Levoplant

Levonorgestrel (Levoplant) is used for the prevention of pregnancy (contraception). The implants consist of two thin, flexible rods made of a rubber-like material, that are inserted by a minor surgical procedure just beneath the skin on the inside of the upper arm.
The implants slowly release a small amount of the hormone levonorgestrel, which is one of the active ingredients in many oral contraceptives. Levonorgestrel (Levoplant) is long-acting and are effective for up to three years. Immediately after insertion, low doses of the hormone start to be released continuously into the body.
Levonorgestrel (Levoplant) work by a combination of factors. The most important of these are prevention of regular egg release and thickening of the cervical mucus, making it more difficult for sperm to reach the egg.
Formulation: The active substance is levonorgestrel. Each implant contains 75 mg levonorgestrel.
The other ingredients are: Medical additive methyl-vinyl silicone rubber (LS-4100), White carbon black, Refined methyl hydrogen silicone oil, Platinum chloride complex compound, Medical additive methyl-vinyl silicone rubber (LS-4150), and SDG-A(M). The set contains two flexible, sealed, white or off-white rod-like implants, about 44 mm in length and 2.4 mm in diameter.
Each rod containing 75 mg of levonorgestrel, for a total of 150 mg.

Pharmacotherapeutic group: Progestogens, levonorgestrel.
Pharmacology: Pharmacodynamics: The active ingredient in Levonorgestrel (Levoplant), levonorgestrel, is a synthetic progestin. The primary pharmacologic action of levonorgestrel is its anti-fertility effect. Levonorgestrel has been shown to affect ovarian function in various ways. This ranges from: the absence of follicular and luteal activity through to normal follicular activity but deficient luteal activity to normal ovulatory patterns. Levonorgestrel causes thickening of the cervical mucus, thus preventing the passage of spermatozoa into the uterus. It also suppresses the endometrium and may prevent implantation of the blastocyst.
Pharmacokinetics: Absorption: Levonorgestrel is released from the Levonorgestrel (Levoplant) directly into tissue fluid. Maximum plasma levonorgestrel concentrations of approximately 833 ± 367 pg/mL are reached about 5.4 days after insertion. After the initial phase, levonorgestrel concentrations decline to 430 ± 205 pg/mL within one month, 351 ± 210 pg/mL within six months, 311 ± 197 pg/mL within one year. Plasma levonorgestrel concentrations are inversely related to body weight. However, due to the great variation in plasma levonorgestrel concentrations and in individual response, plasma concentrations alone are not predictive of the risk of pregnancy in an individual woman. Considerable inter- and intra-individual variation occurs, and serum drug concentrations are affected by individual clearance rates and body weight, among other factors. In Levonorgestrel (Levoplant) users, plasma levonorgestrel concentrations are substantially below those observed in women taking oral contraceptives containing levonorgestrel.
Distribution: Levonorgestrel in serum is primarily protein bound. Approximately half is bound to sex hormone binding globulin (SHBG) and half to albumin. SHBG concentrations are depressed by levonorgestrel within a few days of administration, with resultant decreases in circulating levonorgestrel concentrations.
Metabolism: Levonorgestrel metabolic pathways have been only partially delineated. 16β-hydroxylation is an identified pathway of metabolism. Concentrations of metabolites in circulation soon exceed those of levonorgestrel, mostly as conjugated sulfates. Metabolic clearance rates may differ among individuals by several fold, which is believed to account also in part for the wide variation observed in levonorgestrel serum concentrations among implant users.
Excretion: The elimination half-life of levonorgestrel is approximately 13 to 18 hours. Levonorgestrel and its metabolites are primarily excreted in the urine (40% to 68%) and about 16% to 48% are excreted in feces. After removal of the implants, levonorgestrel concentrations decrease below 100 pg/mL by 96 hours and below sensitivity of the assay by 5 days to 2 weeks.

Levonorgestrel (Levoplant) is used for the prevention of pregnancy (contraception).

