Luprolex Special Precautions

Patients should be aware of the following information: Patients should be counselled on the possibility of the development or worsening of depression and the occurrence of memory disorders. In children, emotional lability, such as crying, irritability, impatience, anger and aggression has been reported.
Post-marketing reports of convulsions have been observed in patients on Leuprorelin (Luprolex) therapy. These included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumours and in patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the (comorbid) conditions mentioned previously. Patients receiving a GnRH agonist who experience convulsion should be managed according to current clinical practice.
Patients should not use Leuprorelin (Luprolex) if they are allergic to any of the ingredients.
The following applies to Females: Since menstruation usually stops with effective doses of Leuprorelin (Luprolex), the patient should notify her physician if regular menstruation persists. Patients missing successive doses of Leuprorelin (Luprolex) may experience breakthrough bleeding.
Patients should not use Leuprorelin (Luprolex) if they are pregnant, breastfeeding, or have undiagnosed abnormal vaginal bleeding.
Leuprorelin (Luprolex) is contraindicated for use during pregnancy. Therefore, a non-hormonal method of contraception should be used during treatment. Patients should be advised that if they miss successive doses of Leuprorelin (Luprolex), breakthrough bleeding or ovulation may occur with the potential for conception. If a patient becomes pregnant during treatment, she should discontinue treatment and consult a physician.
Adverse events occurring in clinical studies with Leuprorelin (Luprolex) that are associated with hypoestrogenism include: hot flashes, headaches, emotional lability, decreased libido, acne, myalgia, reduction in breast size and vaginal dryness. Estrogen levels returned to normal after treatment was discontinued.
The following applies to Adult Females: A decrease in bone mass may occur owing to estrogen-reducing effect of Leuprorelin (Luprolex). Therefore, when it is necessary to administer the drug for a long period or to resume its administration, the drug should be cautiously administered after the bone mass is examined as far as possible.
In patients with major risk factors for decreased bone mineral content such as chronic alcohol and/or tobacco use, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids, Leuprorelin (Luprolex) therapy may pose an additional risk. In these patients, the risks and benefits must be weighed carefully before therapy with Leuprorelin Luprolex) alone is instituted.
The following applies to treatment of Endometriosis: The induced hypoestrogenic state also results in a loss in bone density over the course of treatment, some of which may not be reversible. Clinical studies show that concurrent hormonal therapy with norethindrone acetate 5 mg daily is effective in reducing loss of bone mineral density that occurs with leuprorelin (all patients received calcium supplementation with 1000 mg elemental calcium).
In patients with major risk factors for decreased bone mineral content (see as previously mentioned), concomitant treatment with norethindrone acetate 5 mg daily should be considered. Retreatment with gonadotropin-releasing hormone analogs, including Leuprorelin (Luprolex) is not advisable in patients with major risk factors for loss of bone mineral content.
If the symptoms of endometriosis recur after a course of therapy, retreatment with a six-month course of Leuprorelin (Luprolex) and norethindrone acetate 5 mg daily may be considered. Retreatment beyond this one six-month course cannot be recommended. It is recommended that bone density be assessed before retreatment begins to ensure that values are within normal limits. Retreatment with Leuprorelin (Luprolex) alone is not recommended.
Depression may occur or worsen during treatment with norethindrone acetate. Carefully observe women with a history of depression and consider discontinuing norethindrone acetate if depression recurs to a serious degree.
The following applies to treatment of Uterine fibroids: It should be noted that the treatment of uterine fibroids with Leuprorelin (Luprolex), is not a radical treatment. Therefore, as a rule, this drug should be used as a means of providing conservative treatment until operation on patients requiring operation or providing premenopausal conservative treatment.
Retreatment with gonadotropin-releasing hormone analogs, including Leuprorelin (Luprolex) is not advisable in patients with major risk factors for loss of bone mineral content (see as previously mentioned).
In women with submucous fibroids there have been reports of severe bleeding following the administration of Leuprorelin (Luprolex) as a consequence of the acute degeneration of the fibroids. Patients should be warned of the possibility of abnormal bleeding or pain in case earlier surgical intervention is required.
Central precocious puberty: Before starting the therapy, a precise diagnosis of idiopathic and/or neurogenic central precocious puberty is necessary. The therapy is a long-term treatment, adjusted individually. Leuprorelin (Luprolex) should be administered as precisely as possible in regular monthly (for 1.88 mg and 3.75 mg) and 3-monthly (for 11.25 mg) periods. An exceptional delay of the injection date for a few days (30±2 days) (for 1.88 mg and 3.75 mg) and (90±2 days) (for 11.25 mg) does not influence the results of the therapy.
In the event of a sterile abscess at the injection site (mostly reported after I.M. injection of higher than the recommended dosage) the absorption of Leuprorelin (Luprolex) from the depot can be decreased. In this case the hormonal parameters (testosterone, estradiol) should be monitored at 2-week intervals.
The treatment of children with progressive brain tumors should follow a careful individual appraisal of the risks and benefits. The occurrence of vaginal bleeding, spotting and discharge after the first injection may occur as a sign of hormone withdrawal in girls. Vaginal bleeding beyond the first/second month of treatment needs to be investigated.
Bone mineral density (BMD) may decrease during GnRH therapy for central precocious puberty. However, after cessation of treatment subsequent bone mass accrual is preserved and peak bone mass in late adolescence does not seem to be affected by treatment.
Slipped femoral epiphysis can be seen after withdrawal of GnRH treatment. The suggested theory is that the low concentration of estrogen during treatment with GnRH agonists weakens the epiphysial plate.
The increase in growth velocity after stopping the treatment subsequently results in a reduction of the shearing force needed for displacement of the epiphysis.
Pseudotumor cerebri/idiopathic intracranial hypertension: Pseudotumor cerebri (PTC)/idiopathic intracranial hypertension has been reported in pediatric patients receiving leuprorelin acetate. Patients should be monitored for signs and symptoms of PTC, including papilledema, headache, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea. If PTC is confirmed permanently discontinue use of leuprorelin acetate and treat the patient in accordance with the established treatment guidelines.
3.75 mg and 11.25 mg: The following applies to treatment of Premenopausal Breast cancer: The effectiveness and safety in using Leuprorelin (Luprolex) for postoperative supplementary treatment has not been established. Therefore, it should not be used for prevention of relapse after curative operation.
Leuprorelin (Luprolex) does not exhibit antitumor effect or when any progression of the tumor is observed, the administration should be discontinued.
The following applies to treatment of Prostate cancer: Initially, Leuprorelin (Luprolex), like other GnRH agonists, causes increases in serum levels of testosterone to approximately 50% above baseline during the first weeks of treatment. Isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. Transient worsening of symptoms may develop. A small number of patients may experience a temporary increase in bone pain. If such a symptom occurs, pertinent symptomatic treatment should be given. Since urethral obstruction or spinal cord compression may occur, the drug should be cautiously administered, and close observation should be made during the first month after initiation of treatment and appropriate measures taken in patients with metastatic vertebral lesions and/or with urinary tract obstruction.
Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.
Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.
Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.
Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist analog. It can be anticipated that long periods of medical castration in men will have effects on bone density.