Diclofenac Risk Summary
Risk Factor: BM*Class: Central nervous system drugs / Nonsteroidal anti-inflammatory drugs
Fetal Risk Summary
Diclofenac is a nonsteroidal antiinflammatory drug (NSAID) used for the treatment of arthritis, acute and chronic pain, and primary dysmenorrhea. Similar to other agents in this class, it also has antipyretic activity. Diclofenac is in the same subclass (acetic acids) as three other NSAIDs (indomethacin, sulindac, and tolmetin).
In reproduction studies in mice, rats and rabbits, the drug was not teratogenic with doses up to those that produced maternal and fetal toxicity (1). Maternal toxic doses, however, were associated with dystocia, prolonged gestation, decreased fetal survival (1), and intrauterine growth retardation (1,2).
A 1990 report described an investigation on the effects of several nonsteroidal antiinflammatory agents on mouse palatal fusion both in vivo and in vitro (3). The compounds, including diclofenac, were found to induce cleft palate. In the rat, diclofenac, presumably by inhibiting prostaglandin synthesis, has been shown to inhibit implantation and placentation (2).
The tocolytic effect of diclofenac was demonstrated in a study that used mifepristone (RU 486) to induce preterm labor in rats (4). Diclofenac inhibited preterm delivery but had no effect on mifepristone-induced cervical maturation.
Diclofenac crosses the human placenta. In a 2000 study, 30 women undergoing termination of pregnancy at a mean gestational age of 10.2 weeks (range 812 weeks) were given two 50 mg oral doses at a mean 13.5 and 2.5 hours before the procedure (5). Diclofenac was detected in all maternal serum (mean 183.9 ng/mL) and fetal tissue (mean 279.2 ng/mL) samples, producing a mean maternal serum:fetal tissue ratio of 0.95 (range 0.054.26). Only 7 of the 30 amniotic fluid samples contained detectable diclofenac (range 0.63.5 ng/mL), whereas 17 of 30 coelomic fluid samples contained the drug (range 1.133.4 ng/mL) (5).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 51 newborns had been exposed to diclofenac during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One unspecified major birth defect was observed (two expected). 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, these data do not support an association between the drug and congenital defects.
A 29-year-old woman at 33 weeks' gestation was diagnosed by clinical symptoms and ultrasound as having a spontaneous rupture of the right renal pelvis with a small amount of perinephric extravasation of urine (6). She was treated conservatively with diclofenac while hospitalized (50 mg twice daily; duration not specified) and delivered a healthy female infant 5 weeks later. A follow-up examination of her kidney by ultrasonography 5 days postpartum was normal.
A combined 2001 population-based observational cohort study and a case-control study estimated the risk of adverse pregnancy outcome from the use of NSAIDs (7). The use of NSAIDs during pregnancy was not associated with congenital malformations, preterm delivery, or low birth weight, but a positive association was discovered with spontaneous abortions (see Ibuprofen for details).
A 1998 report described a case of premature closure of the ductus arteriosus in a fetus who was exposed to diclofenac, 50 mg twice daily, for 2 weeks from the 34th week of gestation (8). The mother had taken the drug for musculoskeletal back pain and carpal tunnel syndrome. At 41 weeks' gestation, a fetal echocardiogram revealed the ductus defect, enlargement of the right side of the heart, and early cardiac failure (8). An emergency cesarean section was performed and the baby was successfully resuscitated (8).
Constriction of the ductus arteriosus in utero is a pharmacologic consequence arising from the use of prostaglandin synthesis inhibitors during pregnancy, as is inhibition of labor, prolongation of pregnancy, and suppression of fetal renal function (see also Indomethacin) (9). Persistent pulmonary hypertension of the newborn may occur if these agents are used in the 3rd trimester close to delivery (9). Women attempting to conceive should not use any prostaglandin synthesis inhibitor, including diclofenac, because of the findings in a variety of animal models that indicate these agents block blastocyst implantation (10,11). Moreover, as noted above, NSAIDs have been associated with SABs.
[*Risk Factor D if used in 3rd trimester or near delivery.]