For subdermal use.
Levonorgestrel (Levoplant) is a contraceptive method for three years of use. Once the implants are inserted they may be removed at the request of the user at any time.
Method of Administration: Instructions for insertion and removal of the implants: One Levonorgestrel (Levoplant) pouch contains two sterile rods. Only health care providers trained in both insertion and removal should perform these procedures. Aseptic technique must be followed during implant insertion and removal to prevent infection. Contaminated waste must be properly disposed of and instruments and other items should be decontaminated, thoroughly cleaned, and sterilized by autoclaving or dry heat, or high-level disinfected.
Preparation for implant insertion: The following sterile instruments and supplies are needed for insertion of implants: sterile dry surgical drape; a sterile tray for the equipment; a bowl for the antiseptic soaked cotton balls; sterile pair of surgical gloves (free of talc); a 3-5 mL syringe and a 5-5.5 cm long needle (22-gauge); filter needle (if local anesthetic is supplied in glass ampule); a scalpel with blade; tweezers; a skin closure or adhesive bandage or gauze with surgical tape; gauze and compresses and set of two rods in sterile pouch.
The following non-sterile supplies are recommended for insertion of implants: examining table for the patient to lie on; soap for washing the arm; ballpoint pen or marker; antiseptic solution for the skin and 2 mL local anesthetic.
Getting ready for insertion procedure: Explain the procedure to the client and encourage questions.
Determine that required sterile or high-level disinfected instruments and implants are present.
Wash hands thoroughly and dry them.
Check to be sure that the client has thoroughly washed and rinsed her entire arm.
Position the woman's arm and place a clean, dry cloth under her arm.
Mark position on arm for insertion of rods 6 cm to 8 cm from the elbow fold (this should form a "V" pattern).
Put on a sterile pair of hand gloves.
Pre-insertion tasks: Set up sterile field and place implant rods and trocar on it.
Prep insertion site with antiseptic solution.
Place a sterile or high-level disinfected drape over the arm.
Inject 2 mL of local anesthetic applied just under the skin, raising a wheal at the insertion point and advancing up to 5 cm along the first insertion track, injecting 1 mL of local anesthetic along the track as needle is withdrawn. Without completely removing the needle, reorient to the second insertion track, advance up to 5 cm, and again inject 1 mL of local anesthetic along track as needle is withdrawn. Let the arm rest for approximately 5 minutes and check for anesthetic effect before making skin incision.
Step by step implant insertion instructions: Step 1: Make a small incision with a scalpel in the skin on the inside of the upper arm. Alternatively, use the trocar to puncture the skin. Insert the tip of the trocar beneath the skin at a shallow angle. Gently advance the trocar superficially under the skin with the bevel facing up while tenting the skin. Tenting of the skin enables the implant to be placed under the skin and not deeper into the arm.
The rod should be placed parallel to the skin. Take great care not to insert trocar into the arm muscle. Note: The trocar has two marks on it. The mark closest to the hub indicates how far the trocar should be introduced under the skin to place the implants. The mark closest to the tip indicates how much of the trocar should remain under the skin following placement of the first implant.
Step 2: When the trocar has been inserted to the mark closest to the hub, remove the obturator and load the first implant into the trocar, using thumb and forefinger.
Step 3: Using the obturator to push, gently advance the implant towards the tip of the trocar until resistance is felt. Never force the obturator.
Step 4: Holding the obturator stationary, withdraw the trocar to the mark closest to the trocar tip. The implant should be released under the skin at this point. It is important to keep the obturator stationary and to avoid pushing the implant into the tissue. Do not completely remove the trocar until both implants have been placed.
Step 5: To place the second implant, align the trocar so that the second implant will be positioned at about a 30° angle relative to the first implant. Repeat steps 3-4. The rods are placed in the shape of a V opening toward the shoulder. Leave a distance of about 5 mm between the incision and the tips of the implants. Remove the trocar and immediately dispose of it in a sharps container.
Post-insertion tasks: Remove drape and wipe the client's skin with alcohol.
