The combination of isoniazid and rifampicin is an anti-tuberculosis drug whose action is due to the bactericidal properties of its components: isoniazid inhibits the synthesis of mycolic acids, which are the most important component of the cell wall of mycobacteria, rifampicin inhibits the synthesis of bacterial RNA.
| Isoniazid + rifampicin | |
|---|---|
| Isoniazidum + Rifampicinum | |
| Composition | |
| |
| Classification | |
| Pharmacol. Group | ansamycins, synthetic antibacterial agents [1] |
| ATH | |
| ICD-10 | |
| Dosage Forms | |
| coated tablets [2] | |
| Other names | |
| “Izo-Eremfat” [2] | |
Combination drugs with such a combination of active ingredients are included in ATH ( ) [3] , as well as included in the list of vital and essential drugs, approved by the decree of the Government of the Russian Federation of 30.12.2009 No. 2135-r.
In Russia, there is only one registered drug with such a composition - Izo-Eremfat . [4] At the same time, the components of the drug (isoniazid and rifampicin) can be purchased separately from the pharmacy chain.
Content
Pharmacology
Rifampicin and isoniazid have the greatest activity against fast-growing extracellularly located microorganisms, but also have a bactericidal effect on intracellularly located pathogens. [5] According to the developer, with this combination, the resistance of mycobacteria develops slowly. [2]
After taking the drug inside, its active ingredients are quickly and adequately absorbed from the gastrointestinal tract . The maximum concentration of the active components in the plasma is reached by the second hour after administration and remains at a detectable level for up to 8 hours.
Application
The drug is indicated for use in the treatment of the initial stages of pulmonary tuberculosis and its extrapulmonary forms ( A 15-19. ). [five]
There is evidence from randomized controlled clinical trials of the effectiveness of the combination of isoniazid + rifampicin in comparison with isoniazid monotherapy for HIV- infected patients without an open form of tuberculosis. According to the test results, the use of isoniazid compared with placebo gives a reduction in tuberculosis mortality, which is 74 percent likely to be fatal for people with a positive tuberculin test . Using a combination of isoniazid with rifampicin reduces the likelihood of death to 69% for all patients, regardless of the results of the tuberculin test (despite the fact that in patients with a positive test, treatment is more effective). At the same time, it was noted that even short courses of combination chemotherapy often require cessation of treatment due to the negative effects that are formed from the side effects of the components. [6]
According to the developer, the likelihood of side effects is reduced with the simultaneous appointment of pyridoxine and glutamic acid .
Therapy Options
The following treatments are applied:
- Initial phase: isoniazid + rifampicin together with streptomycin or ethambutol for 2 months. The daily dose is determined according to the patient’s body weight.
- The continuation phase (short course of treatment): receive a combination of isoniazid + rifampicin every day or 2-3 times a week for 4 months or more. The total duration of therapy should be at least 6 months and still at least 3 months after cessation of the bacteria excretion.
- Continuation Phase (long course of treatment): Required for patients with resistant strains, extrapulmonary tuberculosis and HIV-infected. In the case of HIV infection, the total duration of treatment should be at least 9 months and still at least 6 months after cessation of the bacteria excretion. [five]
Side Effects
Prolonged isoniazid intake causes peripheral neuropathy in 3.5-17% of patients. There is a feeling of tingling and numbness in the fingers and toes, some patients develop muscle weakness, headache, dizziness, nausea, vomiting, drug-induced hepatitis, gynecomastia in men, and menorrhagia in women. Prophylactic and therapeutic use of isoniazid in monotherapy or in combination with anti-TB drugs is associated with a significant risk of toxic liver damage. [five]
In this regard, the tool is contraindicated for persons with hepatic insufficiency, manifestations of epilepsy and a tendency to convulsive seizures (in the case of previous polio), children under 12 years old and with a body weight less than 45 kg. Careful use is necessary in patients with liver and kidney diseases, chronic alcoholism, as well as in elderly and debilitated patients.
