Acetazolamide in Pregnancy and Breastfeeding

Risk Factor: C
Class: Diuretics

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Shepard reviewed six reproduction studies using acetazolamide in mice, rats, hamsters, and monkeys (1). Forelimb defects were observed in the fetuses of rodents, but not in those of monkeys. One of the studies found that potassium replacement reduced the risk of congenital defects in rats (1). A study with pregnant rabbits found that, with doses producing maternal acidosis and electrolyte changes, acetazolamide produced a dose-related increase in axial skeletal malformations (2). The combination of acetazolamide and amiloride was found to produce abnormal development of the ureter and kidney in fetal mice when given at the critical moment of ureter development (3).

Despite widespread usage, no reports linking the use of acetazolamide with congenital defects have been located. A single case of a neonatal sacrococcygeal teratoma has been described (4). The mother received 750 mg daily for glaucoma during the 1st and 2nd trimesters. A relationship between the drug and carcinogenic effects in the fetus has not been supported by other reports. Retrospective surveys on the use of acetazolamide during gestation have not demonstrated an increased fetal risk (5,6).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 12 of whom had 1st trimester exposure to acetazolamide (7, p. 372). No anomalies were observed in the exposed offspring. For use anytime during pregnancy, 1,024 exposures were recorded (7, p. 441), and 18 infants were found to have malformations (18.06 expected). Thus, no evidence was found to suggest a relationship to large categories of major or minor malformations or to individual defects.

A woman with glaucoma was treated throughout pregnancy with acetazolamide, 250 mg twice daily, and topical pilocarpine and timolol (8). Within 48 hours of birth at 36 weeks' gestation, the infant's condition was complicated by hyperbilirubinemia and asymptomatic hypocalcemia, hypomagnesemia, and metabolic acidosis. The deficiencies of calcium and magnesium resolved quickly after treatment, as did the acidosis, even though the mother continued her medications while breast feeding the infant. Mild hypertonicity of the lower limbs requiring physiotherapy was observed at 1-, 3-, and 8-month examinations (8). Two other healthy infants of an epileptic mother, treated throughout two pregnancies with acetazolamide 250 mg/day and carbamazepine, were delivered at term and showed no effects of exposure to the drugs (8).

Breast Feeding Summary

Acetazolamide is excreted into breast milk (9). A mother, 6 days postpartum, was given 500 mg (sustained-release formulation) twice daily for glaucoma, and she breast-fed her infant for the following week. Nursing was stopped after that time because of the mother's concerns about exposing the infant to the drug. However, no changes attributable to drug exposure were noted in the infant. Breast milk levels of acetazolamide on the 4th and 5th days of therapy, 19 hours after a maternal dose, varied between 1.3 and 2.1 g/mL. A consistent relationship between concentration and time from last dose was not apparent. A milk:plasma ratio 1 hour after a dose was 0.25. Three plasma levels of acetazolamide in the infant were 0.2, 0.2, and 0.6 g/mL. The authors estimated the infant ingested about 0.6 mg/day (i.e., 0.06% of the maternal dose) (9). The American Academy of Pediatrics considers acetazolamide to be compatible with breast feeding (10).

References

  1. Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD:Johns Hopkins University Press, 1989:56.
  2. Nakatsuka T, Komatsu T, Fujii T. Axial skeletal malformations induced by acetazolamide in rabbits. Teratology 1992;45:62936.
  3. Miller TA, Scott WJ Jr. Abnormalities in ureter and kidney development in mice give acetazolamide-amiloride or dimethadione (DMO) during embryogenesis. Teratology 1992;46:54150.
  4. Worsham GF, Beckman EN, Mitchell EH. Sacrococcygeal teratoma in a neonate. Association with maternal use of acetazolamide. JAMA 1978;240:2512.
  5. Favre-Tissot M, Broussole P, Robert JM, Dumont L. An original clinical study of the pharmacologic-teratogenic relationship. Ann Med Psychol 1964;1:389. As cited in Nishimura H, Tanimura T, eds. Clinical Aspects of The Teratogenicity of Drugs. New York, NY:Excerpta Medica, 1976;210.
  6. McBride WG. The teratogenic action of drugs. Med J Aust 1963;2:68993.
  7. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
  8. Merlob P, Litwin A, Mor N. Possible association between acetazolamide administration during pregnancy and metabolic disorders in the newborn. Eur J Obstet Gynecol Reprod Biol 1990;35:858.
  9. Soderman P, Hartvig P, Fagerlund C. Acetazolamide excretion into human breast milk. Br J Clin Pharmacol 1984;17:59960.
  10. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137-50.
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Questions and Answers