Bring edges of incision together and close it using surgical tape, then cover it with tape on a sterile gauze (2x2) or an adhesive bandage.
Instruct client regarding wound care: Keep the area around the insertion site dry and clean for at least 48 hours.
Leave the gauze pressure bandage in place for 48 hours and the surgical tape or adhesive bandage in place until the incision heals (normally 3-5 days).
Apply pressure dressing snugly.
Discuss with the client what to do if she experiences any problems following insertion or side effects from the implant.
Advise client that she can have the rods removed at any time if she desires.
Make a return visit appointment, if necessary.
Observe the client for at least 15-20 minutes before discharging.
Timing of insertion: Implants may be inserted at any time during the menstrual cycle when it is reasonably certain that the client is not pregnant or at risk of being pregnant.
Note on backup methods of contraception: Extra "backup" contraceptive precautions should be advised in many circumstances, as outlined as follows. These should be described to the patient as including barrier methods (e.g. condoms) and refraining from sex altogether. The patient should be advised that the "rhythm" or "temperature" methods are not adequate for backup. (Changes in body temperature and cervical mucus that normally take place during the menstrual cycle may not occur during the use of Levonorgestrel (Levoplant) implants.)
No contraceptive use: If the woman has been using no contraception, advise her to use a backup method or refrain from sexual intercourse for 7 days after insertion.
If insertion is done within 7 days of the start of the woman's usual monthly bleeding, there is no need for a backup method. If insertion is done more than 7 days after the start of the woman's usual monthly bleeding, a backup method should be used for the first 7 days following insertion.
If the woman is switching from an IUD, she can have implants inserted immediately.
Switching from a hormonal method: If the woman has been using a hormonal method consistently and correctly, or if it is otherwise reasonably certain that she is not pregnant, the implant may be inserted immediately. There is no need to wait for the next monthly bleeding. No backup method is needed.
If switching from injectables, the woman can have the implant inserted on the date when the repeat injection would have been given. There is no need for a backup method.
Switching from copper or Levonorgestrel IUD: If the woman is currently in her first 7 days of monthly bleeding, insert the implant now and remove the IUD. There is no need for a backup method.
If the implant is desired 7 days or more after the end of her last monthly bleeding and she has had intercourse since the last monthly bleeding, it may be inserted at once. The IUD should be left in place until after her next monthly bleeding.
If the implant is desired 7 days or more after the end of her last monthly bleeding, and she has not had intercourse since the last monthly bleeding, the IUD can stay in place and be removed during her next monthly bleeding, or the IUD can be removed and she can use a backup method for the next 7 days.
Breastfeeding: If the woman's monthly bleeding has not returned, she can have implants inserted any time between giving birth and 6 months, with no need for a backup method.
If the woman's monthly bleeding has returned, she can have implants inserted as advised for women having menstrual cycles.
No monthly bleeding (not related to childbirth or breastfeeding): She can have implants inserted any time it is reasonably certain she is not pregnant. She will need a backup method for the first 7 days after insertion.
After miscarriage or abortion: Immediately: If implants are inserted within 7 days after first- or second-trimester miscarriage or abortion, there is no need for a backup method.
If it is more than 7 days after first or second trimester miscarriage or abortion: she can have implants inserted any time it is reasonably certain she is not pregnant. She will need a backup method for the first 7 days after insertion.
After taking emergency contraceptive pills (ECPs): Implants can be inserted within 7 days after the start of her next monthly bleeding, or any other time it is reasonably certain she is not pregnant. Give her a backup method, or oral contraceptives to start the day after she finishes taking the ECPs, to use until the implants are inserted.
Implant Removal: Levonorgestrel (Levoplant) should be removed after 3 years of use.
The implants can be removed, for personal or medical reasons, at the request of the client at any time. The implants should be removed by the end of the third year. Removal of implants can be done at any time in the menstrual cycle.
