Safacto AF
Recombinant Human Coagulation Factor VIII - Moroctocog Alfa
Specifications of Safacto AF
| Brand Name | Safacto AF |
| Generic Name | Moroctocog Alfa |
| Strength | 250, 500, and 1000 international units |
| Composition and Quantity | Histidine | 6 mg/mL Sodium chloride | 36 mg/mL Sucrose | 12 mg/mL Calcium chloride dihydrate | 1 mg/mL Tween 80 | 0.4 mg/mL |
| Dosage Form | Powder for solution for infusion |
| Physical Characteristics | White lyophilized powder |
| Reconstitution Solvent | 0.9% Sodium chloride |
| Volume of Solvent | 4 mL |
| Packaging | Each box contains one kit including: one vial of factor VIII, one vial of solvent for factor VIII, one 5 mL syringe, two alcohol swabs, one adhesive bandage, one vial adapter with filter, and one venipuncture set. 24 boxes are packed in one carton. |
Mechanism of Action of Safacto AF
Safacto AF is produced using DNA recombinant technology, acting similarly to coagulation factor VIII in the body. Factor VIII becomes active within the body and, as a cofactor, assists activated factor IX in converting inactive factor X to active factor X. Active factor X then converts prothrombin to thrombin, which converts fibrinogen to fibrin clots. In patients with hemophilia A, there is a severe decrease in the activity of coagulation factor VIII. Injection of Safacto AF increases the plasma level of factor VIII and can temporarily alleviate the coagulation problem in patients with hemophilia A.
Indications and Contraindications - Safacto AF
Indications Safacto AF is used for the control and prevention of Hemophilia Type A or classical Hemophilia. This product does not contain von Willebrand factor and should not be used in patients with a deficiency of this factor. Contraindications The use of Safacto AF has not been studied in patients with a history of hypersensitivity to hamster proteins and should not be used in these individuals. Additionally, Safacto AF should not be used in individuals with a history of hypersensitivity to any of its components. Use with Caution Under the Following Conditions Development of Factor VIII Inhibitors: In patients receiving Factor VIII, antibodies against Factor VIII (inhibitors) may develop. Therefore, patients should be monitored during treatment and the level of inhibitors should be determined using specific biological tests expressed in Bethesda units (BU). If, after receiving an appropriate dose, the plasma level of Factor VIII does not reach the expected level or if bleeding is not controlled, the level of inhibitors should be measured. These inhibitors are of the IgG immunoglobulin type. The development of inhibitors is most likely to occur during the first 20 exposures. Allergy: As with any intravenous injectable product, intravenous administration of Safacto AF may cause allergic reactions. Therefore, patients should be familiar with the symptoms of hypersensitivity reactions such as: hives, skin rashes, widespread hives, chest tightness, difficulty breathing, wheezing, low blood pressure, and anaphylactic shock. When an allergy or anaphylactic reaction occurs, the use of Safacto AF should be immediately discontinued and appropriate treatment for controlling shock and allergic reactions should be initiated. Patients who have experienced allergic reactions must be tested for the presence of inhibitors. Since Safacto AF contains very small amounts of hamster protein (less than 10 ppm), the likelihood of hypersensitivity reactions to non-human mammalian proteins is very low.
Use During Pregnancy and Breastfeeding - Safacto AF
Use During Pregnancy Savactoo is classified as Category C for use during pregnancy. Because hemophilia A is rare in women, there have been no studies on factor VIII during pregnancy. Therefore, it is unclear whether factor VIII could adversely affect fertility or the human fetus. However, factor VIII products can be used during pregnancy if necessary and under the guidance of a physician. Use During Breastfeeding As hemophilia A is rare in women, the use of Savactoo during breastfeeding has not been studied, and it is unclear whether this drug is secreted in breast milk. However, if necessary and upon the physician's recommendation, this drug can be used during breastfeeding.
