Source: Marketing Authorisation Holder Revision Year: 2019
The product is contraindicated in patients with a known hypersensitivity to leuprolide acetate, similar nonapeptides or any of the other excipients of the formulation.
It has been reported in the medical literature, anaphylactic reaction to GnHR agonists.
The use in patients insensitive to endocrine therapy or in those patients post-orchiectomy.
As a single treatment in patients with prostate cancer with compression of the spinal cord or evidence of spinal metastasis (see section 4.4).
Lectrum is contraindicated in women who are or may become pregnant while receiving the drug. Lectrum should not be used in women who are breastfeeding or who have undiagnosed abnormal vaginal bleeding.
Initially, Lectrum, 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, which can be managed symptomatically.
Patients with metastatic vertebral lesions and/or urinary tract obstruction should be monitored carefully during the first weeks of treatment.
In most patients testosterone levels are elevated above baseline values in the first week of treatment but return to the initial values or below by the end of the second week. Castration levels are reached within 2 to 4 weeks and, once achieved, are maintained for the time the patient is using the drug.
Transient increases in acid phosphatase levels sometimes occur at the beginning of treatment. However, at around the fourth week these values return to baseline values.
Isolated cases of worsening of signs and symptoms during the first weeks of treatment may be related to LHRH analogues. The worsening of symptoms may contribute to paralysis, with or without fatal complications.
Hyperglycaemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycaemia may represent development of diabetes mellitus or worsening of glycaemic control in patients with diabetes. Monitor blood glucose and/or glycosylated haemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycaemia 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 medicinal products known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.
Based on findings in animal studies, leuprorelin may cause fetal harm when administered to a pregnant woman. In animal developmental and reproductive toxicology studies, administration of the monthly formulation of leuprolide acetate on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-foetal toxicity in animals at doses less than the human dose, based on body surface area, using an estimated daily dose. Advise pregnant patients and females of reproductive potential of the potential risk to the foetus (see section 4.6).
Postmarketing reports of convulsions have been observed in patients on Lectrum 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 conditions mentioned above.
Patients receiving a GnRH agonist who experience convulsion should be managed according to current clinical practice.
Monitor serum levels of testosterone following injection of Lectrum 7.5 mg for 1-month administration, 22.5 mg for 3-month administration, 30 mg for 4-month administration, or 45 mg for 6-month administration. In the majority of patients, testosterone levels increased above baseline, and then declined thereafter to castrate levels (<50 ng/dl) within four weeks. (see sections 4.8 and 5.1).
Administration of Lectrum in therapeutic doses results in suppression of the pituitary-gonadal system. Normal function is usually restored within three months after treatment is discontinued. Due to the suppression of the pituitary-gonadal system by Lectrum, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to three months after discontinuation of Lectrum may be affected.
During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the medicinal product. Therefore, an increase in clinical signs and symptoms of puberty may be observed (see section 5.1).
Psychiatric events have been reported in patients taking GnRH agonists, including leuprorelin. Postmarking reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger and aggression. Monitor for development or worsening of psychiatric symptoms during treatment with leuprorelin (see section 4.8)
Response to Lectrum for 1-month administration should be monitored with a GnRHa stimulation test, basal LH or serum concentration of sex steroid levels beginning 1-2 months following initiation of therapy, with changing doses, or potentially during therapy in order to confirm maintenance of efficacy. Measurement of bone age for advancement should be done every 6-12 months.
Response to Lectrum for 3-month administration should be monitored with a GnRHa stimulation test, basal LH or serum concentration of sex steroid levels at months 2-3, month 6 and further as judged clinically appropriate, to ensure adequate suppression. Additionally, height (for calculation of growth rate) and bone age should be assessed every 6-12 months.
Once a therapeutic dose has been established, gonadotropin and sex steroid levels will decline to prepubertal levels. Gonadotropins and/or sex steroids may increase or rise above prepubertal levels if the dose is inadequate. Noncompliance with medicinal product regimen or inadequate dosing may result in inadequate control of the pubertal process with gonadotropins and/or sex steroids increasing above prepubertal levels (see sections 4.8 and 5.1).
Administration of Lectrum in therapeutic doses results in suppression of the pituitary-gonadal system. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to six months after discontinuation of Lectrum may be affected.
Normal pituitary-gonadal function is usually restored within six months after treatment with Lectrum is discontinued.