Preparation for implant removal: The following items are needed for removal: examining table for the woman to lie on; soap for washing the arm; ballpoint pen or marker; sterile dry surgical drape; a bowl for the antiseptic solution; pair of sterile surgical gloves; antiseptic solution for the skin; 2 mL local anesthetic; a sterile tray for the equipment; a sterile 3-5 mL syringe and a 2.5-4 cm long needle (22-gauge); scalpel with #11 blade; 1 curved and 1 straight Crile or Kelly forceps; 1 tissue forceps (optional) and a skin closure or adhesive bandage or sterile gauze with surgical tape.
Removal procedure: Getting ready for removal procedure: Determine that required sterile or high-level disinfected instruments are present.
Check that the client has thoroughly washed and rinsed her arm.
Explain the procedure to the client and encourage questions.
Position the woman's arm and place a clean, dry cloth under her arm.
Palpate the rods to determine point of removal.
Mark position on arm where the tip of the rods is palpated.
Pre-removal tasks: Wash hands thoroughly and dry clean them.
Put on a sterile pair of hand gloves.
Arrange instruments and supplies.
Prep removal site with antiseptic solution twice.
Place a sterile or high-level disinfected drape over the arm.
Inject 1 mL of local anesthetic applied at the incision site and under the end of the rods.
Check for anesthetic effect before making skin incision.
Step by Step implant removal instructions: Step 1: Before starting the removal, the implants must be located by palpation with ungloved fingers and the position of each rod marked. To help view the proximal tip near the insertion incision (bottom of the V), push down on the distal end of the implant. After cleaning the skin with an antiseptic, a small amount of local anesthetic is infiltrated under the implant ends. Anesthetic injected over the implants may obscure their position and make removal more difficult.
Step 2: A small skin incision of 2-4 mm is made close to the ends of the implants (below the bottom of the V). Do not make a large incision.
Step 3: Push each implant gently with fingers towards the incision. When the tip is visible in the incision, grasp it with the straight Crile/Kelly forceps and gently pull out the rod without twisting or pulling on the rod, as this may lead to rod breakage.
If the tip of the implant does not become visible in the incision, gently insert the curved Crile/Kelly forceps into the incision, trying to grasp the implant. Flip the forceps over with the other hand and with the scalpel, carefully dissect the tissue around the implant to expose it and then grasp the implant with the straight Crile/Kelly forceps. The implant can then be removed, being careful to avoid a twisting or pulling motion.
If the implant is encapsulated, grasp and stabilize the exposed rod with the curved Crile/Kelly forceps. Use the scalpel to very gently make a small incision into the tissue sheath to expose the tip of the rod. Use the tip of the scalpel to gently separate the encapsulated tissue from the rod, moving distally, keeping light but steady traction on the rod until the rod is completely freed from the tissue.
After the procedure is completed, close the incision and bandage it as after insertion.
The arm should be kept dry for 24-28 hours.
Note: Mosquito forceps can be used if Crile/Kelly forceps are not available; however, use of Crile/Kelly forceps has been shown to minimize damage to the implants during removal.
The implants should be removed very gently. This will take more time than the insertion. The implants may be nicked, cut or broken during removal. If removal proves difficult or both implants cannot be removed, the patient should be asked to return for a second visit after the removal area has healed. A non-hormonal method of contraception should be used until both implants have been completely removed. If the patient wishes to continue using the method, a new set of Levonorgestrel (Levoplant) may be inserted through the same incision, either in the same or in the opposite direction. Loss of contraceptive effect occurs practically immediately after removal, and another contraceptive method should be applied unless pregnancy is desired. Following removal, pregnancy may occur at any time.
Levonorgestrel (Levoplant) is different from other contraceptive methods. It must be inserted and removed by a health care provider familiar with the minor surgical procedure.
Before inserting the implants, the health care provider will: ask about the medical history, perform a physical examination, and make sure that the patient is not pregnant.

