Levonorgestrel Contraindications and Precautions
- breast cancer
- cervical cancer
- ectopic pregnancy
- hepatic disease
- hepatocellular cancer
- incomplete abortion
- jaundice
- pregnancy
- uterine cancer
- vaginal bleeding
- vaginal cancer
- acquired immunodeficiency syndrome (AIDS)
- anticoagulant therapy
- Asian patients
- bradycardia
- breast-feeding
- cardiac disease
- cerebrovascular disease
- children
- coagulopathy
- congenital heart disease
- coronary artery disease
- corticosteroid therapy
- depression
- diabetes mellitus
- heart failure
- human immunodeficiency virus (HIV) infection
- hyperlipidemia
- menstrual irregularity
- migraine
- renal disease
- seizure disorder
- syncope
- thromboembolic disease
- thrombophlebitis
- tobacco smoking
- uterine leiomyomata
- valvular heart disease
Levonorgestrel Contraindications and Precautions
For all formulations of levonorgestrel:
Available data suggest that a rapid return of fertility and normal ovulation occurs following discontinuation of levonorgestrel containing contraceptives.
Levonorgestrel is classified in FDA pregnancy category X and is contraindicated for use during pregnancy or suspected pregnancy. The majority of recent studies do not indicate a teratogenic effect of progestin-only contraceptives when taken inadvertently during early pregnancy; however, the progestin should be discontinued as soon as pregnancy is suspected or detected. Levonorgestrel, especially the Mirena® IUD, should not be used if there is a suspicion of current ectopic pregnancy. The IUD-form should not be inserted if a history of ectopic pregnancy exists, but such a history does not contraindicate oral or implantable levonorgestrel use. Health care providers should be alert to the possibility of ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on levonorgestrel. Up to 10% of pregnancies reported in the routine use of progestin-only contraceptives are ectopic.
Small amounts of levonorgestrel are excreted into breast-milk during routine contraceptive use, resulting in infant plasma levels that are 1 - 6% of those found in maternal plasma. However, no adverse effects due to progestin-only contraceptive pills have been observed in breast-feeding infants. No adverse effects on lactation production or the growth or development of infants have been reported. The American Academy of Pediatrics generally considers the use of levonorgestrel to be compatible with breast-feeding.
Levonorgestrel is absolutely contraindicated in undiagnosed abnormal vaginal bleeding or incomplete abortion. Levonorgestrel implants are contraindicated in patients with known or suspected cancers of reproductive organs, such as cervical cancer, uterine cancer, or vaginal cancer, except as palliative therapy in selected patients.
Levonorgestrel implants are contraindicated in patients with known or suspected breast cancer. A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR=1.24) of having breast cancer diagnosed in women who are currently using combination oral contraceptives compared to never-users. The increased risk gradually disappears during the course of the 10 years after cessation of combination oral contraceptive use. These studies do not provide evidence for causation. The observed pattern of increased risk of breast cancer diagnosis may be due to earlier detection of breast cancer in combination oral contraceptive users, the biological effects of combination oral contraceptives, or a combination of both. Because breast cancer is rare in women < 40 years of age, the excess number of breast cancer diagnoses in current and recent combination oral contraceptive users is small in relation to the lifetime risk of breast cancer. Breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users. Although the results were broadly similar for progestin-only oral contraceptives, the data are based on much smaller numbers of progestin-only oral contraceptive users and therefore are less conclusive than for combination oral contraceptives. This information should be considered when prescribing levonorgestrel implants.
Levonorgestrel contraceptives should be avoided in patients with significant hepatic disease, jaundice, or hepatic tumors (benign or hepatocellular cancer).
With levonorgestrel contraceptives, there can be alterations in menstrual bleeding patterns, including amenorrhea. Some of these changes may be expected during the early months of treatment. Patients should be instructed that menstrual irregularity may occur and to notify their prescriber of any persistent changes in bleeding patterns; these may require medical evaluation.
Like all hormonal contraceptives, levonorgestrel use does not protect against the transmission of human immunodeficiency virus (HIV) infection or other sexually transmitted diseases.
Levonorgestrel should be used cautiously in patients with diabetes mellitus. Although the effects appear to be minimal during therapy with progestins, altered glucose tolerance secondary to decreased insulin sensitivity has been reported during hormonal contraceptive therapy.
The safety and efficacy of levonorgestrel products have only been established in females of reproductive age. Safety and efficacy of levonorgestrel is expected to be the same for postpubertal children under the age of 16 and for users 16 years of age and older. Use of levonorgestrel products in female children before menarche is not indicated.
For oral emergency contraception, Plan-B™:
Levonorgestrel tablets for emergency contraception are not intended to be used as a routine contraceptive. It is unknown if all precautions that apply with the use of other progestin-only oral contraceptives for routine contraception also apply to the intermittent use of levonorgestrel emergency contraception. In addition to the other listed contraindications for levonorgestrel in general, levonorgestrel should not be used in patients hypersensitive to any component of the oral product.
Plan B™ is not effective for the termination of pregnancy. In the use of levonorgestrel for emergency contraception, the patient should be instructed to see her health care provider if there is a delay in the expected onset of menses beyond 1 week. A pregnancy test may be needed.
No formal studies have evaluated the effect of race on the efficacy of oral emergency contraceptive regimens. Asian patients, specifically Chinese women, have been observed in clinical trials, however, to demonstrate a higher pregnancy rate with both Plan B™ and Yuzpe emergency contraceptive regimens. The reason for the apparent increase in pregnancy rates is not known.
For the Mirena® IUD system:
Contraindicated in anyone hypersensitive to the IUD components, including the drug, silicone, and polyethylene.
