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Apropovir

Apropovir - General Information

Apropovir, marketed by Gilead Sciences under the trade name Viread®, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. [Wikipedia]

 

Pharmacology of Apropovir

Apropovir belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NtRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. Apropovir is currently in late-stage clinical trials for the treatment of hepatitis B. Apropovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Apropovir requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Apropovir diphosphate is a weak inhibitor of mammalian DNA polymerases α, β, and mitochondrial DNA polymerase γ.

 

Apropovir for patients

VIREAD™ (VEER ee ad)

Generic Name: tenofovir disoproxil fumarate

(te NOE' fo veer dye soe PROX il FYOU-mar-ate)

Read this leaflet carefully before you start taking VIREAD. Also, read it each time you get your VIREAD prescription refilled, in case something has changed. This information does not take the place of talking with your doctor when you start this medicine and at check ups. You should stay under a doctor's care when taking VIREAD. Do not change or stop your medicine without first talking with your doctor. Talk to your doctor if you have any questions about VIREAD.

What is VIREAD and how does it work?

VIREAD is a type of medicine called an HIV (human immunodeficiency virus) nucleotide analog reverse transcriptase inhibitor (NRTI). VIREAD is always used in combination with other anti-HIV medicines to treat people with HIV infection. VIREAD is for adults age 18 and older.

HIV infection destroys CD4 (T) cells, which are important to the immune system. After a large number of T cells are destroyed, acquired immune deficiency syndrome (AIDS) develops.

VIREAD helps to block HIV reverse transcriptase, a chemical in your body (enzyme) that is needed for HIV to multiply. VIREAD lowers the amount of HIV in the blood (called viral load) and may help to increase the number of T cells (called CD4 cells). Lowering the amount of HIV in the blood lowers the chance of death or infections that happen when your immune system is weak (opportunistic infections).

Does VIREAD cure HIV or AIDS?

VIREAD does not cure HIV infection or AIDS. The long-term effects of VIREAD are not known at this time. People taking VIREAD may still get opportunistic infections or other conditions that happen with HIV infection. Opportunistic infections are infections that develop because the immune system is weak. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.

Does VIREAD reduce the risk of passing HIV to others?

VIREAD does not reduce the risk of passing HIV to others through sexual contact or blood contamination.

Continue to practice safe sex and do not use or share dirty needles.

Who should not take VIREAD?

Together with your doctor, you need to decide whether VIREAD is right for you.

Do not take VIREAD if

• you have kidney problems. VIREAD has not been studied in people with kidney problems

• you are allergic to VIREAD or any of its ingredients

What should I tell my doctor before taking VIREAD?

Tell your doctor

• If you are pregnant or planning to become pregnant: The effects of VIREAD on pregnant women or their unborn babies are not known.

• If you are breast-feeding: Do not breast-feed if you are taking VIREAD. Do not breast-feed if you have HIV. If you are a woman who has or will have a baby, talk with your doctor about the best way to feed your baby. If your baby does not already have HIV, there is a chance that the baby can get HIV through breast-feeding.

Tell your doctor about all your medical conditions, especially liver and kidney problems.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines and dietary supplements. VIREAD may increase the amount of Videx (didanosine) in your blood. You may need to be followed more carefully if you are taking these two drugs together.

It is a good idea to keep a complete list of all the medicines that you take. Make a new list when medicines are added or stopped. Give copies of this list to all of your healthcare providers every time you visit your doctor or fill a prescription.

How should I take VIREAD?

• Stay under a doctor's care when taking VIREAD. Do not change your treatment or stop treatment without first talking with your doctor.

• Take VIREAD every day exactly as your doctor prescribed it. Follow the directions from your doctor, exactly as written on the label. Set up a dosing schedule and follow it carefully.

• The usual dose of VIREAD is 1 tablet once a day, in combination with other anti-HIV medicines.

• Take VIREAD with a meal. The amount of VIREAD in your blood increases with food. Taking it with food helps it work better.

• When your VIREAD supply starts to run low, get more from your doctor or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to VIREAD and become harder to treat.

• Only take medicine that has been prescribed specifically for you. Do not give VIREAD to others or take medicine prescribed for someone else.

What should I do if I miss a dose of VIREAD?

It is important that you do not miss any doses. If you miss a dose of VIREAD, take it as soon as possible and then take your next scheduled dose at its regular time. If it is almost time for your next dose, do not take the missed dose. Wait and take the next dose at the regular time. Do not double the next dose.

What happens if I take too much VIREAD?

If you suspect that you took more than the prescribed dose of VIREAD, contact your local poison control center or emergency room right away.

As with all medicines, VIREAD should be kept out of reach of children.

What should I avoid while taking VIREAD?

Do not breast-feed. See "What should I tell my doctor before taking VIREAD?"

What are the possible side effects of VIREAD?

• The most common side effects of VIREAD are: diarrhea, nausea, vomiting, and flatulence (intestinal gas).

• VIREAD caused harm to the bones of animals. These effects have not been seen in persons taking VIREAD for up to one year. It is not known if the effects will be seen in persons taking VIREAD for longer periods of time.

• Changes in body fat have been seen in some patients taking anti-HIV medicine. These changes may include increased amount of fat in the upper back and neck ("buffalo hump"),breast, and around the main part of your body (trunk). Loss of fat from the legs, arms and face may also happen. The cause and long term health effects of these conditions are not known at this time.

• There have been other side effects in patients taking VIREAD. However, these side effects may have been due to other medicines that patients were taking or to the illness itself. Some of these side effects can be serious.