No case of overdose has been reported.
The toxicity profile of levonorgestrel is well-established and reveals no particular human health risks.

Hypersensitivity to levonorgestrel or to any other component of Levonorgestrel (Levoplant).
Current (history of) breast cancer.
Other diagnosed or suspected sex hormone-dependent neoplasia.
Severe liver disease, infection, or tumor.
Thromboembolic disease.
Unexplained vaginal bleeding.
Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies.

Clinical trials have demonstrated the contraceptive efficacy of Levonorgestrel (Levoplant) for three years of use. The serum levonorgestrel concentration is lower at the end of the implant use and it is inversely related to the user's body weight.
Expulsion of an implant may occur before the incision has healed if the implants have been inserted very near the skin surface or too close to the incision or when the insertion site is infected. An expelled implant must always be replaced with a new, sterile implant.
Breakage of Levonorgestrel (Levoplant) at or near removal occurred at a rate of 16% over 4 years in the pivotal clinical trial.
Reports have been published on slight displacement of similar levonorgestrel implants, most of which have involved minor changes in the position of the implants. Infrequent reports on significant displacement (a few to several centimetres) have been received. Some of these cases have been associated with pain or discomfort. In the event of displacement, the removal technique may have to be modified and may involve additional incisions or visits.
Altered serum lipoprotein levels have been observed in clinical trials on levonorgestrel implants. Although statistically significant decreases in total cholesterol, HDL (high-density lipoprotein) and LDL (low-density lipoprotein) and triglycerides have been detected, all mean values have remained within the normal ranges. The long-term clinical significance of these changes has not been determined.
The effects of levonorgestrel implants on clotting factors have varied. In patients with a history of thromboembolic disease, Levonorgestrel (Levoplant) should only be used if other contraceptive methods are unsuitable and after careful assessment of the risk-benefit ratio. Thromboembolic and cardiovascular undesirable effects have been reported in users of other levonorgestrel implants. Cases of stroke, myocardial infarction, pulmonary embolism and deep venous thrombosis have been reported in users of other levonorgestrel implants. Patients who develop thrombotic or embolic disease should have their Levonorgestrel (Levoplant) implants removed. Thrombophlebitis and superficial phlebitis have occurred more commonly in the arm of insertion. Some cases have been associated with trauma to that arm. Special caution should be observed in prescribing Levonorgestrel (Levoplant) for patients with recognized risk factors for or any predisposition to arterial disease.
If a sustained hypertension develops during the use of Levonorgestrel (Levoplant) implants, or if a significant increase in blood pressure does not adequately respond to antihypertensive therapy, the use of Levonorgestrel (Levoplant) implants should be discontinued.
If a patient has a history of or develops focal or crescendo type migraine or exhibits worsening of such migraine during the use of Levonorgestrel (Levoplant), the situation should be carefully assessed.
Contact lens wearers who develop loss of vision or changes in lens tolerance should be assessed by an ophthalmologist. The patient may be advised to stop wearing contact lenses for a while or completely.
Altered glucose tolerance and insulin sensitivity in oral glucose tests have been reported in users of levonorgestrel implants in some studies. The clinical significance of these findings is unknown but diabetic patients using Levonorgestrel (Levoplant) should be carefully monitored. A gain in weight is possible during the use of Levonorgestrel (Levoplant).
If cholestatic hepatitis or jaundice develops in a patient with Levonorgestrel (Levoplant), the implants must be removed. A mild or moderate transient rise in total serum bilirubin is usual at the start of the implant use. A slightly increased risk of cholelithiasis has been reported during the use of other levonorgestrel implants of similar type. Levonorgestrel metabolism may be slower than normal in patients with impaired liver function.
Removal of Levonorgestrel (Levoplant) should also be considered in women who become significantly depressed, since the symptom may be hormone-related. Women with a history of depression should be carefully monitored and removal of Levonorgestrel (Levoplant) should be considered if clear symptoms develop.
Steroid hormones may cause some degree of fluid retention, which may result in weight gain. The use of Levonorgestrel (Levoplant) should be considered carefully in patients with conditions that might be aggravated by fluid retention, and their condition should be monitored closely during the use of Levonorgestrel (Levoplant).
Idiopathic intracranial hypertension has been reported on rare occasions in users of levonorgestrel implants. Evidence is based on isolated reports only. This diagnosis should be considered if persistent headache and/or visual disturbances occur in a woman with Levonorgestrel (Levoplant), particularly if the patient is obese or has recently gained weight. If idiopathic intracranial hypertension is diagnosed, Levonorgestrel (Levoplant) should be removed.
Levonorgestrel (Levoplant) implants affect the menstrual bleeding pattern in most women. Irregular, prolonged and intermenstrual bleeding, spotting and amenorrhea have been reported. In general, such irregularities decrease with continuing use. Significant blood loss leading to anemia is rare, and average concentrations of hemoglobin normally rise slightly in Levonorgestrel (Levoplant) users.
Since some users of Levonorgestrel (Levoplant) experience periods of amenorrhea, missed menstrual periods should not be relied on as the sole means of diagnosing pregnancy. A pregnancy test should be performed whenever pregnancy is suspected. Six or more weeks of amenorrhea after a period of regular menses may indicate pregnancy. The implants must be removed if pregnancy occurs.
Ectopic pregnancy occurs rarely with levonorgestrel implants: at a rate less than 1 per 1,000 woman-years. If a woman using Levonorgestrel (Levoplant) presents with lower abdominal pain or is found to be pregnant, she should be examined to exclude ectopic pregnancy.
Follicles develop during the use of Levonorgestrel (Levoplant) but their atresia may be delayed and they may continue to grow beyond the normal size. In most women, such enlarged follicles will disappear spontaneously. In rare cases, however, they may twist or rupture, causing abdominal pain. Even in the presence of symptoms, conservative management is indicated but ectopic pregnancy must be excluded. Surgical intervention is rarely warranted.
In some rare cases, autoimmune diseases such as scleroderma, LED (lupus erythematosus disseminata) or rheumatoid arthritis have been reported in users of levonorgestrel implants. No causal relationship to implants containing levonorgestrel has been established. Both during pregnancy and during the use of sex steroids, the following conditions have been observed, without confirmed relationship to the use of progestogens: cholestatic icterus and/or itching, cholelithiasis, hemolytic-uremic syndrome, herpes gestationis, and hearing loss associated with otosclerosis.
Even though there is no clear causal connection between the use of oral contraceptives and breast cancer, a meta-analysis of 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 combined oral contraceptives (COCs). The increased risk gradually disappears during the course of 10 years after cessation of COC use. The risk of having breast cancer diagnosed in progestogen-only contraceptive users is possibly of a similar magnitude to that associated with COCs.