During the initial phase of therapy, sex steroids increase above baseline values owing to the physiological effect of the medication. Therefore, an increase in clinical signs and symptoms may be observed during the initial days of therapy. However, these will disappear with continued treatment at appropriate doses.
Bone loss may occur when a medication brings about a hypo-oestrogenic state, similarly to what takes place in menopause naturally. The bone loss may be reversible after the conclusion of a 6-month treatment period. However, no data are available on the use of Lectrum in women for a longer period.
A pregnancy test is recommended for women of childbearing potential if treatment is not started during menstruation or in patients with irregular cycles or if the dosage plan is delayed. Regular administration every 4 weeks of 3.75 mg Lectrum continuously causes hypogonadotrophic amenorrhoea. The occurrence of metrorrhagia during treatment is abnormal. In this case, the plasma oestradiol concentrations should be checked, and if these are less than 50 mg/ml, any potential organic lesions should be investigated.
In the case of uterine fibroids, it is mandatory to confirm the diagnosis of fibroids and exclude ovarian mass, either visually by laparoscopy or by ultrasonography or other investigative techniques as appropriate, before Lectrum therapy is instituted.
During the initial phase of treatment an increase in clinical signs and symptoms may be observed. Non-adherence to treatment or inappropriate doses may result in inadequate control of the pubertal process. The consequences of this inadequate control include the return of pubertal signs, such as menstruation, breast development and testicular growth. The longterm results of inadequate control of gonadal steroid secretion are unknown, but may include a compromising of adult stature.
Organic response to Lectrum should be monitored 1 to 2 months after starting therapy, with a GnRH stimulation test and by determining sex steroid levels. Determining the progression of bone age should be carried out every 6 – 12 months. The sex hormones may increase or exceed prepubertal levels if the dose is inappropriate. Once the therapeutic dose has been determined, gonadotrophin and sex steroid levels will fall to prepubertal levels.
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. Lectrum should be administered as precisely as possible in regular periods. An exceptional delay of the injection date for a few days (± 2 days) 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 dose) the absorption of Lectrum from the depot can be decreased. In this case the hormonal parameters (testosterone, oestradiol) should be monitored at 2-week intervals (see section 4.2).
The treatment of children with progressive brain tumours 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 GnRHa 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 concentrations of oestrogen during treatment with GnRH agonists weaken the epiphyseal 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.
There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH agonists, such as Lectrum. Patients should be informed accordingly and treated as appropriate if symptoms occur.
Androgen deprivation therapy may prolong the QT interval.
In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Lectrum.
Lack of clinical efficacy may occur due to incorrect reconstitution of the product.
This medicine contains mannitol. It can produce a mild laxative effect.
This medicine contains sodium. It should be taken into account in patients with a low sodium diet.
No interaction studies have been performed.
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of l Lectrum with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).
Based on findings in animal studies and mechanism of action, leuprorelin may cause foetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk.
In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide acetate on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-foetal toxicity in animals at doses less than the human dose based on body surface area using an estimated daily dose.
Advise pregnant patients and females of reproductive potential of the potential risk to the foetus.
Major foetal abnormalities were observed in rabbits after a single administration of the monthly formulation of Lectrum on day 6 of pregnancy at doses of 0.00024, 0.0024, and 0.024 mg/kg (approximately 1/1600 to 1/16 the human dose based on body surface area using an estimated daily dose in animals and humans). Since a depot formulation was utilised in the study, a sustained exposure to Lectrum was expected throughout the period of organogenesis and to the end of gestation. Similar studies in rats did not demonstrate an increase in foetal malformations, however, there was increased foetal mortality and decreased foetal weights with the two higher doses of the monthly formulation of Lectrum in rabbits and with the highest dose (0.024 mg/kg) in rats.
The safety and efficacy of leuprorelin have not been established in females. There is no information regarding the presence of leuprorelin in human milk, the effects on the breastfed child, or the effects on milk production. Because many medicinal products are excreted in human milk and because of the potential for serious adverse reactions in a breastfed child from leuprorelin, a decision should be made to discontinue breastfeeding or discontinue the medicinal product taking into account the importance of the medicinal product to the mother.
Based on findings in animals and mechanism of action, leuprorelin may impair fertility in males of reproductive potential (see section 5.3).
Leuprorelin is contraindicated in women who are or may become pregnant while receiving the medicinal product (see section 4.3).
Safe use of leuprolide in pregnancy has not been established in clinical studies.
