Terbutaline FAQ

There is considerable disagreement in the medical community about the use of terbutaline (also known as Brethine) as a preterm labor drug. Some doctors believe it is an effective treatment for preterm labor. However, other doctors have concerns about whether it is safe and whether it works and either do not prescribe it or prescribe it only for short periods of time.

This FAQ should not be interpreted as either an endorsement or condemnation of terbutaline's use in treating preterm labor. We hope it will help women make informed choices about their health care and serve as a starting point for discussions with their physicians.

Preterm Labor

Using Terbutaline To Treat Preterm Labor

The Terbutaline Pump

Questions To Discuss With Your Doctor

Preterm Labor

Different doctors have different criteria for diagnosing preterm labor. However, preterm labor's hallmarks are contractions with cervical changes (effacement and dilation) before full-term gestation.

Yes, a transvaginal sonographic measure of cervical length early in the third trimester has been shown to be a good predictor of whether a woman will deliver prematurely. Also, the presence of fetal fibronectin in cervicovaginal secretions is associated with preterm delivery in both high-risk and low-risk women. This can be tested with a vaginal swab. Transvaginal ultrasounds appear to work pretty well at screening out women pregnant with twins who probably *won't* develop preterm labor. The test is not quite as accurate in twin gestations as it is in singleton pregnancies in determining exactly who will develop preterm labor. Fetal fibronectin is not as accurate in twin gestations as it is in singleton pregnancies.

A woman's saliva also can be tested for the presence of salivary estriol, which is thought to be a predictor of preterm and term labor. However, the test's manufacturer says the test is designed for singleton pregnancies.

3. Do women pregnant with multiples run a higher risk of preterm labor?

Yes, they do tend to experience it more often than women pregnant with singletons, who have an overall preterm labor rate of 10 percent. The table (below) lists the probabilities.

Risk of Preterm Labor in Multiple Pregnancies

Pregnancy	Risk of Preterm Labor
Twin	50%
Triplet	90%
Quad	100%
Source: Luke, Barbara and Eberlein, Tamara, When You're Expecting Twins, Triplets or Quads, New York: HarperPerennial, 1999.

Using Terbutaline To Treat Preterm Labor

Terbutaline (also known as Brethine and Bricanyl) is an asthma drug in the drug class of beta-adrenergics. It is not approved by the FDA for use as a preterm labor drug; it is used "off label" for this purpose. It is typically prescribed in the pill form (2.5 or 5 mg pills at 3- 4- or 6-hour intervals) or by subcutaneous injection of terbutaline sulfate (aka the terbutaline pump, with dosages of at least 3 mg per 24-hours). Terbutaline relaxes bronchial tubes and eases asthma symptoms. It also is thought to relax the muscles of the uterus.

The most common side effects are:

• jitteriness
  
• increased heart rate
  
• tremors
  

Most of the other side effects are less common. If you experience any of these symptoms, you should contact your doctor promptly. If your doctor does not respond to your reports of adverse side effects, consider seeking a second opinion. Also, because of the risks of terbutaline, you should be screened carefully for any pre-existing health conditions.

Mild adverse effects

• Headache, dizziness, drowsiness, restlessness, insomnia (infrequent)
  
• Rapid, pounding heartbeat; increased sweating; muscle cramps in arms and legs (infrequent to frequent)
  
• Nausea, heartburn, vomiting (rare with oral form, frequent with IV)
  
• Increased blood sugar (frequent- 40% abnormal one-hour glucose test)
  

Serious adverse effects

• Rapid or irregular heart rhythm, intensification of angina, increased blood pressure (infrequent)
  
• Lowered blood calcium or potassium (especially with intravenous use) (possible)
  
• Liver toxicity (case reports)
  
• Severe lowering of blood pressure (hypotension) (case reports)
  
• Increased blood sugar (infrequent)
  
• Seizures (rare reports)
  

Effects of overdosage

• Nervousness, palpitation, rapid heart rate, sweating, headache, tremor, vomiting, chest pain
  

Sources: Rybacki, James, and Long, James, The Essential Guide to Prescription Drugs, New York: 1998, pp. 915-916.
1999 Physicians' Desk Reference, 52nd Ed., Montvale, NJ, pp. 1306-1307.

Terbutaline's side effects are more severe at higher dosages. As a reference point, the maximum dose of oral terbutaline for asthmatics is 15 mg per 24-hour period (The Essential Guide to Prescription Drugs, 1998 and 1999 Physicians' Desk Reference). However, women experiencing preterm labor will take terbutaline around-the-clock and often in significantly higher doses. At a dose of 5 mg every six hours, a woman is taking a total of 20 mg per 24 hour period, or 33% more than this maximum dose for asthmatics. At 5 mg every 4 hours, she is taking 30 mg per 24-hour period, or double the maximum dose for asthmatics. Sometimes the dosages of terbutaline for preterm labor can be even higher than 30 mg.

Some of terbutaline's more serious side effects include cardiovascular complications. These symptoms include:

• Dizziness or blackout
  
• Heart palpitations
  
• Tachycardia (rapid heart rate)*
  
• Irregular heart rate
  
• Frequent skipping of a heartbeat
  
• Chest pain
  
• Shortness of breath
  
• Severe anxiety or restlessness

Source : Adapted from article by Roger B. Newman, M.D. Director, Maternal-Fetal Medicine, Medical University of South Carolina, on the Triplet Connection Web Page.

