Active ingredients: Heparin (calcium heparin)
CALCIPARINE 20,000 IU / 4 ml solution for injection for intravenous use
Why is Calciparin used? What is it for?
PHARMACO-THERAPEUTIC CATEGORY
Antithrombotic.
THERAPEUTIC INDICATIONS
Prophylaxis and therapy of venous and arterial thromboembolic disease
Contraindications When Calciparin should not be used
Sodium or calcium heparin should not be used in patients:
- with hypersensitivity to the active substance or to any of the excipients;
- with severe thrombocytopenia;
- in which clotting tests such as whole blood clotting time and activated partial thromboplastin time (APTT) cannot be conducted at appropriate intervals. This contraindication refers to "sodium or calcium heparin at anticoagulant doses; there is generally no need to monitor coagulation parameters in patients receiving heparin at low prophylactic doses (less than or equal to 0.2 ml 3 times a day for "calcium heparin or 15,000 units per day for sodium heparin);
- with an uncontrolled bleeding state; if it is associated with disseminated intravascular coagulation (DIC), the use of heparin will be evaluated in the specific clinical context;
- loco-regional anesthesia for elective surgical procedures is contraindicated in patients receiving heparin at anticoagulant doses;
- with hemorrhagic cerebrovascular accidents;
- in the presence of organic lesions with a high risk of bleeding, the use of heparin will be evaluated in the specific clinical context considering the risk-benefit ratio in the individual case;
- period of therapeutic activity of antivitamins K.
Precautions for use What you need to know before taking Calciparin
The treatment of elderly people, people with a history of allergy or with hepatic or renal insufficiency requires special surveillance.
Hemorrhages
They can occur anywhere in the body in patients receiving sodium and calcium heparin. An unexplained drop in hematocrit, a drop in blood pressure, or any other sign or symptom not attributable to other causes should raise suspicion of a bleeding event. Sodium or calcium heparin should be used with extreme caution in conditions where there is a risk of bleeding. Some of these conditions are:
- cardiovascular: sub-acute bacterial endocarditis, severe hypertension not controlled by antihypertensive therapy;
- haematological: conditions associated with an increased tendency to bleed such as haemophilic syndromes or deficiency of coagulation factors, thrombocytopenia, thrombocytopathies and some haemorrhagic vascular purpura (type Rendu-Osler disease);
- gastrointestinal: peptic ulcer, esophagitis or erosive gastritis, inflammatory bowel disease in the active phase, other gastroenterological pathologies with haemorrhagic risk, continuous drainage of the stomach or small intestine;
- surgical: during and immediately after: a) rachycentesis or spinal anesthesia or b) major surgery involving the brain, spine or eye;
- others: liver diseases with alterations in coagulation parameters and / or esophageal varices or gastropathy from portal hypertension at high risk of bleeding, threat of abortion.
Coagulation test
When sodium or calcium heparin is administered in anticoagulant doses, their dosage should be adjusted with frequent coagulation tests. If coagulation tests are above the therapeutic range or if bleeding occurs, the dose should be reduced or, if appropriate, heparin should be discontinued. (see "Dose, method and time of administration).
Given the transient action of sodium heparin, haemocoagulation tests will return to normal limits within a few hours; longer times may be required for calcium heparin.
Heparin-induced thrombocytopenia
Thrombocytopenia is a well-known complication of sodium or calcium heparin therapy and can appear 4 to 10 days after starting treatment, but also earlier in the case of previous heparin-induced thrombocytopenia. In 10 - 20% of patients, a mild thrombocytopenia (platelet count greater than 100,000 / mm3), which may remain stable or regress, even if heparin administration is continued.
In some cases instead (from 0.3 to 3% of cases) a more severe form (type II heparin thrombocytopenia), immune-mediated, characterized by the formation of antibodies against the heparin-platelet factor 4 complex can be determined. they may develop new thrombus associated with thrombocytopenia, resulting from the "irreversible aggregation of platelets induced by" heparin, the so-called "white thrombus syndrome".
