Labetalol

 Risk Factor: CM*
 Class: CARDIOVASCULAR DRUGS / Antihypertensives / Other Antihypertensives

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Labetalol, a combined a/b-adrenergic blocking agent, has been used for the treatment of hypertension occurring during pregnancy (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24, 25,26,27,28 and 29). No teratogenicity was observed in rats and rabbits at oral doses 6 and 4 times the maximum recommended human dose (MRHD), respectively (30). However, increased fetal resorptions occurred in both species at doses approximately equivalent to the MRHD. In rabbits, IV doses up to 1.7 times the MRHD revealed no drug-related fetal harm (30).

Labetalol crosses the human placenta to produce cord serum concentrations averaging 40%80% of peak maternal levels (1,2,3,4 and 5). Maternal serum and amniotic fluid concentrations are approximately equivalent 13 hours after a single IV dose (4). After oral dosing (142 days) in eight women, amniotic fluid concentrations of labetalol were in the same range as, but lower than, the plasma concentrations in six of the women (6). The pharmacokinetics of labetalol in pregnant patients have been reported (7,8). A 1988 article briefly reviewed some of the experience with labetalol in pregnancy (31).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 29 newborns had been exposed to labetalol during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Four (13.8%) major birth defects were observed (one expected). Details on the malformations were not available, but no anomalies were observed in six defect categories (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. Although the number of exposures is small, the incidence of malformations is suggestive of an association, but other factors, including the mother's disease, concurrent drug use, and chance, may be involved.

No published reports of fetal malformations attributable to labetalol have been located, but experience during the 1st trimester, except for the surveillance study described above, is lacking. Most reports have found no adverse effects on birth weight, head circumference, Apgar scores, or blood glucose control after in utero exposure to labetalol (9,10,11,12 and 13). One case of neonatal hypoglycemia has been mentioned, but the mother was also taking a thiazide diuretic (2). Offspring of mothers treated with labetalol had a significantly higher birth weight than infants of atenolol-treated mothers, 3280 g vs. 2750 g (p<0.001), respectively (14). However, in a study comparing labetalol plus hospitalization with hospitalization alone for the treatment of mild preeclampsia presenting at 2635 weeks' gestation, labetalol treatment did not improve perinatal outcome, and a significantly higher number of labetalol-exposed infants were growth retarded, 19.1% (18 of 94) vs. 9.3% (9 of 97) (p<0.05), respectively (15).

Fetal heart rate is apparently unaffected by labetalol treatment of hypertensive pregnant women. However, two studies have observed newborn bradycardia in a total of five infants (16,17). In one of these infants, bradycardia was marked (<100 bpm) and persistent (17). All five infants survived. Hypotension was noted in another infant delivered by cesarean section at 28 weeks' gestation (1). In a study examining the effects of labetalol exposure on term (37 weeks or greater) newborns, mild transient hypotension, which resolved within 24 hours, was observed in 11 infants compared with 11 matched controls (18). Maternal dosage varied from 100 to 300 mg 3 times daily with the last dose given within 12 hours of birth. The mean systolic blood pressures at 2 hours of age in exposed and nonexposed infants were 58.8 and 63.3 mm Hg (p<0.05), respectively. Other measures of b-blockade, such as heart and respiratory rates, palmar sweating, blood glucose control, and metabolic and vasomotor responses to cold stress, did not differ between the groups. The investigators concluded that labetalol did not cause clinically significant b-blockade in mature newborn infants (18).

Several investigations have shown a lack of effect of labetalol treatment on uterine contractions (1,2 and 3,16,19,20 and 21). One study did report a higher incidence of spontaneous labor in labetalol-treated mothers (6 of 10) than in a similar group treated with methyldopa (2 of 9) (22). In another report, 3 of 31 patients treated with labetalol experienced spontaneous labor, one of whom delivered prematurely (23). The authors attributed the uterine activity to the drug because no other causes were found. However, because most trials with labetalol in hypertensive women have not shown this effect, it is questionable whether the drug has any direct effect on uterine contractility.

