Leuprorelin

Leuprorelin is a synthetic nonapeptide analogue of gonadotropin-releasing hormone (GnRH), more potent than the natural hormone. Depot products release it slowly over one, three or six months. Whatever condition is treated, the mechanism is the same: after a short initial stimulation, leuprorelin switches off the pituitary–gonadal axis and lowers sex-steroid levels, an effect that is reversible when treatment stops. This page covers three EU products whose SmPCs were reviewed: Camcevi (centrally authorised, EMA; 21 mg and 42 mg), Eligard Trimestral and Lutrate Depot Mensual (nationally authorised, Spanish AEMPS SmPCs). Their doses and intervals are not interchangeable.

Mechanism of Action

• Initial stimulation: as a GnRH-receptor agonist, leuprorelin first increases the pituitary release of luteinising hormone (LH) and follicle-stimulating hormone (FSH). In men this causes a transient rise in testosterone and dihydrotestosterone, which is responsible for some early adverse effects (tumour flare).
• Down-regulation: with continuous exposure over 2 to 4 weeks, the receptors are down-regulated and LH and FSH fall, suppressing testicular steroidogenesis in men and oestrogen production in women. In men, testosterone falls below the castrate threshold (50 ng/dL or less) within 3 to 4 weeks and stays there while treatment continues.
• Reversibility: the effect reverses after stopping, but the agonist is more potent than the natural hormone and the time for testosterone to recover varies between patients.
• Long-term control: in long-term studies, continued therapy kept testosterone below the castrate level for up to seven years.
• Response in prostate cancer: tumour size was not measured directly in the Camcevi programme; the indirect tumour response was a 96.7% fall in mean PSA.
• Other conditions: the same suppression of sex steroids underlies use in endometriosis, uterine fibroids, hormone-sensitive breast cancer in pre- and perimenopausal women, ovarian protection and central precocious puberty. In women the initial rise in oestradiol may briefly worsen symptoms such as pain and bleeding.

Pharmacokinetics

• Absorption: with Camcevi 21 mg, serum leuprorelin rose rapidly after the first and second doses (mean 37.8 and 37.7 ng/mL about 4 hours after injection), fell quickly over the first 3 days, then stayed on a plateau (mean 0.30–1.59 ng/mL) over the 12-week interval. There was no significant accumulation with repeated 12-week dosing. For depot leuprorelin in general, DrugBank describes peak levels 4 to 5 hours after injection and steady state after about four weeks.
• Distribution: steady-state volume of distribution 27 L after an intravenous bolus in healthy men; in vitro binding to plasma proteins 43–49%.
• Metabolism: no metabolism study was done for the Camcevi SmPC. As a peptide, leuprorelin is broken down by peptidases, not cytochrome P450 enzymes, to inactive penta-, tri- and dipeptides.
• Elimination: after a 1 mg intravenous bolus in healthy men, mean systemic clearance was 8.34 L/h and terminal half-life about 3 hours. No excretion studies were conducted; in three patients given a 3.75 mg depot, less than 5% of the dose appeared in urine as unchanged drug or the pentapeptide metabolite.
• Special populations: no clinical studies in renal or hepatic impairment.

Indications differ by product. Camcevi and Eligard Trimestral are for men with prostate cancer only; Lutrate Depot Mensual has a wider range.

Camcevi (21 mg every 3 months, 42 mg every 6 months) and Eligard Trimestral (22.5 mg, every 3 months)

• Prostate cancer: hormone-dependent advanced prostate cancer.
• Prostate cancer with radiotherapy: high-risk localised and locally advanced hormone-dependent prostate cancer, in combination with radiotherapy.

Lutrate Depot Mensual (3.75 mg, every month)

• Prostate cancer: hormone-dependent advanced prostate cancer; locally advanced hormone-dependent prostate cancer in combination with radiotherapy; localised hormone-dependent prostate cancer of intermediate or high risk in combination with radiotherapy.
• Uterine fibroids (leiomyoma): before surgery or as an adjunct to it, or as a definitive alternative symptomatic treatment in perimenopausal women who do not want surgery.
• Endometriosis: alone or as an adjunct to surgery.
• Breast cancer: advanced breast cancer in pre- and perimenopausal women for whom hormonal treatment is appropriate; and, in combination with tamoxifen or an aromatase inhibitor, adjuvant treatment of early-stage hormone-sensitive breast cancer in pre- and perimenopausal women at high risk of recurrence (young age, high-grade tumour, lymph-node involvement). In women who have had chemotherapy, premenopausal status must be confirmed after chemotherapy is finished.
• Ovarian protection: preserving ovarian function in premenopausal women with cancer who receive chemotherapy that may cause premature ovarian failure.
• Central precocious puberty: in children, diagnosed clinically by secondary sexual characteristics appearing before age 9 in girls and before age 10 in boys.

