Dosing & Uses
Dosage Forms & Strengths
lyophilized powder for injection plus diluent
- 0.9mg/vial (Xiaflex)
- 0.92mg/vial (Qwo)
- 1.84mg/vial (Qwo)
Dupuytren Contracture
Xiaflex only
Indicated for Dupuytren contracture with a palpable cord
Inject 0.58 mg into palpable Dupuytren cord with a contracture of metacarpophalangeal (MP) joint or proximal interphalangeal (PIP) joint
If contracture persists 24-72 hr following injection, perform finger extension procedure
May repeat injection and finger extension procedures up to 3 times per cord at 4-week intervals
Inject only 1 cord at a time; if other cords with contractures exist, inject each cord in sequential order
Each vial of drug and sterile diluent should only be used for a single injection; if 2 joints on the same hand are to be treated during a treatment visit, separate vials and syringes should be used for each reconstitution and injection
Approximately 24-72 hr after injection, perform a finger extension procedure if a contracture persists to facilitate cord disruption
May reinject four weeks after the initial injection if MP or PIP contracture still present; may reinject with a single dose of collagenase C histolyticum
2 injections on same hand per treatment visit
- Perform up to 2 injections in the same hand during a treatment visit
- Two palpable cords affecting 2 joints may be injected or 1 palpable cord affecting 2 joints in the same finger may be injected at 2 locations during a treatment visit
- If a patient has other palpable cords with contractures of MP or PIP joints, these cords may be injected at other treatment visits ~4 wk apart
Peyronie Disease
Xiaflex only
Available for treatment of Peyronie disease only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program called the XIAFLEX REMS Program
Indicated in men with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy
Inject 0.58 mg into a Peyronie plaque; if >1 plaque present, inject into the plaque causing the curvature deformity
Treatment course consists of a maximum of 4 treatment cycles; each treatment cycle consists of 2 injection procedures and 1 penile modeling procedure for a maximum of 8 injection procedures and 4 modeling procedures
Perform 2nd injection procedure 1-3 days after the 1st
Interval between treatment cycles is ~6 weeks
Induce a penile erection; to achieve it, may use a single intracavernosal injection of 10 or 20 mcg of alprostadil
With the penis in the erect state, identify and mark the target area in the Peyronie plaque to be injected
The penis should be in flaccid state before injecting
Inject 0.58 mg into target plaque once on each of 2 days, 1 to 3 days apart, according to injection procedure
Perform a penile modeling procedure 1 to 3 days after second injection of each treatment cycle
For each plaque causing the curvature deformity, may administer up to four treatment cycles; may repeat each treatment cycle at approximately six-week intervals; if curvature deformity is <15 degrees after 1st, 2nd, or 3rd treatment cycle, or if further treatment not clinically indicated, do not administer subsequent treatment cycles
If curvature deformity is <15 degrees after 1st, 2nd, or 3rd treatment cycle, or if healthcare provider determines that further treatment not clinically indicated, then do not administer subsequent treatment cycles
Cellulite
Qwo only
Up to twelve 0.07-mg (0.3-mL) SC injections totaling 0.84 mg per treatment area (ie, single buttock)
Treatment visit may consist of up to 2 treatment areas
Repeat q21Days for 3 treatment visits
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (13)
- antithrombin alfa
antithrombin alfa increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- antithrombin III
antithrombin III increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- argatroban
argatroban increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- aspirin
aspirin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- bivalirudin
bivalirudin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- dabigatran
dabigatran increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- dalteparin
dalteparin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- desirudin
desirudin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- enoxaparin
enoxaparin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- fondaparinux
fondaparinux increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- heparin
heparin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- protein C concentrate
protein C concentrate increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
- rivaroxaban
rivaroxaban increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).
