Enantone L.P. Adverse Reactions

Enantone L.P. 1.88 mg: The following table shows the incidence of adverse reactions, including abnormalities in laboratory data, according to the indicated diseases and phase of investigation. (See Table 3.)

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The adverse reactions listed below have been observed in the above investigations, spontaneous reports, etc.
Clinically significant adverse reactions: Since interstitial pneumonia, accompanied by fever, coughing, dyspnea, abnormal chest X-ray, etc. may occur (< 0.1%), the patient's condition should be closely observed. If any abnormality is observed, appropriate measures, such as treatment with adrenal cortical hormones, should be taken.
Since anaphylactoid symptoms may occur (< 0.1%), careful inquiry should be made, and close observation should be made after the administration of Enantone L.P. 1.88 mg. If any abnormality is observed, appropriate measures should be taken.
Hepatic dysfunction or jaundice, with increased AST (GOT), ALT (GPT) etc., may occur (frequency unknown). Therefore, close observation should be made, and if any abnormality is observed, appropriate measures should be taken. Development or aggravation of diabetes may occur (frequency unknown). If any abnormality is observed, appropriate measures should be taken.
As with other agents in this class, very rare cases of pituitary apoplexy have been reported following initial administration in patients with pituitary adenoma. Therefore, if headache, vision impairment, visual field disorder, etc. are observed immediately after the first dose of Enantone L.P. 1.88 mg appropriate measures, such as surgical treatment, should be taken after conducting examination.
Other adverse reactions: See Table 4.

