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Fixed Dose Combination (FDC) : Presented by - Batch B (R O L L N O. 1 7 To 3 4)

This document discusses the components and rationale of a fixed-dose combination of tenofovir, emtricitabine, and lopinavir/ritonavir. It provides details on the mechanisms and pharmacokinetics of each individual drug. Tenofovir and emtricitabine are nucleoside reverse transcriptase inhibitors while lopinavir/ritonavir is a protease inhibitor. The combination provides coverage of multiple stages of the viral replication cycle. A 4-week regimen with two NRTIs and a third agent from a different class can significantly reduce the risk of HIV infection dissemination for post-exposure prophylaxis.

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Brajesh Meena
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43 views17 pages

Fixed Dose Combination (FDC) : Presented by - Batch B (R O L L N O. 1 7 To 3 4)

This document discusses the components and rationale of a fixed-dose combination of tenofovir, emtricitabine, and lopinavir/ritonavir. It provides details on the mechanisms and pharmacokinetics of each individual drug. Tenofovir and emtricitabine are nucleoside reverse transcriptase inhibitors while lopinavir/ritonavir is a protease inhibitor. The combination provides coverage of multiple stages of the viral replication cycle. A 4-week regimen with two NRTIs and a third agent from a different class can significantly reduce the risk of HIV infection dissemination for post-exposure prophylaxis.

Uploaded by

Brajesh Meena
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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FIXED DOSE

COMBINATION
(FDC)
P R E S E N T E D B Y – B AT C H B
( R O L L N O. 1 7 TO 3 4 )
1) CLOTRIMAZOLE +
BECLOMETHASONE +
NEOMYCIN CREAM
 CLOTRIMAZOLE
 an antifungal medication, belonging to IMIDAZOLE groups of azoles.
 MOA- acts by inhibiting fungal cytochrome P450 enzyme ‘lanosterol 14-demethylase’ and
thus impair ergosterol synthesis. This leads to the alteration in the permeability of the cell
wall.
 Uses:-
• tinea infections like ringworm
• Atheletes’ foot
• Otomycosis
• candidiasis
 BECLOMETHASONE
 Beclomethasone dipropionate is a second-generation synthetic corticosteroid agent.
 MOA- It is a prodrug of an active metabolite beclomethasone 17-monopropionate (17-
BMP) which acts on the glucocorticoid receptor to mediates its therapeutic action.
 Uses- Due to its anti-inflammatory, antipruritic, and anti-allergy properties, beclomethasone
dipropionate is used in various inflammatory conditions, such as asthma, allergic rhinitis, and
dermatoses to reduce symptom
NEOMYCIN
 Obtained from Streptomyces fradiae. It is a bactericidal aminoglycoside antibiotic.
 MOA- It binds to the 30S ribosome of susceptible organisms. Prevent polysome formation
and promote their disaggregation to non-functional monosmes. Bimding to 30-50S juncture
causes distortion of mRNA codon recognition resulting in misreading of the code. Hence,
non functional or toxic chains are produced.
 Spectrum- active against most gram-negative bacilli and some gram-positive cocci.
FORMULATIONS
HOW DOES THE COMBINATION WORKS?
• This cream and ointment are prescribed to treat various inflammatory skin
conditions that are either already infected or likely to get infected. These
include eczema and dermatitis of various types, psoriasis, lichen simplex, lichen
planus, insect bite reactions, fungal infections.
• Beclomethasone works by stopping skin cells releasing various inflammatory
substances that make blood vessels widen and cause the skin to become red,
swollen, itchy and painful. It reduces the swelling, redness and itching and so
helps prevent scratching that can further irritate the skin.
• Neomycin works by causing bacteria to produce abnormal and faulty proteins.
This ultimately kills the bacteria and clears up any infection.
• While Clotrimazole is an azole antifungal that works by preventing the growth
of fungus.
WHY IT IS IRRATIONAL ?
FDCs consisting of potent topical corticosteroids such as clobetasol or betamethasone
or Fluticasone, in combination with antifungal agents such as miconazole or
clotrimazole or tolnaftate added with topical antibacterial agents such as gentamicin,
neomycin, nadifloxacin, and fusidic acid. Sometimes, compounds such as lignocaine,
zinc sulfate, and lodochlorohydroxyquinone were added to the above combination
without any rationale.
These combinations were used by physicians or general practitioners (GPs) when
etiology of the majority of skin diseases was not properly understood and no effective
and specific drug was available.
Reports of adverse role of steroid-containing FDC in the development of resistance to
a number of current generation of antifungal agents.
This has resulted in a lot of side effects and has caused an immense loss to a vital and
the largest organ of the human body, i.e., skin. Local side effects included
 irreversible or permanent local skin atrophy,
 Telangiectasia,
 Purpura,
 Striae,
 Hypertrichosis,
 acneiform eruptions,
 secondary bacterial or viral infections,
 perioral dermatitis
 hypopigmentation.
• As it has produced temporary but rapid benefits, self use or abuse of these FDCs
spread like a wild fire!
TENOFOVIR+
E M T R I C I TA B I N E +
LO P I N AV I R / R I T O N AV I R
EMTRICITABINE