if you took a acute glaucoma attack and were put on acetazolamide ?, at the er room to bring down the raised pressure how long would you be on it for before laser treatment only i heard that they did not keep you on acetazolamide for long

follow up with your opthalmologist for an answer.

i have been on acetazolamide for 2 weeks now and i am still on it ?, i was put on it for a acute glaucoma attack, i constantly feel tired and nausea is very bad .is this a side effect of the acetazolamide ? i have heard you are not usually on this medication long,does anyone know about it?

in the box of tablets there should have been a leaflet explaining the side effects, if theres not, then you are best off phoning your gp and asking him/her about possible side effects

is acetazolamide the usual treatment for a acute glaucoma attack?, and how long would you be on it for is this the on going treatment for it to keep the raised pressure down or would you get something else

An acute attack of glaucoma is always due to angle closure.Oral acetazolamide is used to rapidly bring down the eye pressure.Once the pressure comes down, a laser procedure called iridotomy is performed.This will open up the angle and acetazolamide wont be needed thereafter.

Why acetazolamide is such a potent inhibitor of carbonic anhydrase?, explain base on the structure if the molecules invilved, and the knowledge of ligand-receptor interaction.

This page also shows you a wikapedia excerpt on molecular structure I hope it helps you

Acetazolamide

Definition

Acetazolamide (a-set-a-ZOLE-a-mide) is a carbonic anhydrase inhibitor. Carbonic anhydrase is an enzyme that shifts the rate of reaction to favor the conversion of carbon dioxide and water into carbonic acid, bicarbonate ions, and free protons. Carbonic anhydrase activity is key to the regulation of pH and fluid balance in many different reactions throughout the body.

Fluid buildup can alter the shape of the eye and cause pressure on the optic nerve. Clinically, this condition is described as glaucoma. Inhibition of the enzymatic work of carbonic anhydrase activity (e.g., through the action of a carbonic anhydrase inhibitor) can lower fluid pressure in the eye.

Purpose

Acetazolamide is used to treat a number of disorders, including the control of epileptic seizures in those individuals who suffer epilepsy.

Acetazolamide is also used to treat non-neurological disorders such as glaucoma (acetazolamide decreases pressure in the eye), and to reduce the symptoms of edema (an excess storage of water by the body that leads to localized swelling or puffiness) and altitude sickness.

Description

Acetazolamide is prescription medication and is available only with a licensed physician's prescription. Acetazolamide is available in oral form in extended release capsules and tablets. Acetazolamide can also be administered by injection.

Recommended dosage

For both adults and children the recommended dosage for use in epilepsy cases is based upon actual body weight. In all cases, the exact dosage is determined by an experienced physician and/or pharmacist. In the most common cases, the normal recommended dosage is 4.5 mg per pound of body weight (10 mg per kg of body weight) and is administered in multiple (divided) doses delivered in the form of tablets or capsules.

Doses must be taken on a regular schedule but individuals should not double dose to make up for a missed dose.

When used to control anticonvulsive seizures, acetazolamide doses should not be stopped all at once. In most cases, physicians usually curtail (gradually lower) the dose an individual takes over time.

Precautions

As with most prescription medicines, acetazolamide should stored in a safe place—away from the reach of children. Acetazolamide should also be stored in a dry area away from excessive heat or light. Outdated medicine (medicines past their expiration date) should be discarded in a container that is safe from the reach of children.