This process can lead to serious thromboembolic complications such as skin necrosis, gangrene of the extremities which may in some cases require amputation, myocardial infarction, pulmonary embolism, stroke and sometimes death. Therefore, the administration of sodium or calcium heparin should be discontinued further that for the onset of thrombosis, even if the patient develops a new thrombosis or a worsening of a previous thrombosis. "heparin, with an alternative anticoagulant. The use of low molecular weight heparins in these cases is risky due to the possibility of cross reactivity, as is that of an immediate introduction of oral anticoagulant therapy (described cases of worsening of thrombosis). Therefore thrombocytopenia of any nature must be carefully monitored. If the platelet count falls below 100000 / mm3, or if recurrent thrombosis occurs, sodium or calcium heparin should be discontinued. A platelet count should be evaluated before treatment and twice weekly thereafter for the first month in case of prolonged administration.
Decreased sensitivity to heparin:
a decreased sensitivity to sodium or calcium heparin can occur in fever, thrombosis, thrombophlebitis, infections with a thrombotic tendency, inflammatory states, sometimes during myocardial infarction, cancer, antithrombin III deficiency and in post-surgical patients. of heparin treatment at anticoagulant doses to avoid intramuscular administration of drugs.
In patients undergoing spinal or epidural anesthesia, epidural analgesia or lumbar puncture, prophylaxis with low doses of unfractionated heparin may very rarely be associated with spinal or epidural hematomas which can lead to prolonged or permanent paralysis. The risk is increased by the use of indwelling peridural catheters for continuous infusion, by the concomitant intake of drugs that affect haemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), inhibitors of platelet aggregation or anticoagulants, from trauma or from repeated spinal puncture, by the presence of an underlying haemostatic disorder and by old age. The presence of one or more of these risk factors must be carefully evaluated before proceeding with this type of anesthesia / analgesia, during prophylaxis with unfractionated heparins.
As a rule, the insertion of the spinal catheter must be carried out at least 8-12 hours after the last administration of unfractionated heparin (usually calcium) at low prophylactic doses. Subsequent doses should not be administered until at least 2-4 hours have elapsed after catheter insertion or removal, or further delayed or not administered in the case of hemorrhagic aspirate during initial spinal or epidural needle placement. Removal of an "indwelling" epidural catheter should be done as far away as possible (approximately 8-12 hours) from the last prophylactic dose of heparin performed under anesthesia.
If it is decided to administer unfractionated heparin before or after a "epidural or spinal anesthesia, extreme caution and frequent monitoring should be performed to identify signs and symptoms of neurological alterations such as: lumbar pain, sensory and motor deficit (numbness and weakness lower limbs), changes in bladder or bowel function Nursing staff should be instructed to identify these signs and symptoms.
Patients should be instructed to notify medical or nursing staff immediately if any of the above symptoms occur. If signs or symptoms of epidural or spinal hematoma are suspected, an immediate diagnosis should be made and treatment that includes spinal cord decompression initiated.
Interactions Which drugs or foods can modify the effect of Calciparin
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Combinations with drugs that increase the risk of bleeding
Oral anticoagulants
Sodium or calcium heparin with anticoagulant dosage may slightly prolong the prothrombin time (increase of about 0.5 of the INR). This aspect must be considered when evaluating this parameter, especially when the heparin therapy is combined with the oral anticoagulant one. Great clinical-laboratory attention is recommended (frequent evaluation of PT and APTT) in case of combined use of unfractionated heparin at anticoagulant doses with these drugs.
Antiplatelet agents
Drugs such as acetylsalicylic acid, salicylates, dipyridamole, hydroxychloroquine, ticlopidine, glycoprotein Iib / IIIa inhibitors or other drugs that interfere with platelet aggregation (which is the main haemostatic defense of the heparinized patient) can induce bleeding and should be used with great caution in patients treated with sodium or calcium heparin, especially if at anticoagulant doses.
Thrombolytics
Possible increased risk of bleeding.
Dextran 40 (injectable)
Increased risk of bleeding (due to inhibition of platelet function)
Non-steroidal anti-inflammatory drugs (NSAIDs)
Increased risk of bleeding (inhibition of platelet function and damaging effect on the gastro-duodenal mucosa).