Minor (0)
Adverse Effects
>10%
Dupuytren contracture
- Peripheral edema (ie, swelling of injected hand) (73%)
- Contusion (70%)
- Injection site hemorrhage (38%)
- Injection site reaction (35%)
- Pain in injected extremity (35%)
- Tenderness (24%)
- Injection site swelling (24%)
- Pruritus (15%)
- Lymphadenopathy (13%)
Peyronie Disease
- Penile hematoma (65.5%)
- Penile swelling (55%)
- Penile pain (45.4%)
- Penile ecchymoses (14.5%)
Cellulite
- Bruising (84%)
- Pain (48%)
- Nodule (33%)
- Pruritus (15%)
1-10%
Dupuytren contracture
- Skin laceration (9%)
- Lymph node pain (8%)
- Erythema (6%)
- Axillary pain (6%)
Peyronie Disease
- Blood blister (4.5%)
- Penile blister (3.3%)
- Pruritus genital (3.1%)
- Painful erection (2.9%)
- Erectile dysfunction (1.8%)
- Procedural pain (1.6%)
- Injection site vesicles (1.3%)
- Localized edema (1.3%)
- Dyspareunia (1.1%)
- Injection site pruritus (1.1%)
- Nodule (1.1%)
- Suprapubic pain (1.1%)
Cellulite
- Erythema (9%)
- Discoloration (8%)
- Swelling (8%)
- Warmth (3%)
<1%
Peyronie Disease
- Corporal rupture
Postmarketing Reports
Syncope and presyncope
Back pain
Localized skin and soft tissue necrosis, occurring as sequelae of penile hematoma
Cellulite
- Immune system disorders: serious hypersensitivity reactions including anaphylaxis
Warnings
Black Box Warnings
Peyronie disease
- Corporal rupture (penile fracture) was reported as adverse reaction in clinical trials
- Promptly evaluate signs or symptoms reflecting serious penile injury to assess for corporal rupture or severe penile hematoma which may require surgical intervention
- Because of risks of corporal rupture or other serious penile injury, available for the treatment of Peyronie’s disease only through the XIAFLEX REMS Program
Contraindications
Hypersensitivity
Peyronie plaques that involve the penile urethra
Cautions
Do not substitute injectable collagenase products (ie, do not use Xiaflex for cellulite treatment of use Qwo for Dupuytren contracture or Peyronie disease)
Serious hypersensitivity, including anaphylaxis, reported; if hypersensitivity occurs, discontinue and institute appropriate medical therapy
Pruritus experienced especially after more injections
Use with caution in patients with coagulation disorders, including in patients who have received anticoagulant medications other than low- dose aspirin within 7 days of the injection
Administration in patients with abnormal coagulation may result in ecchymosis/contusion or an injection site hemorrhage
Post-injection back pain
- Acute post-injection back pain reactions reported in postmarketing period in patients treated for Peyronie’s disease; these events typically have an onset immediately or within minutes of injection
- The acute lower back pain can be mild to severe in intensity and can radiate to the legs, arms and chest; other systemic symptoms, such as chest pain, headache, and dyspnea, reported along with back pain episodes
- None of the events were reported to occur after the patient’s first injection and a few were reported to occur during a second treatment course
- Reported events typically resolved within 15 minutes, but some lasted up to 30 minutes, and one event lasted 1.5 hours; reported events typically did not require intervention, but some required observation and treatment with analgesics
Dupuytren contracture
- Tendon rupture of other serious injury to the injected extremity reported in clinical trials; avoid injecting into tendons, nerves, blood vessels, or other collagen-containing structure of the hand
- Healthcare providers should be prepared to address hypersensitivity reactions, including anaphylaxis, following injections
- Incidence of skin laceration (22%) was higher when treating 2 concurrent injections compared with up to 3 single injections in the placebo-controlled premarketing trials (9%)
- Postmarketing cases of skin laceration requiring skin graft after finger extension procedures and local skin and soft-tissue necrosis, some requiring skin grafting or, other surgical interventions including finger amputation reported; signs or 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 & Lactation
Pregnancy
Data are not available regarding use in pregnant females to evaluate for a drug- associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal studies
- IV administration to pregnant rats during organogenesis at doses up to 0.13 mg/rat (43x human equivalent dose [HED] on a mg/kg basis) revealed no evidence of fetal harm
Lactation
Data are not available regarding presence in human milk, effects on breastfed children, or on milk production
Following SC injection, systemic concentrations were below the bioanalytical assay limit of quantification
Pregnancy 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.Pharmacology
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
Administration
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
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Santyl topical - | 250 unit/gram ointment |  | |
| Santyl topical - | 250 unit/gram ointment |  | |
| Xiaflex injection - | 0.9 mg vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
collagenase 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 frequently.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 not known whether 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 center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.
MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature. Do not freeze. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised October 2022. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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