Drug Interactions and Side Effects - Safacto AF
Drug Interactions
No official studies have been conducted on interactions between Safacto and other drugs. To date, no interactions have been observed between recombinant factor VIII and other medications.
Side Effects
Since Safacto has not yet been widely marketed, no side effects have been observed. However, based on similar drugs such as Refacto and Xyntha, the side effects are categorized according to their effects on various organs as follows:
1- Immune System Disorders
Anaphylactic reactions (0.01%)
2- Metabolism and Nutrition Disorders
Anorexia (0.01%)
3- Nervous System Disorders
Headache (1%) and ≤ 0.01%
Dizziness, drowsiness, altered taste, and neuropathy (0.01%)
4- Vascular Disorders
Vasodilation (0.1%) and ≤ 0.01%
Bleeding/hematoma, hypotension, thrombophlebitis, flushing, and congestion (0.01%)
5- Cardiac Disorders
Chest pain, tachycardia, palpitations (0.01%)
6- Respiratory Disorders
Shortness of breath, cough (0.01%)
7- Gastrointestinal Disorders
Vomiting (1%) and ≤ 0.01%
Nausea, diarrhea (0.1%) and ≤ 0.01%
Abdominal pain (0.01%)
8- Skin and Subcutaneous Disorders
Hives (0.1%) and ≤ 0.01%
Itching and redness, sweating (0.01%)
9- Connective Tissue and Muscular Disorders
Joint pain, muscle pain (0.1%) and ≤ 0.01%
10- General Disorders and Injection Site Reactions
Weakness, pain at the injection site, reactions at the injection site, injection site inflammation, fever (0.1%) and ≤ 0.01%
Chills and feeling cold, muscle weakness, difficulty in finding veins (0.01%)
11- Eye Disorders
Blurred vision (0.01%)
12- Factor VIII Inhibitors
*Patients with ≤ 50 inhibitor titer (10%)
*Patients with > 50 inhibitor titer (10%) and ≤ 1%
# These side effects include all hemophilia-related adverse events observed during the study, regardless of the studied drug. Other side effects during the study are related to the drug and hemophilia.
* The frequency of side effects is calculated per infusion. For patients undergoing surgery who received continuous infusions, each day of continuous infusion is considered one infusion.
The most common side effect per infusion reported is vomiting. Most side effects are mild to moderate in severity. As with any protein product administered intravenously, there is a possibility of hypersensitivity reactions. Symptoms of hypersensitivity include hives, widespread hives, chest tightness, shortness of breath, wheezing, hypotension, and anaphylaxis. If hypersensitivity reactions occur, the infusion should be stopped, and supportive treatment for the patient should be initiated.
Dosage and Proper Use of the Medication - Safacto AF
Treatment with Safacto should be under the supervision of a specialist in the treatment of Hemophilia A. The duration of this medication depends on the severity of Factor VIII deficiency, the location and extent of bleeding, and the clinical condition of the patient. Each patient may respond differently to Factor VIII, resulting in varying clinical improvement compared to other patients. This indicates differences in the half-life of Factor VIII among individuals.
Dosage adjustment should be based on the patient's clinical response. In the presence of inhibitors, higher doses of Safacto or alternative treatments may be required. Dosage adjustment for patients with liver or kidney failure has not yet been studied. Safacto is used in both adults and children.
The amount of Factor VIII administered is expressed in international units (IU), corresponding to the WHO international standard for Factor VIII activity. One international unit of Factor VIII corresponds to the amount of Factor VIII activity in one milliliter of normal human plasma. The required dosage of Factor VIII is calculated based on the average of one international unit of Factor VIII per kilogram of body weight, which can approximately increase the plasma Factor VIII level by 2 IU/dl. The required dose is calculated using the following formula:
Required units (IU) = Body weight (kg) X Desired percentage increase in Factor VIII level (%) X 0.5 IU/kg
Dosage During Bleeding or Surgery
In case of bleeding or surgery, the dose of Safacto should be calculated according to the mentioned formula to ensure that Factor VIII activity does not fall below the normal plasma level during the surgery.