Health care professionals should be thoroughly familiar with insertion procedures before inserting the Mirena® IUD. The insertion of the IUD is a simple office procedure that really only takes a couple of minutes; very effective birth control can last for up to 5 years. The manufacturer recommends that levonorgestrel IUD be used in women who have had at least one child (i.e., not nulliparous). The levonorgestrel IUD is recommended for women who are in a stable, mutually monogamous relationship and have no history of ectopic pregnancy or condition that would predispose to ectopic pregnancy. Should an intrauterine pregnancy occur while the Mirena® IUD is in place, the prescriber should refer to the specific IUD literature that states considerations during such events.
The Mirena® IUD should not be inserted in patients with a congenital or acquired uterine anomaly, including uterine leiomyomata (fibroids) if such conditions distort the uterine cavity.
Do not insert the Mirena® IUD in patients with postpartum endometritis, infected abortion in the past 3 months, untreated acute cervicitis, or untreated acute vaginitis, including bacterial vaginosis (BV) or other pelvic infections until the infection is controlled. Do not insert the IUD in patients with genital actinomycosis.
Do not insert the Mirena® IUD in patients with conditions that increase the patients susceptibility to infection. Such conditions include leukemia, acquired immunodeficiency syndrome (AIDS), intravenous substance abuse, some patients on chronic corticosteroid therapy, patients with multiple sexual partners, and others. This list may not be inclusive of all conditions that might increase a patient’s risk of infection. Use of IUDs has been associated with an increased risk of pelvic inflammatory disease (PID); the Mirena® IUD is not the best choice of contraception for those with a previous history of PID. The highest risk of PID occurs shortly after insertion (usually within the first 20 days).
Patients with certain types of valvular heart disease or congenital heart disease and surgical systemic-pulmonary shunts are at increased risk of infective endocarditis and the IUD may represent a potential source of septic emboli. Patients at increased risk for endocarditis may need appropriate antimicrobial prophylaxis on device insertion and removal.
Syncope, bradycardia, or other neurovascular episodes may occur during insertion or removal of the Mirena® IUD, especially in patients predisposed to these conditions or those with cervical stenosis. If decreased pulse, diaphoresis, or pallor are observed, the patient should remain supine until these signs have disappeared.
Because of the potential for uterine injury from the IUD device, use the Mirena® IUD with caution in patients on anticoagulant therapy or with coagulopathy.
For the Norplant® sub-dermal implant system:
NOTE: This drug product is discontinued in the US.
Levonorgestrel sub-dermal implants should be used cautiously in patients with hyperlipidemia. Although hyperlipidemia is associated with estrogen-progestin combinations, the effects of progestin-only oral contraceptives on serum lipids have not been studied. Serum lipoproteins (HDL and LDL) should be monitored during therapy with levonorgestrel.
Levonorgestrel sub-dermal implants should be used cautiously in patients with a history of thrombophlebitis or thromboembolic disease. Although thromboembolic disease is believed to be an estrogen-related effect, some studies have shown that patients receiving hormonal contraceptives or hormonal replacement therapy regimens containing progestins may have a higher risk of venous thromboembolic (VTE) disease. In addition, because of the higher risk of thromboembolic disease in tobacco smoking women, women should be advised not to smoke, particularly if they are over the age of 35 years. Hormonal contraceptives should also be used cautiously in patients with history of coronary artery disease, progestin intolerance, or cerebrovascular disease.
Levonorgestrel sub-dermal implants should be discontinued if any unexplained visual disturbance occurs. Hormonal contraceptives have been associated with retinal thrombosis. Although this effect is generally believed to be related to estrogen, patients should be monitored carefully for the development of ocular lesions.
Levonorgestrel sub-dermal implants should be prescribed cautiously in patients with congestive heart failure, nephrotic syndrome or other renal disease, or cardiac disease. Hormonal contraceptives can cause fluid retention and may exacerbate any of the above conditions.
Levonorgestrel subdermal implants should be used cautiously in patients with a history of major depression, migraine, or seizure disorder. Progestins may exacerbate these conditions in some patients. Some cases of seizures following administration of progestins have been reported.
A surgical incision is required to insert and remove the levonorgestrel subdermal implants; insertion and removal instructions must be followed closely. Complications related to insertion such as pain, edema, and bruising may occur. Other effects related to implant insertion such as infection (including cellulitis and abscess formation), blistering, ulcerations, sloughing, excessive scarring, phlebitis, and hyperpigmentation at the insertion site are possible. If infection develops after insertion, suitable treatment should be instituted. If infection persists, the implant system should be removed. Nerve injury is possible and is most commonly associated with deep placement and removal. Expulsion of the individual capsules of the implants is possible and occurs more often when placement is shallow or too close to the incision, or when infection is present. If expulsion of a capsule occurs, the expelled capsule must be replaced using a new, sterile capsule as contraceptive efficacy may be inadequate with fewer than 6 capsules. If infection is also present, it should be treated and cured before the capsule is replaced. The implants can become displaced; while most reports involve minor changes in the positioning, significant displacement (a few to several inches) can occur (< 1%). Some of these reports have been associated with pain and difficult removal. Removal may take longer, be more difficult, and/or cause more pain than insertion and may be associated with difficulty locating the implants. If all six capsules cannot be located by palpation, they may be localized by ultrasound (7 MHz), X-ray, or compression mammography. If all capsules cannot be removed at the first attempt, removal should be attempted later when the site has healed. The use of general anesthesia during removal should generally be avoided. Removal difficulties affecting subjects (including multiple incisions, capsule fragments remaining, pain, multiple office visits, deep placement, or lengthy removal procedure) have been reported with a frequency of 6.2%, which is based on 849 removals occurring through 5 years of use.
[ Last revised: 4/11/2006 4:38:00 PM ]
References
. American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776 - 89.
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