LUPANETA PACK- leuprolide acetate and norethindrone acetate
LUPANETA PACK (leuprolide acetate for depot suspension and norethindrone acetate tablets) is indicated for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms.
Limitation of Use: Duration of use is limited due to concerns about adverse impact on bone mineral density [see Warnings and Precautions (5.1)]. The initial treatment course of LUPANETA PACK is limited to six months. A single retreatment course of not more than six months may be administered after the initial course of treatment if symptoms recur. Use of LUPANETA PACK for longer than a total of 12 months is not recommended.
- 11.25 mg of leuprolide acetate by intramuscular injection once every three months for up to two injections (6 months of therapy); to be administered by a healthcare provider
- 5 mg of norethindrone acetate orally once daily for up to 6 months of therapy
If the symptoms of endometriosis recur after the initial course of therapy, consider retreatment with LUPANETA PACK for up to another six months. It is recommended that bone density be assessed before retreatment begins [see Warnings and Precautions (5.1)].
Due to different release characteristics, a fractional dose of the leuprolide acetate for depot suspension 3-month depot formulation is not equivalent to the same dose of the monthly formulation and should not be given.
- Reconstitute and administer the lyophilized microspheres as a single intramuscular injection.
- Inject the suspension immediately or discard if not used within two hours, because leuprolide acetate for depot suspension does not contain a preservative.
- Visually inspect the leuprolide acetate for depot suspension powder. DO NOT USE the syringe if clumping or caking is evident. A thin layer of powder on the wall of the syringe is considered normal prior to mixing with the diluent. The diluent should appear clear.
- To prepare for injection, screw the white plunger into the end stopper until the stopper begins to turn (see Figure 1 and Figure 2).
- Hold the syringe UPRIGHT. Release the diluent by SLOWLY PUSHING (6 to 8 seconds) the plunger until the first middle stopper is at the blue line in the middle of the barrel (see Figure 3).
- Keep the syringe UPRIGHT. Mix the microspheres (powder) thoroughly by gently shaking the syringe until the powder forms a uniform suspension. The suspension will appear milky. If the powder adheres to the stopper or caking/clumping is present, tap the syringe with your finger to disperse. DO NOT USE if any of the powder has not gone into suspension (see Figure 4).
- Keep the syringe UPRIGHT. With the opposite hand pull the needle cap upward without twisting.
- Keep the syringe UPRIGHT. Advance the plunger to expel the air from the syringe. Now the syringe is ready for injection.
- After cleaning the injection site with an alcohol swab, administer the intramuscular injection by inserting the needle at a 90 degree angle into the gluteal area, anterior thigh, or deltoid (see Figure 5).
NOTE: If a blood vessel is accidentally penetrated, aspirated blood will be visible just below the luer lock (see Figure 6) and can be seen through the transparent LuproLoc safety device. If blood is present, remove the needle immediately. Do not inject the medication.
- Inject the entire contents of the syringe intramuscularly.
- Withdraw the needle. Once the syringe has been withdrawn, immediately activate the LuproLoc® safety device by pushing the arrow on the lock upward towards the needle tip with the thumb or finger, as illustrated, until the needle cover of the safety device over the needle is fully extended and a CLICK is heard or felt (see Figure 7).
- Dispose of the syringe according to local regulations/procedures [see References (15)].
- Leuprolide acetate for depot suspension 11.25 mg for 3-month administration: Leuprolide acetate lyophilized powder for reconstitution with supplied diluent in a prefilled dual chamber syringe
- Norethindrone acetate 5 mg tablets: White to off-white oval, flat-faced beveled edged, uncoated debossed with ‘G with breakline’ on one side and 304 on other side
- Hypersensitivity to gonadotropin-releasing hormone (GnRH), GnRH agonist analogs, any of the excipients in leuprolide acetate for depot suspension, or norethindrone acetate
- Undiagnosed abnormal uterine bleeding
- Known, suspected or planned pregnancy during the course of therapy [see Use in Specific Populations (8.1)]
- Lactating women [see Use in Specific Populations (8.3)]
- Known, suspected or history of breast cancer or other hormone-sensitive cancer
- Current or history of thrombotic or thromboembolic disorder
- Liver tumors or liver disease
Leuprolide acetate for depot suspension induces a hypoestrogenic state that results in loss of bone mineral density (BMD), some of which may not be reversible. Concurrent use of norethindrone acetate is effective in reducing the loss of BMD that occurs with leuprolide acetate [see Clinical Studies (14)]. Nonetheless, duration of use of LUPANETA PACK is limited to two six-month courses of treatment due to concerns about the adverse impact on BMD. It is recommended that BMD be assessed before retreatment. Retreatment with leuprolide acetate for depot suspension alone is not recommended.
In women with major risk factors for decreased BMD such as chronic alcohol (> 3 units per day) or tobacco use, strong family history of osteoporosis, or chronic use of drugs that can decrease BMD, such as anticonvulsants or corticosteroids, use of LUPANETA PACK may pose an additional risk, and the risks and benefits should be weighed carefully.
Leuprolide acetate for depot suspension may cause fetal harm if administered to a pregnant woman. Exclude pregnancy before initiating treatment with LUPANETA PACK. When used at the recommended dose and dosing interval, leuprolide acetate for depot suspension usually inhibits ovulation and stops menstruation. Contraception, however, is not ensured by taking leuprolide acetate for depot suspension. Therefore, patients should use nonhormonal methods of contraception. Advise patients to notify their healthcare provider if they believe they may be pregnant. Discontinue LUPANETA PACK if a patient becomes pregnant during treatment and inform the patient of potential risk to the fetus [see Contraindications (4) and Use in Specific Populations (8.1)].