Hydroxychloroquine in Pregnancy and Breastfeeding

Risk Factor: C
Class: Immunologic agents / Antirheumatic agents

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Hydroxychloroquine is used for the treatment of malaria, discoid and systemic lupus erythematosus (SLE), and rheumatoid arthritis. A 1988 review described several References relating to animal studies with the closely related agent, chloroquine (1). In pregnant mice, rats, rabbits, and monkeys, chloroquine crosses the placenta to the fetus (1). In fetal mice and monkeys, the drug accumulates for long intervals, up to 5 months in mice, in the melanin structures of the eyes and inner ears (1,2). Teratogenicity studies with chloroquine using monkeys have not been published. However, in rats, only high doses were teratogenic, producing skeletal and ocular defects (1). In pregnant mice, chloroquine alone was not teratogenic, but in combination with radiation, a significant increase in cleft palates and tail anomalies was observed (1). No similar data are available for hydroxychloroquine.

Published data relating to the use of hydroxychloroquine during human pregnancy are scarce but do not indicate that the drug poses a significant risk to the fetus. The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 2 of which had 1st trimester exposure to hydroxychloroquine (3). Neither child had a congenital malformation. A 1974 Reference reported no abnormalities in a fetus after a therapeutic abortion at 14 weeks' gestation (4). The fetus had been exposed to the antimalarial agent, 200 mg twice daily, since the time of conception. Examination of the temporal bones, the embryonal precartilage, the anlages of the auditory ossicles, and the membranous labyrinth demonstrated a normal 14-week stage of development, indicating an apparent lack of drug-induced ototoxicity in this fetus (4). A short 1983 communication described the use of 200 mg/day of hydroxychloroquine during the first 16 weeks of gestation for the treatment of maternal discoid lupus erythematosus (5). A male infant was eventually delivered who was alive and well at 2 years of age.

The use of hydroxychloroquine during 27 pregnancies in 23 women with mild to moderate SLE was described in a 1995 abstract (6). In 17 of the pregnancies, the drug was used at a dose of 200400 mg daily throughout gestation. The outcomes of these cases included 2 miscarriages, 2 perinatal deaths, 1 infant with congenital heart block (in a Ro-positive mother), and 12 normal newborns. In 6 other pregnancies, hydroxychloroquine was started after conception, three during the 1st trimester. In the remaining four cases, therapy was stopped after diagnosis of pregnancy, resulting in a worsening of the disease and higher doses of prednisolone, and pregnancy termination in 1 because of severe renal lupus. No fetal or newborn adverse effects related to hydroxychloroquine were observed. A follow-up of 20 newborns for at least 3 years found that all were healthy. The authors concluded that hydroxychloroquine was safe in pregnancy, and because of the risk of lupus flare, discontinuing therapy during pregnancy represented a greater danger to the fetus (6).

Other investigators have reached similar conclusions as to the safety of hydroxychloroquine in the treatment of SLE during pregnancy (7,8). These authors described nine pregnancies (plus seven from an earlier paper) in which hydroxychloroquine (200 mg/day) was used throughout gestation without producing congenital malformations. In the present series of nine pregnancies, five newborns were delivered preterm and four at term. Long-term follow-up of the children exposed in utero has been normal. Because of the very long elimination half-life of the drug from maternal tissues (weeks to months), the authors concluded that discontinuing the drug when pregnancy was known would not eliminate fetal exposure, but could jeopardize the pregnancy from a lupus flare (7,8).

The use of hydroxychloroquine as an antimalarial, instead of chloroquine, has been recommended because of the belief that hydroxychloroquine is less toxic (1). However, little data are available to substantiate this practice, either in terms of congenital malformations or in optic or otic toxicity. From published reports of fetal exposure to either chloroquine or hydroxychloroquine, one source cited an incidence of 7 infants with congenital anomalies from 188 live births, a rate of 4.5% (1). This value is within the expected 3%6% incidence of congenital malformations in a nonexposed population.

In summary, hydroxychloroquine does not seem to pose a significant risk to the fetus, especially with lower doses. No reports of retinal or ototoxicity after in utero exposure have been located. The Centers for Disease Control stated that hydroxychloroquine may be used during pregnancy for antimalarial prophylaxis since, in prophylactic doses, the agent has not been shown to be harmful to the fetus (9, 10). The adult antimalarial prophylactic dose is 400 mg/week (2). The use of higher doses for prolonged periods, such as those used for SLE, acute attacks of malaria, and rheumatoid arthritis probably represents an increased fetal risk, but the magnitude of this increase is unknown. At least one source has recommended that the use of hydroxychloroquine for rheumatoid arthritis or SLE be avoided during pregnancy (1), but recent reports (6,7 and 8) do not support this conclusion. Moreover, stopping therapy when a pregnancy became known would not, as discussed above, stop exposure of the embryo and fetus to the drug, but could increase the risk because of a lupus flare.

