Chymopapain

(BAN, USAN, rINN)
Synonyms: BAX-1526; Chymopapaïne; Chymopapainum; Kymopapaiini; Kymopapain; NSC-107079; Quimopapaína; Quimopapaina.
Cyrillic synonym: Химопапаин.

💊 Chemical information

CAS — 9001-09-6.
ATC — M09AB01.
ATC Vet — QM09AB01.

Description.

Chymopapain is a proteolytic enzyme isolated from the latex of papaya (Carica papaya), differing from papain in electrophoretic mobility, solubility, and substrate specificity. Molecular weight about 27 000.

💊 Units

One nanokatal (nKat) is defined as the amount of chymopapain which produces 1 nanomole of p-nitroaniline per second from DL-benzoylarginine-p-nitroanilide substrate at pH 6.4 and 37°. In some countries CTE units have been used, defined as the amount of chymopapain that produces a hydrolysate from aciddenatured haemoglobin at pH 4.0 in one minute with an optical density at 275 nm equivalent to that of a tyrosine solution 0.0001%.

💊 Adverse Effects

The most important adverse effect of chymopapain is anaphylaxis, which can occur in up to about 1% of patients. It has resulted in fatalities and restricts use to a single treatment session per patient. Typical symptoms include angioedema, hypotension, laryngeal oedema and bronchospasm, shock, and cardiac arrest. Allergic skin reactions may also occur. Other reported reactions include headache, nausea and vomiting, paralytic ileus, urinary retention, thrombophlebitis, paraesthesias, foot-drop, and discitis. Severe muscle spasm and an increase in back pain are common. Paraplegia, acute transverse myelitis, and intracerebral and subarachnoid haemorrhage have occurred.

Incidence of adverse effects.

A 1984 postmarketing surveillance study on a US chymopapain preparation for intradiscal injection (Chymodiactin) involved data from 29 075 patients (representing about 50% of the total number of vials sold).1Anaphylactic reactions were confirmed in 194 patients (0.67%), 2 of whom died. The incidence was higher in women than in men. In 52 cases the reaction occurred after the test dose. Serious neurological reactions reported were: cerebral haemorrhage (6 cases, 3 fatal; autopsy revealed that they had underlying cerebrovascular abnormalities); paraplegia (11 cases, 5 of which may have been due to incorrect needle placement); transverse myelitis with paraplegia (2 cases, after 2 and 3 weeks, with subsequent recovery); and seizures (2 cases on injection and 1 several days after the procedure). Twenty-two patients had discitis with severe back pain and spasm. In 9 cases bacteria could be cultured, and 1 patient subsequently developed fatal Staphylococcus aureus meningitis. Another review2 of serious reactions associated with chymopapain between 1982 and 1991 (including data from the earlier postmarketing study) involved 121 reports among about 135 000 patients. They included fatal anaphylaxis (7), infections (24), haemorrhage (32), and neurological reactions (32). Both reviews concluded that careful attention to proper patient selection and correct techniques of intradiscal needle placement are the most important factors in avoiding adverse effects with chymopapain.
1. Agre K, et al. Chymodiactin postmarketing surveillance: demographic and adverse experience data in 29075 patients. Spine 1984; 9: 479–85
2. Nordby EJ, et al. Safety of chemonucleolysis: adverse effects reported in the United States, 1982–1991. Clin Orthop 1993; 293: 122–34.

💊 Precautions

Chymopapain should not be used in those patients with a known sensitivity to papaya proteins or in patients with progressive paralysis, or tumours of the spinal cord, or lesions of the cauda equina. Severe spondylolisthesis is also a contra-indication. It should not be given to patients with heart failure, coronary artery disease, or respiratory failure who may be at increased risk if anaphylaxis occurs, nor to patients receiving beta blockers. Care is required in administering chymopapain to ensure that the injection is into the disc and not intrathecal. However, discography is not recommended since the use of contrast media may exacerbate neurotoxicity and may inactivate the enzyme. The risk of allergic reactions associated with chymopapain is so high that no patient should ever receive it more than once. Tests to identify those most at risk and pretreatment with antihistamines (H1 and H2) and corticosteroids may be used, but facilities for the emergency management of anaphylactic reactions should always be to hand when giving patients chymopapain. The risk of anaphylaxis is higher in women. Injection of more than one disc is associated with an increased frequency of neurological reactions; therefore, such injection should only be carried out following confirmation of definite further disc involvement.

💊 Uses and Administration

Chymopapain is used as an injection into the intervertebral disc in the treatment of sciatic pain and other symptoms secondary to herniation of intervertebral discs of the lumbar spine (chemonucleolysis). Chymopapain injection should preferably be given under local, rather than general, anaesthesia. The dose for a single intervertebral disc is 2 to 4 nanokatals, with a maximum dose per patient of 8 nanokatals.

Chemonucleolysis.

Dissolution of the disc by injection of chymopapain or other enzymes (chemonucleolysis) has been used as an effective alternative to surgery in patients with lumbar disc herniation. However, concerns about its safety have led to a decline in its use, and discectomy is often preferred.
1. Nordby EJ, et al. Chemonucleolysis. Spine 1996; 21: 1102–5
2. Brown MD. Update on chemonucleolysis. Spine 1996; 21 (24 suppl): 62S–68S
3. Poynton AR, et al. Chymopapain chemonucleolysis: a review of 105 cases. J R Coll Surg Edinb 1998; 43: 407–9
4. Wittenberg RH, et al. Five-year results from chemonucleolysis with chymopapain or collagenase: a prospective randomized study. Spine 2001; 26: 1835–41.

💊 Preparations

Proprietary Preparations

Austral.: Chymodiactin; Spain: Chymodiactin†.
Published March 23, 2019.