Indications for intravenous anti-TB therapy: • severe overall physical condition of the patient (severe course of TB, need for

treatment in Intensive Care Units);• impaired GI absorption of drugs/malabsorption syndrome;• TB patients who had surgical procedures on GIT organs;• Pre- and postoperative period (surgical intervention for TB);• Disseminated forms of tuberculosis with massive tissue involvement (caseous

pneumonia, disseminated TB, miliary TB, extrapulmonary TB, TB of the CNS);• Adverse GI tract reactions to oral ATDs (vomiting, nausea, toxic gastritis);• Low patient compliance.

PASKONATStandard treatmentfor Resistant TB

YURiA-PHARM EAST AFRICA LTD

Biashara Business Center, Plot 4, Old Portbell road, Industrial Area, Kampala, Ugandatel.: +256 414 697510yuria.eastafrica@gmail.comwww.uf.ua/int

PASKONAT is an intravenous form of PAS- Atfirst,administerhalfthedailydoseofPASKONATat15drops/

minute. - In the absence of common adverse reactions, increase the dose

to the full daily dose requirements and the rate of introduction should be 40-60 drops / minute.

- Administer daily or alternate with oral PAS.

When administering PASKONAT, consider the possibility of hematomas and phlebitis; To prevent these complications: - Usefineneedles;- Alternate vein for the administration of the solution; - Donotexceedtherecommendedrateofadministration(40-60 dropsperminute).- Alternate intravenous administration with oral intake of PAS.

It is very important to observe the PASKONAT conditions of storage: at temperatures from +8 to +180 C in a dark place!

The average daily dose of PASKONAT for patient is:8-12 g (300-400 ml of 3% solution of PASKONAT).

IV administration of PAS compared to oral reduces the time of hospitalization of patients with MDRTB by 1.1 months due to shortening time of sputumconversion (4.7 vs. 5.8 months).

Intravenous PAS significantly reduces the risk of adverse reactionson the GI tract due to the lack of direct aggressive influence of the drug on the mucosa. Intravenous PAS compared with oral administration 20% less accompanied by severe adverse reactions.*

Poor compliance of patients and treatment interruption are among the main reasons for the ineffectiveness of TB treatment

Slows down the metabolism of isoniazid; Prevents the development of resistance to isoniazid and streptomycin; Prevents the formation of coarse fibrous tissue;Improves blood rheology, reduces inflammatory edema; Improves penetration of drugs in affected tissue.

1. GENERAL INFORMATION

PASKONAT is a 2nd-line anti-TB drug;- PAS has been used in TB treatment since 1946;- Resistance level of MTB to PAS remains low;- PAS has a complex action (actually impact on MTB, potentiates

the activity of other drugs (isoniazid, streptomycin, kanamycin, ethionamide,cycloserine),posessesnon-specificanti-inflammatoryeffect).

- PAS is recommended by WHO for use in the treatment of drug-resistantTB*

2. EFFICACY

BioavailabilityofPASafteroralintakedoesnotexceed60%**PASKONAT — 100% bioavailability regardless of the individual features of thepatient(conditionoftheintestines,pH,microcirculation,hydrationandhemoconcentration, etc.).

PASKONAT creates 3–4 times higher concentrations of PAS in plasma and tissues thanafteroraladministration(200-250 mcg/mlVS66mcg/ml)***.

MaximumefficientimpactontheMTB.

*Treatmentoftuberculosis:guidelines/4thed.–WHO.-2010.–147p.**K.M.Kametal.Determinationofcriticalconcentrationsofsecondlineantituberculosisdrugswithclinicalandmicrobiologicalrelevance//Int.J.Tuberc.LungDis.–2010.–V.14,№3.–P.282–288.**Е.Deberschauser(1963),О.М.Иванюта(1980).

*S.O.Cherenkoetal.EfficiencyandtolerabilityofinjectablePASintheindividualizedregimensofchemoterapyforthetreatmentofpatientswithMDRTB.//Ukr.Chem.J.-2012.-№1-2(25).-P.43-46.**К.Paul.Contributiontothecurrentstatusofchemotherapyofpulmonarytuberculosis.ActaTubercScand.1960;38:82-90.

3. SAFETY

The most frequently observed side effects associated with oral PAS are adverse reactions of the GI tract - nausea, vomiting, abdominal pain.

4. CONTROL

5. ADDITIONAL EFFECTS OF PASKONAT

Intravenous administration of PAS is the best way to prevent hepatotoxic adverse reactionsduetothereductionofnumberofsubstancesacetilatedbytheliver.**

PASKONAT – 100% control –ThebestDOT!The doctor is always sure that the patient received the full dose.

PAS is not very «powerfull» anti-TB drug. But,givenitsadditionalbenefits,itisindispensableinthetreatmentofdrug-resistant TB.

Comparison of peak concentrations and areas under AUC between intravenous (1) and peroral (2) administration

Concentration Concentration

TimeTime

AUC iv AUC per os

Cmax

Cmax

0

1 2

0