symptoms that may reflect serious injury to injected finger/hand should be promptly evaluated because surgical intervention may be required Peyronie Disease Advise patients not to have sex between first and second injections of treatment cycle; patients should wait 2 weeks after second injection of treatment cycle before resuming sexual activity, provided pain and swelling have subsided May cause corporal rupture (penile fracture) or other serious injury to penis; avoid injecting into urethra, nerves, blood vessels, corpora cavernosa or other collagen-containing structures of the penis since may result in possible permanent injury (eg, corporal rupture) If patient experiences severe pain or swelling of the penis, severe purple bruising and swelling of the penis, difficulty urinating or blood in the urine, sudden loss of ability to maintain an erection, should contact health care provider In the postmarketing setting, cases of localized skin and soft tissue necrosis occurring as sequelae of penile hematoma reported; some cases required surgical intervention Syncope and Presyncope Cases of syncope and presyncope reported in postmarketing period in patients treated with this medication Most, but not all, cases in patients with Peyronie’s disease, occurred in association with post- injection penile pain and hematoma, penile pain with spontaneous erections, and pain during micturition; these potential triggers for the syncopal events suggest a vasovagal mechanism. Make Peyronie’s disease patients aware of the potential for penile pain and painful penile hematoma that could trigger syncope and presyncope after treatment with this drug In most cases in patients with Dupuytren’s Contracture, the injection procedure, finger extension procedure, or pain following the procedures were reported as potential triggers for the events, suggesting a vasovagal mechanism; most, but not all cases in patients with Dupuytren’s contracture occurred in the immediate treatment period (injection or finger extension procedure) or within 1-2 days following injection or finger extension procedure If presyncope symptoms occur, patients should remain recumbent until symptoms resolve. Syncope may be associated with bodily injuries, including concussion, head abrasion, and other accidental injuries Cellulite Injection site bruising is common; patients with coagulation disorders or using anticoagulants or antiplatelets (except aspirin <150 mg/day) were excluded from clinical trials Caution if administered to patients with coagulation disorders or coadministered with anticoagulant or antiplatelet agents Drug interaction overview Safety and efficacy when coadministered with anticoagulants (other than low-dose aspirin up to 150 mg/day) within 7 days of administration is unknown Pregnancy Available data from case reports in pregnant woman are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; following injection into a Dupuytren’s cord, systemic concentrations of this product were below the bioanalytical assay limit of quantification Animal data In animal reproduction studies, intravenous administration of collagenase clostridium histolyticum to pregnant rats during organogenesis revealed no evidence of fetal harm with maternal doses up to approximately 27 times maximum recommended human dose (MRHD) on a mg/kg basis Lactation There are no data on presence of collagenase clostridium histolyticum in human milk, effects of collagenase clostridium histolyticum on breastfed infants, or on milk production; following injection into a Dupuytren’s cord, the systemic concentrations of this product were below bioanalytical assay limit of quantification The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from this drug, or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Proteinase that hydrolyzes collagen in its native triple-helical conformation, resulting in lysis of collagen deposits Injection of into a Dupuytren’s cord, which is comprised mostly of collagen, may result in enzymatic disruption of the cord Believed to work for Peyronie’s disease by breaking down the buildup of collagen (a structural protein in connective tissue) that causes the curvature deformity Mechanism for treatment of moderate-to-severe cellulite is unknown Pharmacokinetics Absorption: Not absorbed Xiaflex Preparation Reconstitution of lyophilized powder Must reconstitute lyophilized powder with provided diluent prior to use Remove lyophilized powder and diluent from refrigerator and allow to stand at room temperature for at least 15 min (not to exceed 60 min) Remove flip off cap from each vial, utilize aseptic technique and swab rubber stoppers of each vial with sterile alcohol Use only the supplied diluent for reconstitution (contains calcium required for activity of collagenase clostridium histolyticum Use 1-mL syringe with 0.01 mL gradations and 27-ga 0.5-in needle to withdraw diluent Inject diluent slowly into side of lyophilized powder vial, then slowly swirl solution to ensure al powder has gone into solution Do not invert vial or shake the solution Sterile diluent volume for specific indication Dupuytren contracture MP joints: Reconstitute with 0.39 mL diluent (resulting concentration 0.58 mg/0.25 mL) PIP joints: Reconstitute with 0.31 mL diluent (resulting concentration 0.58 mg/0.2 mL) Peyronie disease Reconstitute with 0.39 mL diluent (resulting concentration 0.58 mg/0.25 mL) Qwo Preparation Before reconstitution, remove vials from refrigerator and let stand at room temperature for at least 15 minutes Inspect vials; lyophilized powder cake should be white in color and intact, showing no