Collagenase Clostridium Histolyticum - Mechanism of Action, Indications, Dosage, and Adverse Drug Reactions

Overview:

Clostridium histolyticum is a bacteria that produces an enzyme called collagenase. It helps break down collagen plaques in treating Peyronie's disease and Dupuytren's contracture (an abnormal thickening of the hand's palm tissue). The topical preparation is applied to debride necrotic tissue resulting from burns or long-term ulcers. In December 2013, the FDA (Food and Drug Administration) approved using the Collagenase Clostridium histolyticum (CCH) to treat Peyronie's disease. This resulted from two large investigations called the Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies (IMPRESS), which were randomized and placebo-controlled. In February 2010, the Collagenase Clostridium histolyticum (CCH) was initially approved; however, in 2013, it was also approved for Peyronie's disease. The FDA's approval, which offers a successful non-surgical therapy alternative, represents a major turning point in managing Peyronie's disease.

Drug Group

The drug Collagenase Clostridium histolyticum (CCH) is a combination of two Clostridium histolyticum Collagenases (AUX-I and AUX-II), which aid in the breakdown of thickened tissue in diseases such as Peyronie's disease and Dupuytren's contracture. It is a biotech medication that fits within the class of protein-based therapies. On drug classification platforms, CCH is occasionally included under "miscellaneous uncategorized agents."

Indications

Collagenase Clostridium histolyticum is a blend of two bacterial collagenases used for:

• The management of adult patients with palpable cord Dupuytren's contracture.

• The treatment for adult males diagnosed with Peyronie's disease who have a palpable plaque and a curvature deformity that is at least 30 degrees when treatment begins.

Contraindications

• Penile urethral Peyronie's plaques.

• Hypersensitivity to collagenase utilized in other therapeutic applications or Collagenase Clostridium histolyticum in the past.

Dosage Forms and Available Strengths

Collagenase Clostridium histolyticum is available as single-use glass vials that contain 0.9 mg (milligrams) of Collagenase Clostridium histolyticum, a sterile lyophilized powder, and a sterile diluent for reconstitution.

Warnings and Precautions

• Tendon Rupture or Severe Damage to the Injected Finger or Hand: Avoid injecting Collagenase Clostridium histolyticum into the hand's tendons, nerves, blood vessels, or any other structure that contains collagen. Injections into these tissues risk causing long-term harm, such as lacerations in the skin, ligament damage, or tendon rupture.

• Corporal Rupture or Other Severe Damage to the Penis: Persistent damage like a corporeal rupture (penile fracture) could arise from injection into the structures like the urethra, blood vessels, nerves, corpora cavernosa (the spongy tissue observed in the vagina or penis), or any other collagen-containing tissue of the penis, so avoid injecting into these structures.

• Hypersensitivity Responses, Including Anaphylaxis: After administering Collagenase Clostridium histolyticum injections, medical personnel need to be ready to handle hypersensitivity events, including anaphylaxis (a common medical emergency and potentially fatal acute hypersensitivity reaction).

• Individuals With Coagulation Abnormalities: Use with caution, especially in individuals who have had low-dose Aspirin or other anticoagulant drugs within seven days of the injection.

• Acute Post-injection Back Pain Reactions: Keep an eye on the patients and offer palliative care if required. Treat the patient's curvature deformity with the fewest treatment cycles required.

• Syncope and Presyncope: Inform patients that syncope (fainting) and presyncope (the feeling that an individual is going to pass out or faint) may occur as a result of pain following an injection. Patients experiencing presyncope should stay in a reclining position until their symptoms subside.

For Patients

What Is Peyronie's Disease?

Fibrous scar tissue in the penis is caused by Peyronie's disease, a condition that causes painful erections and a curved penis. Penis shrinking, scar tissue, and erection issues are among the symptoms. Unknown causes are present, although risk factors include genetic disorders, medical issues, and recurrent penile injuries. Age and family history are risk factors. Erectile dysfunction, difficulty in sexual relations, and long-term untreated disorders can all lead to these issues.