Breast Feeding Summary
No reports describing the use of diclofenac during lactation have been located. The manufacturer states that diclofenac is excreted into the milk of nursing mothers but does not cite quantitative data (1). One reviewer classified diclofenac as one of several low-risk alternatives, because of its short adult serum half-life (1.1 hours) and toxicity profile compared with other similar agents, if a nonsteroidal antiinflammatory agent was required while nursing (12). Other reviewers have also stated that diclofenac can be safely used during breast feeding (13,14). Another NSAID in the same subclass as diclofenac is considered compatible with breast feeding by the American Academy of Pediatrics (see Indomethacin).
References
- Product information. Voltaren. Geigy Pharmaceuticals, 1995.
- Carp HJA, Fein A, Nebel L. Effect of diclofenac on implantation and embryonic development in the rat. Eur J Obstet Gynecol Reprod Biol 1988;28:2737.
- Montenegro MA, Palomino H. Induction of cleft palate in mice by inhibitors of prostaglandin synthesis. J Craniofac Genet Del Biol 1990;10:8394.
- Cabrol D, Carbonne B, Bienkiewicz A, Dallot E, Alj AE, Cedard L. Induction of labor and cervical maturation using mifepristone (RU 486) in the late pregnant rat. Influence of a cyclooxygenase inhibitor (diclofenac). Prostaglandins 1991;42:719.
- Siu SSN, Yeung JHK, Lau TK. A study on placental transfer of diclofenac in first trimester of human pregnancy. Hum Reprod 2000;15:24235.
- Royburt M, Peled Y, Kaplan B, Hod M, Friedman S, Ovadia J. Non-traumatic rupture of kidney in pregnancycase report and review. Acta Obstet Gynecol Scan 1994;73:6637.
- Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of nonsteroidal antiinflammatory drugs: population based observational study and case-control study. Br Med J 2001;322:26670.
- Adverse Drug Reactions Advisory Committee. Premature closure of the fetal ductus arteriosus after maternal use of nonsteroidal anti-inflammatory drugs. Med J Aust 1998;169:2701.
- Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:3544.
- Matt DW, Borzelleca JF. Toxic effects on the female reproductive system during pregnancy, parturition, and lactation. In Witorsch RJ, editor. Reproductive Toxicology. 2nd ed. New York, NY:Raven Press, 1995:17593.
- Dawood MY. Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol 1993;169:125565.
- Anderson PO. Medication use while breast feeding a neonate. Neonatal Pharmacol Q 1993;2:314.
- Goldsmith DP. Neonatal rheumatic disorders. View of the pediatrician. Rheum Dis Clin North Am 1989;15:287305.
- Needs CJ, Brooks PM. Antirheumatic medication during lactation. Br J Rheumatol 1985;24:2917.
Questions and Answers
Diclofenac?, my doctor gave me diclofence for my knee pain that i have trouble walking and working.
He gave me diclofenac sod 75mg and a refill 12X , why that long to take it what happen after that? thanks
How soon will Diclofenac sodium suppositories take to work?, I have been prescribed 100mg of Diclofenac sodium to take when I get severe period pain.
What I would like to know is, how quick is it to work?
Should I start taking it a day before the pain starts or wait till the actual day.And do I wait for the pain to start or take it a it before?
Thank you.
read the direction leaflet that will tell you but if i were you i would wait until the pain starts and then take it it should be quick to work
What is the purpose of potassium in Diclofenac?, i was asked by my clinical instructor on what is the action/purpose of potassium in diclofenac potassium. I really have no idea. please help me. thanks!
It is likely sold as the potassium salt in order to enhance water solubility. This will help to improve bioavailability and enhance its pharmacokinetic properties.
Is there any diclofenac sodium medicine available over the counter in the USA?, Please this is very urgent.
Is there any diclofenac sodium medicine available over the counter in the USA ? If you know any tablet with this salt, available over the counter please let me know. This is non steroidal anti inflammatory medicine for acute and chronic rheumatoid arthritis, osteoarthritis, ankylosing spondylitis..
No, diclofenac Na is a prescription only item in the U.S.
How long does Diclofenac (Voltaren) last in the body?, I was told not to take it with Zoloft. I took Zoloft this morning, although I did take 150 mg of Diclofenac yesterday, my last dose being about 5.30 pm and my first dose of Zoloft being about 9.30 am today. I know the half-life is 1.2-2 hr, but I'm not good with math, I just want to know if it was safe for me to take Zoloft when I did, and if Diclofenac was out my system by that time. Thanks
It takes approximately 5.5 half lives before the drug is completely out of your system. As the half life is 2 hours it would take about 11 hours (2 hours x 5.5 half lives) before diclofenac would have been out of your system,so theoretically you would have been diclofenac free by 4.30 am. So it was safe for you to take Zoloft at 9.30 am.