signs of erosion; diluent solution should appear colorless and free of particulate matter After removal of the flip-off cap from the vial(s), using aseptic technique swab the rubber stopper and surrounding surface of the vial(s) with sterile alcohol (no other antiseptics should be used) Use only the supplied diluent for reconstitution Using appropriate sized syringe and needle (not supplied), withdraw the amount of supplied diluent based on the number of injection sites Inject diluent slowly into the sides of vial containing lyophilized powder Do not invert or shake solution; slowly swirl solution to ensure that all of the lyophilized powder has gone into solution Sterile diluent volume 1 treatment area: Reconstitute 0.92-mg vial with 4 mL diluent 2 treatment areas: Reconstitute 1.84-mg vial with 8 mL diluent Resulting concentration is 0.23 mg/mL Xiaflex Administration See prescribing information for specific injection techniques for Dupuytren contracture or Peyronie disease Dupuytren contracture: Follow-up visit needed 24-72 hr following injection for finger extension procedure Peyronie disease: Follow-up visit needed 24-72 hr following injection for penile modeling procedure Qwo SC Administration Using 1-mL syringes with removable needles (not supplied), draw up 0.9 mL of the reconstituted solution into each syringe (0.21 mg/0.9 mL) Single treatment visit: Four syringes totaling 0.84 mg Two treatment visit: Eight syringes totaling 1.68 mg Mark injection sites while the patient is standing Inject SC while patient is in prone position Each injection should be administered as three 0.1-mL aliquots to 3 different positions (see prescribing information image for angle and direction of each injection); for a total injection volume of 0.3 mL Injection depth is 0.5 inches (corresponding to the length of the needle) without downward pressure Each treatment area may receive up 12 injections Patient should remain prone for at least 5 minutes after completion Storage Xiaflex Before reconstitution: Refrigerate lyophilized powder for injection and diluent at 2-8ºC (36-46ºF); do not freeze Reconstituted solution: May store at room temperature (20-25ºC [68-77ºF]) up to 1 hr, or refrigerate (2-8ºC [36-46ºF) up to 4 h before administration Qwo Before reconstitution: Refrigerate lyophilized powder and diluent at 2-8ºC (36-46ºF); do not freeze Reconstituted solution: May store at room temperature (20-25ºC [68-77ºF]) up to 8 hr, or refrigerated (2-8ºC [36-46ºF) up to 72 hr before administration BRAND FORM. UNIT PRICE PILL IMAGE Santyl topical- 250 unit/gram ointmentSantyl topical- 250 unit/gram ointmentXiaflex injection- 0.9 mg vialCopyright © 2010 First DataBank, Inc.Select a drug:collagenase clostridium histolyticum topicalcollagenase clostridium histolyticum injectionPrint Patient Educationcollagenase clostridium histolyticum topical COLLAGENASE OINTMENT - TOPICAL (coal-ADGE-ih-naze) COMMON BRAND NAME(S): Santyl USES: This product is used to help the healing of burns and skin ulcers. Collagenase is an enzyme. It works by helping to break up and remove dead skin and tissue. This effect may also help antibiotics to work better and speed up your body's natural healing process. HOW TO USE: This medication is for use on the skin only. It is usually applied once daily or as directed by your doctor. If the dressing becomes soiled, collagenase may be applied more often.To apply, wash hands first. Clean the area as directed by your doctor. Cleaning solutions such as hydrogen peroxide, normal saline, or Dakin's solution may be used. If your doctor has directed you to use an antibiotic powder, apply it first before applying this medication. Use a wooden spatula or a gauze pad to carefully apply the collagenase ointment directly to the affected area. Bandage securely. If you are unclear about how to clean the affected area or apply this medication, consult your doctor.Avoid applying near the eyes. Be careful to apply the ointment only within the affected area. Wash hands thoroughly after applying the ointment. SIDE EFFECTS: Pain or a burning feeling at the affected area may occur. Temporary redness/irritation may also occur in the skin around the affected area. If any of these effects last or get worse, tell your doctor or pharmacist promptly. To avoid redness/irritation in the surrounding skin, be careful to apply the ointment only within the affected area.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Treatment of burns and skin ulcers by breaking up and removing dead skin and tissue may rarely increase the risk for serious infection (sepsis). Tell your doctor right away if you notice any symptoms of serious infection, including: fever/chills, fast breathing (hyperventilation), fast heartbeat, warm skin, weakness.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before using collagenase, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history.Avoid using solutions that contain acid or metal as soaking liquids because these will decrease the effect of collagenase ointment (see also Drug Interactions section).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding. DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: antiseptic skin products (especially those containing heavy metals such as lead, mercury, silver).Skin products containing heavy metals may decrease the effect of collagenase. If the affected area has been exposed to one of these products, wash the area well with normal saline solution before applying this ointment. OVERDOSE: This medicine may be harmful if swallowed. If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control