How Effective Is Collagenase Clostridium Histolyticum?

Peyronie's disease in adult males can be effectively treated with the Collagenase Clostridium histolyticum (CCH). The physical and psychosocial elements of the condition were improved by the Collagenase Clostridium histolyticum, according to two double-blind, global phase III studies. Numerous real-world studies attest to its therapeutic success, with 38 percent of men reporting a decrease of fifty percent or more and 64 percent of men reporting a reduction of at least 25 percent in penis curvature. Clinical studies have shown that the Collagenase Clostridium histolyticum is safe and effective, reducing penile curvature and plaque consistency and improving patient satisfaction.

What Are the Clinical Uses of Collagenase Clostridium Histolyticum?

Adult women's buttocks with cellulite, Peyronie's disease, and Dupuytren's contracture can all be treated with the Collagenase Clostridium histolyticum injection. It can be challenging to straighten fingers due to the painless thickening and stiffness of the tissue under the skin in the palm. It belongs to the class of drugs called enzymes. By identifying a tissue chord, the injection treats the disease. Peyronie's disease and Dupuytren's contracture are disorders in which the body's fibrous tissue is broken down, enabling the penis and fingers to straighten. Fibrous bands are released in women with cellulite, which repositions fat cells and promotes collagen formation.

How Is Collagenase Clostridium Histolyticum Administered?

• A physician can inject a mixture of powder and liquid called a Collagenase Clostridium histolyticum injection. Cellulite, Peyronie's disease, and Dupuytren's contracture are all treated with it. The injection is given subcutaneously into the buttocks, into the plaque producing the penis curve, or beneath the skin of the affected hand. The doctor will determine the optimum injection site to treat the particular condition. The affected disease is treated with the injection subcutaneously.

• Treatment for Dupuytren's contracture is keeping the injected hand elevated until bedtime and not bending or straightening the fingers following the injection. The day following the injection, go back to the doctor's office to examine the hand and have the finger extended to cut the tendon. More injections can be required if the issue does not get better. Wait for the doctor's instructions before engaging in vigorous activity with the injected hand. Wear a splint at night for four months and perform daily finger exercises. Carefully follow the doctor's directions, and ask questions if any areas need to be clarified.

• Treatment for Peyronie's disease is injecting Collagenase Clostridium histolyticum into the penis once and then again one to three days later. One to three days following the second injection, patients must return to the doctor's clinic for a penile modeling operation. After that, patients should spend the next six weeks at home stretching and straightening their penis. Patients should carefully follow their doctor's recommendations and ask questions if any points are unclear. Until patients are cleared to restart following each treatment cycle, these individuals should refrain from having intercourse in between injections. Individuals should also not strain their stomach muscles while receiving treatment. Depending on how the patient reacts to the injection, doctors may need to administer up to three more treatment cycles.

• Collagenase Clostridium histolyticum injections, up to 12 per area and two each visit, are used in the treatment of cellulite in the buttocks. Three visits are required for a total of 21 days of repeated treatments.

What Are the Side Effects of Collagenase Clostridium Histolyticum?

Injections of the Collagenase Clostridium histolyticum may have adverse effects. Inform the physician if any or all of these symptoms worsen or persist:

Regarding patients taking the Collagenase Clostridium histolyticum for Dupuytren's contracture:

• Discomfort in the treated hand.

• Redness, warmth, swelling, soreness, bruising, or bleeding around the injection site.

• Itching in the treated hand.

• Uncomfortable, enlarged glands in the elbow or underarm area.

Regarding men undergoing Peyronie's disease treatment with the Collagenase Clostridium histolyticum:

• Sensitivity in the vicinity of the injection site (along and above the penis).

• Blisters where the injection was made.

• A lump where the injection was made.

• Variations in the color of the penis's skin.

