Active ingredients: Tetracosactide hexacetate
SYNACTHEN 0.25 mg / 1 mL SOLUTION FOR INJECTION
Synacthen package inserts are available for pack sizes:- SYNACTHEN 0.25 mg / 1 mL SOLUTION FOR INJECTION
- SYNACTHEN 1 mg / mL PROLONGED-RELEASE INJECTABLE SUSPENSION FOR INTRAMUSCULAR USE
Why is Synacthen used? What is it for?
Pharmacotherapeutic group
Hormones of the anterior pituitary lobe and analogues - ACTH.
Therapeutic indications
Diagnostic use: Synacthen 0.25 mg / 1 mL (short-acting) is used primarily as a diagnostic tool to evaluate adrenocortical function when adrenal cortex hypofunctionality is suspected.
Therapeutic use: Synacthen 0.25 mg / 1 mL can also be used as a replacement for Synacthen prolonged-release suspension for injection, when tetracosactide infusion is preferable to intramuscular injection.
Note: Unlike Synacthen prolonged-release suspension for injection, Synacthen solution for injection has a short duration of action and, in case of diagnostic use, can be administered both intramuscularly and intravenously.
In contrast, when used as a therapeutic agent, Synacthen 0.25 mg / 1 mL solution for injection is effective only with an intravenous infusion lasting several hours and not with a single dose with short term effect.
Contraindications When Synacthen should not be used
- Hypersensitivity to the active substance, other ACTH (adrenocorticotropic hormones) or to any of the excipients.
- Acute psychosis.
- Infectious diseases.
- Peptic ulcer.
- Treatment-resistant heart failure.
- Cushing's syndrome.
- Primary adrenocortical insufficiency.
- Adrenogenital syndrome.
- Pregnancy and breastfeeding.
- Severe hypertension.
- Severe forms of osteoporosis.
Due to an increased risk of anaphylactic reactions, Synacthen should not be used to treat asthma or other allergic conditions (see "Appropriate precautions for use").
Finally, Synacthen should not be given to patients with ocular herpes simplex, as it can cause corneal perforation.
Precautions for use What you need to know before taking Synacthen
Synacthen should only be administered under medical supervision.
Precautions for use related to tetracosactide
Hypersensitivity reactions (see also "Contraindications")
Patients with a predisposition to allergies (especially asthma) should not be treated with Synacthen unless other therapeutic measures have caused the desired response and the situation is severe enough to warrant treatment.
Synacthen testing should only be performed in patients who have not previously been treated with ACTH drugs. The physician must be ready to implement immediate therapeutic measures in the event of a "possible anaphylactic reaction following a" Synacthen injection.
Before using Synacthen the physician must ascertain whether the patient has a predisposition to allergies (especially asthma). It is also important to establish whether ACTH-based preparations have been used in the past and in this case to ensure that the treatment has not triggered hypersensitivity reactions (see "Contraindications").
If local or systemic hypersensitivity reactions occur during or after an injection (eg severe erythema and pain at the injection site, hives, itching, redness, severe malaise or dyspnoea), treatment with tetracosactide should be discontinued and the use of any ACTH-based preparations should be avoided for the future.
If hypersensitivity reactions occur, they generally occur within 30 minutes of injection, so the patient should be kept under observation for this period.
If a severe anaphylactic reaction occurs, immediately administer epinephrine (0.4-1 mL of a 1 mg / 1 mL solution intramuscularly or 0.1-0.2 mL of the same solution diluted in 10 mL of physiological saline , slowly intravenously) and high doses of intravenous corticosteroids, with repeated administration if necessary.
Precautions for use related to glucocorticoid and mineralocorticoid effects
The water and saline retention resulting from the use of Synacthen can often be avoided or eliminated by prescribing a low-sodium diet. During prolonged treatments it may occasionally be necessary to supplement with potassium. The effect of tetracosactide therapy may be enhanced in patients with hypothyroidism or liver cirrhosis.
