Rosiglitazone in Pregnancy and Breastfeeding
Fetal Risk Summary
Rosiglitazone, a thiazolidinedione antidiabetic agent, is used as an adjunct to diet and exercise to improve glycemic control in patients with type II diabetes (non-insulin-dependent diabetes mellitus). It is used either alone or in combination with metformin. Rosiglitazone is not an insulin secretagogue, but acts to decrease insulin resistance in the periphery and in the liver (i.e., decreases insulin requirements). Rosiglitazone undergoes extensive metabolism to inactive metabolites.
Reproduction studies with rosiglitazone have been conducted in rats and rabbits at doses up to 20 and 75 times, respectively, the human area under the plasma concentration curve at the maximum recommended human daily dose (MRHD) (1). No teratogenicity or adverse effects on implantation or the embryo were observed in either species, but placental pathology was noted in rats. Moreover, dosing during mid- to late gestation was associated with fetal death and growth retardation in both rats and rabbits. Treatment extending through the lactation period in rats was associated with reduced litter size and decreased neonatal viability and postnatal growth. Growth retardation was reversible after puberty. For effects on the placenta, embryo, fetus, and offspring, the no-effect dose levels were approximately 4 times the MRHD for both species.
It is not known if rosiglitazone crosses the human placenta, but the molecular weight of the free base (about 357) is low enough that transfer to the fetus should be expected.
No reports describing the use of rosiglitazone during human pregnancy have been located. Insulin is the treatment of choice for pregnant diabetic patients because, in general, other hypoglycemic agents do not provide adequate glycemic control. Moreover, insulin, unlike most oral agents, does not cross the placenta to the fetus, thus eliminating the additional concern that the drug therapy itself will adversely effect the fetus. Carefully prescribed insulin therapy provides better control of the mother's glucose, thereby preventing the fetal and neonatal complications that occur with this disease. High maternal glucose levels, as may occur in diabetes mellitus, are closely associated with a number of maternal and fetal adverse effects, including fetal structural anomalies if the hyperglycemia occurs early in gestation. To prevent this toxicity, most experts, including the American College of Obstetricians and Gynecologists, recommend that insulin be used for types I and II diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (2,3).
Breast Feeding Summary
No reports describing the use of rosiglitazone during human lactation have been located. The molecular weight of the free base (about 357) is low enough, however, that excretion into breast milk should be expected. Either the parent drug or its metabolites have been detected in the milk of lactating rats (1). The effects on a nursing infant from exposure to the drug in milk are unknown.
- Product information. Avandia. SmithKline Beecham Pharmaceuticals, 2000.
- American College of Obstetricians and Gynecologists. Diabetes and pregnancy. Technical Bulletin. No. 200, December 1994.
Coustan DR. Management of gestational diabetes, Clin Obstet Gynecol 1991;34:55864.
Questions and Answers
is rosiglitazone a safe drug for diabetes patients who have heart disease?,
Don't play around with meds.....see a doctor.
Has anyone else with diabetes type 2 experienced problems with metformin?, When first diagnosed 7 years ago I was prescribed metformin, then a couple of years ago for no apparent reason it stopped working and I was prescribed Avandamet, a combined metformin and rosiglitazone. A month ago a blood test showed my overall sugar level to have risen from the usual 5 to 6 and my doctor put me back on metformin only. (I know there was some concern about rosiglitazone at the time so that could have been the reason for the change) Now it is, again, as if I was not taking any medication at all.
I am due for another check up this week, and wondering what the doctor will suggest next. Is it that the metformin is not suitable for me and what alternatives can I expect. My doctor is not a great one for discussing anything with patients, so it's a case of being forwarned is forarmed.
The obvious answer would be to wait until your HbA1C result confirms any abnormality. I presume you have been continuously taking metformin for at least one clear month so it may be advisable to have another HbA1C three months after discontinuing the rosiglitazone. Your blood glucose levels do not indicate any cause for concern and could easily be attributed to changes to your normal routine of diet/exercise/health/social factors. Examine these possibilities and ask to speak to the Diabetes Nurse at your G.P. practice if you need another sounding board other than your Doctor.
Which of the following drug is most likely to cause hypoglycaemia if taken orally without food?, A. Mixtard 30
E. Soluble insulin
The risk of hypoglycemia depends on the type and nature of the diabetes a patient has. Understanding this is important, for there can be no universally exact answers to this question. Diabetic drugs and their levels should be selected in cooperation with a physician or physician's associate; not by answers to questions here..
That said, any insulin will cause hypoglycemia if it is not covered by adequate glucose intake from food. Especially in diabetics whose hypoglycemic defense responses have broken down. Usually, glucagon is secreted in response to low blood glucose levels; in many long term diabetics, this response has been more or less lost and doesn't always work effectively. Differences between insulins depend on the action timing of the insulin used (eg, onset, peak action, duration of action). Quick acting insulin will need food sooner and in higher quantities than longer acting insulin, and the constant level analog insulins (glargine and equivalent) will require food distributed over a longer time than the others..
Drugs which increase internal insulin production, such as gliciazide will have the effect iof insulin injections with the proviso that most such drugs also depend on glucose levels in the blood. Without blood glucose, even gliclazide will not force insulin release. With sufficiently high levels of gliclazide, even a small amount of blood glucose will evoke insulin release and a possible episode of hypoglycemia.
Drugs which reduce insulin insensitivity, such as rosiglitazone (Actos), should not cause hypoglycemia if other medications (eg, injected insulin) are adjusted properly.
Drugs which regulate liver release of glucose from glycogen stores, such as metformin, are unlikly to cause hypoglycemia in the absence of additional drugs such as injected insulin. These drugs largely affect timing of glucose release in the absence of insulin.
Medical treatment using a combination of drugs?, My elderly Mother has recently been admitted to hospital with suspected renal failure. She had been prescribed the following medicines by her GP,Furosemide, Digoxin, Ramipril, Rosiglitazone, Gliclazide, Atenolol, Allopurinol, Aspirin & Cyclizine. She had been admitted two weeks previously complaining of stomach and chest pains. I have written to the GP concerned who refuses to reply. I would like to know what effect the drugs listed would have as each was to be taken 4 times a day i.e. a total of 36 tablets daily. Please help.
Furosemide is a diuretic, it gets rid of "fluid" in the body, often from the lugs or lungs from heart failure. It is usually taken once or twice a day.
Digoxin in a drug to try and slow down an irregular heartbeat, taken once a day.
Ramipril is a bood pressure lwering tablet, taken once a day
Rosiglitazone is a diabetes drug ususally taken once a day.
Gliclazide is a very popular diabetic drug taken up to twice a day.
Atenolol is called a beta blocker and reduces blood pressure and can slow the heart a little. Usually taken once a day.
Allopurinol is used to prevent gout.
Aspirin in used to prevent platlet aggregation in the blood (in effect thining the blood, but not that simple) and is very effective in reducing heart disease. It is take once a day.
Cyclazine is a anti-sickness tablet taken 3 times a day. It has some sedative properties.
This is quite a typical drug list for an eldery person, seen with many, many people.
You have not mentioned ANY doses.
A person taken all these drugs 4 time a day is NOT reading the instructions on the packet or those given to them by their GP. They could suffer many effects from extreem low blood pressure to low blood sugar reading.
Souind like this person needs a medication review to me, with an understanding relative to help her understand what she should b taking. Prehaps a daily pill box would help.