Associations requiring special precautions
Other concomitant therapies
Digitalis, tetracyclines, nicotine, glucocorticoids, penicillins, phenothiazines, antihistamines can partially reduce the anticoagulant action of heparin.
Mixtures of CALCIPARIN with solutions of other drugs can give rise to precipitates and loss of at
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
Heparin does not cross the placental barrier. CALCIPARINE must be used under particular surveillance during pregnancy, especially in the last trimester and in the immediate post-partum, due to the risk of utero-placental haemorrhage.
Pregnancy
CALCIPARINE is not excreted in breast milk.
Effects on ability to drive and use machines
CALCIPARINE does not affect the ability to drive or use machines
Dosage and method of use How to use Calciparin: Dosage
Intravenous administration: Do not inject intramuscularly.
According to medical prescription.
When sodium or calcium heparin is administered at an anticoagulant dose, their dosage should be determined by frequent coagulation tests. If coagulation tests are above the therapeutic range or if bleeding occurs, the dose should be reduced or, if appropriate, heparin should be discontinued (see Precautions for use).
Antagonistic action of protamine
Protamine serves for the rapid neutralization of heparin activity in the event of significant bleeding (see "Overdose"). The amount required depends on the blood level of heparin administered and the time elapsed from the injection. The administration of protamine must be done by slow intravenous infusion; 50 mg of protamine neutralizes 5,000 IU of heparin. The dose of protamine that must be administered to neutralize a heparin bolus decreases in proportion to the time elapsed from the administration of the bolus (100% of the dose immediately after the bolus, 50% after 1 hour, 25% after 2 hours).
The protamine dose to be administered in case of continuous infusion of heparin is the one useful to neutralize the IU of heparin infused in the last 4 hours.
Overdose What to do if you have taken too much Calciparin
Accidental overdose of heparin can cause bleeding complications.
The risk of bleeding is proportional to the level of hypocoagulability and to the patient's vascular integrity.
Neutralization of heparinemia is achieved immediately by means of an intravenous injection of protamine sulphate which neutralizes heparin to form an inactive complex: see Dose, method and time of administration: "Protamine antagonistic action".
However, the use of this antidote must take into account its side effects.
In case of accidental ingestion / intake of an overdose of CALCIPARINE, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of CALCIPARIN, ask your doctor or pharmacist.
Side Effects What are the side effects of Calciparin
Like all medicines, CALCIPARIN can cause side effects, although not everybody gets them.
Adverse reactions are listed below by organ, organ / system and by frequency.
Frequencies are defined as: very common (≥1 / 10), common (≥1 / 100,
Disorders of the blood and lymphatic system
Common: haemorrhage. Hemorrhage is the main complication that can occur during treatment with sodium or calcium heparin, especially at anticoagulant doses.
Hemorrhagic phenomena have been recorded both in the form of hematoma at the injection site, and at various localization: hematoma of the surgical wound, bleeding of the gastro-intestinal tract, retro-peritoneal or intracranial haemorrhages, haematuria, epistaxis, gingival haemorrhage, subconjunctival haemorrhage and hematoma eyelid, haemorrhoidal bleeding, minor bleeding.
Clotting times above the therapeutic range or small bleeding during therapy can usually be resolved by reducing the dosage or, if necessary, temporarily stopping the drug.
Gastro-enteric or urinary bleeding during anticoagulation therapy may indicate the presence of an underlying occult lesion. Bleeding can occur in any part of the body but certain specific bleeding complications may be difficult to detect:
a) Adrenal haemorrhage, resulting in acute adrenal insufficiency has been described during anticoagulation therapy. Therefore, treatment should be discontinued if the patient develops signs and symptoms of acute adrenal insufficiency;
b) ovarian haemorrhage (corpus luteum) has developed in women of childbearing age on long or short-term anticoagulant therapy;
c) retroperitoneal haemorrhages.
In any case of no minor haemorrhage, heparin therapy will be interrupted and in case of major haemorrhage the heparin still in circulation will be neutralized by administering protamine (see "Dose, method and time of administration").
Rare: eosinophilia, thrombocytopenia. There have been reports of thrombocytopenia in patients receiving sodium or calcium heparin (see "Precautions for use"). Although mild and clinically insignificant, thrombocytopenia is sometimes accompanied by severe thrombotic and / or embolic complications.
