tolmetin and Pregnancy studies

Tolmetin: A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.
tolmetin : A monocarboxylic acid that is (1-methylpyrrol-2-yl)acetic acid substituted at position 5 on the pyrrole ring by a 4-methylbenzoyl group. Used in the form of its sodium salt dihydrate as a nonselective nonsteroidal anti-inflammatory drug.

Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.

Research Excerpts

Excerpt	Relevance	Reference
"In gestations with preterm labor at <32 weeks, ketorolac appears to be an appropriate first-line tocolytic agent."	2.69	A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor. ( Ascarelli, MH; Calfee, EL; Morrison, JC; Perry, KG; Ross, EL; Rust, OA; Schorr, SJ, 1998)
"Ketorolac is a potent analgesic agent with antiplatelet properties which is known to cross the placenta."	2.66	Effect of maternal ketorolac administration of platelet function in the newborn. ( Greer, IA; Johnston, J; Tulloch, I; Walker, JJ, 1988)
" The absorption of ketorolac is rapid, Cmax being attained between 20 to 60 min."	2.38	Clinical pharmacokinetics of ketorolac tromethamine. ( Brocks, DR; Jamali, F, 1992)
"Tolmetin and ibuprofen were administered three times a day."	1.33	Skeletal developmental effects of selective and nonselective cyclooxygenase-2 inhibitors administered through organogenesis and fetogenesis in Wistar CRL:(WI)WUBR rats. ( Burdan, F; Dudka, J; Klepacz, R; Marzec, B; Szumilo, J, 2005)
"The fetal body weight was significantly lower in COX-exposed group of fetuses when compared with untreated control."	1.33	Celosomy is associated with prenatal exposure to cyclooxygenase inhibitors. ( Burdan, F; Dudka, J; Klepacz, R; Korobowicz, A; Szumilo, J, 2006)
"Both COX inhibitors were toxic to dams in the highest doses evaluated, which caused a significantly greater incidence of intrauterine growth retardation and developmental variations."	1.32	Developmental toxicity evaluation of ibuprofen and tolmetin administered in triple daily doses to Wistar CRL:(WI)WUBR rats. ( Burdan, F, 2004)

Research

Studies (21)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Anti-emetic Doses

Timeframe	Studies, this research(%)	All Research%
pre-1990	5 (23.81)	18.7374
1990's	11 (52.38)	18.2507
2000's	4 (19.05)	29.6817
2010's	1 (4.76)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Kulo, A	1
Hendrickx, S	1
de Hoon, J	1
Mulabegovic, N	1
van Calsteren, K	1
Verbesselt, R	1
Allegaert, K	1
Burdan, F	3
Szumilo, J	2
Marzec, B	1
Klepacz, R	2
Dudka, J	2
Korobowicz, A	1
Dairam, A	1
Müller, AC	1
Daya, S	1
Creasy, GW	1
Kousen, M	1
Walker, WR	1
Tzeng, JI	1
Mok, MS	1
Gin, T	1
Kan, AF	1
Lam, KK	1
O'Meara, ME	1
Laifer, SA	2
Rauk, PN	2
Diemunsch, P	1
Alt, M	1
Diemunsch, AM	1
Treisser, A	1
Schorr, SJ	1
Ascarelli, MH	1
Rust, OA	1
Ross, EL	1
Calfee, EL	1
Perry, KG	1
Morrison, JC	1
Ho, ML	1
Chang, JK	1
Chuang, LY	1
Hsu, HK	1
Wang, GJ	1
Huskisson, EC	1
Walker, JJ	3
Johnston, J	2
Fairlie, FM	1
Lloyd, J	2
Bullingham, R	1
Brocks, DR	1
Jamali, F	1
Buckley, MM	1
Brogden, RN	1
Johnstone, J	1
Rocha, CL	1
Greer, IA	1
Tulloch, I	1
Kollenberg, LO	1
Hudyma, EO	1
Robbins, JM	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Disposition of Intravenous Ketorolac After Cesarean Section[NCT01291472]	Phase 4	42 participants (Actual)	Interventional	2011-06-30	Completed
Prospective Evaluation of the Effects of IV Ketorolac on Platelet Function Post-Cesarean Delivery[NCT03805607]	Phase 4	40 participants (Actual)	Interventional	2021-01-18	Active, not recruiting
A Prospective, Randomized, Control Trial of Ketorolac Versus Placebo on Opioid Analgesic Use, Estimated Blood Loss and Complications Following Cesarean Delivery With Epidural Morphine[NCT02509312]	Phase 4	70 participants (Actual)	Interventional	2016-05-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Total doses of medications to treat pruritus (opioid side-effect) including ondansetron and promethazine. (NCT02509312)
Timeframe: 0 - 24 hours post-partum

Corrected Change in Hct on POD1.