• All three products: hypersensitivity to leuprorelin, to other GnRH (LHRH) agonists or to any excipient. Anaphylactic reactions to synthetic LHRH or its agonist analogues have been described.
• Camcevi and Eligard Trimestral: women and paediatric patients; previous orchiectomy (leuprorelin does not lower testosterone further after surgical castration); use as the sole treatment in prostate cancer with spinal cord compression or evidence of spinal metastases.
• Lutrate Depot Mensual, men: previous orchiectomy; not as sole treatment in prostate cancer with signs of spinal cord compression or spinal metastases.
• Lutrate Depot Mensual, women: pregnancy or possible pregnancy during treatment; breastfeeding; undiagnosed vaginal bleeding; in breast cancer, starting an aromatase inhibitor before adequate ovarian suppression with leuprorelin has been achieved.
• Lutrate Depot Mensual, girls with central precocious puberty: pregnancy or possible pregnancy during treatment, breastfeeding, and undiagnosed vaginal bleeding.

Most reactions follow from the hormonal action of leuprorelin, that is, rises and falls in certain hormone levels. In men with advanced prostate cancer the most common are hot flushes (mild or moderate in about 58% of patients), nausea, malaise, fatigue and transient local irritation at the injection site. Frequencies differ between products and populations, so each is given separately below.

Men With Prostate Cancer (Camcevi and Eligard Trimestral)

The groups follow the table in the Camcevi SmPC for injectable leuprorelin products in advanced prostate cancer. The Eligard Trimestral SmPC gives a very similar table; for example, it lists QT prolongation with frequency not known.

Very common (≥1/10): hot flushes, ecchymoses, erythema, fatigue, injection-site burning, injection-site paraesthesia.

Common (≥1/100 to <1/10): nasopharyngitis, haematology changes, anaemia, nausea, diarrhoea, gastroenteritis or colitis, pruritus, night sweats, arthralgia, pain in the extremities, myalgia, stiffness, weakness, decreased urinary frequency, difficulty urinating, dysuria, nocturia, oliguria, breast tenderness, testicular atrophy, testicular pain, infertility, breast enlargement, erectile dysfunction, reduced penis size, malaise, injection-site pain, haematoma and stinging, increased blood creatine phosphokinase, prolonged coagulation time.

Uncommon (≥1/1,000 to <1/100): urinary tract infection, local skin infection, aggravated diabetes mellitus, abnormal dreams, depression, decreased libido, dizziness, headache, hypoaesthesia, insomnia, taste and smell disturbance, vertigo, QT prolongation, myocardial infarction, hypertension, hypotension, rhinorrhoea, dyspnoea, constipation, dry mouth, dyspepsia, vomiting, clamminess, increased sweating, back pain, muscle cramps, bladder spasm, haematuria, increased urinary frequency, urinary retention, gynaecomastia, impotence, testicular disorder, injection-site pruritus and induration, lethargy, pain, pyrexia, increased alanine aminotransferase, increased blood triglycerides, prolonged prothrombin time, weight increase.

Rare (≥1/10,000 to <1/1,000): abnormal involuntary movements, syncope, collapse, flatulence, eructation, alopecia, skin eruption, breast pain, injection-site ulceration.

Very rare (<1/10,000): injection-site necrosis.

Not known: idiopathic intracranial hypertension (pseudotumor cerebri), interstitial lung disease, Stevens-Johnson syndrome or toxic epidermal necrolysis, toxic skin eruption, erythema multiforme.

Men With Prostate Cancer (Lutrate Depot Mensual)

This monthly intramuscular product has its own table, from a trial with six monthly doses followed for 26 weeks.