Before initiating or reinstituting treatment, a complete medical and family history should be taken. Blood pressure should be measured and a physical examination should be performed, guided by the contraindications and warnings and precautions for use. The woman should also be instructed to carefully read the user leaflet and to adhere to the advice given and to contact her physician if any problems occur at the insertion area. The frequency and nature of examinations should be based on established practice guidelines and be adapted to the individual woman.
The insertion area should be examined at every control visit. If undiagnosed, persistent or recurrent vaginal bleeding occurs, appropriate measures should be taken to rule out malignancy.
Women with a family history of breast cancer or who have benign breast nodules or mastopathy should be monitored with particular care.

Pregnancy: The implants must be removed if pregnancy occurs during the use of Levonorgestrel (Levoplant). Animal studies have shown that very high doses of progestogenic substances may cause masculinization of female fetuses. The results of most epidemiological studies to date with relevant inadvertent fetal exposure to combinations of estrogens and progestogens indicate no teratogenic or fetotoxic effect. No studies are available on the effect of Levonorgestrel (Levoplant) during or prior to pregnancy.
Lactation: Levonorgestrel passes over into milk but epidemiological studies to date have not revealed serious adverse effects on the child. Studies have not shown any significant effects on the growth or other development of breast-fed babies whose mothers used other levonorgestrel implants from the sixth week after childbirth. Levels of levonorgestrel obtained with implants do not affect the quality or quantity of breast milk. However, it is not known if levonorgestrel is found in breast milk in the first 6 weeks after giving birth.
Fertility: The usual level of fertility will return after the implants are removed.

