Rifampicin undergoes slow post-collection degradation. Literature derived data as well as our in-house stability evaluation suggest that Rifampicin in whole blood or as serum or plasma is sufficiently stable up to 7 hours at room temperature even if the sample has been continuously exposed to laboratory light.
Nevertheless in suboptimum conditions Rifampicin will continue to degrade at a rate estimated to be 10-15% at 12 hours and around 20-30% by 24 hours post collection. Protecting the specimen from light does not necessarily reduce this slow rate of degradation.
While light protection is preferred, the sample can be transported as whole blood at room temperature and without light protection provided it can be separated, light protected and stored frozen at the receiving laboratory within 7 hours from time of collection.
If test is to be delayed, the separated serum should be stored frozen and transport on ice.
It can be further stabilised by adding 5mg ascorbic acid to the specimen.
Tubes containing gel (SST and PST) are NOT acceptable
Units: mg/L
|
Therapeutic interval : |
5 - 10 |
at 2 hour post-dose (peak ) |
Uncertainty of measurement: 16%
Conversion factors:
mg/L = umol/L x 0.82
umol/L = mg/L x 1.22
Performed Weekly.
Principle : High performance liquid chromatography
Rifampicin is commonly used for the treatment of tuberculosis. One of the major side effects of rifampicin is hepatotoxicity which is an idiosyncratic reaction rather than dose dependent toxicity. Periodic monitoring of hepatic enzyme tests is desirable for this purpose. Dose related flu-like syndrome usually appears only in those on >900mg/day, given as once or twice weekly regime. For patients on daily or alternate day regime, therapeutic drug monitoring of rifampicin is mainly used not for toxicity, but for monitoring anti TB efficacy especially in those suspected of poor compliance or having poor gastrointestinal absorption.
Rifampicin is best administered in a fasted state about 1hr before food. That is because oral bioavailability of rifampicin is reduced or delayed when the drug is co-administered with high fat and carbohydrate food. . At steady state, a dose of 600-750mg of rifampicin usually produces peak at 2 hours from time of intake. Serum half life of rifampicin is around 3 hours.
For those with 2 hour level below the therapeutic interval , check for:
1. Possibility of post-collection degradation. Repeat 2hr post dose blood test ensuring sample integrity (see above under Specimen Collection section).
2. 1 hour post dose level - some patients exhibit peak plasma concentrations at <2hrs - no need for dose adjustment.
3. 6 hours post dose level - help to differentiate delayed absorption (late peak, close to normal range) from malabsorption (low concentrations at all time points).
- If the 2hr and 6hr values are roughly the same and slightly below the therapeutic range or the 6hr level higher than the 2hr, then delayed absorption is likely. Delayed but near normal concentration does not require dose adjustment. It is possible that the actual peak occurred sometime between the 2hr and 6hr blood draws. Recommend taking the drugs on an empty stomach.
- If the 2hr and 6hr values are well below the lower limit of therapeutic interval, malabsorption is very likely. Consider dose escalation if poor compliance has been ruled out.
4. After discussion with ADHB respiratory team in April 2021, a 4 hours post dose level can also be clinically useful to document if a therapeutic level is achieved, and confirm adequate dosing.
References:
Philip O Anderson Handbook of clinical drug data 10 th edition (2001) McGraw-Hill Professional
Ray J et al Managing antituberculosis drug therapy by therapeutic drug monitoring of rifampicin and isoniazid Int Med J 2003; 33(5-6): 229-234
Peloquin CA Therapeutic drug monitoring in the treatment of tuberculosis Drugs 2002; 62(15): 2169-2183
Peloquin CA. Rifampin stability Therapeutic Drug Mon 1998; 20(4): 450-1
Le Guellec Stability of rifampin in plasma: consequences for therapeutic monitoring and pharmacokinetic studies Therapeutic Drug Mon 1997; 19(6): 669-674
Maze MJ et al. Therapeutic Drug Monitoring of Isoniazid and Rifampicin during anti-tuberculosis treatment in Auckland, New Zealand. Int J Tuberc Lung Dis 2016; 20(7): 955-960
Emails to chemicalpathologist@adhb.govt.nz will receive priority attention from the on-call chemical pathologist.
If the query concerns a specific patient please include the NHI number in your email.
If email is not a suitable option, please contact the on-call chemical pathologist via Lablink (Auckland City Hospital ext. 22000 or 09-3078995).
Individual chemical pathologists may be contacted but will not be available at all times.
After-hours : contact Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours.
Dr Samarina Musaad (Clinical Lead) : SamarinaM@adhb.govt.nz ext. 22402
Dr Cam Kyle: CampbellK@adhb.govt.nz ext 22052
Dr Weldon Chiu: WeldonC@adhb.govt.nz ext. 23427
Dr Campbell Heron: CHeron@adhb.govt.nz ext. 23427
Dr Sakunthala Jayasinghe: Sakunthala@adhb.govt.nz ext. 23427
While light protection is preferred, the sample can be transported as whole blood at room temperature and without light protection provided it can be separated, light protected and stored frozen at the receiving laboratory within 7 hours from time of collection. Mark as urgent.
If sample will be delayed, it should be separated, light protected, stored frozen and transported on ice.
It can be further stabilised by adding 5mg ascorbic acid to the specimen.