With prolonged use, systematic monitoring of liver function (at least 1 time per month) and pictures of peripheral blood are shown. With the development of persistent abnormal liver function, treatment is interrupted and resumed after full normalization of clinical and laboratory parameters with low initial doses, with a gradual increase. [2]
The drug can not be used in the first trimester of pregnancy, as well as during breastfeeding. The possibility of using the drug in future pregnancy can only be solved by a doctor after assessing the degree of risk / benefit. When used in the last weeks of pregnancy, it can cause postpartum bleeding in the mother or newborn, for the treatment of which vitamin K is used.
History
“Izo-Eremfat” was developed by the German company Fatol Arzneimittel (“Fatol Artsnaymittel”) and was first registered in Russia on June 27, 2003 under the number 015081 / 01-2003. [2] The name of the drug comes from the names of its components: Iso niazid and Eremfat (the trademark of rifampicin of the same company).
In addition to this drug, the following drugs with the same composition were registered in Russia (the registration is now canceled) [7] :
| Trademark | Manufacturer | Country of origin | Registration number | Date of registration | Cancellation Date |
|---|---|---|---|---|---|
| Rifinag | "Babbling Group" | Italy | P-8-242 N005855 | 03/15/1995 | 05.02.2008 |
| "Of-Eremfat 150" | "Fatol Artsnaymittel" | Germany | P-8-242 N006976 | 01/12/1996 | 05.02.2008 |
| "Tibineks" | Temis Medicare | India | P-8-242 N006982 | 01/16/1996 | 03/12/2008 |
| "P-zinex" | Lupine Laboratories | India | P-8-242 N010771 | 01/18/1999 | 03/12/2008 |
| Zukoks Plus | Lazor Laboratories ("Glaxo India") | India | P N011517 / 01-1999 | 11/24/1999 | 04/18/2005 |
| "Rimaktazid" | Novartis Enterprises | India | P N012686 / 01-2001 | February 14, 2001 | 03/12/2008 |
| "Rimaktazid" | Novartis Enterprises | India | P N012686 / 02-2001 | February 14, 2001 | 13.03.2007 |
| "Tibineks" | Temis Medicare (CJSC “Gedeon Richter-RUS”) | India | P N014149 / 01-2002 | 06.20.2002 | 09/20/2007 |
| "Rimaktazid" | Novartis Enterprises | India | P N014455 / 01-2002 | 10/15/2002 | 03/12/2008 |
| Rifinag | "Babbling Group" | Italy | P N014788 / 01-2003 | 02.11.2003 | 08.04.2008 |
| "Rimaktazid" | "Sandoz Private" | India | П N014455 / 01 | 12/22/2006 | 03/12/2008 |
Dosage Forms
"Iso-Eremfat" is available in the form of coated tablets in two versions, differing in different ratios of components:
- isoniazid 100 mg + rifampicin 150 mg;
- isoniazid 150 mg + rifampicin 300 mg.
Notes
- ↑ Iso-Eremfat Unsolved . Register of medicines . ReLeS.ru Circulation date August 7, 2010. Archived April 27, 2012.
- ↑ 1 2 3 4 5 Search in the database of drugs, search options: INN - Isoniazid + rifampicin , flags “Search in the register of registered drugs” , “Search for TKFS” , “Show lecture forms” . Circulation of drugs . FGU "Scientific Center for the Expertise of Medical Devices" of the Federal Service for Health and Social Development of the Russian Federation (05.07.2010) - A typical clinical and pharmacological article is a bylaw and is not protected by copyright under Part Four of the Civil Code of the Russian Federation No. 230-FZ of December 18, 2006. Circulation date August 7, 2010. Archived August 22, 2011.
- ↑ As of 10.27.2009.
- ↑ As of 04/22/2010.
- ↑ 1 2 3 4 Iso-Eremfat (Iso-Eremfat) Unidentified . Handbook of drugs . Medical portal about health Eurolab (09/17/2009). The appeal date is June 13, 2010. Archived on April 27, 2012.
- Olo Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of persons with HIV . Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No .: CD000171. DOI: 10.1002 / 14651858.CD000171.pub3 . The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. (2010). The appeal date is June 12, 2010. Archived on April 27, 2012.
- ↑ Isoniazid + Rifampicin . 4Doktor.ru (2009). The appeal date is June 13, 2010. Archived on April 27, 2012.