

There are a lot of human data available on streptokinase: None of the reports have shown an association with congenital defects or other major risks to the fetus. No human pregnancy data are available for anistreplase.

* Aggregation or antiplatelet agents. There are three aggregation inhibitors: ciostazol (Pletal), rated C; clopidogrel (Plavix), rated B; and ticlopidine (Ticlid), rated B. There are no human reports for ciostazol, but in animals it is teratogenic and toxic at five times the human dose.

Ticlid is fetotoxic in mice, rabbits, and rats, but is not teratogenic. The one available human report is in a woman treated with Ticlid and aspirin for an MI. Her pregnancy ended in a spontaneous abortion in the second trimester. The pregnancy was complex, and it is unclear whether the miscarriage was related to treatment. In her next pregnancy; she received clopidogrel and had a healthy infant. No recommendations can be made based on this report, the one known report of clopidogrel in human pregnancy. Clopidogrel is not teratogenic or toxic in rabbits or rats at doses up to 78 times the human dose.

* Aggregation inhibitors/vasodilators. Treprostinil (Remodulin), rated B and approved this year for pulmonary arterial hypertension, is not teratogenic in animals.

Three glycoprotein IIB / IIIA inhibitors are given along with heparin and aspirin for treating acute coronary syndromes. No animal reproductive studies have been done on abciximab (ReoPro), rated C; I am not aware of any human pregnancy reports. There is no evidence that eptifibatide (Integrilin), rated B, is harmful in rats or mice. Tirofiban (Aggrastat), rated B, crosses the placenta, but there is no evidence that it causes fetal harm in animals.

RELATED ARTICLE: Progressive Management of Hyperemesis in Pregnancy

Dietary Interventions

The best-tolerated tastes are salty and sour, as in chips, French fries, and lemonade. Begin with liquids before moving to solid food.

* Step 1: Take sips of sports drinks and bouillon to avoid dehydration.

* Step 2: Add brothy soups with noodles, avoiding those that are cream-based.

* Step 3: Add potatoes, pasta, and rice.

Oral Medications

Follow the stepwise sequence below advancing to the next step if the patient does not respond to the previous one.

* Step 1: Pyridoxine 25-75 mg/day.

* Step 2: Ground ginger capsules 250 mg every 6 hours.

* Step 3: Add doxylamine succinate 12.5 mg (one-half tablet of Unisom) to the pyridoxine to make do-it-yourself Bendectin.

* Step 4: Promethazine hydrochloride (Phenergan) 25 mg every 6 hours or dimenhydrinate 50-100 mg every 4-6 hours.

If the patient shows no improvement after following these four steps and is NOT dehydrated, try one of the following. If no response is achieved, try the other two agents in turn.

Metodopramide 10-15 mg q.i.d.

Prochlorperazine 5-10 mg every hours.

Ondansetron 8 mg every 8-12 hours.

Intravenous Medications

If the patient shows no improvement after following the four steps outlined above but IS dehydrated, use intravenous fluid replacement with a multivitamin. If vomiting has gone on for at least 3 weeks, intravenous fluids must be accompanied by 100 mg IV of thiamine daily to prevent Wernicke's encephalopathy, marked by nystagmus, ataxia, visual disturbance, memory loss, and in some cases maternal death.

Regardless of how long they have been vomiting, all dehydrated women should start with any of the following. If no response is achieved, switch to one of the other agents:

* IV metoclopramide 10 mg every 6 hours.

* IV promethazine 12.5-25 mg every 6 hours.

* IV prochlorperazine 5-10 mg given over 2 minutes every 6 hours.


* IV ondansetron 0.15 mg/kg every 8 hours.

Other Options

If still no resolution of symptoms, consider the following:

* Systemic corticosteroids.


* Try enteral feeding via nasogastric tube.

Source: Dr. Jodi Schucker

GERALD G. BRIGGS is pharmacist clinical specialist, Women's Hospital, Long Beach Memorial Medical Center; clinical professor of pharmacy University of California, San Francisco; and adjunct professor of pharmacy University of Southern California, Los Angeles. He is coauthor of the reference book "Drugs in Pregnancy and Lactation."
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Article Details
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Author:Briggs, Gerald G.
Publication:OB GYN News
Date:Oct 1, 2002
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