Before starting and during treatment with Lectrum, it is advisable to establish whether the patient is pregnant. Lectrum is not a contraceptive. If contraception is required, a non-hormonal method of contraception should be used.
When leuprolide was administered subcutaneously to groups of rabbits as one time dosing on day 6 of pregnancy at test dosages of 0.00024, 0.0024, and 0.024 mg/kg (1/1900 to 1/19 of the human paediatric dose) it produced a dose-related increase in major foetal abnormalities. Similar studies in rats failed to demonstrate an increase in foetal malformations. There was increased fetal mortality and decreased foetal weights with the two higher doses of leuprolide in rabbits and with the highest dose in rats. No foetal malformations but increase in foetal resorptions and mortality were observed in rat and rabbit when the daily injection formulation of leuprolide acetate was dosed subcutaneously once daily at lower doses (0.1-1 µg/kg/day in rabbit; 10 µg/kg/day in rat) during the period of organogenesis. The effects on fetal mortality are logical consequences of the alterations in hormonal levels brought about by this drug. Therefore, the possibility exists that spontaneous abortion may occur if the drug is administered during pregnancy.
Patients should be advised that if they miss successive doses of Lectrum, breakthrough bleeding or ovulation may occur with the potential for conception. Patients should be advised to see their physician if they believe they may be pregnant.
If a patient becomes pregnant during treatment, the medicinal product must be discontinued. Studies in animals have shown reproductive toxicity. There have been reports of foetal malformation when Lectrum has been given during pregnancy.
The patient must be apprised of this evidence and the potential for an unknown risk to the foetus.
Particularly sensitive patients, in whom medications can induce infrequent reactions, should be attentive for reactions that occur with the use of this medication before driving vehicles, operating machinery or performing any other activity requiring concentration.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a medicinal product cannot be directly compared to rates in the clinical trials of another medicinal product and may not reflect the rates observed in practice.
In the majority of patients treated with Lectrum testosterone levels increased above baseline values during the first week, subsequently decreasing to baseline or lower values at the end of the second week of treatment. This transient increase in hormone levels was occasionally associated with a temporary worsening of signs and symptoms. Special attention should be given to patients with vertebral metastases and/or urinary obstruction or haematuria, since a potential aggravation of signs and symptoms at the start of treatment may bring about neurological problems, such as weakness and/or paraesthesia of the lower limbs or a worsening of urinary symptoms. (see section 4.4).
In clinical studies, the following adverse reactions occurred in 5% or more of patients who received Lectrum:
Cardiovascular system: oedema
Gastrointestinal system: nausea and vomiting
Endocrine system: decrease of testicular size*, hot flushes*, sweating*, impotence*
Central/peripheral nervous system: general pain
Respiratory system: dyspnoea
Miscellaneous: asthenia
In these same studies, the following adverse reactions were reported in less than 5% of patients receiving Lectrum:
Cardiovascular system: angina, cardiac arrhythmia
Gastrointestinal system: anorexia, diarrhoea
Endocrine system: gynaecomastia, decreased libido
Musculoskeletal system: bone pain, myalgia
Central/peripheral nervous system: paraesthesia, insomnia
Respiratory system: haemoptysis
Tegmental system: dermatitis, local skin reactions, hair growth
Urogenital system: dysuria, pollakiuria, urinary urgency, testicular pain
Miscellaneous: diabetes, fever, chills, hard nodules in the oropharynx, increased serum calcium, weight gain, increased serum uric acid. Reactions at the injection site have been reported, including pain, inflammation, sterile abscess, induration and haematoma.
* Physiological effects of decreased testosterone
Oestradiol levels may increase during the first weeks after the initial injection of Lectrum 3.75 mg, but later fall to baseline values. This transient increase of oestradiol may be associated with a temporary worsening of signs and symptoms. Laboratory test findings have shown changes in the HDL/LDL ratio, when a transient therapeutic menopausal state is induced. However, the clinical implication of these changes in this patient population for a restricted therapeutic period is not clear. Isolated elevations of serum aspartate aminotransferase were observed.