Disorders of the immune system
Common: generalized hypersensitivity reactions with chills, fever, and hives and, more rarely, asthma, rhinitis, lacrimation, shock
Endocrine pathologies
Rare: osteoporosis - after long-term therapy with high doses, suppression of aldosterone synthesis.
Metabolism and nutrition disorders
Rare: rebound hyperlipidaemia on discontinuation of therapy.
Nervous system disorders:
Uncommon: anorexia, dizziness, headache, paraesthesia, stroke.
Frequency not known: postural instability.
Cardiac pathologies
Rare: Bradycardia-asystole, declining edema.
Vascular pathologies
Uncommon: acute hypotension.
Frequency not known: acute ischemia of the upper limb.
Gastrointestinal disorders
Uncommon: nausea, vomiting, epigastralgia, gastritis, periodontal disease, haemorrhoids.
Frequency not known: diarrhea.
Skin and subcutaneous tissue disorders
Uncommon: eczema, alopecia, transient delayed alopecia.
Rare: skin necrosis.
Frequency not known: maculo-papular or impetiginous rash, exudative erythema, urticarial toxicoderma, eczematous dermatitis, polymorphic erythema, punctate eruption.
Musculoskeletal and connective tissue disorders
Rare: cramps, low back pain.
Diseases of the reproductive system and breast
Rare: priapism.
General disorders and administration site conditions
Common: Local irritation with pruritus, erythema, skin nodules, mild pain, hematoma, ulceration, subcutaneous abscess or phlebitis may follow subcutaneous heparin administration.
These complications are much more common after intramuscular administration, so this last use is absolutely to be avoided, even occasionally.
Frequency not known: asthenia, malaise, pain, chest tightness, thrombophlebitis, sweating.
Diagnostic tests
Rare: increased transaminases.
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 tell your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
COMPOSITION
1 vial of 4 ml contains:
Active principle
Calcium heparin * 20,000 I.U.
Excipient
Water for injections
* (purified from EDTA)
PHARMACEUTICAL FORM AND CONTENT
Solution for injection intravenously. 10 ampoules of 4 ml (20,000 I.U.)
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
CALCIPARINE SOLUTION FOR INJECTION FOR SUBCUTANEOUS USE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
a) CALCIPARINE 0.2 ml (5,000 I.U.)
Each unit dose of 0.2 ml contains:
Calcium heparin (purified from EDTA) 5,000 I.U.
b) CALCIPARINE 0.5 ml (12,500 I.U.)
Each 0.5 ml unit dose contains:
Calcium heparin (purified from EDTA) 12,500 I.U.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Solution for injection for subcutaneous use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Prophylaxis and therapy of venous and arterial thromboembolic disease.
04.2 Posology and method of administration
According to medical prescription.
When sodium or calcium heparin is administered at an anticoagulant dose, their dosage should be determined by frequent coagulation tests. If coagulation tests are above the therapeutic range or if bleeding occurs, the dose should be reduced or, if appropriate, heparin should be discontinued (see section 4.4 Special warnings and precautions for use).
Antagonistic action of protamine
Protamine serves for the rapid neutralization of heparin activity in the event of significant bleeding (see section 4.9 Overdose). The amount required depends on the blood level of heparin administered and the time elapsed from the injection. The administration of protamine must be done by slow intravenous infusion; 50 mg of protamine neutralizes 5,000 IU of heparin. The dose of protamine that must be administered to neutralize a heparin bolus decreases in proportion to the time elapsed from the administration of the bolus (100% of the dose immediately after the bolus, 50% after 1 hour, 25% after 2 hours).
The protamine dose to be administered in case of continuous infusion of heparin is the one useful to neutralize the IU of heparin infused in the last 4 hours.
In case of treatment with subcutaneous calcium heparin at an anticoagulant dose, a dose of protamine should be administered to neutralize about 25% of the last heparin dose, repeating this administration every 3 hours up to 4 times.