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Immune system disorders: Hypersensitivity including Anaphylactic reaction, Rash and Pruritus.
Metabolism and nutrition disorders: Weight fluctuation, Decreased appetite.
Psychiatric disorders: Libido decreased, Affect lability, Depression, Sleep disorder.
Nervous system disorders: Headache, Dizziness, Paresthesia, Pituitary Haemorrhage, Seizure.
Eye disorders: Visual impairment.
Vascular disorders: Hot flush.
Gastrointestinal disorders: Nausea, Vomiting.
Hepatobiliary disorders: Liver function test abnormal, usually transient.
Skin and subcutaneous tissue disorders: Alopecia, Hyperhydrosis.
Musculoskeletal and connective tissue disorders: Arthralgia, Myalgia.
Reproductive system and breast disorders: Breast atrophy, Vulvovaginal dryness, Vulvovaginitis.
General disorders and administration site conditions: Injection site reaction, Oedema.
Enantone L.P. 3.75 mg/Enantone L.P. 11.25 mg: General (all indications): As with other agents in this class, very rare cases of pituitary apoplexy have been reported following initial administration in patients with pituitary adenoma.
Prostate cancer: Flare phenomenon: Bone pain, Urinary tract obstruction (as urinary symptoms), Weakness of lower extremity, Paresthesia (as neurologic symptoms).
Immune system disorders: Hypersensitivity including Anaphylactic reaction, Rash and Pruritus.
Metabolism and nutrition disorders: Decreased appetite.
Psychiatric disorders: Decreased libido, depression.
Nervous system disorders: Paresthesia, Dizziness, Headache, Pituitary Haemorrhage, Seizure.
Cardiac disorders: QT prolongation (see Precautions and Interactions).
Vascular disorders: Hot flush.
Gastrointestinal disorders: Nausea, Vomiting, Diarrhea.
Hepatobiliary disorders: Abnormal liver function test, usually transient.
Skin and subcutaneous tissue disorders: Hyperhydrosis.
Musculoskeletal and connective tissue disorders: Bone pain, decreased bone density, Muscular weakness.
Renal and urinary disorders: Urinary tract obstruction.
Reproductive system and breast disorders: Erectile dysfunction, Testicular atrophy, Gynaecomastia.
General disorders and administration site conditions: Injection site reaction, Oedema.
Endometriosis, Uterine myoma, Breast cancer/Premenopausal breast cancer: Immune system disorders: Hypersensitivity, including Anaphylactic reaction, Rash and Pruritus.
Metabolism and nutrition disorders: Weight fluctuation, Decreased appetite.
Psychiatric disorders: Decreased libido, Affect lability, Depression, Sleep disorder.
Nervous system disorders: Headache, Dizziness, Paresthesia, Pituitary Haemorrhage, Seizure.
Eye disorders: Visual impairment.
Vascular disorders: Hot flush.
Gastrointestinal disorders: Nausea, Vomiting.
Hepatobiliary disorders: Liver function test abnormal, usually transient.
Skin and subcutaneous tissue disorders: Alopecia, Hyperhydrosis.
Musculoskeletal and connective tissue disorders: Arthralgia, Myalgia.
Reproductive system and breast disorders: Breast atrophy, Vulvovaginal dryness, Vulvovaginitis.
General disorders and administration site conditions: Injection site reaction, Oedema.
Enantone L.P. 3.75 mg: Central precocious puberty: 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.
The following convention is used (where available) for the classification of the frequency of an adverse drug reaction (ADR) and is based on the Council for International Organizations of Medical Sciences (CIOMS) guidelines: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to< 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
Immune system disorders: Very rare: Hypersensitivity, Anaphylactic reaction.
Psychiatric disorders: Common: Affect lability.
Nervous system disorders: Common: Headache. Very rare: Pituitary haemorrhage. Frequency not known: Seizure.
Gastrointestinal disorders: Common: Abdominal pain, Nausea, Vomiting.
Skin and subcutaneous tissue disorders: Common: Acne.
Reproductive system and breast disorders: Common: Vaginal haemorrhage, Vaginal 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-dosage. The pituitary suppression should then be determined by an LHRH test.
General disorders and administration site conditions: Common: Injection site reaction.
Enantone L.P. 11.25 mg: Premenopausal breast cancer: Adverse reactions, including abnormalities in laboratory data, were observed in 90 (96.8%) of 93 patients that were evaluated for the safety in the clinical studies conducted in Japan. As for the subjective and objective adverse reactions, symptoms resulting from decreased estrogen, disorder in the administration site, etc. were mainly investigated. Major adverse reactions were feeling of warmth/ hot flashes /feeling of hot flashes/ in 72 patients, headache/dull headache in 45 patients, diaphoresis/night sweats in 18 patients, disorder in the administration site in 42 patients (mainly mild induration), and nausea/vomiting in 21 patients. Administration of Enantone L.P. was discontinued because of feeling of warmth/dull headache/nausea in 1 patient and because of administration site induration/pain in 1 patient.
Also major abnormalities in laboratory data were increased γ-GTP in 16 patients, increased ALT (GPT) in 14 patients, and increased AST (GOT) in 11 patients, etc.
Adverse reactions, including abnormalities in laboratory data, were observed in 280 (95.2%) of 294 patients that were evaluated for the safety in the clinical studies conducted abroad. Major adverse reactions were hot flushes in 245 patients, weight increase in 234 patients, and excessive sweating in 228 patients, etc.
Adverse reactions, including abnormalities in laboratory data, were observed in 121 (19.1%) of 635 patients in the post-marketing investigation of the results of drug use (as of the end of the reexamination period). Major adverse reactions were disorder in the injection site (injection site induration in 40 patients, injection site pain in 17 patients, injection site erythema in 15 patients, injection site swelling in 10 patients), and hot flushes in 35 patients, etc.
Since a depressed state like climacteric disturbance resulting from estrogen reducing effect of Enantone L.P. may occur (0.1% -< 5%), the patient's condition should be closely observed.
Other adverse ractions: See Table 5.

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In Children: 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.
Immune system disorders: Very rare: General allergic reactions (fever, rash, e.g. itching, anaphylactic reactions).
Psychiatric disorders: Common: Emotional lability.
Nervous system disorders: 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.
Gastrointestinal disorders: Common: Abdominal pain / abdominal cramps, nausea, vomiting.
Skin and subcutaneous tissue disorders: Common: Acne.
Reproductive system and breast disorders: Common: 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 dosage. The pituitary suppression should then be determined by an LHRH test.
General disorders and administration site conditions: Common: Injection site reactions.