Lupter 22.5 – Barter & Marcin Pharma

Lupter

Leuprolide Acetate for Injection (Depot) 22.5mg

Prostate Cancer

Leuprolide acetate for Injection (Depot) is indicated in the palliative treatment of advanced prostatic cancer. It offers an alternative treatment when orchidectomy or estrogen administration is either not indicated or unacceptable to the patient.

Administered 3-monthly as a single intramuscular injection. Therapy should not be discontinued when remission or improvement occurs.

Endometriosis

LEUPROLIDE DEPOt-3 Month 22.5 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions, LEUPROLIDE DEPOT with norethindrone acetate 5 mg daily is also indicated for initial management of endometriosis and for management of recurrence of symptoms. Duration of initial treatment or retreatment should be limited to 6 months.

Uterine Leiomyomata (Fibroids)

LEUPROLIDE DEPOT-3 Month 22.5 mg concomitantly with iron therapy is indicated for the preoperative hematologic improvement of patients with anemia caused by uterine leiomyomata. The clinician may wish to consider a one-month trial period on iron alone inasmuch as some of the patients will respond to iron alone. LEUPROLIDE may be added if the responce to iron alone is considered inadequate. Recommended therapy is a single injection of LEUPROLIDE DEPOT-3 Month 22.5 mg. This dosage form is indicated only for women for whom three months of hormonal suppression is deemed necessary.

Experience with LEUPROLIDE DEPOT-3 Month 22.5 mg in females has been limited to women 18 years of age and older treated for no more than 6 months.

Dose & Method Of Administration

LEUPROLIDE DEPOT Must Be administered Under the Supervision of a Physician.

Endometriosis

The recommended duration of treatment with LEUPROLIDE DEPOT-3 Month 22.5 mg alone or in combination with norethindrone acetate is six months. The choice of LEUPROLIDE DEPOT alone or LEUPROLIDE DEPOT plus norethindrone acetate therapy for initial management of the symptoms and signs of endometriosis should be made by the health care professional in consultation with the patient and should take into consideration the risks and benefits of the addition of norethindrone to LEUPROLIDE DEPOT alone.

If the symptoms of endometriosis recur after a course of therapy, retreatment with a six-month course of LEUPROLIDE DEPOT-3 Month 22.5 mg administered every three months and norethindrone acetate 5 mg daily may be considered. Retreatment beyond this six-month course cannot be recommended. It is recommended that bone density be assessed before retreatment. If norethindrone acetate is contraindicated for the individual patient, then retreatment is not recommended.

An assessment of cardiovascular risk and management of risk factors such as cigarette smoking is recommended before beginning treatment with LEUPROLIDE DEPOT and norethindrone acetate.

Uterine leiomyomata (Fibroids)

The recommended dose of LEUPROLIDE DEPOT-3 Month 22.5 mg is one injection. the symptoms associated with uterine leiomyomata will recur following discontinuation of therapy. if additional treatment with LEUPROLIDE DEPOT-3 month 22.5 mg is contemplated, bone density should be assessed prior to intiation of therapy to ensure that values are within normal limits.

Use Case In Special Populations

Pregnancy

Teratogenic Effects

Pregnancy category X (See CONTRAINDICATIONS section). When administered on day 6 of pregnancy at test dosages of 0.00024, 0.0024, and 0.054 mg/kg (1/300 to 1/3 of the human dose) to rabbits, LEPUPROLIDE DEPOT produced a dose-related increase in major fetal abnormalities. Similar studies in rates failed to demonstrate an increase in fetal malformations. There was increased fetal mortality and decreased fetal weights with the two higher doses of LEUPROLIDE DEPOT in rabbits and with the highest dose (0.024 mg/kg) in rats.

Nursing Mothers

It is not know whether LEUPROLIDE DEPOT is excreted in human milk. Because many drugs are excreted in human milk, and because the effects of LEUPROLIDE DEPOT on lactation and/or the breast-fed child have not been determined, LEUPROLIDE DEPOT should not be used by nursing mothers.

Pediatric Use

Safety and effectiveness of LEUPROLIDE DEPOT-3 month 22.5 mg have not been established in pediatric patients. Experience with LEUPROLIDE DEPOT for treatment of endometriosis has been limited to women 18 years of age and older.

Geriatric Use

This product has not been studied in women over 65 years of ages and is not indicated in this population.

Contradictions

Hypersensitivity to GnRH, GnRH agonist or any of the excipients in LEUPROLIDE DEPOT.
Undiagnosed abnormal vaginal bleeding.
LEUPROLIDE DEPOT is contraindicated in women who are or may become pregnant while receiving the drug. LEUPROLIDE DEPOT may cause fetal harm when administered to a pregnant women. Major fetal abnormalities were observed in rabbits but not in rats after administration of LEUPROLIDE DEPOT throughout gestation. There was increased fetal mortaility and decreased fetal weights in rats and rabbits. The effects on fetal mortailty are expected consequences of the alterations in hormonal levels brought about by the drug. If this drug is used during pregnancy of if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Use in women who are breastfeeding.
Norethindrone acetate is contraindicated in women with the following conditions.
- Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions.
- Markedly impaired liver function or liver disease
- Know or suspected carcinoma of the breast.