• Penis or scrotal irritation

• Painful erection.

• Erection issues.

• Severe headache.

• Discomfort during sexual activity.

For females undergoing Collagenase Clostridium histolyticum (QWO) treatment for cellulite:

• Pain in the treated buttock.

• Redness, warmth, swelling, hardness, changes in skin color, or bruises around the injected area.

Certain adverse effects of the Collagenase Clostridium histolyticum may be dangerous. Call the doctor right away if patients exhibit any of these symptoms or seek emergency care:

• Rash.

• Hives.

• Breathing or swallowing difficulties.

• Hoarseness.

• Chest discomfort.

• Lower back discomfort advances to the arms, legs, feet, and chest.

• Muscle spasms.

• Swelling in the hands, feet, ankles, eyes, throat, tongue, lips, and lower limbs.

• Fever, chills, sore throat, cough, and other infection-related symptoms.

• Tingling, numbness, or worsening discomfort in the hand or finger treated (either following the injection or the follow-up appointment).

Dupuytren's contracture is treated with injections of the Collagenase Clostridium histolyticum; however, this may result in hand damage that needs surgery or is permanent. If patients have trouble using the treated hand or bending over, speak with the doctor about the possible adverse effects.

What Are the Things to Inform the Doctor Before Taking Collagenase Clostridium Histolyticum?

• If patients are allergic to Collagenase Clostridium histolyticum injection, collagenase ointment, collagenase injection's contents, other medications, or any combination of these, let the doctor and pharmacist know. For an ingredient list, consult the pharmacist.

• Inform the physician and pharmacist about any additional prescription and over-the-counter drugs, vitamins, dietary supplements, and herbal remedies patients now take or intend to use. The doctor might need to carefully monitor for any negative effects or adjust the dosages of the medications.

• Let the doctor know if patients have an infection in the afflicted area. The physician will likely advise against using Collagenase Clostridium histolyticum injections to treat cellulitis.

• Inform the physician if patients now have or have previously had a bleeding disorder that interferes with their ability to form clots, such as using anticoagulant drugs seven days before getting a collagenase injection (for example, Warfarin, Enoxaparin, Aspirin more than 150 mg daily, etc.). Additionally, let the doctor know if patients have ever had an injection of the Collagenase Clostridium histolyticum for a different illness.

• Patients should be aware that injecting the Collagenase Clostridium histolyticum can result in lightheadedness, dizziness, and fainting. This is more likely to occur if patients have pain either right away following the injection or one to two days later. After receiving an injection of the Collagenase Clostridium histolyticum, if patients experience lightheadedness or fainting, patients should stay still until their symptoms subside.

• Inform the doctor if patients are nursing a baby, intend to get pregnant, or are already pregnant. Contact the physician if patients become pregnant after having an injection of the Collagenase Clostridium histolyticum.

Dietary Considerations:

Maintain the same diet unless advised by the doctor.

Missed Dose:

Consult the doctor for instructions if patients miss a Collagenase Clostridium histolyticum (CCH) dosage, as treatment plans may be affected by missed appointments. Maintaining regular communication is essential to successful treatment.

Overdose:

An overdose of the Collagenase Clostridium histolyticum necessitates supportive care and symptomatic therapy because it may produce severe local consequences, such as tendon or corporal ruptures.

Storage and Handling:

Vials containing the Collagenase Clostridium histolyticum and diluent should be refrigerated, not frozen. The reconstituted Collagenase Clostridium histolyticum solution can be refrigerated or stored at room temperature.

For Doctors

What Are the Pharmacological Aspects of Collagenase Clostridium Histolyticum?

1. Pharmacodynamics

Collagenase breaks down collagen, which helps cure diseases like cellulite, Peyronie's disease, burns, and contractures.