• Very common: hot flushes.
• Common: increased appetite, headache, hyperhidrosis, night sweats, cold sweat, back pain, erectile dysfunction, fatigue, asthenia, pyrexia and local injection-site reactions. Local reactions affected 18.1% of patients: injection-site pain 8.1%, irritation 4.4%, discomfort 1.9%, erythema 1.3% and bruising 1.3%.
• Uncommon: anorexia, hypercholesterolaemia, hyperlipidaemia, sleep disorders, insomnia, decreased libido, mood alteration and depression, somnolence, vertigo, lower abdominal pain, diarrhoea, nausea, vomiting, hyperbilirubinaemia, periorbital oedema, urticaria, pruritus, arthralgia, muscle spasms, pain in a limb, urinary retention, urinary incontinence, pollakiuria, breast swelling and tenderness, ejaculation failure, weakness, increased AST, ALT, bilirubin and gamma-glutamyltransferase.
• Not known: idiopathic intracranial hypertension, Stevens-Johnson syndrome or toxic epidermal necrolysis, toxic skin eruption, erythema multiforme, interstitial lung disease, QT prolongation.
• Severity: 98% of treatment-related events were mild or moderate; 89% of hot flushes were mild, 9% moderate and 0.2% severe. Mood changes and depression were frequent in a post-marketing study of chronic treatment.
• Other events described with leuprorelin acetate: impotence and loss of libido (consequences of testosterone deprivation), peripheral oedema, pulmonary embolism, palpitations, myalgia, muscle weakness, chills, dyspnoea, amnesia, visual disturbance and altered skin sensation. Infarction of a pre-existing pituitary adenoma has been described in isolated cases after LHRH agonists, rare cases of thrombocytopenia and leukopenia have been reported, and changes in glucose tolerance have been noted.

Women (Lutrate Depot Mensual)

Effects mostly reflect low oestrogen: hot flushes, mood changes including depression (occasionally severe) and vaginal dryness. Oestrogen levels return to normal after treatment. The low-oestrogen state causes a small loss of bone density, part of which may not be reversible. After 6 months of treatment for endometriosis, mean vertebral bone density fell by 3.9%, returning to within 2% of baseline 6 or 12 months after stopping. After 3 months for fibroids, trabecular vertebral bone density fell by a mean of 2.7%, with a trend to recovery 6 months after stopping. Serious venous and arterial thromboembolic events (deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, transient ischaemic attack) have been reported; most cases had other risk factors or concomitant medicines, and a causal link with GnRH agonists is not known.

Very common (≥1/10): insomnia, headache (occasionally severe), hot flushes.

Common (≥1/100 to <1/10): weight fluctuation, mood alteration, depression, paraesthesia, dizziness, nausea, arthralgia, muscle weakness, breast tenderness, breast atrophy, vulvovaginal dryness, peripheral oedema, local injection-site reactions.

Uncommon (≥1/1,000 to <1/100): decreased appetite, abnormal lipids, visual impairment, palpitations, diarrhoea, vomiting, abnormal liver function tests (usually transient), hair loss, myalgia, pyrexia, fatigue.

Rare (≥1/10,000 to <1/1,000): pituitary haemorrhage after the first dose in patients with a pituitary adenoma.

Not known: anaemia (reported for this class), thrombocytopenia, leukopenia, hypersensitivity reactions (rash, pruritus, urticaria and, rarely, wheezing, interstitial pneumonitis and anaphylaxis), abnormal glucose tolerance that may affect diabetes control, paralysis, convulsions, idiopathic intracranial hypertension, pulmonary embolism, hypertension, hypotension, abnormal liver function, jaundice, Stevens-Johnson syndrome or toxic epidermal necrolysis, toxic skin eruption, erythema multiforme, spinal fracture, reduced bone mass, interstitial lung disease, vaginal bleeding.

In early breast cancer treated with a GnRH agonist plus tamoxifen or an aromatase inhibitor, the most frequent reactions were hot flushes, musculoskeletal disorders, fatigue, insomnia, hyperhidrosis, vulvovaginal dryness and depression.

Children With Central Precocious Puberty (Lutrate Depot Mensual)

At the start of treatment sex hormones rise briefly before falling to the prepubertal range, so reactions may occur especially early on.

Common (≥1/100 to <1/10): emotional lability, headache, abdominal pain or cramps, nausea and vomiting, acne, vaginal bleeding, spotting or discharge, injection-site reactions.

Very rare (<1/10,000): pituitary apoplexy after administration in patients with a pituitary adenoma; general allergic reactions (fever, rash such as itching, anaphylactic reactions).

