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Do Rifampicin, Isoniazid And Pyrazinamide Cause Drug Induced Hepatitis?

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Posted on Mon, 25 Jul 2016
Question: I was on TB treatment for 14 days and then liver tests showed elevated enzymes and Dr stopped medication for 4 days. Is this normal to stop the medications? They now want to monitor me for liver response and want me to stay in hospital. The initial TB medicines included Rifampicin, Isoniazid, Pyrazinamide and Ethmbutol. Please help me clear my doubts. My concern is once medications started should it be not continued to avoid bacteria becoming resistant?
doctor
Answered by Dr. Drkaushal85 (14 minutes later)
Brief Answer:
You should start modified regimen.

Detailed Answer:
Thanks for your question on Healthcare Magic.
I can understand your concern.
You are having anti tubercular drugs induced hepatitis.
Rifampicin, isoniazid and pyrazinamide are known to cause drug induced hepatitis.
And 10% patients can develop hepatitis after starting these drugs.
Ideally, modified regimen should be started.
Modified regimen includes ethambutol, levofloxacin and streptomycin. These three drugs are safe for liver.
So start these three drugs, get done liver enzymes on alternate days. Along with them also take liver supplemental drugs.
Once your liver functions are normal, you can resume four drug (rifampicin, isoniazid, pyrazinamide and ethambutol) schedule.
Yes, you are right. Sudden stoppage of anti tubercular drugs can cause drug resistance.
So modified regimen is given to such patients.
Please let me know exact value of your elevated liver enzymes, so that I can guide you better.
I will be happy to help you further. Wish you good health. Thanks.
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Drkaushal85 (5 minutes later)
Thanks for your prompt reply. According to hospital enzymes levels were 480. I guess it's SGPT or ALT. Please advise whether it's too high or not? How soon the Dr should start modified treatment? Thanks.
doctor
Answered by Dr. Drkaushal85 (2 minutes later)
Brief Answer:
It is not two high.

Detailed Answer:
Thanks for your follow up question on Healthcare Magic.
I can understand your concern.
It is not too high.
Don't worry, it will regress soon.
In my opinion, doctor should start modified regimen as soon as possible.
Please let me know
1. Before how many days you tested for liver enzymes?
2. Since how many days you are not taking any drugs?
Please reply me answers of above asked questions, so that I can guide you better. I will be happy to help you further. Wish you good health. Thanks.
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Drkaushal85 (2 days later)
Hi, yesterday's ALT came at 403. Before 3 days it was 440. Dr said that we will wait until it comes to 200 and start medicines one by one and test my liver regularly. I am off all medicines since last 6 days.

Do you think my ALT will come down soon? Is this Dr taking appropriate steps? Will this slow process of giving medicines affect TB spread in my body? Please let me know. Thanks.
doctor
Answered by Dr. Drkaushal85 (11 minutes later)
Brief Answer:
Do you have pulmonary tuberculosis?

Detailed Answer:
Thanks for your follow up question on Healthcare Magic.
I can understand your concern.
YrdtYesterday, your ALT will definitely come down. No need to worry for this.
To stop all TB treatment and gradually administer it one by one once ALT is less than 200 is another way to treat drug induced hepatitis.
But it can delay the recovery. So better option is to switch to hepatosafe drugs and wait till ALT normalize.
By doing this, we can at least ensure that tb patient is getting anti tubercular drugs continuously.
Please let me know
1. Do you have pulmonary tuberculosis?
2. Have you talked about this modified regimen to your treating doctor?
Please reply me answers of above asked questions, so that I can guide you better. I will be happy to help you further. Wish you good health. Thanks
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Drkaushal85 (9 minutes later)
Thanks for your prompt reply. Yes I am diagnosed with pulmonary TB. I asked Dr about modified regime but they don't follow it until necessary. This Dr will introduce same drugs once ALT close to 200. He also said most likely he needs to change Pyrazinamide and replace with streptomycin. He said liver is important so waiting a week or 10 days will not affect TB problem. Is this ok? How quick my ALT should come down if I am off medicines 2-3 days or more? I do not drink alcohol and eat healthy foods. Thanks
doctor
Answered by Dr. Drkaushal85 (16 minutes later)
Brief Answer:
Which other drugs you are taking?