Breast Feeding Summary

Two reports have described the excretion of small amounts of hydroxychloroquine into breast milk. A 27-year-old woman was treated with hydroxychloroquine, 400 mg (310 mg base) each night, for an exacerbation of lupus erythematosus (11). She had been breast-feeding her infant for 9 months. No mention of the infant's condition or of the presence of toxic effects was made by the authors of this report. Milk samples were collected 2.0, 9.5, and 14.0 hours after one dose and 17.7 hours after a second dose. Milk concentrations of hydroxychloroquine base at the four times were 1.46, 1.09, 1.09, and 0.85 g/mL, respectively. A maternal blood sample was collected 15.5 hours after the first dose. Hydroxychloroquine base concentrations in whole blood and plasma were 1.76 and 0.20 g/mL, respectively. The authors estimated that the infant was consuming, based on 1000 mL of milk, a daily dose of 1.1 mg hydroxychloroquine base, or approximately 0.35% of the mother's daily dose (11).

Much lower milk concentrations of drug were obtained from a 28-year-old woman who was being treated with hydroxychloroquine, 200 mg twice daily, for rheumatoid arthritis (12). Treatment had been stopped for 6 months during pregnancy and then restarted 2 months later because of arthritis relapse. A total of 3.2 g of the drug was recovered from her milk over a 48-hour interval, representing 0.0005% of the mother's dose. The highest milk concentration of the agent, 10.6 ng/mL, was found in the 3948 hour sample. It was not stated whether the infant was allowed to breast-feed.

Because of the slow elimination rate and the potential for accumulation of a toxic amount in the infant, breast feeding during daily therapy with hydroxychloroquine should be undertaken cautiously (11,12 and 13). The administration of once-weekly doses, such as those used for malaria prophylaxis, would markedly reduce the amount of drug available to the nursing infant and, consequently, produce a much lower risk of accumulation and toxicity. Although breast feeding during maternal malarial prophylaxis is not thought to be harmful, the amount of hydroxychloroquine in milk is insufficient to provide protection against malaria in the infant (10). The American Academy of Pediatrics classifies the drug as compatible with breast feeding (14).

References

  1. Roubenoff R, Hoyt J, Petri M, Hochberg MC, Hellmann DB. Effects of antiinflammatory and immunosuppressive drugs on pregnancy and fertility. Semin Arthr Rheum 1988;18:88110.
  2. Product information. Plaquenil. Sanofi Winthrop Pharmaceuticals, 1997.
  3. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:299.
  4. Ross JB, Garatsos S. Absence of choroquine-induced ototoxicity in a fetus. Arch Dermatol 1974;109:573.
  5. Suhonen R. Hydroxychloroquine administration in pregnancy. Arch Dermatol 1983;119:1856.
  6. Buchanan NMM, Toubi E, Khamashta MA, Lima F, Kerslake S, Hughes GRV. The safety of hydroxychloroquine in lupus pregnancy: experience in 27 pregnancies (abstract). Br J Rheumatol 1995;34(Suppl 1):14.
  7. Parke AL, Rothfield NF. Antimalarial drugs in pregnancythe North American experience. Lupus 1996;5(Suppl 1):5679.
  8. Parke A, West B. Hydroxychloroquine in pregnant patients with systemic lupus erythematosus. J Rheumatol 1996;23:17158.
  9. Centers for Disease Control. Adverse reactions and contraindications to antimalarials. MMWR 1988;37:2823.
  10. Centers for Disease Control. Recommendations for the prevention of malaria among travelers. MMWR 1990;39:110.
  11. Nation RL, Hackett LP, Dusci LJ, Ilett KF. Excretion of hydroxychloroquine in human milk. Br J Clin Pharmacol 1984;17:3689.
  12. Ostensen M, Brown ND, Chiang PK, Aarbakke J. Hydroxychloroquine in human breast milk. Eur J Clin Pharmacol 1985;28:357.
  13. Anderson PO. Drug use during breast-feeding. Clin Pharm 1991;10:594624.
  14. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.