*Tachycardia is defined as having a heart rate greater than 100 beats per minute. Different doctors have different definitions of unacceptably high tachycardia rates. However, terbutaline is considered to be working at a "therapeutic level" when a woman's resting heart rate is between 90 and 105 beats per minute (American College of Obstetrics and Gynecology (ACOG) technical bulletin #206). As a reference point, a 32-year-old pregnant woman should not exceed 112 beats per minute while exercising for 30 minutes (ACOG guidelines).

Again, please consult your doctor if you have any troublesome symptoms.

3. Do certain women run a greater risk of complications from terbutaline?

Yes, studies show some conditions put women at greater risk for serious complications. These conditions include: a pre-existing heart condition, diabetes, pre-eclampsia and twin or higher order pregnancy. Women with pre-existing heart conditions should check with their cardiologist before taking terbutaline. In addition, fluid overload and combining terbutaline with other preterm labor drugs and/or corticosteroids (drugs, such as betamethasone, that mature the baby's or babies' lungs) also can increase a woman's risk of complications.

The dosage of terbutaline also affects the incidence and severity of side effects. Specifically, the risk of severe side effects is higher at higher doses.

4. Does terbutaline have any effect on my baby(ies)?

Terbutaline's effect on babies has not been widely studied. However, terbutaline is generally believed to have fewer side effects on the neonate than on the mother. A link with a list of neonatal side effects can be found here.

5. Don't all preterm labor drugs pose some risk?

Yes, all drugs taken during pregnancy pose a risk. After considering your options carefully, only you and your doctor can decide if a preterm labor drug is right for your situation.

6. What are the alternatives to terbutaline?

Magnesium sulfate

Magnesium sulfate also is used as a preterm labor drug. It is typically given by IV in the hospital. It must be administered in high levels; the line between a "therapeutic" dose and one that is "toxic" is quite thin. Therefore, women on it must be monitored carefully for complications. Magnesium sulfate also has been thought to be safe for babies, although a recent study has raised some doubts.

Procardia

A heart drug called Procardia (aka nifedipine) is viewed as causing fewer maternal side effects than terbutaline. However, it has not been widely studied.

Ritodrine

Ritodrine, the only FDA-approved drug to treat preterm labor, has similar side effects to terbutaline. It had fallen out of favor in comparison to terbutaline because it is more expensive. Ritodrine recently was voluntarily taken off the market by its manufacturer.

Indomethacin

Research about Indomethacin is limited, although some studies have linked its use to adverse effects on the baby or babies.

Bedrest and hydration

In addition to prescription drugs, bedrest and drinking plenty of water are often prescribed to treat preterm labor. Bedrest is frequently prescribed although research is lacking on whether it actually works. Sometimes dehydration will cause a woman to have contractions. Drinking lots of fluids can help lessen this problem.

7. Does terbutaline work?

Some studies have found terbutaline to be effective for 24 to 48 hours. These same studies have shown it is no better than a placebo in prolonging pregnancies beyond that time. However, other studies have found it to be an effective tocolytic (preterm labor drug). Anecdotally, terbutaline has been successfully used by some pregnant women and physicians.

Table summaries of studies

The Terbutaline Pump

1. My doctor is recommending I try the terbutaline pump. What are its advantages?

The pump may make it easier for the pregnant woman to maintain an around-the-clock schedule of terbutaline doses. It provides a continuous low dose of terbutaline along with larger doses (called boluses) at regular intervals. The pump may allow a woman to sleep more at night since she won't have to get up to take a pill. The pump also can fine-tune doses to a greater degree than pills. The overall dose of terbutaline is lower on the pump than with terbutaline pills. However, it is important to note that terbutaline by pump is a *concentrated* and injected dose that reaches the bloodstream more quickly. Because part of a terbutaline pill is absorbed by the stomach lining, the dosages of terbutaline pump and pills can be quite comparable and equally strong.

2. What are the terbutaline pump's disadvantages?

The FDA issued a letter to doctors warning them against using the terbutaline pump because of concerns that the pump is not safe and doesn't work. The FDA considers the terbutaline pump to be comparable to terbutaline by IV, which must be administered and monitored in the hospital. However, the terbutaline pump is typically prescribed for women to use at home. The pump also requires the woman to stick herself in the leg with a needle every three to four days. She must change the terbutaline cartridges every 12 hours and carry around the pump with her.

Questions To Discuss With Your Doctor

• Am I really experiencing preterm labor (dilated and effaced cervix)?
  
• What dosage of terbutaline will I be taking?
  
• What form of terbutaline will I take?
  
• Do you prescribe the terbutaline pump and under what conditions?
  
• How long will I take terbutaline?
  
• At what gestational age do you think the risks outweigh the benefits of taking terbutaline?
  
• How will you monitor my health while I'm on terbutaline and how often?
  
• What happens if I experience adverse side effects?
  
• What's your position on combining preterm labor drugs?
  
• What's your position on the use of corticosteroids (drugs to mature the baby or babies' lungs)?
  
• Are there any non-drug alternatives to terbutaline?
  

Please send comments or questions to Karen.