Labetalol does not change uteroplacental blood flow despite a drop in blood pressure (2,4,5,24,25). The lack of effect on blood flow was probably caused by reduced peripheral resistance.

Labetalol apparently reduces the incidence of hyaline membrane disease in premature infants by increasing the production of pulmonary surfactant (1,2,4,16,26). The mechanism for this effect may be mediated through b2-adrenoceptor agonist activity that the drug partially possesses (1,2,4,16,26).

Follow-up studies have been completed at 6 months of age on 10 infants exposed in utero to labetalol (27). All infants demonstrated normal growth and development. In addition, no ocular toxicity has been observed in newborns, even though labetalol has an affinity for ocular melanin (1,2,26).

In summary, the use of labetalol for the treatment of maternal hypertension does not seem to pose a risk to the fetus, except possibly in the 1st trimester, and may offer advantages over the use of agents with only b-blocker activity. However, one study has demonstrated intrauterine growth retardation (IUGR) when the drug was used for the treatment of mild preeclampsia. Some b-blockers may cause IUGR and reduced placental weight (e.g., see Atenolol and Propranolol). Treatment beginning early in the 2nd trimester results in the greatest weight reductions. This toxicity has not been consistently demonstrated in other agents within this class or with labetalol. The lack of toxicity documentation may reflect the number and type of patients studied, the duration of therapy, or the dosage used. Although growth retardation is a serious concern, the benefits of maternal therapy with labetalol (or b-blockers) may, in some cases, outweigh the risks to the fetus and must be judged on a case-by-case basis. As for other toxicity, the majority of newborns have shown no adverse clinical signs after exposure except for mild transient hypotension, but they should be closely observed during the first 2448 hours for bradycardia, hypotension, and other symptoms of a/b blockade. Long-term (>6 months) studies of infants exposed in utero to labetalol have not yet been conducted.

[*Risk Factor D if used in 2nd or 3rd trimesters.]

Breast Feeding Summary

Labetalol is excreted into breast milk (1,6). In 24 lactating women, 3 days postpartum, administration of 330800 mg/day produced a mean milk level of 33 ng/mL. No adverse effects were observed in the nursing infants. One patient, consuming 1200 mg/day, had a mean milk concentration of 600 ng/mL, but this woman did not breast-feed. Three women, 69 days postpartum, consumed daily doses of labetalol of 600, 600, and 1200 mg and produced peak milk concentrations of the drug of 129, 223, and 662 ng/mL, respectively (6). Peak concentrations of labetalol in the milk occurred between 23 hours after a dose. Measurable plasma concentrations of labetalol were found in only one infant: 18 ng/mL at 4 hours and 21 ng/mL at 8 hours. Although no adverse effects have been reported, nursing infants should be closely observed for bradycardia, hypotension, and other symptoms of a/b-blockade. Long-term effects of exposure to labetalol from milk have not been studied but warrant evaluation. The American Academy of Pediatrics considers labetalol to be compatible with breast feeding (32).