Intervention	doses (Median)
Ketorolac	0
Placebo	0

Corrected change in Hct on POD1. Performed by subtracting POD1 Hct from POD0 Hct. Correction for transfusion by further subtracting 3 per unit of pRBC transfused to account for the typical change seen per unit transfused. (NCT02509312)
Timeframe: POD1

Estimated Blood Loss (EBL)

Intervention	mg/dl (Mean)
Ketorolac	-5.1
Placebo	-3.5

Estimation of blood loss during surgery (NCT02509312)
Timeframe: Immediately post-op

Post-Partum Hemorrhage

Intervention	ml (Median)
Ketorolac	900
Placebo	800

Rate of Post-Partum Hemorrhage between groups during the first 24 hours pst-partum. (NCT02509312)
Timeframe: 0 - 24 hours post-partum

Pruritus Doses

Intervention	Participants (Count of Participants)
Ketorolac	7
Placebo	4

Total doses of medications to treat pruritus (opioid side-effect) including diphenhydramine, nalbuphine and naloxone. (NCT02509312)
Timeframe: 0 - 24 hours post-partum

Total Hydromorphone Dose

Intervention	doses (Median)
Ketorolac	0
Placebo	0

Total hydromorphone doses in mg in the first 24 hours post-partum. (NCT02509312)
Timeframe: 0 - 24 hours post-partum.

Units of Packed Reb Blood Cell Transfused

Intervention	mg (Median)
Ketorolac	0
Placebo	0.2

Total number of Units of Packed Reb Blood Cell Transfused in intra-op until 24 hours post-partum. (NCT02509312)
Timeframe: Intra-op until 24 hours post-partum.

Uterotonic Doses

Intervention	units of pRBCs (Median)
Ketorolac	0
Placebo	0

Total number of uterotonic doses including methylergonovine, carboprost and misoprostol. (NCT02509312)
Timeframe: 0 - 24 hours post-partum

Change in Pain Score Post-Cesarean Delivery

Intervention	doses (Median)
Ketorolac	0
Placebo	0

Pain score post-Cesarean Delivery using 11-point numerical rating scale (NRS): 0-10 where 0 is no pain and 10 is the worst pain imaginable (NCT02509312)
Timeframe: Up to 24 hours post-cesarean delivery

Percentile Change in Diastolic Blood Pressure (DBP) at 6,12, and 24 Hours

Intervention	units on NRS (Median)
	Baseline	15 mins	1 hour	6 hours	12 hours	24 hours
Ketorolac	0	0	0	1	2	4.5
Placebo	0	0	0	3	3.5	5.5

Percentile change in diastolic Blood Pressure at 6,12, and 24 hours for each patient's baseline defined by immediate post-op PACU vitals. (NCT02509312)
Timeframe: 0 - 24 hours post-partum

Percentile Change in Systolic Blood Pressure at 6,12, and 24 Hours

Intervention	Percent change (Mean)
	6 hours	12 hours	24 hours
Ketorolac	12.30	8.8	12.0
Placebo	7.6	8.8	11.1

Percentile change in Systolic Blood Pressure at 6,12, and 24 hours for each patient's baseline defined by immediate post-op PACU vitals. (NCT02509312)
Timeframe: 0 - 24 hours post-partum

Article	Year
Antiinflammatory drugs. Seminars in arthritis and rheumatism, 1977, Volume: 7, Issue:1 Topics: Adult; Anti-Inflammatory Agents; Apazone; Arthritis, Rheumatoid; Aspirin; Benzylidene Compounds; Chi	1977
Clinical pharmacokinetics of ketorolac tromethamine. Clinical pharmacokinetics, 1992, Volume: 23, Issue:6 Topics: Absorption; Aging; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Drug Combinations; Drug Inte	1992
Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs, 1990, Volume: 39, Issue:1 Topics: Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Ketorolac Tromethamine; Male; Pregnancy; Ra	1990

Article	Year
Combination of intramuscular Ketorolac and low dose epidural morphine for the relief of post-caesarean pain. Annals of the Academy of Medicine, Singapore, 1994, Volume: 23, Issue:6 Suppl Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Analgesics, Non-Narcotic; Anti-Inflammatory Agen	1994
Analgesia after caesarean section with intramuscular ketorolac or pethidine. Anaesthesia and intensive care, 1993, Volume: 21, Issue:4 Topics: Adult; Analgesics; Anesthesia, General; Cesarean Section; Double-Blind Method; Elective Surgical Pro	1993
A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor. Southern medical journal, 1998, Volume: 91, Issue:11 Topics: Adult; Birth Weight; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases;	1998
A comparative study of intramuscular ketorolac and pethidine in labour pain. European journal of obstetrics, gynecology, and reproductive biology, 1992, Sep-23, Volume: 46, Issue:2-3 Topics: Adolescent; Adult; Analgesia, Obstetrical; Apgar Score; Double-Blind Method; Female; Humans; Hypnoti	1992
Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs, 1990, Volume: 39, Issue:1 Topics: Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Ketorolac Tromethamine; Male; Pregnancy; Ra	1990
The transfer of ketorolac tromethamine from maternal to foetal blood. European journal of clinical pharmacology, 1988, Volume: 34, Issue:5 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Double-Blind M	1988
Effect of maternal ketorolac administration of platelet function in the newborn. European journal of obstetrics, gynecology, and reproductive biology, 1988, Volume: 29, Issue:4 Topics: Anti-Inflammatory Agents, Non-Steroidal; Female; Fetus; Humans; Infant, Newborn; Ketorolac; Maternal	1988