Can you take Diclofenac or Sulindac with Lisinopril?, My fiancee has kidney failure and is on dialysis. He's on several blood pressure medications, including Lisinopril. He has inflammation that he's been taking Advil for, but is concerned about the potassium. However, he feels he needs to take something stronger.
Can he take Sulindac (Clinoril) or Diclofenac (Voltaren) with Lisinopril?
Will this have the same potassium problem?
And if you can't take them together, why not?
Clinoril - NSAID
Renal Insufficiency
Sulindac pharmacokinetics have been investigated in patients with renal insufficiency. The disposition of sulindac was studied in end-stage renal disease patients requiring hemodialysis. Plasma concentrations of sulindac and it sulfone metabolite were comparable to those of normal healthy volunteers whereas concentrations of the active sulfide metabolite were significantly reduced. Plasma protein binding was reduced and the AUC of the unbound sulfide metabolite was about half that in healthy subjects.
Sulindac and its metabolites are not significantly removed from the blood in patients undergoing hemodialysis.
Since Clinoril is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored.
A lower daily dosage should be anticipated to avoid excessive drug accumulation.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, patients who are volume-depleted and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease
No information is available from controlled clinical studies regarding the use of Clinoril in patients with advanced renal disease. Therefore, treatment with Clinoril is not recommended in these patients with advanced renal disease. If Clinoril therapy must be initiated, close monitoring of the patient's renal function is advisable.
Voltaren - NSAID
Caution should be used when initiating treatment with Voltaren in patients with considerable dehydration.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Any patient that is currently on dialysis should discuss any medications that are considering to incorporate in their daily regime with their doctor.
Is it necessary to finish my Diclofenac?, My doctor prescribed a 7 day supply of Diclofenac for my ankle. I have taken it for one day and it's caused minor stomach cramps/aches for me... which is one of the possible side effects. My question is: is it necessary for me to finish the entire prescribed amount or can I just stop taking it now?
It is advised that you stop taking Diclofenac and call your Doctor if you experience stomach pain (as well as other symptoms such as heartburn, vomiting a substance that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools).
Can I take cough medicine if I already took diclofenac?, I had this awfullly sudden sharp pain in my lower left back area earlier, so I took some diclofenac to ease the pain. (My mom usually gives me this for headaches, so I figured it would help with this pain).
So tonight I need to take some cough medicine. Is this combination safe?
Diclofenac is a NSAID like Advil, Aleve, Motrin, etc.
You can take cough medicine as long as it doesn't have a lot of a NSAID in it.
If you have a very sharp pain in your lower back, you ought to tell your mother. You might have a kidney or other type of infection.
Feel better.
What is Combaren Diclofenac the medication, and for what is it used?, I see it sometimes listed with Codeine. Sometimes called Oxa Forte? Anyone have any idea?
Diclofenac (marketed as Voltaren®, Voltarol®, Diclon®, Dicloflex® Difen, Difene, Cataflam® and Rhumalgan®) is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and an analgesic reducing pain in conditions such as in arthritis or acute injury. It can also be used to reduce menstrual pain.
In the United Kingdom and the United States it may be supplied as either the sodium or potassium salt, while in some other countries only as the potassium salt. Diclofenac is available as a generic drug in a number of formulations. Over the counter (OTC) use is approved in some countries for minor aches and pains and fever associated with common infections.
Diclofenac is well-tolerated after 30 years experience by the general human population, but may unexpectedly become intolerated in some of the elderly population of long term users.[citation needed]
It has been reported that veterinary diclofenac use in India has caused a crash of the vulture population,[1] with "major ecological consequences" and a sub-cultural Zoroastrian Parsi "sky burial" crisis.[2] Diclofenac causes kidney failure in vultures that eat treated domestic animals. (See Ecological problems)
Whats the best counter alternative to Diclofenac?, I've tried taking ibuprofen before when i'd run out but it didn't really have much of an effect. Are there any other medicines that you could suggest that are available in th UK without mail order? Diclofenac seems to be the only thing that works well...
I have been on Diclofenac for ten years and it works for me. As my GP stated 'If it works why stop it, or try anything else?' Therefore return to your GP and get the prescription. Best of Luck
Continue reading here: Guanfacine Risk Summary
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