HOW TO FILL THE SYRINGE
Make sure that the contents of the vial are not collected in the neck: in this case transfer it to the bottom by repeatedly shaking the vial and then keeping it in an upright position for at least 30 "in order to allow the complete collection of the liquid on the bottom.
Then operate as follows:
- break the vial
- aspirate with the needle attached to the syringe avoiding the formation of air bubbles.
If these occur:
1) Place the syringe in a vertical position with the needle pointing upwards
2) suck in an "additional quantity of" air
3) tap the syringe lightly and repeatedly with a fingernail in order to collect all the air in the upper part of the syringe
4) let the air out.
INJECTION TECHNIQUE
The injection, using a 1 ml syringe graduated in tenths and a needle 45/100 thick and 10 mm long, must be carried out in the subcutaneous cellular tissue, preferably in the buttocks or in the region of the iliac crest, both on the right and to the left.
The needle must be introduced entirely, perpendicularly and not tangentially, into the thickness of a skin fold made between the thumb and the index finger of the operator.
The fold must be maintained throughout the duration of the injection. If the introduction of the needle resulted in severe pain (injury to a vessel), withdraw it and inject from the opposite side.
04.3 Contraindications
Sodium or calcium heparin should not be used in patients:
• with hypersensitivity to the active substance or to any of the excipients;
• with severe thrombocytopenia;
• in which clotting tests such as whole blood clotting time and activated partial thromboplastin time (APTT) cannot be conducted at appropriate intervals. This contraindication refers to "sodium or calcium heparin at anticoagulant doses; there is generally no need to monitor coagulation parameters in patients receiving heparin at low prophylactic doses (less than or equal to 0.2 ml 3 times a day for "calcium heparin or 15,000 units per day for sodium heparin);
• with an uncontrolled bleeding state; if it is associated with disseminated intravascular coagulation (DIC), the use of heparin will be evaluated in the specific clinical context;
• loco-regional anesthesia for elective surgical procedures is contraindicated in patients receiving heparin at anticoagulant doses;
• with haemorrhagic cerebrovascular accidents;
• in the presence of organic lesions with a high risk of bleeding, the use of heparin will be evaluated in the specific clinical context considering the risk-benefit ratio in the individual case;
• period of therapeutic activity of K antivitamins.
04.4 Special warnings and appropriate precautions for use
The treatment of elderly people, people with a history of allergy or with hepatic or renal insufficiency requires special surveillance.
Hemorrhages:
They can occur anywhere in the body in patients receiving sodium and calcium heparin. An unexplained drop in hematocrit, a drop in blood pressure, or any other sign or symptom not attributable to other causes should raise suspicion of a bleeding event.
Sodium or calcium heparin should be used with extreme caution in conditions where there is a risk of bleeding. Some of these conditions are:
• cardiovascular: sub-acute bacterial endocarditis, severe hypertension not controlled by anti-hypertensive therapy;
• haematological: conditions associated with an increased tendency to bleed such as haemophilic syndromes or deficiency of coagulation factors, thrombocytopenia, thrombocytopathies and some haemorrhagic vascular purpura (type Rendu-Osler disease);
• gastrointestinal: peptic ulcer, esophagitis or erosive gastritis, inflammatory bowel disease in an active phase, other gastroenterological pathologies at risk of bleeding, continuous drainage of the stomach or small intestine;
• surgical: during and immediately after:
a) rachycentesis or spinal anesthesia o
b) major surgery involving the brain, spine or eye;
• others: liver diseases with alterations in coagulation parameters and / or esophageal varices or gastropathy from portal hypertension with high bleeding risk, threat of abortion.
Coagulation test
When sodium or calcium heparin is administered in anticoagulant doses, their dosage should be adjusted with frequent coagulation tests. If coagulation tests are above the therapeutic range or if bleeding occurs, the dose should be reduced or, if appropriate, heparin should be discontinued (see section 4.2 Posology and method of administration).
Given the transient action of sodium heparin, haemocoagulation tests will return to normal limits within a few hours; longer times may be required for calcium heparin.