Article	Year
The impact of pregnancy on urinary ketorolac metabolites after single intravenous bolus. European journal of drug metabolism and pharmacokinetics, 2013, Volume: 38, Issue:1 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Belgium; Biotransformation; Case-Control Studies; De	2013
Developmental toxicity evaluation of ibuprofen and tolmetin administered in triple daily doses to Wistar CRL:(WI)WUBR rats. Birth defects research. Part B, Developmental and reproductive toxicology, 2004, Volume: 71, Issue:5 Topics: Animals; Aspirin; Body Weight; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Female;	2004
Skeletal developmental effects of selective and nonselective cyclooxygenase-2 inhibitors administered through organogenesis and fetogenesis in Wistar CRL:(WI)WUBR rats. Toxicology, 2005, Dec-15, Volume: 216, Issue:2-3 Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Development; Cathepsin K; Cathepsins; Chondro	2005
Celosomy is associated with prenatal exposure to cyclooxygenase inhibitors. Pharmacological research, 2006, Volume: 53, Issue:3 Topics: Abnormalities, Drug-Induced; Animals; Aspirin; Cyclooxygenase Inhibitors; Female; Fetal Weight; Fetu	2006
Non-steroidal anti-inflammatory agents, tolmetin and sulindac attenuate quinolinic acid (QA)-induced oxidative stress in primary hippocampal neurons and reduce QA-induced spatial reference memory deficits in male Wistar rats. Life sciences, 2007, Mar-20, Volume: 80, Issue:15 Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Survival; Cells, Cultured; Female; Glutathion	2007
A zomepirac reaction mimicking ectopic pregnancy. Drug intelligence & clinical pharmacy, 1984, Volume: 18, Issue:6 Topics: Adult; Diagnosis, Differential; Drug Hypersensitivity; Female; Humans; Hypotension; Pain; Pregnancy;	1984
Ritodrine increases leukotriene B4 concentrations in pregnant sheep. American journal of obstetrics and gynecology, 1993, Volume: 169, Issue:4 Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arteries; Female; Infusions, Intravenous; Ketorola	1993
The prostaglandin synthesis inhibitor ketorolac blocks ritodrine-stimulated production of prostaglandin F2 alpha in pregnant sheep. Obstetrics and gynecology, 1993, Volume: 81, Issue:3 Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dinoprost; Female; Ketorolac; Pregnancy; Pregnancy	1993
Post cesarean analgesia with ketorolac tromethamine and uterine atonia. European journal of obstetrics, gynecology, and reproductive biology, 1997, Volume: 72, Issue:2 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cesarean Section; Female; Humans; Ketorolac Trometha	1997
Post cesarean analgesia with ketorolac tromethamine and uterine atonia. European journal of obstetrics, gynecology, and reproductive biology, 1997, Volume: 72, Issue:2 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cesarean Section; Female; Humans; Ketorolac Trometha	1997
Post cesarean analgesia with ketorolac tromethamine and uterine atonia. European journal of obstetrics, gynecology, and reproductive biology, 1997, Volume: 72, Issue:2 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cesarean Section; Female; Humans; Ketorolac Trometha	1997
Post cesarean analgesia with ketorolac tromethamine and uterine atonia. European journal of obstetrics, gynecology, and reproductive biology, 1997, Volume: 72, Issue:2 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cesarean Section; Female; Humans; Ketorolac Trometha	1997
Toradol in the L&D. AWHONN lifelines, 1997, Volume: 1, Issue:4 Topics: Contraindications; Female; Humans; Ketorolac Tromethamine; Labor, Obstetric; Lactation; Platelet Agg	1997
Characteristics of primary osteoblast culture derived from rat fetal calvaria. The Kaohsiung journal of medical sciences, 1999, Volume: 15, Issue:5 Topics: Alkaline Phosphatase; Animals; Cells, Cultured; Dinoprostone; Female; Fetus; Ketorolac; Osteoblasts;	1999
Nonsteroidal anti-inflammatory agents. A review of the literature. Journal of the American Podiatric Medical Association, 1985, Volume: 75, Issue:10 Topics: Absorption; Anti-Inflammatory Agents; Aspirin; Diflunisal; Drug Interactions; Female; Fenoprofen; Ha	1985

tolmetin and Pregnancy