• Nucleoside reverse transcriptase inhibitor


• Fluorinated cytidine analogue
• Cellular kinase converts to active compound
• Inhibit viral reverse transcriptase
• Little metabolised and excreted mainly by kidneys
• Hyperpigmentation of palm and soles
• Hepatomegaly and lactic acidosis
TENOFOVIR DISOPROXIL

• Nucleotide analogue, phosphorylated in cells to active compound


• Acts by inhibiting viral reverse transcriptase via chain termination
• Inhibitor of cytochrome P450 1A2
• Excreted mainly by kidneys
TENOFOVIR TOXICITY
• Serious adverse effects includes
• Lactic acidosis
• Hepatotoxicity and hepatomegaly
• Nephrotoxicity and bone loss, can present as Fanconi syndrome
• Fanconi syndrome: damage to proximal convoluted tubules leads to
inefficient reabsorption of metabolites like amio acids, glucose, uric acid,
phosphate(a/w osteomyelitis) , bicarbonates(renal tubular acidosis)
RITONAVIR

• Protease inhibitor
• Rarely used for its own antiviral activity, potent inhibitor of cyt P450-3A4 inhibitor
• And inducer of cyp1A2
• This property used to boost bioavailability of other protease inhibitors by inhibiting their
hepatic metabolism
• Also affect the efficacy of several other medicines.
LOPINAVIR
• Protease inhibitor
• Protease cleaves protein precursors to proteins which take part in
production of new infective viral particles
• Non infective viral particles produced
• Mainly metabolised by liver
• Always given in a preparation with ritonavir to decrease its metabolism.
• Drug interaction of the combination of lopinavir and ritonavir is frequent
with the drugs which are metabolised by cyp3a system
• Hyperlipidaemia, raised liver enzymes
• ECG changes observed during treatment
RATIONALE

• 4 week regimen of at least 2 NRTI ARV drugs and a 3rd drug of a different class found to significantly
decrease the risk of dissemination of infection

• Therapy used for post exposure prophylaxis of HIV infection


• Tenofovir and emtricitabine are NRTI, Lopinavir/ritonavir are protease inhibitor
• Desirable qualities of the FDC
• Patient compliance
• Availability of all components of
• Cost
• The above NRTI drugs are excreted unchanged by kidneys and lopinavir/R is metabolised by liver,
both of kidney diseases and liver diseases require dosage modifications of medications which is not
possible in a FDC.
HALF LIFE

• Tinofovir 17 hours
• Lopinavir/ritonavir
• Emtricitabine intracellular 40 hours serum 10hrs
THANK YOU

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