Not known: convulsions, idiopathic intracranial hypertension, Stevens-Johnson syndrome or toxic epidermal necrolysis, toxic skin eruption, erythema multiforme, interstitial lung disease.

Spotting during continued treatment, after possible withdrawal bleeding in the first month, can signal underdosing; pituitary suppression is then checked with an LHRH test.

Important serious reactions across the products include tumour flare in the first weeks of prostate cancer treatment, QT prolongation, myocardial infarction and stroke, pituitary apoplexy, convulsions, severe depression, anaphylaxis, idiopathic intracranial hypertension and severe skin reactions.

• Pharmacokinetic interactions: no interaction studies have been performed with Camcevi or Eligard Trimestral, and none have been reported. Leuprorelin is a peptide broken down by peptidases rather than cytochrome P450 enzymes and is only 43–49% protein-bound, so pharmacokinetic interactions are not expected.
• QT-prolonging medicines: androgen deprivation may prolong the QT interval. Use with medicines known to prolong the QT interval or to cause torsade de pointes needs careful evaluation. These include class IA antiarrhythmics (quinidine, disopyramide), class III antiarrhythmics (amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin and antipsychotics.
• Medicines that lower the seizure threshold: convulsions have been reported with leuprorelin in patients also taking medicines associated with seizures, such as bupropion or selective serotonin reuptake inhibitors (Lutrate Depot Mensual SmPC).

All leuprorelin depots are prepared and injected by a healthcare professional; they are not self-injected. Treatment of prostate cancer is directed by a healthcare professional with the expertise to monitor the response. Intravenous or intra-arterial injection must be strictly avoided, and the injection site should be varied from time to time. The products below differ in strength, route and interval and must not be substituted for one another. Depots with other intervals, including further one-monthly and six-monthly products, exist in national registers; only these three products are described here (Camcevi in both its 21 mg and 42 mg strengths).

Prostate Cancer: Camcevi and Eligard Trimestral (Every Three or Six Months)

• Camcevi 21 mg: one subcutaneous injection every three months, from a pre-filled syringe of prolonged-release suspension supplied with a safety needle. The injected suspension forms a solid depot that releases leuprorelin continuously for three months.
• Camcevi 42 mg: one subcutaneous injection every six months, from a pre-filled syringe of prolonged-release suspension supplied with a safety needle. The injected suspension forms a solid depot that releases leuprorelin continuously over a six-month period.
• Eligard Trimestral 22.5 mg: one subcutaneous injection every three months. The contents of the two sterile pre-filled syringes (powder and solvent) are mixed immediately before injection. Only healthcare professionals familiar with the procedure should prepare, reconstitute and inject it, the instructions must be followed strictly, and a product that was not prepared correctly must not be given. It should be at room temperature before injection (take it out of the refrigerator about 30 minutes beforehand).
• Duration: usually long-term, and treatment is not stopped when remission or improvement occurs. It can be used as neoadjuvant or adjuvant therapy with radiotherapy in high-risk localised and locally advanced prostate cancer.
• Monitoring: response is followed by clinical signs and serum PSA. In trials, testosterone rose during the first 3 days in most men who had not had an orchiectomy, then fell below medical castration levels within 3 to 4 weeks and stayed there (breakthroughs in less than 1%). If the response seems poor, confirm that testosterone has reached and stays at castrate levels. For Eligard Trimestral, testosterone should be checked when incorrect preparation or administration is suspected or known, because efficacy can be lost.
• Metastatic castration-resistant prostate cancer: in men who are not surgically castrated and are eligible for androgen biosynthesis inhibitors or androgen receptor inhibitors, GnRH agonist treatment may be continued.

Lutrate Depot Mensual (Every Month, Intramuscular)