2. Mechanism of Action

The elasticity and function of the skin are impacted by Peyronie's disease, cellulite, and Dupuytren's contracture. Cellulite is a fibrotic disorder that causes the buildup of dermal septae and subcutaneous fat; Peyronie's disease is a fibrous lesion in the tunica albuginea; and Dupuytren's contracture is a fibroproliferative disease that causes collagen deposition in the hands, limiting movement. By hydrolyzing the triple-helical structure of collagen, collagenase enzyme treatment tackles these disorders by causing the lysis of collagen deposits and the release of necrotic tissue and plaques.

3. Pharmacokinetics

• Absorption: In volunteers given one dose of the Collagenase Clostridium histolyticum combination product at a dose of up to 3.36 mg (milligrams) in four body areas, serum concentrations of clostridium type I collagenase (AUX-I) and clostridium type II collagenase (AUX-II) were found to be under the lower limit of quantitation of 5 ng/mL (nanograms per milliliter) and 25 ng/mL, respectively.

• Distribution: It is unknown if collagenase is present in bodily fluids, absorbed by particular organs, or can cross the blood-brain barrier. Studies examining systemic pharmacokinetics have not assessed its volume of distribution. Collagenase Clostridium histolyticum will likely cause localized degradation without influencing elastic or vascular tissue.

• Metabolism and Excretion: On the Collagenase Clostridium histolyticum, no systematic studies have been carried out.

Chemical Taxonomy

The bacteria Clostridium histolyticum produces an enzyme known as Collagenase Clostridium histolyticum (CCH). Combining two collagenases, ColH and ColG, is categorized as enzymes and protein-based therapies.

Toxicity:

Collagenase overdoses have not been associated with any adverse clinical effects, according to clinical investigations, and if necessary, povidone-iodine washing can be used to inactivate the enzymes.

Drug Interactions

Anticoagulant Medications: Except for low-dose Aspirin, patients currently using concurrent anticoagulants must use the Collagenase Clostridium histolyticum with caution.

Clinical Studies

Clinical research has shown that the Collagenase Clostridium histolyticum (CCH) is useful in the treatment of adult male Peyronie's disease.

• In two worldwide, double-blind phase III trials, the Collagenase Clostridium histolyticum helped adult males with the disease's physical and psychological symptoms. Two international, open-label phase III trials also noted these positive outcomes.

• The therapeutic efficacy of the Collagenase Clostridium histolyticum was widely supported by large-scale real-world research.

• Following a complete course of eight injections, the IMPRESS trials showed a mean improvement in curvature deformity of 34 percent. In these patient categories, Collagenase Clostridium histolyticum was generally well tolerated. Most treatment-related side effects were mild to moderate in severity, did not require medical attention, and went away on their own. Around one percent of patients experience more severe problems like corporal rupture and penile hematoma.

In comparison to surgery, these studies indicate that the Collagenase Clostridium histolyticum is a less intrusive, typically well-tolerated, and successful therapeutic option for adult males with Peyronie's disease.

Specific Considerations

• Pregnancy: A small percentage of pregnant women and women of reproductive age have consumed medicines, but animal studies have not revealed any evidence of fetal harm from these substances. Pregnancy in humans lacks controlled data, and research on animals has not demonstrated a rise in deformity or negative consequences for the human fetus. Neither appropriate nor well-controlled studies in pregnant women have been conducted, and US FDA pregnancy category B studies have not shown harm to the fetus.

• Breastfeeding: Nursing infants must be cautious while handling the Collagenase Clostridium histolyticum, as it may affect their breast milk and have unclear effects on human and animal milk.

• Pediatric Use: It is unknown if the Collagenase Clostridium histolyticum is safe and effective for pediatric patients under eighteen.

• Geriatric Use: In double-blind, placebo-controlled clinical studies, 249 patients 65 and older who received Collagenase Clostridium histolyticum treatment were compared to 551 people 65 and older. Collagenase Clostridium histolyticum is safe and effective for patients of all ages, as there were no appreciable changes in safety or efficacy between these individuals and younger ones.