Heparin-induced thrombocytopenia
Thrombocytopenia is a well-known complication of sodium or calcium heparin therapy and may appear 4 to 10 days after starting treatment, but also earlier in the case of previous heparin-induced thrombocytopenia. In 10 - 20% of patients, a mild thrombocytopenia (platelet count greater than 100,000 / mm3), which may remain stable or regress, even if heparin administration is continued.
In some cases instead (from 0.3 to 3% of cases) a more severe form (type II heparin thrombocytopenia), immune-mediated, characterized by the formation of antibodies against the heparin-platelet factor 4 complex can be determined. they may develop new thrombus associated with thrombocytopenia, resulting from the "irreversible aggregation of platelets induced by" heparin, the so-called "white thrombus syndrome". This process can lead to severe thromboembolic complications such as skin necrosis, gangrene of the extremities which may require amputation in some cases, myocardial infarction, pulmonary embolism, stroke and sometimes death.
Therefore, the administration of sodium or calcium heparin should be stopped in addition to the onset of thrombosis, even if the patient develops a new thrombosis or a worsening of a previous thrombosis.
The continuation of anticoagulant therapy, for thrombosis that is the cause of the treatment in progress or for a new appearance or worsening, should be undertaken, after heparin suspension, with an alternative anticoagulant.
The use of low molecular weight heparins in these cases is risky due to the possibility of cross reactivity, as is that of an immediate introduction of oral anticoagulant therapy (described cases of worsening of thrombosis). Therefore thrombocytopenia of any nature must be carefully monitored. If the platelet count falls below 100,000 / mm3, or if recurrent thrombosis occurs, sodium or calcium heparin should be discontinued. A platelet count should be evaluated before treatment and twice weekly thereafter for the first month in case of prolonged administration.
Decreased sensitivity to heparin:
a decreased sensitivity to sodium or calcium heparin can occur in fever, thrombosis, thrombophlebitis, infections with a thrombotic tendency, inflammatory states, sometimes during myocardial infarction, cancer, antithrombin III deficiency and in post-surgical patients.
In case of heparin treatment at anticoagulant doses, avoid the intramuscular administration of drugs.
In patients undergoing spinal or epidural anesthesia, epidural analgesia or lumbar puncture, prophylaxis with low doses of unfractionated heparin may very rarely be associated with spinal or epidural hematomas which can lead to prolonged or permanent paralysis. The risk is increased by the use of indwelling peridural catheters for continuous infusion, by the concomitant intake of drugs that affect haemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), inhibitors of platelet aggregation or anticoagulants, from trauma or from repeated spinal puncture, by the presence of an underlying haemostatic disorder and by old age. The presence of one or more of these risk factors must be carefully evaluated before proceeding with this type of anesthesia / analgesia, during prophylaxis with unfractionated heparins.
As a rule, the insertion of the spinal catheter must be carried out at least 8-12 hours after the last administration of unfractionated heparin (usually calcium) at low prophylactic doses. Subsequent doses should not be administered until at least 2-4 hours have elapsed after catheter insertion or removal, or further delayed or not administered in the case of hemorrhagic aspirate during initial spinal or epidural needle placement. Removal of an "indwelling" epidural catheter should be done as far away as possible (approximately 8-12 hours) from the last prophylactic dose of heparin performed during anesthesia.
If it is decided to administer unfractionated heparin before or after a "epidural or spinal anesthesia, extreme caution and frequent monitoring should be performed to identify signs and symptoms of neurological alterations such as: lumbar pain, sensory and motor deficit (numbness and weakness lower limb), changes in bladder or bowel function Nursing staff should be instructed to identify these signs and symptoms Patients should be instructed to notify medical or nursing staff immediately if any of the above symptoms occur.
If signs or symptoms of epidural or spinal hematoma are suspected, an immediate diagnosis should be made and treatment that includes spinal cord decompression initiated.
04.5 Interactions with other medicinal products and other forms of interaction
Combinations with drugs that increase the risk of bleeding
Oral anticoagulants
Sodium or calcium heparin with anticoagulant dosage may slightly prolong the prothrombin time (increase of about 0.5 of the INR). This aspect must be considered when evaluating this parameter, especially when the heparin therapy is combined with the oral anticoagulant one. Great clinical-laboratory attention is recommended (frequent evaluation of PT and APTT) in case of combined use of unfractionated heparin at anticoagulant doses with these drugs.