• Preparation and route: the freeze-dried microsphere powder is reconstituted immediately before use and injected into a muscle once a month. No other route may be used; if it is given subcutaneously by mistake, the patient should be monitored closely because there are no data for other routes. Only healthcare professionals familiar with the procedure should prepare and inject it.
• Prostate cancer: 3.75 mg once a month. Testosterone rose over the first 4 days in most men without orchiectomy, then fell to castrate level (below 0.5 ng/mL) within 3 to 4 weeks and stayed there. Serum testosterone and PSA are checked periodically; brief rises in acid phosphatase usually settle by week 4. Treatment of advanced disease is long-term. With radiotherapy, trials showed that 3 years of androgen deprivation after radiotherapy is preferable to 6 months, and guidelines recommend 2 to 3 years in locally advanced or high-risk localised disease. In intermediate-risk localised disease, radiotherapy is combined with 4 to 6 months of LHRH-agonist therapy.
• Uterine fibroids and endometriosis: 3.75 mg once a month for up to six months.
• Breast cancer: 3.75 mg once a month with tamoxifen or an aromatase inhibitor. In women having chemotherapy, start leuprorelin after chemotherapy ends, once premenopausal status is confirmed. Adjuvant treatment with other hormone therapy lasts up to 5 years. With an aromatase inhibitor, begin leuprorelin at least 6 to 8 weeks earlier, with at least two injections one month apart before the inhibitor starts. Confirm ovarian suppression by low blood FSH and oestradiol before starting the inhibitor and repeat every three months during the combination. Do not interrupt leuprorelin during aromatase inhibitor treatment, to avoid a rebound rise in oestrogen in premenopausal women.
• Ovarian protection: 3.75 mg once a month, with the first dose two weeks before chemotherapy so that sex hormones are suppressed in time, then monthly for as long as chemotherapy lasts.
• Central precocious puberty: under the general supervision of a paediatric endocrinologist, with the schedule tailored to the child. Children of 20 kg or more receive 3.75 mg once a month (2 mL of the reconstituted product, the whole dose). Children below 20 kg (rare) receive 1.88 mg once a month (1 mL of the reconstituted product, discarding the rest), with weight gain monitored. The dose may need to rise if suppression is inadequate (for example spotting or inadequate gonadotropin suppression on an LHRH test); the lowest effective monthly dose is found with that test. The smallest possible injection volume is used. Doses above those recommended often caused sterile abscesses at the injection site, and absorption from the depot may fall. The interval should be 30 ± 2 days to prevent symptoms returning.
• Duration in children: depends on final height prognosis, growth velocity, bone age and its acceleration, and is decided jointly by the paediatrician, the legal guardian and, where appropriate, the child. Bone age is checked every 6 to 12 months. Stopping should be considered in girls with bone maturation above 12 years and boys above 13 years. In girls, pregnancy must be excluded before treatment; it cannot generally be excluded during treatment, in which case medical advice should be followed.

Special Populations

• Renal and hepatic impairment: no clinical studies with Camcevi or Eligard Trimestral; the pharmacokinetics of Lutrate Depot Mensual have not been determined in hepatic or renal impairment.
• Elderly: the Lutrate Depot Mensual dose is the same as for adults.
• Women and children: Camcevi and Eligard Trimestral are contraindicated, and safety and efficacy in children aged 0 to 18 years are not established. The only paediatric use is Lutrate Depot Mensual in central precocious puberty.

Correct Preparation (Eligard Trimestral)

Handling errors at any step of preparation have been reported and can cause loss of efficacy. The reconstitution and administration instructions must be followed strictly, and when incorrect handling is known or suspected the patient should be monitored appropriately, including testosterone levels.

Transient Testosterone Flare

Leuprorelin, like other GnRH agonists, causes a brief rise in serum testosterone, dihydrotestosterone and acid phosphatase during the first week. Symptoms can worsen or new ones appear, including bone pain, neuropathy, haematuria and ureteral or bladder outlet obstruction; they usually settle with continued treatment. Adding an appropriate antiandrogen from 3 days before the first dose and for the first two to three weeks should be considered, as it has been reported to prevent the effects of the initial testosterone rise. Leuprorelin alone is contraindicated in patients with spinal cord compression or spinal metastases.

QT Prolongation and Cardiovascular Disease

Androgen deprivation may prolong the QT interval. In patients with a history of, or risk factors for, QT prolongation, or taking medicines that may prolong it, the benefit–risk balance including the potential for torsade de pointes should be assessed before starting; periodic ECG and electrolyte monitoring should be considered. An increased risk of myocardial infarction, sudden cardiac death and stroke has been reported with GnRH agonists in men. The risk appears low and must be weighed against cardiovascular risk factors, and patients should be watched for signs of cardiovascular disease.

Bone Density

Decreased bone density has been reported in men after orchiectomy or GnRH agonist treatment. Androgen deprivation therapy significantly increases the risk of fractures from osteoporosis; in the limited data, such fractures occurred in 5% of patients after 22 months and in 4% after 5 to 10 years of treatment. Long-standing testosterone deficiency, older age, smoking, alcohol, obesity and too little exercise add to the risk. In women, the low-oestrogen state causes a small loss of bone density during treatment (see Side Effects).