Warnings

As the effects of LEUPROLIDE DEPOT-3 Month 22.5 mg are present throughout the course of therapy, the drug should only be used in patients who require hormonal suppression for at least three months.
Experience with LEUPROLIDE DEPOT-3 Month 22.5 mg in females has been limited to six months; therefore, exposure should be limited to six months of therapy.
Safe use of leuprolide acetate or norethindrone acetate in pregnancy has not been established clinically, before starting treatment with LEUPROLIDE DEPOT pregnancy must be excluded.
When used at the rcommended dose and dosing interval, LEUPROLIDE DEPOT usually inhibits ovulation and stops menstruation. Contraception is not insured, however, by taking LEUPROLIDE DEPOT. Therefore, patients should use non-hormonal methods of contraception. Patients should be advised to see their physician if they believe they may be pregnant. If a patient becomes pregnant during treatment, the drug must be discontinued and the patient must be apprised of the potential risk to the fetus.
During the early phase of therapy, sex steroids temporarily rise above baseline because of the physiologic effect of the drug. Therefore an increase in clinical signs and symptoms may be observed during the initial days of therapy, but these will dissipate with continued therapy.
Symptoms consistent with an anaphylactoid or asthmatic process have been rarely reported.
The following applies to co-treatment with LEUPROLIDE and norethindrone acetate: Norethindrone acetate treatment should be discontinued if there is a sudden partial or complete loss of vision or if there is a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be withdrawn. Because of the occasional occurrence of thrombophlebitis and pulmonary embolism in patients taking progestogens, the physician should be alert to the earliest manifestations of the disease in women taking norethindrone acetate. Assessment and management of risk factors for cardiovascular disease is recommended prior to initiation of add-back therapy with norethindrone acetate. Norethindrone acetate should be used with caution in women with risk factors, including lipid abnormalities or cigarette smoking.

Precautions

Since menstruation usually stops with effective doses of LEUPROLIDE DEPOT, the patient should notify her physician if regular menstruation persists. Patients missing successive doses of LEUPROLIDE DEPOT may experience breakthrough bleeding.
Patients should not use LEUPROLIDE DEPOT if they are pregnancy, breast feeding, have undiagnosed abnormal vaginal bleeding, or are allergic to any of the ingredients is LEUPROLIDE DEPOT.
LEUPROLIDE DEPOT 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 LEUPROLIDE DEPOT, breaktrough bleeding or ovulation may occur with the potential for conception. If a patient becomes pregnant during treatment, she should discontinue treatment and consult her physician.
Adverse events occurring in clinical studies with LEUPROLIDE DEPOT that are associated with hypoestrogensim 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.
Patients should be counseled on the possibility of the development or worsening of depression and the occurrence of memory disorders.
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 LEPROLIDE, (All patients received calcium supplementation with 1000 mg elemental calcium.)
If the symptoms of endometriosis recur after a course of therapy, retreatment with a six-month course of LEUPROLIDE DEPOT and norethindrone acetate 5 mg daily may be considered. Retreatment beyond this one six-month course cannot be recommended that bone densityshould be assessed before retreatment begins to ensure that values are within normal limits. Retreatment with LEUPROLIDE DEPOT alone is not recommended.
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, LEUPROLIDE DEPOT therapy may pose an additional risk. In these patients, the risks and benefits must be weighed carefully before therapy with LEUPROLIDE DEPOT alone is instituted, and concomitant treatment with norethindrone acetate 5 mg daily should be considered. Retreatment with gonadotropin-releasing hormone analogs, including LEUPROLIDE, is not advisable in patients with major risk factors for loss of bone mineral content.
Because norethindrone acetate may cause some degree of fluid retention, conditions which might be influenced by this factor, such as epilepsy, migraine, asthma, cardiac or renal dysfunction, require careful observation during norethindrone acetate add-back therapy.
Patients who have a history of depression should be carefully observed during treatment with norethindrone acetate and norethindrone acetate should be discontinued if severe depression occurs.

Drug Interaction

No pharmacokinetic-based drug-drug interaction studies have been conducted with LEUPROLIDE DEPOT. However, because leuprolide acetate is a peptide that is primarly degraded by peptidase and not by cytochrome P-450 enzymes as noted in specific studies, and the drug is only about 46% bound to plasma proteins, drug interactions would not be expected to occur.

Undesirable Effects

The following adverse reactions were reported in less than 5% of the patients on LEUPROLIDE DEPOT.

Body As Whole: Enlarged abdomen, Fever.
Cardiovascular System: Arrhythmia, Bradycardia, Heart failure, Hypertension, Hypotension, Varicose vein.
Digestive System: Anorexia, Duodenal ulcer, Increased appetite, Thirst/dry mouth.
Hemic and Lymphatic System: Anemia, Lymphedema.
Central/Peripheral Nervous System: Anxiety, Delusions, Depression, Hypesthesia, Libido decreased, Nervousness, Paresthesia.
Respiratory System: Epistaxis, Pharyngitis, Pleural effusion, Pneumonia
Special Senses: Abnormal vision, Amblyopia, Dry eyes, Tinnitus.
Urogenital System: Gynecomastia, Impotence*, Penis disorders, Testis disorders, *Physiologic effect of decreased testosterone.

Overdosage

In clinical trials using daily subcutaneous leuprolide acetate in patients with prostate cancer, doses as high as 20 mg/day for up to two years caused no adverse effects differing from those observed with the 1 mg/day dose.