Prolonged treatment with tetracosactide may be associated with the development of posterior subcapsular cataracts and glaucoma. Psychological changes (eg euphoria, insomnia, mood and personality changes, severe depression or symptoms of true psychosis) may occur during tetracosactide therapy. Existing emotional instability or psychotic tendencies can also be aggravated.
Synacthen can activate "latent amoebiasis, so it is recommended to rule out" latent or active amoebiasis before starting therapy. If Synacthen is administered to patients with latent tuberculosis or a positive response to tuberculin, close surveillance is required, as a reactivation of the disease may occur. During prolonged therapy such patients should receive chemoprophylaxis.
Patients receiving Synacthen should not be vaccinated against smallpox. Any other immunization techniques should be undertaken with caution due to decreased antibody response.
Use in pediatric age
When the dosage is carefully individualized, Synacthen is unlikely to inhibit the growth of children. However it is good that it is supervised in case of prolonged treatments.
Reversible myocardial hypertrophy may occur during prolonged treatment with high doses, so regular echocardiography in infants and children should be performed (see "Undesirable effects").
The risk / benefit ratio must be carefully evaluated when Synacthen is used in the following conditions: ulcerative colitis, diverticulitis, recent intestinal anastomosis, renal failure, arterial hypertension, predisposition to thromboembolism, osteoporosis, myasthenia gravis.
In patients who sustain an injury or undergo surgery during or in the year following treatment, the associated stress should be treated with an increase or resumption of Synacthen therapy. Additional use of acting corticosteroids may be necessary. quick. Use the lowest effective dose to control the disease being treated. In case it is necessary to reduce the dosage, the reduction should be done gradually.
Prolonged use of Synacthen induces relative insufficiency of the pituitary-adrenal axis, which may persist for several months after discontinuation of treatment. In this case, the advisability of instituting suitable adrenocortical therapy should be considered.
Interactions Which drugs or foods can modify the effect of Synacthen
Since Synacthen results in increased adrenocortical production of glucocorticoids and mineralocorticoids, interactions similar to those seen with these corticosteroids may occur. Patients already being treated with medications for diabetes mellitus or moderate or severe hypertension should adjust the dosages of these medications by starting treatment with Synacthen.
Synacthen contains an active ingredient which may interfere with routine diagnostic tests of athletes (see also "Special warnings"). Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Warnings It is important to know that:
Pregnancy and breastfeeding
Synacthen is contraindicated in pregnancy and during lactation.
Ask your doctor or pharmacist for advice before taking any medicine.
Effects on the ability to drive or use machines
Since Synacthen can have an effect on the central nervous system, patients should be especially careful when driving or using machines.
For those who carry out sporting activities
The use of the drug without therapeutic necessity constitutes doping; it can cause doping effects and cause positive anti-doping tests even for therapeutic doses
Dosage and method of use How to use Synacthen: Dosage
Diagnostic use
Rapid Synacthen test (30 minutes)
Plasma cortisol is measured immediately before and exactly 30 minutes after an i.m. or i.v. injection of 0.25 mg of Synacthen solution for injection.
Adrenocortical function is considered normal if the plasma rate of cortisol increases by at least 200 nmol / L (70 µg / L), that is, if the values recorded 30 minutes after the injection of Synacthen solution for injection exceed 500 nmol / L (180 µg / L).
Therapeutic use
For therapeutic use, as an alternative to Synacthen 1 mg / mL prolonged release suspension for injection, Synacthen solution for injection can be administered as an infusion in glucose (5% or 12.5%) or physiological (0.9% NaCl) solution.
Treatment is started with daily dosing and after about 3 days intermittent therapy is started. The infusion lasts a maximum of 4 hours.
If, for example, 0.5 mg or 1 mg of tetracosactide (= 2 or 4 ampoules of Synacthen) is diluted in 250 mL of infusion fluid, the infusion could be completed in approximately 4 hours at a rate of 20 drops ( 1 mL) per minute.
Adults
The starting dose is 1 mg / day.