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Questions and Answers

My doctor gave me Hydroxychloroquine as part of RA treatment. Is the medicine good? ?, My doc gave me Hydroxychloroquine to control my joint pain and swelling. It may take 3 to 6 months to work.

He told me about a possible rare complication where I may have eye damage. Has any taken the medication, have you had any problems with it?

My wife is on it. No problems.

I'd suggest a baseline exam by an eye doctor now. Then follow up with him/her as recommended.

What happens if you take to much hydroxychloroquine?, I realy realy need to know this please help me!!!!!!!!!!

Seek emergency medical attention.

Symptoms of a hydroxychloroquine overdose include headache, drowsiness, nausea, vomiting, visual changes, seizures, difficulty breathing, and unconsciousness.

what is the effect of the drug hydroxychloroquine sulphateon the fetus if it is taken during fertilizatio?, I was taking hydroxy chloroquine sulphate 200mg when i conceived and i i took it for 14 days after fertilization of ovum .As i was not aware of pregnancy which i came to know after 2 days of missing my period. What will be effect of the drug on fertilized ovum. Whether it will abort ?or can it produce madevelopment of the child. Should i go for an termination of pregnancy? Before the expected date of mensis i had already stopped the drug 4 days before. Still it can produce any malformation in fetus?

Hydroxychloroquine Sulphate




How does it work?

Hydroxychloroquinine is used in the treatment of some auto-immune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In these diseases the body's immune system is over-active and slightly defective. The body develops antibodies which attack and cause damage to its own cells. Damage can occur anywhere in the body, such as in the joints or cartilage as in the case of rheumatoid arthritis. As a result of the damage to the joints, reduced mobility and stiffness in the affected joints is experienced. Hydroxychloroquine is thought to act by interfering with the production and release of blood cells that are involved in the body's immune defence system. Hence the autoimmune response of the antibodies against its own body, is reduced and as result the amount of damage to the cells is minimized and prevented. As it has the potential to prevent progression of the disease, by limiting the damage caused, it is often referred to as a disease-modifying antirheumatic drug (DMARDS) and is commonly used very early in the treatment of rheumatoid arthritis. Hydroxychloroquine is also used in treating skin conditions that are caused or aggravated by sunlight.

What is it used for?

# Inflammatory disease of the joints
# Long-term inflammation of skin and some internal organs (systemic lupus erythematosus) or related diseases e.g. scleroderma
# Severe inflammatory diease of the joint that commonly occurs in children and adolescents (juvenile arthritis)
# Skin damaged by the sun
# Skin disorders caused or made worse by sunlight

Warning!

# This medication may cause a blurring of vision. If affected do not drive or operate machinery.
# People taking this medicine should have regular blood tests to check the levels of their blood components.
# It is recommended that eye examinations are carried out before starting treatment with this medicine and repeated every six months in the course of the treatment. This medicine should be discontinued if any visual problems develop.

Use with caution in

# Disease affecting the brain and nervous system (neurological disease)
# Gastro-intestinal conditions
# Individuals taking medicines that may cause skin reactions or impair vision
# Kidney disease
# Lack of the chemical G6PD in the blood (G6PD deficiency)
# Life long inherited blood diseases which can cause a variety of symptoms, including mental health problems (porphyrias)
# Liver disease
# Psoriasis
# Severe blood disorders

Not to be used in

# Allergy to quinine
# Pre-existing abnormality of the eye (eye maculopathy)
# Pregnancy

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy. If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and Breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

# This medicine should not be used in pregnancy. Seek medical advice from your doctor.
# This medicine passes into breast milk in small amounts. Seek medical advice from your doctor before breastfeeding.

Why hydroxychloroquine is said to be very effective in treating Systemic Lupus Erythematosus?,

Antibodies "tag" your healthy cells as if they were invaders. Macrophages come and attach to the tag and try to destroy your healthy cells. Hydroxychloroquine changes the ph on the cells which interrupts the errant immune response.

Is Hydroxychloroquine a steroid drug?, I have Lupus, Thyroid Disease and High Blood Pressure. I've been exercising since January and I haven't lost a pound. I'm wondering if the medicine Hydroxychloroquine is a Steroid or not.

It is not considered a steroid. It is an antimalarial drug and an analgesic. It is used to treat and prevent malaria, and also used to treat rheumatoid arthritis and lupus erythematosus.

HydroxyChloroquine availability in India to treat Lupus?, My daughter has a rare condition called Lupus. It can be treated (or contained) by taking HydroxyChloriquine. I live in India. Unfortunately I have been unsuccessful in getting this from any pharmacy so far.