Detailed Answer:
Thanks for your follow up question on Healthcare Magic.
I can understand your concern.
Pulmonary TB is major TB infection. It carries high bacillary load. So I don't think you should stop anti tubercular drugs.
Yes, he is right. Liver is important. But at the same time lungs especially if infected by tuberculosis is also very important.
First let me know
1. Was your sputum sample positive for tb at the time of diagnosis?
2. Can you send me chest x ray report?
Both these points are important to decide if it is harmful for you to wait or not.
And it will take almost 12-15 days to normalize your ALT.
And also let me know if you are taking other liver protective drugs or not.
I will be happy to help you further. Wish you good health. Thanks.
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Drkaushal85 (25 hours later)
Hi, thanks for your reply. Yes, my sputum was positive for TB. Another sample is under lab for culture test which result will come in next 2-3 weeks.
My chest x-Ray is not available with me. But I was told my left lung has some patches and right lung is clear. They did not see any cavities.
Again yesterday my ALT came down to 380. Dr will wait until it comes to 200 which he thinks could be in next 4-5 days. I am not on any medications. No liver drugs. Only vitamin D injection was given yesterday. They will do daily ALT test so they can start medication as soon as ALT is 200.
What do you think? Is my TB very severe? 5 Days back's sputum is still positive but much less than first sputum test.
Please advise stopping medicines for about total 14 days will not make TB worse. Thanks
doctor
Answered by Dr. Drkaushal85 (15 minutes later)
Brief Answer:
You should take liver supplements.

Detailed Answer:
Thanks for your follow up question on Healthcare Magic.
I can understand your concern.
See, if you ask my opinion, I would go for alternative regimen (levofloxacin, ethambutol and streptomycin) because you are having sputum positive pulmonary tuberculosis.
Your tuberculosis is not severe, this can be 100% cured. But sudden stoppage of all anti tubercular Drugs can increase risk of drug resistance tuberculosis.
And I am surprised why you have not given liver supplements like syrup Liv 52, tablet Udiliv.
In my patients (drug induced hepatitis), I start modified regimen (so that tuberculosis got covered) and liver supplements (so that liver starts healing) simultaneously.
Please let me know
1. Are you consulting pulmonologist?
Please reply me answer of above asked question, so that I can guide you better. I will be happy to help you further. Wish you good health. Thanks.
Above answer was peer-reviewed by : Dr. Raju A.T
doctor
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Follow up: Dr. Drkaushal85 (22 minutes later)
Hi, thanks for your reply. Your process is proper way it seems. But Dr here in UK have to follow hospital guidelines to treat TB. They are not at complete freedom to take decisions. The main consultant I guess is Pulmonologist and from XXXXXXX Other Dr under him just follow guidelines.

I feel much better than before starting medicines. Very little cough, no fever, no night sweats, no more weight loss. That means medicines worked. Dr said this could mean I do not have drug resistant bectaria which is good. That's why probably they are taking it easily.
It should be fine, right?
doctor
Answered by Dr. Drkaushal85 (4 minutes later)
Brief Answer:
Yes, it will be fine. Don't worry.

Detailed Answer:
Thanks for your follow up question on Healthcare Magic.
I can understand your concern.
I thought you are living in XXXXXXX and taking treatment from XXXXXXX doctor.
Since you are in UK, you have to follow them.
Yes, possibility of drug resistance is very less in your case as you are improving in symptoms.
Don't worry, you will be alright.
You will be fine.
Hope I have solved your query. If you are not having further queries, then please close the conversation and rate my answer.
You can ask me directly on bit.ly/askdrkaushalbhavsar. Wish you good health. Thanks.
Above answer was peer-reviewed by : Dr. Raju A.T
doctor
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Follow up: Dr. Drkaushal85 (25 minutes later)
Thank you very much for your help so far. I will ask further questions as and when arise. Thanks a lot.
doctor
Answered by Dr. Drkaushal85 (3 minutes later)
Brief Answer:
I will be always ready to answer them.

Detailed Answer:
Thanks for your follow up question on Healthcare Magic.
I can understand your concern.
Thanks for your kind words.
You can ask me directly on bit.ly/askdrkaushalbhavsar at any time.
I will be happy to receive your questions. I am always ready to answer them.
If you are not having further queries, then please close this conversation and rate my answer.
You can ask me directly on clicking above link.
Thanks.
Above answer was peer-reviewed by : Dr. Raju A.T
doctor
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Dr. Drkaushal85

Pulmonologist

Practicing since :2008

Answered : 15003 Questions

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Do Rifampicin, Isoniazid And Pyrazinamide Cause Drug Induced Hepatitis?

Brief Answer: You should start modified regimen. Detailed Answer: Thanks for your question on Healthcare Magic. I can understand your concern. You are having anti tubercular drugs induced hepatitis. Rifampicin, isoniazid and pyrazinamide are known to cause drug induced hepatitis. And 10% patients can develop hepatitis after starting these drugs. Ideally, modified regimen should be started. Modified regimen includes ethambutol, levofloxacin and streptomycin. These three drugs are safe for liver. So start these three drugs, get done liver enzymes on alternate days. Along with them also take liver supplemental drugs. Once your liver functions are normal, you can resume four drug (rifampicin, isoniazid, pyrazinamide and ethambutol) schedule. Yes, you are right. Sudden stoppage of anti tubercular drugs can cause drug resistance. So modified regimen is given to such patients. Please let me know exact value of your elevated liver enzymes, so that I can guide you better. I will be happy to help you further. Wish you good health. Thanks.