Treatment of acute conditions can be started with 1 mg every 12 hours. If acute symptoms are controlled, 1 mg is usually given every 2-3 days. In patients who respond well, the dose can be reduced to 0.5 mg every 2-3 days or 1 mg once a week.
Children
Dosage in infants, young children and school-aged children should be tailored to the effects on the individual child.
With this in mind, the rules below apply:
Infants (28 days-23 months): the initial dose is 0.25 mg / day; the maintenance dose is 0.25 mg every 2-8 days.
Young children (2-5 years): the starting dose is 0.25 mg-0.5 mg / day; the maintenance dose is 0.25 mg-0.5 mg every 2-8 days.
School-age children (6-12 years): the starting dose is 0.25 mg-1 mg / day; the maintenance dose is 0.25 mg-1 mg every 2-8 days.
INSTRUCTIONS FOR OPENING THE VIALS AT PREDETERMINED BREAKAGE
Take the vial as indicated in the drawing with the colored point facing upwards, and break it with a sharp movement.
Overdose What to do if you have taken too much Synacthen
Signs and symptoms
If signs of water retention (weight gain) or excessive activity of the adrenal glands (Cushing's syndrome) occur, treatment with Synacthen should be temporarily interrupted or its dosage reduced.
It is also advisable to notify your doctor immediately or to go to the nearest hospital.
Side Effects What are the side effects of Synacthen
Like all medicines, Synacthen can cause side effects, although not everybody gets them.
Undesirable effects may be related to tetracosactide or to stimulation of glucocorticoid and mineralocorticoid secretion while using Synacthen.
Undesirable effects related to tetracosactide
Hypersensitivity reactions
Tetracosactide can cause hypersensitivity reactions which tend to be more severe (anaphylactic shock) in patients predisposed to allergies (especially asthma) (see "Special warnings" and "Precautions for use"). Hypersensitivity reactions may include skin reactions at the site injection, dizziness, nausea, vomiting, hives, itching, redness, malaise, dyspnoea and angioneurotic edema or Quincke's edema.
Adrenal hemorrhage
Isolated cases have been reported with Synacthen.
Undesirable effects related to glucocorticoid and mineralocorticoid effects
The undesirable effects, described in the table below, are difficult to observe in case of short-term use of Synacthen as a diagnostic, but can be observed when Synacthen is used in the therapeutic indications.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
Warning: do not use the medicine after the expiry date indicated on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
Store between 2 ° C and 8 ° C.
To keep the vial out of light, keep it in the original package.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN
Composition and pharmaceutical form
Composition
One vial contains: Active ingredient: tetracosactide hexacetate 0.27 mg (equivalent to 0.25 mg of tetracosactide base). Excipients: acetic acid, sodium acetate, sodium chloride, water for injections.
Pharmaceutical form and content
Injectable solution.
Carton of 1 ampoule of 0.25 mg / 1 mL.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SYNACTHEN 0.25 MG / 1 ML SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One vial contains: tetracosactide hexacetate 0.27 mg (equivalent to 0.25 mg of tetracosactide base).
For the full list of excipients see 6.1.
03.0 PHARMACEUTICAL FORM
Injectable solution.
Colorless aqueous solution for intramuscular injection, injection or intravenous infusion.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Diagnostic use: Synacthen 0.25 mg / 1 ml (short-acting) is mainly used as a diagnostic tool to evaluate adrenocortical function when adrenal cortex hypofunctionality is suspected.
Therapeutic use: Synacthen 0.25 mg / 1 ml can also be used as a replacement for Synacthen prolonged-release suspension for injection, when tetracosactide infusion is preferable to i.m. injection.
Note: Unlike Synacthen prolonged-release solution for injection, Synacthen solution for injection has a short duration of action and, in case of diagnostic use, can be administered both intramuscularly and intravenously.
On the contrary, when used as a therapeutic agent, Synacthen 0.25 mg / 1 ml solution for injection is only effective with an intravenous infusion lasting several hours and not with a single dose with short term effect.