Can some one tell me where I can get this medicine in India or whether (and how) it can be imported from any other country.

I live in India.

Thanks,
Raghu

Lupus is not rare. About 5 million people worldwide have it. 90% of lupus patients are women. Women of color, including Indian women, get it 3 times more often than white women.

Hydroxychloroquine is an antimalarial. You need a prescription to get it. This is the link for the manufacturer of the drug. Call or email them.

You daughter needs to be under the care of a rheumatologist familiar with lupus.

Please learn about lupus at the link below.

Best wishes from a lupus patient in the USA.

http://www.contactus.sanofi-aventis.us/c...

Is hydroxychloroquine effective in preventing RA from progressing?, I've taken methatreate and predizone for about 8 months, hoping to see some positive results. All I've gotten was nearly bald (in spots) and weight gain. But I worry about not taking additional medicine.

In the world of rheumatoid arthritis there are two kinds of therapy: therapy aimed at treating the symptoms of the disease and drugs that slow the progression of rheumatoid arthritis (these can also and often do treat symptoms).

Hydroxychloroquine is considered to be in the category of drugs that slow the progression of rheumatoid arthritis. These drugs are called DMARDs (Disease Modifying Anti-Rheumatic Drugs). In addition to slowing the progression of the disease, they can also help relieve symptoms. Hydroxychloroquine, and anti-malaria drug, is one of the older drugs in the DMARD class. It is usually used to decrease inflammation of the joints and hopefully reduce progression. It is probably less effective in slowing the disease than some of the newer DMARDs but is effective in the earlier stages of RA. Other drugs in this class include methotrexate, sulfasalazine, tetracycline derivatives, and leflunomide. There are also drugs that are used less often such as gold salts or D-penicillamine.

Newer DMARDs include immunosupressive agents such as azathioprine and cyclosporin. But the newest agents (and possibly the most effective drugs in slowing progression of the disease) are drugs that inhibit a joint destroying chemicals called cytokines. Enetanercept, infliximab and adalimumab, and anakinra are the newest drugs available to fight RA, but also have many side effects. This is why they are usually not prescribed early on in RA.

Other drugs, such as Rituxan, are used stop immune cells, as B-cells (a kind of white blood cell) that contribute to the inflammation. There are even newer drugs that work against inflammation caused by white blood cells and other parts of the immune system that are just on the horizon.

Different drugs are often used in combination with each other and with non-DMARD medications to treat RA. Once again, all these drugs have different toxicities and side-effects. This is why it is best to have an experienced rheumatologist monitor your therapy.

FYI, the non-DMARD drugs include:
1. analgesics (topicals like capsaicin), tylenol, opioids (oxycodone, darvon...), etc.

2. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as advil, motrin, celebrex and

3. Glucocorticoids (such as Prednisone)

The non-DMARDs help symptomatically but do not help with disease progression.

There is a nice overview at the link below. If for some reason it doesn't work just go to www.arthritis.com and look for RA and then treatments of RA.

RA is a complicated disease and has a very complicated treatment regimen. This is why you need to make sure you are followed by a competent rheumatologist. The outlook for RA is better and better each year as newer DMARDs are coming out which treat this disease more specifically. Best of luck!

I have Palindromic Rheumatism for 4 years. Can I have a baby using Hydroxychloroquine?,

Although the drug hydroxychloroquine is used in the treatment of malaria, it is also effective for rheumatoid arthritis and systemic lupus erythematosus (SLE). It can reduce inflammation and so reduce pain, swelling and stiffness of joints and improve the rash of SLE. You should not normally take hydroxychloroquine during pregnancy as it may harm the unborn child. If you are planning a family you should seek advice from your doctor. You also, should not breastfeed if you are taking hydroxychloroquine. If you have any need for further medical information on this subject, you would be advised to consult your doctor, rheumatology nurse or pharmacist.
I add a link with details of this subject


http://arthritisinsight.com/
medical/meds/plaq.html


Hope this helps
matador 89

how does hydroxychloroquine cause side effects?,

All medication has side effects. These are some for hydroxychloroquine:

* allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).
* fever;
* visual disturbances such as blurred vision, misty vision, and difficulty focusing;
* changes in eye color; or
* hearing loss or ringing in the ears.
* diarrhea, nausea, stomach pain or upset, vomiting, or loss of appetite;
* muscle weakness; or
* itching or a rash.