In clinical studies for treatment of endometriosis and uterine fibroma, the following adverse reactions occurred in 5% or more of patients receiving Lectrum 3.75 mg:
Cardiovascular system: oedema
Gastrointestinal system: nausea and vomiting, gastrointestinal disturbances*
Endocrine system: hot flushes* and sweating*, breast changes* (tenderness and hypersensitivity), decreased libido*, androgen-dependent effects (virilism, acne, seborrhoea, hirsutism, voice change)
Musculoskeletal system: myalgia*, joint disorders*
Central/peripheral nervous system: depression*/emotional lability*, headache*, dizziness, insomnia*/sleep disturbances, general pain, neuromuscular disorders*; nervousness*, paraesthesias
Tegmental system: local skin reactions
Urogenital system: vaginitis*
Miscellaneous: asthenia, weight gain or loss
In these same studies, the following adverse reactions were reported in less than 5% of patients receiving Lectrum 3.75 mg:
Cardiovascular system: palpitations, syncope, tachycardia
Gastrointestinal system: dry mouth, constipation, diarrhoea, flatulence, appetite changes
Musculoskeletal system: myalgia, hypertonia
Central/peripheral nervous system: anxiety, personality disorders, memory disorders, delirium
Tegmental system: ecchymosis, alopecia, hair disorders, ungual changes
Urogenital system: dysuria, lactation
Miscellaneous: ophthalmologic disturbances, lymphadenopathy, weight gain or loss, taste perversions, vaginal odour, flu symptoms. Reactions at the injection site were reported, including pain, inflammation, sterile abscess, induration and haematoma.
Other adverse reactions in adult women: amenorrhoea or mild and irregular vaginal haemorrhage
* Physiological effects of decreased oestrogen
In the initial phase of therapy, a short-term increase as flare-up of the sex hormone level occurs, followed by a decrease to values within the pre-pubertal range. Due to this pharmacological effect, adverse events may occur particularly at the beginning of treatment.
Very rare: General allergic reactions (fever, rash, e.g. itching, anaphylactic reactions)
Common: Emotional lability
Common: Headache
As with other medicinal products of this class, very rare cases of pituitary apoplexy have been reported following initial administration in patients with pituitary adenoma.
Common: Abdominal pain/abdominal cramps, nausea/vomiting
Common: Acne
Common: Vaginitis, vaginal bleeding, spotting, discharge
Note
In general, the occurrence of vaginal spotting with continued treatment (subsequent to possible withdrawal bleeding in the first month of treatment) should be assessed as a sign of potential under-dose. The pituitary suppression should then be determined by an LHRH test.
Common: Injection site reactions
General pain, aggravation of preexisting tumour and decreased vision, allergic reaction, body odour, fever, flu syndrome, hypertrophy, infection
Vasodilation, bradycardia, hypertension, peripheral vascular disorder, syncope, hypotension, pallor
Constipation, dyspepsia, dysphagia, gingivitis, increased appetite
Accelerated sexual maturity, feminisation, goitre
Purpura
Growth retarded, peripheral oedema, weight gain, decreased appetite, obesity, diabetes mellitus
Arthralgia, joint disorder, myalgia, myopathy, musculoskeletal pain, pain in extremity, tenosynovitis-like symptoms
Depression, hyperkinesia, nervousness, somnolence, mood altered, crying, dizziness, neuropathy peripheral, convulsion, spinal fracture/paralysis
Tearfulness
Asthma, epistaxis, pharyngitis, rhinitis, sinusitis, cough
Seborrhoea, rash incl. erythema multiforme, alopecia, hair disorder, hirsutism, leukoderma, nail disorder, skin hypertrophy, hyperhidrosis, hot flush, flushing
Cervix disorder/neoplasm, dysmenorrhoea, gynaecomastia/breast disorders, menstrual disorder, urinary incontinence, prostate pain
Injection site pain, injection site swelling, asthenia, gait disturbance, injection site abscess sterile, injection site haematoma, injection site induration, injection site warmth, irritability, chest pain
Decreased white blood cell count, weight increased
The following laboratory events were reported as adverse reactions: antinuclear antibody present and increased sedimentation rate.
