 |
|
Viewpoint Indian Pediatrics 2001; 38: 400-406 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Antitubercular Drug Formulations for Children |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
The guidelines for treatment of childhood tuberculosis have been laid down by the IAP Working Group on Childhood Tuber-culosis(1). The treatment regimen for pulmonary tuberculosis has been divided into intensive and maintenance phases. The objective of intensive phase is to (i) make the patient noninfectious by rapidly killing mycobacteria, (ii) forestall dissemination of the disease and (iii) prevent drug resistance. Maintenance phase of anti tubercular therapy is directed towards clearing the infection and complete healing of the lesion. Therefore, three or four drugs namely isoniazid (H) rifampicin (R), pyrazinamide (Z) and streptomycin (S) or ethambutol (E) are given for a period of two months during intensive phase. R and H are given for 410 months in maintenance phase (2-5). The rationale of antitubercular treatment (ATT) is proper drug doses, good compliance, adequate duration and minimal side effects. It is important for a pediatrician to know the exact composition of anti tubercular drugs available in the market. Single drug formulations as well as combinations are available but in different drug dosages. This causes lot of confusion in recalling the exact composition of antitubercular formulations marketed by different pharmaceutical companies. It may lead to prescription of inappropriate doses leading to poor cure rate, risk of developing drug resistance and increased rate of side effects. Keeping this in mind we studied all the antitubercular formulations for the pediatric age group available in the market.
The information on drug formulation was obtained from monthly index of medical specialities (MIMS)(6), Drug Today(7), product literature supplied along with the medicines and interaction with the medical representatives. The available formulations of ATT are depicted in Tables I-IV. Many companies are manufacturing single drug formulations for children. Isoniazid, rifampicin and pyrazinamide are available in single formulations as liquid, tablets and capsules. Some of the tablets are dispersible in nature. Ethambutol is available only in tablet form (Table I). Various combinations of rifampicin and isoniazid are available. Combinations of isoniazid, rifampicin and pyrazinamide are also manufactured by numerous companies. None of the combinations are available as liquid preparation (Table II). A few companies are also marketing combination of four drugs i.e., R+H+Z+E.
It was found that there was a wide variation in the composition of single drug as well as combination preparations. All pharmaceutical companies are manufacturing ethambutol as 200 mg tablet only and isoniazid as 100 mg tablet or 100 mg/5 ml liquid preparation. On the other hand rifampicin is available as liquid in strength of 100/150 mg per 5 ml as 150 mg capsules and as 50 mg/100 mg tablets. Pyrazinamide is available in liquid as well as tablet form. The liquid contains 250 mg/5 ml but tablet contains either 250 mg or 300 mg. Similarly, the quantity of each drug in two drug combinations is widely variable in different products. Rifarmpicin is dispensed as 100 mg, 150 mg or 200 mg along with isoniazid as 50 mg, 100 mg and 150 mg per tablet. In three drug combinations the strength of rifampicin per tablet varies widely from 100 mg, 120 mg, 150 mg to 225 mg. Isoniazid is dispensed in the strength of 75 mg, 80 mg, 100 mg and 150 mg per tablet and pyrazinamide is dispensed in the strength of 250 mg, 500 mg and 750 mg. Some of these formulations also contain vitamin B6. Same variation is prevalent in the four drug combination.
According to rational drug therapy, combination of drugs should be avoided. However as antitubercular treatment requires multidrug therapy for relatively longer duration with stringent compliance, use of drug combinations are justified. The use of combination of drugs is advantageous only if the ratio of fixed doses corresponds to the needs of individual patients(8). To the best of our knowledge 26 companies are manufacturing antitubercular drugs in single or combination preparations for children in Indian market. The quantity of antitubercular drugs in these products is neither uniformly marketed nor the ratio of individual drugs is appropriate. This may create two practical problems. One, the pediatrician has to remember quantity of individual antitubercular drugs in different formulation and recall them at the time of prescribing them to the patient which may on occasions be difficult and confusing. Second, as the ratio of drugs is not appropriate, dose of one of drugs in combination may either be given in higher doses or at suboptimal doses. This may result into increased side effects and non compliance or development of resistance. All drugs in pediatric practice are prescribed according to the body weight or surface area. Each prescription has to be individualized. It is neither required nor logistically possible to manufacture drugs for individual patients. If quantity of each drug in a pharmaceutical product is known to the pediatrician it will be easy to prescribe them in proper doses. Isoniazid is given in the dose of 5 mg/ kg/d, rifampicin in the dose of 10 mg/kg/d and pyrazinamide in the dose of 25 mg/kg/d(1). A higher dose of isoniazid upto 10-15 mg/kg/d is recommended by some(9). It seems reasonable to have a combination of two drugs i.e., rifampicin and isoniazid in the ratio of 2 : 1. Similarly, a three drug combination should have rifampicin, isoniazd and pyrazinamide in the ratio of 2:1 : 5. If ethambutal has to be added, then the relative ratio should be 2. On this basis a two drug combination should have rifampicin 100 mg, isoniazide 50 mg and pyrazinamide and ethambutol can be added as a third or fourth drug in the dose of 250 mg or 200 mg, respectively. Pyridoxine is essential for proper functioning of nervous system, deficiency of which may lead to seizures and to peripheral neuropathy. Both human and cows milk and cereals have sufficient amount of pyriodoxine. Secondary deficiency may occur with prolonged administration of isoniazid and cycloserine, as both of them are pyridoxine antagonists. It is controversial whether pyriodoxine should be routinely supplemented to patients receiving isoniazid or not. There is growing evidence that pyridoxine supplementation is not required routinely if the child is taking adequate diet and the IAP expert group as well as other workers have not recommended its routine use(1,5). However, if peripheral neuritis develops during antitubercular therapy, pyridoxine may be added in the dose of 10-20 mg/day(2). In our opinion pyridoxine should not be added in the antitubercular drug combinations as it increases the cost without any benefit. In USA a fixed dose combination is considered a new drug and must be approved by FDA before it can be marketed(8). In our country also all pharmaceutical companies have to obtain a licence from Drug Controller of India to manufacture a drug. Almost all antibiotics available in the market are dispensed uniformly by all companies for both oral and parenteral forms. It is therefore suggested that Drug Controller of India may look into the matter in this light so that antibutercular drugs may also be available in uniform dose preparations. It will facilitate proper prescription of antitubercular drugs with individual requirement. Contributors: RR collecteed the data and performed the literature search. MMAF designed and coordinated the study; he will act as the guarantor for the paper. KNA interpreted and drafted paper. PG was responsible for co-drafing. Funding: None.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