References

1. Michael CA. Use of labetalol in the treatment of severe hypertension during pregnancy. Br J Clin Pharmacol 1979;8(Suppl 2):211S5S.
2. Riley AJ. Clinical pharmacology of labetalol in pregnancy. J Cardiovasc Pharmacol 1981;3(Suppl 1):S53S9.
3. Andrejak M, Coevoet B, Fievet P, Gheerbrant JD, Comoy E, Leuillet P, Verhoest P, Boulanger JC, Vitse M, Fournier A. Effect of labetalol on hypertension and the renin-angiotensin-aldosterone and adrenergic systems in pregnancy. In Riley A, Symonds EM, eds. The Investigation of Labetalol in The Management of Hypertension in Pregnancy. Amsterdam:Excerpta Medica, 1982:7787.
4. Lunell NO, Hjemdahl P, Fredholm BB, Lewander R, Nisell H, Nylund L, Persson B, Sarby J, Wager J, Thornstrom S. Acute effects of labetalol on maternal metabolism and uteroplacental circulation in hypertension of pregnancy. In Riley A, Symonds EM, eds. The Investigation of Labetalol in The Management of Hypertension in Pregnancy. Amsterdam:Excerpta Medica, 1982:3445.
5. Nylund L, Lunell NO, Lewander R, Sarby B, Thornstrom S. Labetalol for the treatment of hypertension in pregnancy. Acta Obstet Gynecol Scand 1984;118(Suppl):713.
6. Lunell NO, Kulas J, Rane A. Transfer of labetalol into amniotic fluid and breast milk in lactating women. Eur J Clin Pharmacol 1985;28:5979.
7. Rubin PC. Drugs in pregnancy. In Riley A, Symonds EM. eds. The Investigation of Labetalol in The Management of Hypertension in Pregnancy. Amsterdam:Excerpta Medica, 1982:2833.
8. Rubin PC, Butters L, Kelman AW, Fitzsimons C, Reid JL. Labetalol disposition and concentration-effect relationships during pregnancy. Br J Clin Pharmacol 1983;15:46570.
9. Lamming GD, Broughton Pipkin F, Symonds EM. Comparison of the alpha and beta blocking drug, labetalol, and methyl dopa in the treatment of moderate and severe pregnancy-induced hypertension. Clin Exp Hypertens 1980;2:86595.
10. Lotgering FK, Derkx FMH, Wallenburg HCS. Primary hyperaldosteronism in pregnancy. Am J Obstet Gynecol 1986;155:9868.
11. Mabie WC, Gonzalez AR, Sibai BM, Amon E. A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol 1987;70:32833.
12. Plouin P-F, Breart G, Maillard F, Papiernik E, Relier J-P. Comparison of antihypertensive efficacy and perinatal safety of labetalol and methyldopa in the treatment of hypertension in pregnancy: a randomized controlled trial. Br J Obstet Gynaecol 1988;95:86876.
13. Pickles CJ, Symonds EM, Broughton Pipkin F. The fetal outcome in a randomized trial of labetalol versus placebo in pregnancy-induced hypertension. Br J Obstet Gynaecol 1989;96:3843.
14. Lardoux H, Gerard J, Blazquez G, Chouty F, Flouvat B. Hypertension in pregnancy: evaluation of two beta blockers atenolol and labetalol. Eur Heart J 1983;4(Suppl G):3540.
15. Sibai BM, Gonzalez AR, Mabie WC, Moretti M. A comparison of labetalol plus hospitalization versus hospitalization alone in the management of preeclampsia remote from term. Obstet Gynecol 1987;70:3237.
16. Michael CA, Potter JM. A comparison of labetalol with other antihypertensive drugs in the treatment of hypertensive disease of pregnancy. In Riley A, Symonds EM. eds. The Investigation of Labetalol in The Management of Hypertension in Pregnancy. Amsterdam:Excerpta Medica, 1982:11122.
17. Davey DA, Dommisse J, Garden A. Intravenous labetalol and intravenous dihydralazine in severe hypertension in pregnancy. In Riley A, Symonds EM, eds. The Investigation of Labetalol in The Management of Hypertension in Pregnancy. Amsterdam:Excerpta Medica, 1982:5261.
18. MacPherson M, Broughton Pipkin F, Rutter N. The effect of maternal labetalol on the newborn infant. Br J Obstet Gynaecol 1986;93:53942.
19. Redman CWG. A controlled trial of the treatment of hypertension in pregnancy: labetalol compared with methyldopa. In Riley A, Symonds EM, eds. The Investigation of Labetalol in The Management of Hypertension in Pregnancy. Amsterdam:Excerpta Medica, 1982:10110.
20. Walker JJ, Crooks A, Erwin L, Calder AA. Labetalol in pregnancy-induced hypertension: fetal and maternal effects. In Riley A, Symonds EM, eds. The Investigation of Labetalol in The Management of Hypertension of Pregnancy. Amsterdam:Excerpta Medica, 1982:14860.
21. Thulesius O, Lunell NO, Ibrahim M, Moberger B, Angilivilayil C. The effect of labetalol on contractility of human myometrial preparations. Acta Obstet Gynecol 1987;66:23740.
22. Lamming GD, Symonds EM. Use of labetalol and methyldopa in pregnancy-induced hypertension. Br J Clin Pharmacol 1979;8(Suppl 2):217S22S.
23. Jorge CS, Fernandes L, Cunha S. Labetalol in the hypertensive states of pregnancy. In Riley A, Symonds EM, eds. The Investigation of Labetalol in The Management of Hypertension of Pregnancy. Amsterdam:Excerpta Medica, 1982:12430.
24. Lunell NO, Nylund L, Lewander R, Sarby B. Acute effect of an antihypertensive drug, labetalol, on uteroplacental blood flow. Br J Obstet Gynaecol 1982;89:6404.
25. Jouppila P, Kirkinen P, Koivula A, Ylikorkala O. Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in pre-eclampsia. Br J Obstet Gynaecol 1986;93:5437.
26. Michael CA. The evaluation of labetalol in the treatment of hypertension complicating pregnancy. Br J Clin Pharmacol 1982;13(Suppl):127S31S.
27. Symonds EM, Lamming GD, Jadoul F, Broughton Pipkin F. Clinical and biochemical aspects of the use of labetalol in the treatment of hypertension in pregnancy: comparison with methyldopa. In Riley A, Symonds EM, eds. The Investigation of Labetalol in The Management of Hypertension in Pregnancy. Amsterdam:Excerpta Medica, 1982:6276.
28. Smith AM. Beta-blockers for pregnancy hypertension. Lancet 1983;1:7089.
29. Walker JJ, Bonduelle M, Greer I, Calder AA. Antihypertensive therapy in pregnancy. Lancet 1983;1:9323.
30. Product information. Normodyne. Schering, 2000.
31. Frishman WH, Chesner M. Beta-adrenergic blockers in pregnancy. Am Heart J 1988;115:14752.
32. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
    