In clinical studies, the following adverse reactions occurred in 2% or more of patients treated with Lectrum:
Very rare: General allergic reactions (fever, rash, e.g. itching, anaphylactic reactions)
Common: Vaginal bleeding, spotting, discharge, vaginitis
Overall body: generalised pain
Tegmental system: acne/seborrhoea, reaction at the injection site, including abscess, skin rash, erythema multiforme
Urogenital system: vaginitis, bleeding, discharge
In these same studies, the following adverse reactions occurred in less than 2% of patients who were treated with Lectrum:
Overall body: body pain, fever, headache, infection
Cardiovascular system: syncope, vasodilatation
Digestive system: dysphagia, gingivitis, nausea and vomiting,
Endocrine system: acceleration of sexual maturity, metabolic and nutritional disorders, peripheral oedema, weight gain
Nervous system: nervousness, personality disorders, drowsiness, emotional lability, pituitary apoplexy
Respiratory system: epistaxis
Tegmental system: alopecia, skin striae
Urogenital system: cervix changes, gynaecomastia/breast changes; urinary incontinence
Cardiovascular system: congestive heart failure, hypertension, hypotension, ECG changes/ischaemia, myocardial infarction, murmur, phlebitis/thrombosis, pulmonary embolism, transient ischaemic episode, QT prolongation, bradycardia, varicose vein (see sections 4.4 and 4.5)
Gastrointestinal system: constipation, dysphagia, gastrointestinal disturbances and bleeding, hepatic dysfunction, peptic ulcer, rectal polyps, abdominal cramps, eructation, enlarged abdomen, duodenal ulcer, increased appetite, thirst/dry mouth
Respiratory system: cough, pleural rub, pulmonary fibrosis, pulmonary infiltration, respiratory changes, sinus congestion, emphysema, haemoptysis, lung oedema, sputum increased, epistaxis, pharyngitis, pneumonia, intestinal lung disease
Hepatobiliary disorder: Serious drug-induced liver injury
Endocrine system: breast pain or tenderness, increased libido, enlarged thyroid
Blood and lymphatic system: anaemia, decrease in white blood cells
Musculoskeletal system: symptoms similar to those of tenosynovitis, ankylosing spondylitis, joint pain, pelvic fibrosis
Central/peripheral nervous system: anxiety, peripheral neuropathy, spinal fractures/paralysis, blurred vision, dizziness, hearing and taste disturbances, lethargy, memory disorders, mood swings, sluggishness, syncope/loss of consciousness, convulsions, agitation, neuromuscular disorders, delusions, hypaesthesia, nervousness, amblyopia,
Tegmental system: exanthem, urticaria, photosensitivity reactions, skin/ear carcinoma, dry skin, ecchymoses, hair loss, pruritis, skin lesions and pigmentation
Urogenital system: prostate pain, bladder spasms, incontinence, increased penis volume, urinary obstruction, urinary tract infection, urinary disorder, balanitis, breast enlargement, penis disorder, testis disorder
Miscellaneous: reactions at the injection site, including pain, inflammation, sterile abscess, enduration and haematoma, hypoglycaemia, depression, infection/inflammation, ophthalmologic changes, tumours (temporal bone) and isolated cases of anaphylaxis, cellulitis, neoplasm, lymphoedema, dehydration
Like other medicinal products in this class, mood swings, including depression, have been reported. There have been very rare reports of suicidal ideation and attempt. Many, but not all, of these patients had a history of depression or other psychiatric illness. Patients should be counselled on the possibility of development or worsening of depression during treatment with Lectrum.
Symptoms consistent with an anaphylactoid or asthmatic process have been rarely (incidence rate of about 0.002%) reported.
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 analogue. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with Lectrum for at least six months, underwent bone density studies as a result of pain. The Lectrum treated group had lower bone density scores than the nontreated control group. It can be anticipated that long periods of medical castration in men will have effects on bone density. Symptoms consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep disorders, gastrointestinal distress, and shortness of breath) have been reported individually and collectively.
Abnormalities of certain parameters were observed, but their relationship to medicinal product treatment are difficult to assess in this population. The following were recorded in ≥5% of patients at final visit: decreased albumin, decreased haemoglobin/haematocrit, decreased prostatic acid phosphatase, decreased total protein, decreased urine specific gravity hyperglycaemia, hyperuricaemia, increased BUN, increased creatinine, increased liver function tests (AST, LDH), increased phosphorus, increased platelets, increased prostatic acid phosphatase, increased total cholesterol, increased urine specific gravity, leukopenia.
Abnormalities of certain parameters were observed, but are difficult to assess in this population. The following were recorded in ≥5% of patients: increased BUN, hyperglycaemia, hyperlipidaemia (total cholesterol, LDL-cholesterol, triglycerides), hyperphosphataemia, abnormal liver function tests, increased PT, increased PTT. Additional laboratory abnormalities reported were: decreased platelets, decreased potassium and increased white blood cell count.
Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