Pituitary Apoplexy

Rare post-marketing cases of pituitary apoplexy, a syndrome caused by infarction of the pituitary gland, have followed GnRH agonists, most within 2 weeks of the first dose and some within the first hour. It presents as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status and sometimes cardiovascular collapse, and needs immediate medical attention.

Metabolic Changes

Hyperglycaemia and an increased risk of diabetes have been reported in men on GnRH agonists. It may mean new diabetes or worse control in people who already have it.

Convulsions, Depression, Anaphylaxis and Liver Effects

• Convulsions have been reported with leuprorelin acetate in patients with a history of seizures, epilepsy, cerebrovascular disorders or central nervous system anomalies or tumours, in patients taking medicines linked to seizures, and also in people without these factors (Lutrate Depot Mensual SmPC).
• Depression, which may be severe, is a high risk with GnRH agonists. Patients should be told and treated appropriately if symptoms appear.
• Anaphylaxis: treatment must stop at once if signs appear (breathlessness, asthma, rhinitis, angioneurotic or glottic oedema, low blood pressure, urticaria, rash, pruritus or interstitial pneumonitis). Patients should be told beforehand to stop and see a doctor. Anyone who has had a hypersensitivity reaction to leuprorelin must be closely monitored and not given Lutrate Depot Mensual again.
• Liver: liver dysfunction and jaundice with raised liver enzymes have been described and call for close observation.
• Idiopathic intracranial hypertension (pseudotumor cerebri) has been reported with leuprorelin. Patients with severe or recurring headache, visual problems or ringing in the ears should seek medical advice.

Women Treated for Gynaecological Conditions

Pregnancy must be excluded before treatment; Lutrate Depot Mensual is contraindicated in pregnancy. The early rise in oestradiol can make pain and bleeding worse for a short time in endometriosis and fibroids, and long-term use causes loss of bone density.

Pregnancy, Breastfeeding and Fertility

• Camcevi and Eligard Trimestral: contraindicated in women. Based on animal findings and the mechanism of action, leuprorelin may impair fertility in men of reproductive potential.
• Lutrate Depot Mensual: contraindicated in women who are or may become pregnant and during breastfeeding.

Sodium

Lutrate Depot Mensual contains less than 1 mmol (23 mg) of sodium per vial, that is, it is essentially sodium-free.

Effect on Driving

Leuprorelin products have a minor influence on the ability to drive and use machines. Fatigue, dizziness and visual disturbances can occur, and patients who have them should not drive or operate machinery.

• Camcevi (21 mg and 42 mg): store in a refrigerator (2–8 °C) in the original package to protect from light. Once out of the refrigerator it may be kept in its original packaging at room temperature (below 25 °C) for up to eight weeks and must be discarded if not used within eight weeks. Each pack holds one pre-filled syringe and one sterile safety needle (18 gauge, 5/8 inch).
• Eligard Trimestral: store in a refrigerator (2–8 °C) in the original package to protect from moisture. It must be at room temperature before injection, so take it out about 30 minutes before use. Once out of the refrigerator it may be kept in its original packaging below 25 °C for up to four weeks.
• Lutrate Depot Mensual: do not store above 25 °C. Do not freeze.
• Cold chain: Camcevi and Eligard Trimestral are held and transported at 2–8 °C until shortly before use.

• Camcevi 21 mg: 30 months.
• Camcevi 42 mg: 2 years.
• Eligard Trimestral: 2 years. After removal from the refrigerator, up to 4 weeks below 25 °C. Once the tray is opened, the powder and solvent must be reconstituted immediately and given to the patient. After reconstitution use at once, because the viscosity of the solution increases with time.
• Lutrate Depot Mensual: 3 years unopened. Once reconstituted with the solvent, the suspension must be administered immediately.

Prescription only (Rx), on medical prescription (Annex II B of the Camcevi authorisation), with treatment directed by a healthcare professional with the expertise to monitor the response. The depot is injected by a healthcare professional, so it is supplied to the hospital, clinic or practice that administers it. Camcevi and Eligard Trimestral are supplied in the cold chain at 2–8 °C; Lutrate Depot Mensual is kept below 25 °C.