Antiplatelet agents
Drugs such as acetylsalicylic acid, salicylates, dipyridamole, hydroxychloroquine, ticlopidine, glycoprotein IIb / IIIa inhibitors or other drugs that interfere with platelet aggregation (which is the main haemostatic defense of the heparinized patient) can induce bleeding and should be used with great caution in patients treated with sodium or calcium heparin, especially if at anticoagulant doses.
Thrombolytics
Possible increased risk of bleeding.
Dextran 40 (injectable)
Increased risk of bleeding (due to inhibition of platelet function).
Non-steroidal anti-inflammatory drugs (NSAIDs)
Increased risk of bleeding (inhibition of platelet function and damaging effect on the gastro-duodenal mucosa).
Associations requiring special precautions
Other concomitant therapies
Digitalis, tetracyclines, nicotine, glucocorticoids, penicillins, phenothiazines, antihistamines can partially reduce the anticoagulant action of heparin.
Mixtures of CALCIPARIN with solutions of other drugs can lead to precipitates and loss of activity.
04.6 Pregnancy and lactation
Pregnancy
Heparin does not cross the placental barrier. CALCIPARINE must be used under particular surveillance during pregnancy, especially in the last trimester and in the immediate post-partum period, due to the risk of utero-placental haemorrhage.
Feeding time
CALCIPARINE is not excreted in breast milk.
04.7 Effects on ability to drive and use machines
CALCIPARINE does not affect the ability to drive or use machines.
04.8 Undesirable effects
Adverse reactions are listed below by organ, organ / system and by frequency.
Frequencies are defined as: very common (≥1 / 10), common (≥1 / 100,
Disorders of the blood and lymphatic system
Common: haemorrhage. Hemorrhage is the main complication that can occur during treatment with sodium or calcium heparin, especially at anticoagulant doses.
Hemorrhagic phenomena have been recorded both in the form of hematoma at the injection site, and at various localization: hematoma of the surgical wound, bleeding of the gastro-intestinal tract, retro-peritoneal or intracranial haemorrhages, haematuria, epistaxis, gingival haemorrhage, subconjunctival haemorrhage and hematoma eyelid, haemorrhoidal bleeding, minor bleeding.
Clotting times above the therapeutic range or small bleeding during therapy can usually be resolved by reducing the dosage or, if necessary, temporarily stopping the drug.
Gastro-enteric or urinary bleeding during anticoagulation therapy may indicate the presence of an underlying occult lesion. Bleeding can occur in any part of the body but certain specific bleeding complications may be difficult to detect:
a) adrenal haemorrhage, resulting in acute adrenal insufficiency has been described during anticoagulation therapy. Therefore, treatment should be discontinued if the patient develops signs and symptoms of acute adrenal insufficiency;
b) ovarian haemorrhage (corpus luteum) has developed in women of childbearing age on long or short-term anticoagulant therapy;
c) retroperitoneal haemorrhages.
In any case of no minor haemorrhage, heparin therapy will be interrupted and in case of major haemorrhage the heparin still in circulation will be neutralized by administering protamine (see section 4.2 "antagonist action of protamine").
Rare: eosinophilia, thrombocytopenia. Cases of thrombocytopenia have been reported in patients receiving sodium or calcium heparin (see section 4.4 Special warnings and precautions for use). Although mild and clinically insignificant, thrombocytopenia is sometimes accompanied by severe thrombotic and / or embolic complications.
Disorders of the immune system
Common: generalized hypersensitivity reactions with chills, fever, and hives and, more rarely, asthma, rhinitis, lacrimation, shock.
Endocrine pathologies
Rare: osteoporosis - after long-term therapy with high doses, suppression of aldosterone synthesis.
Metabolism and nutrition disorders
Rare: rebound hyperlipidaemia on discontinuation of therapy.
Nervous system disorders:
Uncommon: anorexia, dizziness, headache, paraesthesia, stroke.
Frequency not known: postural instability.
Cardiac pathologies
Rare: Bradycardia-asystole, declining edema.
Vascular pathologies
Uncommon: acute hypotension.
