What are the guidelines for using torsemide (a loop diuretic) in the third trimester of pregnancy?

Torsemide Use in Third Trimester of Pregnancy

Torsemide should generally be avoided in the third trimester of pregnancy unless there is a compelling maternal indication such as severe cardiac or renal failure that threatens maternal life, as there are no adequate safety data in pregnant women and diuretics can reduce uteroplacental perfusion. 1

FDA Labeling and Available Safety Data

• The FDA label for torsemide explicitly states there are no available data on use in pregnant women regarding risk of major birth defects or miscarriage 1
• Animal studies showed no teratogenicity at doses up to 10 times the human dose (rats) and 1.7 times the human dose (rabbits), but higher doses caused fetal toxicity including decreased body weight, increased resorption, and delayed ossification 1
• The estimated background risk in the U.S. general population is 2-4% for major malformations and 15-20% for miscarriage 1

Guideline Recommendations on Diuretics in Late Pregnancy

Diuretics are not recommended as first-line therapy in pregnancy-induced hypertension and should be avoided entirely in pre-eclampsia because uteroplacental circulation is already compromised with fetal growth retardation 2, 3

When Diuretics May Be Considered:

• Only in combination with other antihypertensive drugs when vasodilators cause fluid retention, as diuretics potentiate the response to other agents 2, 3
• For maternal cardiac or renal failure: Furosemide (and by extension, other loop diuretics) has been used safely in pregnancy complicated by these life-threatening conditions 2
• If a thiazide is needed for chronic management, it should be chosen over loop diuretics 2, 3

Specific Contraindications:

• Pre-eclampsia with proteinuria and fetal growth restriction: Diuretics reduce plasma volume expansion and may promote pre-eclampsia occurrence 2, 3
• Uteroplacental insufficiency: The already reduced perfusion makes diuretics particularly dangerous 2, 3

Clinical Context for Torsemide Specifically

Potential Advantages Over Furosemide:

• One case report demonstrated torsemide was more effective than furosemide for severe third-trimester lymphorrhea without adverse maternal, fetal, or neonatal outcomes 4
• Torsemide has higher bioavailability (>80%), longer half-life (3-4 hours), and potentially less ototoxicity than furosemide 5, 6
• The incidence of ototoxicity appears greater with furosemide and torsemide compared to bumetanide 2

Evidence from Postpartum Use:

• A randomized trial of torsemide 20 mg/day for 5 days starting within 24 hours postpartum in women with preeclampsia showed no significant reduction in persistent hypertension (44% vs 58%, RR 0.76,95% CI 0.5-1.1) and no adverse events 7
• This suggests torsemide is reasonably well-tolerated in the immediate postpartum period, though efficacy for hypertension was limited 7

Practical Algorithm for Decision-Making

Step 1: Assess Maternal Indication

• Life-threatening cardiac failure (pulmonary edema, severe decompensation) → Consider torsemide 2
• Severe renal failure with volume overload → Consider torsemide 2
• Hypertension alone (including pre-eclampsia) → Do NOT use torsemide; use methyldopa, labetalol, or long-acting nifedipine instead 3

Step 2: Rule Out Contraindications

• Pre-eclampsia with proteinuria → Absolute contraindication 2, 3
• Fetal growth restriction → Absolute contraindication 2, 3
• Isolated peripheral edema → Not an indication; this is physiologic in pregnancy 4

Step 3: If Diuretic is Necessary

• Use the lowest effective dose for the shortest duration 1
• Monitor closely for signs of volume depletion, electrolyte abnormalities, and fetal compromise 2
• Consider thiazide diuretics first if chronic management is needed rather than loop diuretics 2, 3

Important Caveats

• Diuretics can suppress lactation, which is relevant for postpartum planning 1
• The short duration of action of immediate-release torsemide may limit efficacy and permit postdiuretic sodium retention 8
• No data exist on torsemide use in premature infants or neonates, and other loop diuretics have been associated with nephrocalcinosis and persistent patent ductus arteriosus in this population 1
• If a woman is already on torsemide when pregnancy is discovered and has well-controlled cardiac/renal disease, continuation may be considered cautiously with close monitoring, but this should be discussed with maternal-fetal medicine 3