    

Questions and Answers

Has anyone taken the beta blocker Labetalol ? I am pregnant and being told to switch to this one?

Did you have any side effects etc

Did you have high blood pressure before you became pregnant or is your high blood pressure because of the pregnancy ( Pregnancy Induced ) ?? What med were you on previously ?? I ask these questions because it will affect my answer. Labetalol is frequently prescribed for pregnancy induced high blood pressure.This can be a sign of pre-eclampsia. If your Doc switched you to this medication then, you should be ok. The side effects:
Drowsiness, fatigue ( feeling tired), weakness, difficulty sleeping,diminished sexual function, scalp tingling ( this will pass after time). However, this doesn't mean that you will get these side effects. The drug companies have to list every sign or symptom of side effects. If you were previously taken medication for your blood pressure, your body is used to being on such medications. If you do develop some of these side-effects that do not go away or they persist or worsen, let your Doc know. You should reduce your salt intake and watch for swelling of your hands, feet, puffiness of your face or near your eyes, headaches or any change in your vision. I hope that this helps. Congrats on your pregnancy.

iam 5 months pregnant and i was wondering is there any thing i can do to help my body produce more breastmilk?

when i was pregnant with my first 2 children i produced lil to none during my pregnancy and after ..i really want to breast feed my daughter because its my last chance . but i started to lactate alil so i know my body works just not to well what can i take .or do to help ..and if i take some thin i have to b careful because im still pregnant and on med's i take insulin,lovenox(blood thinner),and labetalol(for blood pressure), so i have to make sure they wont interact.. any suggestions?
please help me ..im desperate.. thanks michelle

Drink more water, not milk,if you like only one cup a day eat onion, sesame, Anason Tea, don't drink coffee, don't eat parsley and be more calm, walk in nature or listen music.

How do I help lower my blood pressure during pregnancy?

I am 15 weeks pregnant. I have been battling high blood pressure since day 1. My OB put me on Labetalol, a medication for hbp. It seems to be helping some, but my reading are all over the map during the day. I'm afraid he will put me on bedrest, which I don't know how we will afford. We need my income right now. (I'll do it if I need to though)
Does anyone have any suggestions to go along with the medication? I'd appreciate them greatly.

LISTEN TO ME!!!!! I have the same issue. When you are resting, lay on your LEFT side at all times and make sure you drink plenty of water and stay away from salt. When you lay on your left side it helps with circulation and for some reason lowers blood pressure. I am 35 weeks along and just stopped working.