04.2 Posology and method of administration
Diagnostic use
Rapid Synacthen test (30 minutes)
Plasma cortisol is measured immediately before and exactly 30 minutes after an i.m. or i.v. injection of 0.25 mg of Synacthen solution for injection.
Adrenocortical function is considered normal if the plasma rate of cortisol increases by at least 200 nmol / l (70 mcg / l), i.e. if the values recorded 30 minutes after the injection of Synacthen solution for injection exceed 500 nmol / l (180 mcg / l).
If the rapid test provides inconclusive results, or if the purpose is to determine the functional reserve of adrenocortical, the 5-hour test with Synacthen prolonged-release suspension for injection can be performed (see relevant Summary of Product Characteristics).
Therapeutic use
For therapeutic use, as an alternative to Synacthen 1 mg / 1ml prolonged-release suspension for injection, Synacthen solution for injection can be administered as an infusion in glucose (5% or 12.5%) or physiological (0.9% NaCl) solution ( v. 6.2 "Incompatibility").
Treatment is started with daily dosing and after about 3 days intermittent therapy is started. The infusion lasts a maximum of 4 hours.
If, for example, 0.5 mg or 1 mg of tetracosactide (= 2 or 4 ampoules of Synacthen) is diluted in 250 ml of infusion fluid, the infusion could be completed in approximately 4 hours at a rate of 20 drops ( 1 ml) per minute.
Adults
The starting dose is 1 mg / day.
Treatment of acute conditions can be started with 1 mg every 12 hours. If acute symptoms are controlled, 1 mg is usually given every 2-3 days. In patients who respond well, the dose can be reduced to 0.5 mg every 2-3 days or 1 mg once a week.
Children
Dosage in infants, young children and school-aged children should be tailored to the effects on the individual child.
With this in mind, the rules below apply:
Infants (28 days-23 months): the starting dose is 0.25 mg / day; the maintenance dose is 0.25 mg every 2-8 days
Small children (2-5 years): the starting dose is 0.25 mg-0.5 mg / day; the maintenance dose is 0.25 mg-0.5 mg every 2-8 days
School-age children (6-12 years): the starting dose is 0.25 mg-1 mg / day; the maintenance dose is 0.25 mg-1 mg every 2-8 days
04.3 Contraindications
Hypersensitivity to the active substance, other ACTH (adrenocorticotropic hormones) or to any of the excipients;
- acute psychosis;
- infectious diseases;
- peptic ulcer;
- therapy-resistant heart failure;
- Cushing's syndrome;
- primary adrenocortical insufficiency;
- adrenogenital syndrome;
- pregnancy and breastfeeding
- severe hypertension;
- severe forms of osteoporosis
Due to an increased risk of anaphylactic reactions, Synacthen should not be used to treat asthma or other allergic conditions (see section 4.4).
Finally, Synacthen should not be given to patients with ocular herpes simplex, as it can cause corneal perforation.
04.4 Special warnings and appropriate precautions for use
Synacthen should only be administered under medical supervision.
Special warnings and precautions for use related to tetracosactide
Hypersensitivity reactions (see also section 4.3).
Patients with a predisposition to allergies (especially asthma) should not be treated with Synacthen unless other therapeutic measures have caused the desired response and the situation is severe enough to warrant treatment.
Synacthen testing should only be performed in patients who have not previously been treated with ACTH drugs. The physician must be ready to implement immediate therapeutic measures in the event of a "possible anaphylactic reaction following a" Synacthen injection.
Before using Synacthen the physician must ascertain whether the patient has a predisposition to allergies (especially asthma). It is also important to establish whether ACTH preparations have been used in the past and in this case to ensure that the treatment has not triggered hypersensitivity reactions (see section 4.3).
If local or systemic hypersensitivity reactions occur during or after an injection (eg severe erythema and pain at the injection site, hives, itching, redness, severe malaise or dyspnoea), treatment with tetracosactide should be discontinued and the use of any ACTH preparations should be avoided for the future.
