Lamivudine

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Structural formula
Lamivudine structural formula
General
Non-proprietary name Lamivudine
other names
  • (-) - 2'-Deoxy-3'-thiacytidine
  • 3TC
  • (-) - 4-Amino-1 - [(2 R , 5 S ) -2- (hydroxymethyl) -1,3-oxathiolan-5-yl] pyrimidin-2-one
Molecular formula C 8 H 11 N 3 O 3 S
Brief description

white to almost white, polymorphic powder

External identifiers / databases
CAS number 134678-17-4
EC number 603-844-3
ECHA InfoCard 100.132.250
PubChem 60825
ChemSpider 54812
DrugBank DB00709
Wikidata Q422631
Drug information
ATC code

J05 AF05

Drug class

Antiviral agent , nucleoside reverse transcriptase inhibitors

Mechanism of action

Competitive inhibition of reverse transcriptase

properties
Molar mass 229.257 g · mol -1
Physical state

firmly

Melting point

160-162 ° C

solubility

soluble in water (70 mg ml −1 ), slightly soluble in methanol , sparingly soluble in ethanol

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 315-319-335
P: 261-305 + 351 + 338
Toxicological data

> 2000 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lamivudine , 3TC for short (trade names: Epivir ® , Zeffix ® ; manufacturer: GlaxoSmithKline ) is a drug for the treatment of HIV-1 infected patients as part of an antiretroviral therapy ( HAART ) and chronic HBV infection.

It is a chemical analog of the nucleoside cytidine and belongs to the group of nucleoside reverse transcriptase inhibitors (NRTIs).

history

Lamivudine has been approved in Germany since 1995. In the fixed combination Kivexa with abacavir (ABC), it is currently the second most common NRTI backbone of HIV therapy after Truvada ( tenofovir plus emtricitabine ).

pharmacology

Lamivudine is converted to a 5'-triphosphate intracellularly. Like other nucleoside analogues, it can be incorporated into the viral DNA and leads to the breakdown of DNA synthesis.

Pharmacokinetics

The bioavailability of lamivudine after oral administration is approximately 80%. After the usual dosage (2 mg / kg body weight twice a day), the maximum serum concentrations are 1.5 to 1.9 mg / l. Simultaneous food intake does not significantly affect bioavailability . The volume of distribution is given as 1.3 l / kg body weight. With a half-life of 5 to 7 hours, the drug is eliminated mainly unchanged by the kidneys. The binding to plasma proteins is low. In renal insufficiency (clearance <50 ml / min), a dose of 150 mg is administered only every 24 hours; If the kidney function is restricted to a greater extent, the individual dose should first be halved and then further adjusted according to the individual situation.

Side effects

Side effects that may occur with treatment are:

Common: headache , insomnia , cough , nasal symptoms, nausea, vomiting, abdominal pain, diarrhea, rash, alopecia , arthralgia, muscle discomfort, fatigue, malaise, fever

Uncommon: neutropenia , anemia , thrombocytopenia , transient increase in liver enzymes

Rare: pancreatitis , increased serum amylase , hepatitis , angioedema , rhabdomyolysis

Very rare: erythroblastopenia , lactic acidosis , peripheral neuropathy

Resistances

In monotherapy, HI viruses develop resistance to lamivudine relatively easily: a single mutation in the genetic material (M184V or M184I) is sufficient to make HIV highly resistant to lamivudine. Therefore, lamivudine for HIV therapy must always be given in combination with at least one other antiretroviral drug.

Dosage forms

Lamivudine is administered orally: for example in the form of tablets of 100 mg, 150 mg or 300 mg and an oral solution. There are also fixed combinations with zidovudine or abacavir.

Individual evidence

  1. ↑ a b c LAMIVUDINE CRS data sheet (PDF) at EDQM , accessed on February 26, 2009.
  2. ↑ a b Entry on lamivudine in the DrugBank of the University of Alberta .
  3. ↑ a b Lamivudine data sheet from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).
  4. ↑ a b lamivudine , information from the magazine for chemotherapy, from issue 6, 1996.
  5. ↑ GSK: ViiV Healthcare Fachinformation Epivir , February 2019, accessed on April 10, 2019.

Trade names

Monopreparations

3TC (CH), Epivir (D, A), Zeffix (D, CH),

Combination preparations

Combivir (D, A, CH), Kivexa (D, A, CH), Trizivir (D, CH), Dovato (D)

Web links