|LETTER TO THE EDITOR
|Year : 2013 | Volume
| Issue : 3 | Page : 309-310
Evaluation of prescribing trends and rationality of use of oral proteolytic enzymes
Saumil A Shah, Rajan P Nerurkar
Department of Pharmacology, Topiwala National Medical College and B.Y.L Nair Ch. Hospital, Mumbai, India
|Date of Web Publication||15-May-2013|
Saumil A Shah
Department of Pharmacology, Topiwala National Medical College and B.Y.L Nair Ch. Hospital, Mumbai
|How to cite this article:|
Shah SA, Nerurkar RP. Evaluation of prescribing trends and rationality of use of oral proteolytic enzymes. Indian J Pharmacol 2013;45:309-10
Many expensive drugs are prescribed without verifying the efficacy in a scientific manner or randomized controlled trials. Oral proteolytic enzymes such as serratiopeptidase, chymotrypsins, etc., are aggressively marketed in India for their anti-inflammatory action and are prescribed in a variety of conditions like facial edema, trauma, surgery, parotitis, and carpal tunnel syndrome.  These drugs are sparsely used in developed countries, and do not find mention in the British National Formulary, the United States Pharmacopoeia and in the standard textbooks of pharmacology as anti-inflammatory drugs. Being protein in nature, there are doubts about their absorption in an intact form from the intestine.  Further, human pharmacokinetic data of these drugs are not available. As compared to Nonsteroidal anti-inflammatory drugs (NSAIDs), these drugs are very expensive and their efficacy is not proven despite which they are widely co-prescribed along with NSAIDs for their supposed anti-inflammatory action. Although, anti-inflammatory action has been demonstrated on few animal models, their effectiveness is highly debatable.  Recently, conducted clinical trials have raised further doubts of their efficacy.  Hence, we hypothesized that "Irrational prescribing of proteolytic enzymes is rampant without any evidence for their efficacy". The present study was undertaken to review the prescribing trends of proteolytic enzymes in 100 out-door patients suffering from any inflammatory disorders in orthopedic department, and to see the awareness among 50 doctors regarding rationality of prescribing oral proteolytic enzymes in a tertiary care hospital.
This cross-sectional, prospective, observational study was carried out in two parts after obtaining approval from the Institutional Ethics Committee.
Prescribing trends of proteolytic enzymes in 100 patients attending orthopedic outpatient department in a tertiary care hospital were reviewed and relevant information was collected from their case-papers. The information collected were their particulars, that is, age, sex, occupation, and socio-economic status. The patients were classified into three categories based on their monthly income, that is, those earning less than Rs.3000/- as low, between Rs.3000-8000/- as middle and above Rs.8000/- as high. The number of patients' receiving oral proteolytic enzymes as monotherapy or in combination with NSAIDs was studied. The brand name, generic name, daily dose, and duration of therapy were recorded. The cost of therapy and the duration for which the drug was prescribed were noted. Any adverse effect occurred during the course of therapy was noted.
Awareness of the prescribing doctors regarding their knowledge of oral proteolytic enzymes was assessed with the help of a structured questionnaire. The questionnaire was duly filled by a total of 50 doctors from various surgical departments (30 from general surgery, 16 from orthopedics, 3 from Ear Nose Throat and 1 from Ophthalmology) and the questionnaire included a proforma stating the doctor's name, age, sex, qualification. It also had questions about the doctors' view on the proteolytic enzymes commonly prescribed by them, preference of fixed dose drug combination over monotherapy, contents, and cost of the drug. Other general information on the drug included their opinion on the efficacy of use of oral proteolytic enzymes, their source, and whether these drugs were aggressively marketed by the pharmaceutical companies. Their knowledge about clinical trial reports of proteolytic enzymes was also assessed.
Hundred patients were prescribed oral proteolytic enzymes for various inflammatory conditions. Out of them, 71 were males and the mean age of patients was 40 years. Ninety patients were prescribed proteolytic enzymes for fractures.