Dosage for Prevention
For prevention or reduction of bleeding frequency in patients with Hemophilia A, doses of 10 to 50 international units of Factor VIII per kilogram of body weight (10-50 IU/kg) should be administered at least twice a week.
Instructions for Using Safacto
Safacto is for single-use only for each patient, and any remaining vial should be discarded. Treatment with Safacto should be supervised by a specialist in Hemophilia A. Safacto is administered intravenously (IV) after dissolving the lyophilized powder with the appropriate solvent (4 mL of 0.9% sodium chloride). For infusion of Safacto, use the infusion set provided in the kit. The prepared product should be used immediately or within 3 hours after preparation. Safacto should be injected intravenously over a few minutes. The infusion rate should be defined and determined based on patient comfort. Safacto contains polysorbate 80, which causes the release of di(2-ethylhexyl)phthalate (DEHP) from polyvinyl chloride (PVC). Therefore, care should be taken in preparing and injecting Safacto, especially avoiding long-term exposure to PVC.
Preparation of the Injectable Solution
Always wash your hands thoroughly before preparing and injecting the solution. During the preparation of the solution, aseptic conditions must be maintained. All materials and equipment used to dissolve the Safacto powder and administer it should be used immediately after sterilization to minimize contact with the surrounding environment.
1- Mixing Safacto Powder with Solvent
– First, bring the vial containing the Safacto powder and the vial containing the solvent to room temperature.
– Remove the plastic cap from the vial containing Safacto powder and the vial containing the solvent to expose the central stopper.
– Clean the stopper surfaces of both vials with the alcohol swabs included in the kit or another disinfectant. Ensure the stopper surfaces do not come into contact with your hands or any other surfaces.
– Remove the vial adapter from its packaging but do not remove it from the packaging itself.
– Place the adapter onto the stopper of the Safacto vial and push it downward to pierce the stopper with the adapter's needle.
– Take the 5 mL syringe from the kit and remove it from its packaging.
– Remove the needle cap and insert the needle into the stopper of the solvent vial.
– Then, draw all of the solvent (4 mL) into the syringe.
– Keep the filled syringe inside the vial until ready for the next step.
– Remove the cap from the adapter on the Safacto vial.
– Remove the syringe containing the solvent from the solvent vial.
– Carefully remove the needle from the syringe and place the syringe's hub onto the adapter's hub, twisting it clockwise to secure it.
– Gently push the syringe plunger downward to transfer all the solvent into the Safacto vial.
– While keeping the syringe inside the vial, gently swirl the vial to dissolve the product.
– The prepared solution should be visually inspected. The solution must be clear, colorless, and free of any particles. If not, discard the solution and use a new kit.
Note: If you are using more than one vial for a patient, prepare additional vials following the above method.
– Remove the syringe from the vial while keeping the vial adapter attached.
– Then, take a larger syringe (10 mL or larger, not included in the kit) with the needle removed and attach it to the adapter hub, twisting it to secure it.
– Invert the vial and transfer the contents to the larger syringe by pulling the syringe plunger.
Note: Transfer the contents of all Safacto vials to the larger syringe using the above method.
– Then, gently twist the syringe counterclockwise to detach the syringe from the adapter hub.
Note: If you do not intend to inject the contents of the syringe immediately, replace the syringe cap without letting the syringe tip come into contact with your hands or any other surfaces. Store the syringe in the refrigerator and use the product within 3 hours. Discard the product if not used within 3 hours.
2- Intravenous Injection of Safacto
– Apply a tourniquet around the patient’s arm. Then disinfect the injection site with the alcohol pad included in the kit.
– Insert the infusion set needle into the patient’s vein. Remove the tourniquet. Then insert the syringe containing the product into the infusion set and empty the syringe over a few minutes to administer the medication at a specified rate. The infusion rate should be adjusted by the doctor or nurse based on the patient’s comfort.