If hypersensitivity reactions occur, they generally occur within 30 minutes of injection, so the patient should be kept under observation for this period.
If a severe anaphylactic reaction occurs, immediately administer epinephrine (0.4-1 ml of a 1 mg / 1 ml solution by im or 0.1-0.2 ml of the same solution diluted in 10 ml of physiological saline , slowly intravenously) and high doses of intravenous corticosteroids, repeated as needed.
Special warnings and precautions for use related to glucocorticoid and mineralocorticoid effects
The water and saline retention resulting from the use of Synacthen can often be avoided or eliminated by prescribing a low-sodium diet. During prolonged treatments it may occasionally be necessary to supplement with potassium.
The effect of tetracosactide therapy may be enhanced in patients with hypothyroidism or liver cirrhosis.
Prolonged treatment with tetracosactide may be associated with the development of posterior subcapsular cataracts and glaucoma.
Psychological changes (eg, euphoria, insomnia, mood and personality changes, severe depression, or symptoms of actual psychosis) may occur during tetracosactide therapy. Existing emotional instability or psychotic tendencies can also be aggravated.
Synacthen can activate "latent amoebiasis, so it is recommended to rule out" latent or active amoebiasis before starting therapy. If Synacthen is administered to patients with latent tuberculosis or a positive response to tuberculin, close surveillance is required, as a reactivation of the disease may occur. During prolonged therapy such patients should receive chemoprophylaxis.
Patients treated with Synacthen should not be vaccinated against smallpox. Any other immunization techniques should be undertaken with caution due to decreased antibody response.
Use in pediatric age
When the dosage is carefully individualized, Synacthen is unlikely to inhibit the growth of children. However it is good that it is supervised in case of prolonged treatments.
Reversible myocardial hypertrophy may occur during prolonged treatment with high doses, so regular echocardiography in neonates and children should be performed (see section 4.8).
The risk / benefit ratio must be carefully evaluated when Synacthen is used in the following conditions: ulcerative colitis, diverticulitis, recent intestinal anastomosis, renal failure, arterial hypertension, predisposition to thromboembolism, osteoporosis, myasthenia gravis.
In patients who sustain an injury or undergo surgery during or in the year following treatment, the associated stress should be treated with an increase or resumption of Synacthen therapy. Additional use of acting corticosteroids may be necessary. quick. Use the lowest effective dose to control the disease being treated. In case it is necessary to reduce the dosage, the reduction should be done gradually. Prolonged use of Synacthen induces relative insufficiency of the pituitary-adrenal axis, which may persist for several months after discontinuation of treatment. consider the opportunity to institute suitable adrenocortical therapy.
04.5 Interactions with other medicinal products and other forms of interaction
Since Synacthen causes an increase in adrenocortical production of glucocorticoids and mineralocorticoids, interactions similar to those observed with these corticosteroids may occur. Patients already being treated with medications for diabetes mellitus or moderate or severe hypertension should adjust the dosages of these medications by starting treatment with Synacthen.
Synacthen contains an active ingredient that can interfere with routine diagnostic tests on athletes
04.6 Pregnancy and lactation
Synacthen is contraindicated in pregnancy and during breastfeeding.
04.7 Effects on ability to drive and use machines
Since Synacthen can have an effect on the central nervous system, patients should be especially careful when driving or using machines.
04.8 Undesirable effects
Undesirable effects may be related to tetracosactide or to stimulation of glucocorticoid and mineralocorticoid secretion while using Synacthen.
Undesirable effects related to tetracosactide
Hypersensitivity reactions
Tetracosactide can cause hypersensitivity reactions which tend to be more severe (anaphylactic shock) in patients predisposed to allergies (especially asthma) (see section 4.4). Hypersensitivity reactions may include skin reactions at the injection site, dizziness, nausea, vomiting, hives, itching, redness, malaise, dyspnoea, and angioneurotic edema or Quincke's edema.