The following undesirable effect has been reported during the pivotal clinical trial with Levonorgestrel (Levoplant): Very common (occurring in more than 10% of users): Breakage of the implant during or near removal.
The following very common undesirable effects have also been reported during clinical trials with LNG-releasing implants including Levonorgestrel (Levoplant): Disturbance of menstrual bleeding patterns, such as frequent, irregular, or prolonged menstrual bleeding, spotting, oligomenorrhoea, or amenorrhea, are the most common undesirable effects, occurring in the majority of users during the first year. Other very common undesirable effects are: headache, nervousness, dizziness, nausea, cervicitis, vaginal discharge, genital pruritus, pelvic pain, breast pain, and weight gain. (See table.)

Click on icon to see table/diagram/image

Effects of other medicinal products on Levonorgestrel (Levoplant): Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones and which may lead to changes in the uterine bleeding profile and/or contraceptive failure.
Women on treatment with any of these drugs should temporarily use a barrier method in addition to Levonorgestrel (Levoplant) or choose another method of contraception. The barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation.
Substances increasing the clearance of levonorgestrel (diminished efficacy of Levonorgestrel (Levoplant) by enzyme-induction), e.g.: Phenytoin, barbiturates, primidone, carbamazepine, rifampicin, efavirenz, and possibly also oxcarbazepine, topiramate, bosentan, felbamate, griseofulvin and products containing St. John's wort.
Enzyme induction can already be observed after a few days of treatment.
Maximal enzyme induction is generally seen within a few weeks. After the cessation of drug therapy enzyme induction may be sustained for about 4 weeks.
Levonorgestrel (Levoplant) users should be warned of the possibility of decreased contraceptive efficacy when using medicinal products exhibiting enzyme-inducing activity such as those mentioned previously. Breakthrough bleeding and unintended pregnancies have been reported.
Substances decreasing the clearance of Levonorgestrel (Levoplant) (enzyme inhibitors): Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g. clarithromycin, erythromycin) and diltiazem and grapefruit juice can increase plasma concentrations of the progestin.
Substances with variable effects on the clearance of levonorgestrel: When co-administered, many HIV medications can decrease or increase plasma concentrations of levonorgestrel (decrease [e.g. nevirapine, etravirine, efavirenz], or increase [ritonavir, darunavir/ritonavir, lopinavir/ritonavir, atazanavir/ritonavir, tipranavir/ritonavir, and (fos)amprenavir/ritonavir, indinavir]). These changes may be clinically relevant in some cases. (Note: Women with HIV were excluded from the pivotal clinical study.)
Effects of Levonorgestrel (Levoplant) on other medicinal products: Levonorgestrel (Levoplant) may affect the metabolism of other medicinal products. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine). Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
Other forms of interaction: Laboratory tests: The use of contraceptive steroids may influence the results of certain laboratory tests. Levonorgestrel (Levoplant) implants may have the following effects on the results of some endocrine laboratory tests: 1. Reduce the concentration of SHBG (sex hormone binding globulin).
2. Decrease thyroxine concentration in serum and elevate the values in triiodothyronine binding test.

Instructions and Special Precautions for Handling and Disposal: Information on insertion and removal is provided in Dosage & Administration.
Any unused product or waste material should be disposed of in accordance with local requirements.

Store at temperatures not exceeding 30°C.
Keep the product in the provided outer carton to protect from light.
Shelf-life: 60 months.

Depot Contraceptives

G03AC03 - levonorgestrel ; Belongs to the class of progestogens. Used as systemic contraceptives.

Rx