In all 100 patients, proteolytic enzymes were prescribed along with NSAIDs either as a fixed dose combination (n = 86)
or as a separate medication (n = 14). None of the patients were prescribed proteolytic enzymes without NSAIDs. The most commonly used preparation was a fixed dose combination of (paracetamol 500 mg, diclofenac 50 mg, serratiopeptidase 10 mg), other preparations being a combination of (trypsin:chymotrypsin 100,000 units),or a fixed dose combination of (diclofenac 50 mg, serratiopeptidase20 mg), etc.
The cost of these tablets/day ranged from Rs. 15 to Rs. 27, whereas, the cost of NSAIDs alone ranges from Rs. 2 to Rs. 5.  The cost analysis revealed that there was no significant difference in the cost of therapy among various socio-economic strata. It ranged from Rs. 93/-to Rs.100/- per therapy. The P-value after categorizing all the patients in three separate classes was 0.126 by one way ANOVA and was not significant.
Analysis of questionnaire from 50 doctors revealed that the most commonly prescribed and favored proteolytic enzyme by these doctors was a combination of trypsin:chymotrypsin 100,000 units which was favored by 26 doctors which was followed by 19 doctors who favored fixed dose combination of diclofenac, serratiopeptidase, and paracetamol, 3 out of 50 doctors preferred giving a combination of diclofenac 50 mg and serratiopeptidase 20 mg and 2 doctors favored giving a combination of trypsin, bromelain, and rutoside trihydrate. None of the patients were prescribed proteolytic enzymes alone and was always given with NSAIDs. They were prescribed thrice a day for a period of 5-7 days. The generic name of the drugs prescribed was known to 30 doctors (60%). All the doctors were prescribing these drugs for inflammatory conditions of the soft tissues, fractures, parotitis, etc. The detailed responses of assessment of questionnaires filled by the doctors are shown in [Table 1]
|Table 1: Assessment of the questionnaire filled by the prescribing doctors |
Click here to view
The most commonly prescribed anti-inflammatory drugs are NSAIDs and glucocorticoids as their anti-inflammatory efficacy is well-known. It is important to note that proteolytic enzymes are never prescribed alone without NSAID. Rational use of medicines is based on STEP-criteria, that is, safety, tolerability, efficacy and price. In view of their doubtful efficacy as anti-inflammatory drug, we feel that prescribing proteolytic enzymes is irrational in many ways and it increases the cost of therapy by more than 5 times  the cost of NSAIDs alone. In spite of irrational prescribing of these drugs, 98% of the doctors felt that these drugs are effective. However, they are always given with NSAIDs and the effectiveness may be because of NSAIDs and not because of proteolytic enzymes. Hence, there is a need to conduct a clinical trial to compare anti-inflammatory action of proteolytic enzymes with or without NSAIDs.
The main reservations about the use of proteolytic enzymes are as under:
- Proteolytic enzymes are large protein molecules and there exist a doubt whether they will be absorbed in an active form from the gastrointestinal tract. To overcome their destruction in stomach by hydrolysis, these tablets are given in enteric coated dosage form.
- There are very few reports of well-controlled randomized clinical trials. Thus, anti-inflammatory activity after oral administration has not been convincingly demonstrated. Most of the clinical data are not adequately controlled, and is based on the subjective observations.
- Very little is known about their mechanism of action.
- No clinical data is available on the fate and excretion of proteolytic enzymes.
It also appears that all the proposed mechanisms of action are entirely theoretical and the clinical evidence offered in claims of anti-inflammatory action is not substantial and various studies have raised doubts about their efficacy. ,
Our study has highlighted the irrational prescribing of proteolytic enzymes by doctors and their prescriptions were highly influenced by medical representatives.
It is suggested that our doctors should be properly educated on the principles of rational use of drugs and on the evidence based medicine. Doctors should prescribe these drugs rationally and behave as trend setters. Doctor's prescriptions should not get influenced by medical representatives.
The authors are thankful to Indian Council of Medical Research for providing a grant for carrying their study under Short Term Studentship (STS) scholarship program.
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