Women who are pregnant, plan to become pregnant, or who are breast-feeding infants should inform their physician of this fact before taking acetazolamide.

Side effects

Unwanted side effects while taking acetazolamide include drowsiness, fatigue, or a dizzy lightheaded feeling. Individuals who experience these side effects should rate machinery or drive while experiencing these symptoms. Other common side effects include shortness of breath.

Acetazolamide can also lead to excessive depletion (loss) of potassium from the body. To counter this potential loss, many physicians recommend that patients eat food or drink beverages such as orange juice to replace lost potassium. The loss of potassium does not occur in every case, however, and high levels of potassium can also be dangerous. Individuals who show signs of potassium loss—including, but not limited to, dryness of mouth, increased thirst, or muscle cramps—should alert their physician. Because diet can impact a number of health factors, individuals should only alter their diet after consulting their physician.

Individuals who are diabetic and who take acetazolamide may experience elevated sugar levels in their urine and blood.

Individuals who experience changes in their vision should also consult their physician.

In some rare cases, individuals may suffer depression, pains in the area of the kidneys, and bloody or black tarry stools.

Interactions

Physicians and pharmacists are trained to evaluate the potential for adverse interactions by prescription drugs with other drugs. In the case of acetazolamide physicians evaluate potential adverse reactions with a range of drugs that include—but are not limited to—amphetamines, over-the-counter aspirins, cyclosporine, mood altering drugs (e.g., lithium), drugs used to control mental depression, drugs used to control irregular heartbeats, digoxin, diuretics (also known as water pills), and vitamins.

Resources

PERIODICALS

Varadkar S., J. S. Duncan, and H. Cross. "Acetazolamide and Autosomal Dominant Nocturnal Frontal Lobe Epilepsy." Epilepsia 44 (July 2003): 986.

OTHER

Medline Plus. U.S. National Library of Medicine and the National Institutes of Health. http://www.nlm.nih.gov/medlineplus/drugi... (May 9, 2004).

ORGANIZATIONS

National Eye Institute. 2020 Vision Place, Bethesda, MD 20892-3655. (301) 496-5248. http://www.nei.nih.gov/.

Acetazolamide for altitude sickness?, I know that Acetazolamide can be used to treat altitude sickness but has anyone heard of it being used to prevent it until a person has acclimatized by decreasing the amount of bicarb reabsorbed from the proximal convoluted tubule?

It is used as a prophylactic as well as treatment.

what effects does acetazolamide have on urine pH, blood pH, and respiratory rate?, acetazolamide is a diuretic that blocks the activity of carbonic anhydrase in kidney tubule cells (preventing formation of carbonic acid)

Acetazolamide prevents the formation of protons and bicarbonate, so the urine pH would be more basic and the blood would be more acidic. This will increase the respiratory rate to blow off CO2, and return the pH back toward normal.

Can you have alocholic beverages while taking Acetazolamide and Hydrochlorothiaz.?,

i would'nt.go to drugs.com

Acetazolamide mechanism of action.?, Does anyone know the mechanism of diuresis caused by acetazolamide? I know it is a carbonic anhydrase inhibitor but how does this cause H+ retention and bicarbonate excretion?

The reaction of carbonic acid (H2CO3) to water and CO2 is catalized by carbonic anhydrase, but it's inhibited by acetazolamide, which leaves carbonic acid which is unstable and becomes hydrogen ion (H+) and bicarbonate ion (HCO3). The H+ gets reabsorbed by the renal tubules and the bicarb is excreted in the urine.

is Acetazolamide good for nausea?,

NO, IT IS NOT- GOOD FOR HIGH BLOOD PRESSURE OR METABOLIC ALKALOSIS

ANYONE WHOS SAYS THSI IS GOOD FOR HEADACHE OR NAUSEA IS AN IDIOT- NEVER RX FOR HEADACHE- TAKE TYLENOL (ACETAMINOPHEN) OR IBUPROFEN 400 MG (2 TABS)

diamox with acetazolamide ?, while taking diamox pill and does it caused sense of smell increase???????????

thanks

No.