Frequency not known: acute ischemia of the upper limb.
Gastrointestinal disorders
Uncommon: nausea, vomiting, epigastralgia, gastritis, periodontal disease, haemorrhoids.
Frequency not known: diarrhea.
Skin and subcutaneous tissue disorders
Uncommon: eczema, alopecia, transient delayed alopecia.
Rare: skin necrosis.
Frequency not known: maculo-papular or impetiginous rash, exudative erythema, urticarial toxicoderma, eczematous dermatitis, polymorphic erythema, punctate eruption.
Musculoskeletal and connective tissue disorders
Rare: cramps, low back pain.
Diseases of the reproductive system and breast
Rare: priapism.
General disorders and administration site conditions
Common: Local irritation with pruritus, erythema, skin nodules, mild pain, hematoma, ulceration, subcutaneous abscess or phlebitis may follow subcutaneous heparin administration.
These complications are much more common after intramuscular administration, so this last use is absolutely to be avoided, even occasionally.
Frequency not known: asthenia, malaise, pain, chest tightness, thrombophlebitis, sweating.
Diagnostic tests
Rare: increased transaminases.
04.9 Overdose
Accidental overdose of heparin can cause bleeding complications.
The risk of bleeding is proportional to the level of hypocoagulability and to the patient's vascular integrity.
Neutralization of heparinemia is achieved immediately by means of an intravenous injection of protamine sulphate which neutralizes heparin to form an inactive complex (see section 4.2 "Protamine antagonist action").
However, the use of this antidote must take into account its side effects.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antithrombotic.
ATC code B01AB01.
CALCIPARIN subcutaneous and a concentrated solution of calcium heparin (purified from EDTA). This calcium salt is specifically intended for the subcutaneous heparin treatment: in fact, the calcium heparin, being already saturated with calcium, does not displace this ion from the vessels, therefore, when injected under the skin, it respects the integrity of the capillaries and allows a slow gradual reabsorption , resulting in a lasting and effective heparinemia, without excessive peaks (which protects against bleeding related to excessive hypocoagulability) or sudden flexions. The effect occurs about 30 minutes after the injection and is maintained, when the dosage is adequate, for about 12 hours.
05.2 Pharmacokinetic properties
A subcutaneous injection of 15,000 IU of calcium heparin results in a heparinemia of 0.2 IU / ml (therefore already effective) between the 15th and 30th minutes. The heparin concentration progressively increases up to the 3rd hour and stabilizes around the 0.5 IU / ml between the 3rd and 7th hours.
Subsequently, the heparinemia progressively decreases to reach, at the 12th hour, a value of about 0.15 I.U./ml still capable, in many cases, of inducing a state of hypocoagulability.
05.3 Preclinical safety data
The toxicity of heparin is low (the LD50 in the intravenous mouse is 2 g / kg). Very high doses can be administered to experimental animals without significant toxic effects: if trauma is avoided, no haemorrhagic phenomena appear either.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
a) CALCIPARINE 0.2 ml (5,000 I.U.)
Water for injections q.s. to 0.2 ml
b) CALCIPARINE 0.5 ml (12,500 I.U.)
Water for injections q.s. to 0.2 ml
06.2 Incompatibility
Not known.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Box containing 10 ampoules of 0.2 ml (5,000 I.U.).
1 ml clear glass vials with pre-breaking.
Box containing 10 ampoules of 0.5 ml (12,500 I.U.).
1 ml clear glass vials with pre-breaking.
06.6 Instructions for use and handling
07.0 MARKETING AUTHORIZATION HOLDER
ITALFARMACO S.p.A. - Viale Fulvio Testi 330 - 20126 MILAN
08.0 MARKETING AUTHORIZATION NUMBER
5,000 IU / 0.2ml solution for injection for subcutaneous use 10 ampoules
AIC n. 022579128
12,500 IU / 0.5ml solution for injection for subcutaneous use 10 ampoules
AIC n. 022579193
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Authorization: 17/07/1987
Renewal: 01/06/2010
10.0 DATE OF REVISION OF THE TEXT
AIFA DETERMINATION N. 179/2013 OF 17/06/2013
