Carboprost

Indication

Carboprost is used in postpartum hemorrhage caused by uterine atony not controlled by other methods. One study has shown that carboprost tromethamine is more effective than oxytocin in preventing postpartum hemorrhage in high-risk patients undergoing cesarean delivery.

Carboprost was the first drug widely used for medication abortions. It is still sometimes used for second trimester abortions, but has generally been supplanted by the mifepristone/misoprostol combination."Carboprost" - Drug fact sheet, Mayo Clinic. Last updated: July 01, 2024 https://www.mayoclinic.org/drugs-supplements/carboprost-intramuscular-route/proper-use/drg-20067975

Contraindication

Carboprost is contraindicated in severe cardiovascular, renal, and hepatic disease. It is also contraindicated in acute pelvic inflammatory disease. Hypersensitivity to carboprost or any of its components is also a contraindication.

Precautions

• asthma
• anemia
• jaundice
• diabetes mellitus
• seizure disorders
• past uterine surgery

Adverse effects

• diarrhea (most common, may be sudden in onset)
• flushing or hot flashes
• fever
• chills
• nausea/vomiting

Storage and availability

Carboprost is supplied with its salt derivative tromethamine in 1-milliliter ampules containing a 250 mcg/mL solution of the active drug. The drug must be kept refrigerated at 2 –.

Synthesis

A significant deactivating metabolic transformation of natural prostaglandins is enzymatic oxidation of the C-15 hydroxyl to the corresponding ketone. This is prevented, with retention of activity, by methylation to give the C-15 tertiary carbinol series.

This molecular feature is readily introduced at the stage of the Corey lactone (1) by reaction with methyl Grignard reagent or trimethylaluminium. The resulting mixture of tertiary carbinols (2) is transformed to oxytocic carboprost (3) by standard transformations, including separation of diastereomers, so that the final product is the C-15 analogue. This diastereomer is reputably freeer of prostaglandin side effects than the C-15 (S) isomer.

References

References

1. (28 July 2023). "Carboprost-REACH (Reach Pharmaceuticals Pty Ltd)".
2. (January 2014). "A comparison of oxytocin and carboprost tromethamine in the prevention of postpartum hemorrhage in high-risk patients undergoing cesarean delivery". Experimental and Therapeutic Medicine.
3. Hemabate [Package Insert]. New York, NY: Pharmacia and Upjohn Company; 2014.
4. Vukelić J. Second trimester pregnancy termination in primigravidas by double application of dinoprostone gel and intramuscular administration of carboprost tromethamine. Med Pregl. 2001 Jan-Feb;54(1-2):11-6. English, Croatian. PMID: 11436877.
5. Bygdeman, M., & Gemzell-Danielsson, K. (2008). An Historical Overview of Second Trimester Abortion Methods. Reproductive Health Matters, 16(sup31), 196–204. https://doi.org/10.1016/S0968-8080(08)31385-8
6. Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2 alpha. An overview of 815 cases. J Reprod Med. 1979 Dec;23(6):289-93. PMID: 392084.
7. Bhaskar A, Dimov V, Baliga S, Kinra G, Hingorani V, Laumas KR. Plasma levels of 15 (S) 15-methyl-PGF 2 alpha-methyl ester following vaginal administration for induction of abortion in women. ''Contraception''. 1979 Nov;20(5):519-31. doi: 10.1016/0010-7824(79)90057-x. PMID: 527343.
8. (September 1974). "Total synthesis of 15-methylprostaglandins". Journal of the American Chemical Society.
9. (April 1971). "Novel prostaglandin syntheses". Annals of the New York Academy of Sciences.
10. "Verfahren zur Herstellung nueur Prostansäurederivate [Process for the production of new prostanoic acid derivatives]".