• This list of side effects is not complete. If you have questions about side effects, ask your doctor, nurse, or pharmacist. You should report any new or continuing symptoms to your doctor right away. Your doctor may be able to help you manage these side effects.

Marketing experience: Other side effects reported since VIREAD has been marketed include: weakness, inflammation of the pancreas, low blood phosphate, dizziness, shortness of breath, and rash.

• Some patients treated with VIREAD have had kidney problems. Your doctor may need to perform additional blood tests if you have had kidney problems in the past or need to take another drug that can also cause kidney problems.

 

Apropovir Interactions

At concentrations substantially higher (~ 300-fold) than those observed in vivo, tenofovir did not inhibit in vitro drug metabolism mediated by any of the following human CYP450 isoforms: CYP3A4, CYP2D6, CYP2C9 or CYP2E1. However, a small (6%) but statistically significant reduction in metabolism of CYP1A substrate was observed. Based on the results of in vitro experiments and the known elimination pathway of tenofovir, the potential for CYP450 mediated interactions involving tenofovir with other medicinal products is low.

Tenofovir is primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion. Co-administration of VIREAD with drugs that are eliminated by active tubular secretion may increase serum concentrations of either tenofovir or the co-administered drug, due to competition for this elimination pathway. Drugs that decrease renal function may also increase serum concentrations of tenofovir.

VIREAD has been evaluated in healthy volunteers in combination with didanosine, lamivudine, indinavir, efavirenz, and lopinavir / ritonavir. Tables 1 and 2 summarize pharmacokinetic effects of co-administered drug on tenofovir pharmacokinetics and effects of tenofovir on the pharmacokinetics of co-administered drug.

Table 1. Drug Interactions: Changes in Pharmacokinetic Parameters for Tenofovir1 in the Presence of the Co-administered Drug

Co-administered Drug

Dose of Co-administered Drug (mg)

N

% Change of Tenofovir Pharmacokinetic Parameters2 (90% CI)

Cmax

AUC

Cmin

Lamivudine

150 twice daily x 7 days

15

Ø

Ø

Ø

Didanosine

Enteric coated

400 X 1
25

Ø

Ø

Ø

Didanosine3

Buffered

250 or 400 once daily x 7 days

14

Ø

Ø

Ø

Indinavir

800 three times daily x 7 days

13

14

( 3 to 33)

Ø

Ø

Lopinavir/ Ritonavir

400/100 twice daily x 14 days

21

31

( 12 to 53)

34

( 25 to 44)

29

( 11 to 48)

Efavirenz

600 once daily x 14 days

29

Ø

Ø

Ø

 

1. Patients received VIREAD 300 mg once daily

2. Increase= ; Decrease= ; No Effect= Ø

3. Buffered formulation

Table 2. Drug Interactions: Changes in Pharmacokinetic Parameters for Co-administered Drug in the Presence of VIREAD 300 mg Once Daily

Co-administered Drug

Dose of Coadmin-istered Drug (mg)

N

% Change of Co-administered Drug Pharmacokinetic Parameters1 (90% CI)

Cmax

AUC

Cmin

Lamivudine

150 twice daily x 7 days

15

24

( 34 to 12)

Ø

Ø

Didanosine2 (enteric coated, without food, see PRECAUTIONS)
400 x 1
26

48

( 25 to 76)

48

( 31 to 67)

ñ
Didanosine3 (enteric coated, with food, see PRECAUTIONS)
400 x 1
26

64

( 41 to 89)

60

( 44 to 79)

ñ

Didanosine2

buffered (see PRECAUTIONS)

250 or 400 once daily x 7 days

14

28

( 11 to 48)

44

( 31 to 59)

ñ

Indinavir

800 three times daily x 7 days

12

11

( 30 to 12)

Ø

Ø

Lopinavir

Lopinavir/Ritonavir 400/100 twice daily x 14 days

21

15

( 23 to 6)

15

( 22 to 7)

Ø

Ritonavir 400/100 twice

Lopinavir/Ritonavir daily x 14 days

21

28

( 43 to 9)

24

( 33 to 13)

7

( 22 to 37)

Efavirenz

600 once daily x 14 days

30

Ø

Ø

Ø

 

1. Increase= ; Decrease= ; No Effect= Ø

2. Buffered formulation

 

Apropovir Contraindications

VIREAD is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product.

 

Additional information about Apropovir

Apropovir Indication: For use, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.
Mechanism Of Action: Apropovir inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Tenofovir
Synonyms: Tenofovir disoproxil; Tenofovir disoproxil fumarate; D,L-Tenofovir; TDF; PMPA
Drug Category: Anti-HIV Agents; Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Tenofovir: Apropovir; Viread;
Absorption: The oral bioavailability in fasted patients is approximately 25%. Administration of food (high fat meal containing 40 to 50% fat) increases the oral bioavailability, with an increase in the AUC of approximately 40%.
Toxicity (Overdose): Limited clinical experience at doses higher than the therapeutic dose of tenofovir 300 mg is available. In Study 901 tenofovir disoproxil fumarate 600 mg was administered to 8 patients orally for 28 days. No severe adverse reactions were reported. The effects of higher doses are not known.
Protein Binding: Very low: < 0.7% to human plasma proteins and < 7.2% to serum proteins
Biotransformation: Neither tenofovir disoproxil nor tenofovir are substrates of CYP450 enzymes.
Half Life: Approximately 17 hours.
Dosage Forms of Apropovir: Tablet Oral
Chemical IUPAC Name: [(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphonic acid
Chemical Formula: C9H14N5O4P
Tenofovir on Wikipedia: http://en.wikipedia.org/wiki/Tenofovir
Organisms Affected: Human Immunodeficiency Virus