36 weeks pregnant, will they let me go full term with high BP?

Hi, im 36 weeks pregnant and have had high bloodpressure for 5 years now ( im 21, not overweight, no family history etc just unlucky) my medication was changed to labetalol 100mg 3x daily when i became pregnant and throughout my pregnancy my BP has been ok one minute and then up the next, my medication has been put up on several occassions, at my appointment today my BP was 160/110 on 300mg 3x daily of labetalol so it has been increased again to 300mg 4x daily!! Ive not been feeling great lately but just normal pregnancy things, backache, cramps etc but ive been asymptomatic bloodpressure wise ( no protein, no swelling, no headaches) Was just wondering if anyone has been in the same situation and what happened with regards to your delivery date? Is it likely the doctors will induce me early if my bloodpressure continues to rise or will they let me go full term if i remain symptom free?? thanks

i was induced early with my first but only because it got risky for me. be ready, hope your bags are packed!

My Wife is 24 weeks pregnant and they don't think the baby will make it!!?

My Wife is 24 weeks Pregnant and they say the baby will not survive!!!!!

My wife went 4 weeks ago to the doctor and they said that the baby was 3 weeks behind in development. She went again two days ago and now they say the baby is 5 weeks behind (weighs 7-8oz). There is also very little Amniotic Fluid! The baby is also no longer moving!! This is our first and it took us over a year to conceive... They also put my wife on Labetalol HCL 200mg three times a day to control her high blood pressure at 19 weeks.

What could cause these problems!! My wife had a VERY Healthy Pregnancy until 19 weeks. Now the doctors are telling us we have a 1% chance of the baby surviving :( Please if there is anything we can do to help give our baby a better chance please tell us. (Also my wife quit her job hoping it would help)

I am so sorry that you are going through this difficult time. I am sure that if there was something more that you could be doing to increase this baby's chances, the doctors would have told you already. The most important (and the hardest ) thing that you and your wife need to do right now try not to stress about it. I would not give up your hope, but realize that whatever does come of this, you have each other to hold on to, and together you will get through this. You and your wife married each other because you love each other, and that love will see you through times like this.
Do not try to figure out the whys. Sometimes in this life we are not given the reasons why. When something goes wrong, we always try to figure out why and if there is something they could have done differently. No matter the outcome do not blame yourselves. We really do not have the control over what happens in our lives. But I do believe that everything happens for a reason, and worrying about the future will not change anything. But prayer can.
I will pray for your child (God can do alot with 1%), but understand that whatever happens, it will happen for a reason. You may never know that reason, or you may come to understand a long way into the future. Hang on to each other and reach out to God. He loves you and He cries with you. If this baby does not survive He will be holding it in His arms, just like he will be holding you in His arms. God Bless you both, and I pray that one way or another you WILL soon have a little baby to hold in YOUR arms.

Labetalol? Anyone else have to take this for high blood pressure?

I'm 26 weeks & just saw my CNM for my checkup today. I was agitated because I had to wait over an hour past my appointment time. The first nurse took my blood pressure & it was high. So she waited 5 minutes & then took it again, and it had gone down quite a bit, but was still borderline. But as soon as the CNM came in & looked at my chart, she was worried about the first reading. So she proceeded to go down the hall & get a prescription for Labetalol from a doctor I never even met (this is a large OB/GYN practice). I really hate taking any meds, I haven't even taken Tylenol since I found out I was pregnant. Also, I'm not sure I should take it on the advice of a CNM, not a doctor. The doctor who did sign the Rx doesn't know me, for all I know he didn't even look at my chart.

I have a heart condition and took this during my last pregnancy adn this pregnancy. For me though I have to take ACE inhibitors when not pregnant. Thsi time it's way too much and this is mylast pregnancy. I also take Aldomet for the blood pressure. It's a bit odd though that she took it only one time and then prescribed it. Check it yourself at home. Yu can get a blood pressure cuff forlike 20 at a pharmacy, like walgreens or cvs. Check it at random times. You should be aiming fr 120/80. Lay on your left side and when you're resting. Hope this helps.