Adrenal hemorrhage
Isolated cases have been reported with Synacthen
Undesirable effects related to glucocorticoid and mineralocorticoid effects
The undesirable effects, described in the table below, are difficult to observe with short-term use of Synacthen as a diagnostic, but can be observed when Synacthen is used for therapeutic use.
04.9 Overdose
Signs and symptoms
If signs of fluid retention (weight gain) or excessive adrenocortical activity (Cushing's syndrome) occur, treatment with Synacthen should be temporarily interrupted or its dosage reduced.
Treatment
There is no known antidote. Implement symptomatic treatment.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Therapeutic group: anterior pituitary lobe hormones and analogues - ACTH.
ATC code: H01AA02.
Tetracosactide is made up of the first 24 amino acids of the natural adrenocorticotropic hormone ACTH (1 mg of Synacthen corresponds for activity to about 100 IU of ACTH). minor, of androgens, which explains its therapeutic effect in conditions that respond to treatment with glucocorticoids. However, its pharmacological activity is not comparable to that of corticosteroids since, in case of treatment with ACTH (as opposed to treatment with a single glucocorticoid) the tissues are exposed to a physiological spectrum of corticosteroids.
The site of action of ACTH is the plasma membrane of the adrenal cortical cells, where it binds to a specific receptor. The hormone-receptor complex activates adenyl cyclase, stimulating the production of cyclic adenosine monophosphate and thus promoting the synthesis of pregnenolone from cholesterol. The various corticosteroids are produced from pregnenolone through different enzymatic cycles.
05.2 "Pharmacokinetic properties
Tetracosactide has an apparent volume of distribution of approximately 0.4 L / kg.
The plasma elimination half-life, after an i.v. injection, is approximately 7 minutes in the first hour (first phase), approximately 37 minutes in the following hour (second phase) and then approximately 3 hours (terminal phase).
In serum, tetracosactide is rapidly degraded by enzymatic hydrolysis, first to inactive oligopeptides, then to free amino acids. Its rapid elimination from the plasma is probably due not so much to this process, which is relatively slow, as to the fact that the active substance is rapidly concentrated in the adrenals and kidneys.
After i.v. of 131I-labeled b1-24-corticotropin, 95-100% of the radioactivity is excreted in the urine within 24 hours.
05.3 Preclinical safety data
Acute toxicity after i.v. in mice (LD50 = 190 + 29 mg / kg body weight) and dog (LD50 = 10 mg / kg and 30 mg / kg body weight is negligible. In mice, 8 days of treatment resulted in an LD50 of 255 and 8.7 mg / kg body weight. Chronic toxicity of 0.3 mg / kg, 0.1 mg / kg, 0.03 mg / kg body weight was studied on 4 groups for a total of 48 beagles versus one group treated with placebo for 6/13 weeks. All dosing regimens were tolerated. No fatal cases occurred. The only pathological evidence of ACTH activity was a "dose-dependent increase in gland enlargement. adrenal.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Acetic acid, sodium acetate, sodium chloride, water for injections.
06.2 Incompatibility
Ringer's acetate solution is not suitable for infusion.
Only freshly prepared solutions should be used and, for stability reasons, the infusion duration cannot exceed 4 hours.
It is not recommended to add Synacthen to blood or plasma for transfusions as it can be broken down by enzymes in the blood.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
Store between 2 and 8 ° C.
To keep the vial out of light, keep it in the original package.
06.5 Nature of the immediate packaging and contents of the package
1 type I colorless glass vial of 1 ml
06.6 Instructions for use and handling
Not relevant.
07.0 MARKETING AUTHORIZATION HOLDER
sigma-tau Industrie Farmaceutiche Riunite S.p.A.
Viale Shakespeare, 47 - 00144 Rome
Dealership for sale:
BIOFUTURA PHARMA S.p.A.
Via Pontina km 30,400 - 00040 Pomezia (Rome)
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 020780045
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
First authorization: 19.04.2004
Renewal: June 2010
10.0 DATE OF REVISION OF THE TEXT
February 2014
