Ritonavir: profile and news
Glaxo-Vertex Study tests anti-HIV drugs 16 May 2006
In the 887-person study, patients were given twice a day either 700 milligrams of Lexiva along with 100 milligrams of ritonavir -- the active ingredient in ... - BusinessWeek
Star of the Batman Television Series Leads Crusade for Baby ... 16 May 2006
Do not take UROXATRAL if you have liver problems or if you are taking the antifungal drugs ketoconazole or itraconazole, or HIV drugs like ritonavir. ... - PharmaLive.com (press release),
International Approvals: Invirase and Remicade May 15, 2006
Saquinavir is indicated for use in combination with ritonavir (100 mg twice daily) and other antiretroviral agents in the treatment of HIV infection. ... - Medscape (subscription)
What do we know about the links between recreational drug use ... May 15, 2006
The authors mention individual cases of very high doses of ecstasy and GHB in patients taking ritonavir (Norvir), with at least one death attributed to very ... - Aidsmap,
HIV Pharmacology Workshop: Explaining tenofovir renal toxicities ... May 2, 2006
...at Gilead demonstrated in vitro which drug transporters may be responsible for drug-drug interactions between tenofovir and atazanavir, lopinavir and ritonavir ... - Aidsmap,
Abbott issued positive EU opinion for Kaletra tablets May 2, 2006
The European Commission decision regarding marketing authorization for Kaletra (lopinavir/ritonavir) is expected within 90 days. ... - Pharmaceutical Business Review
Bristol-Myers Squibb and Gilead Sciences Submit New Drug ... Apr 27, 2006
Drug interactions have been observed when didanosine, atazanavir, or lopinavir/ritonavir are co-administered with Viread, a component of Truvada, and dose ... - International News Service,
African Leaders Advised On HIV/AIDS Drugs May 5, 2006
Kaletra, a new drug containing Liponavir and Ritonavir manufactured by Abott Laboratories, a Chicago based company, has been identified as the most appropriate ... - Nigerian Tribune,
More Empty Promises: Abbott Fails to Supply Critical New AIDS Drug ... Apr 27, 2006
MSF urges the Chicago-based drug company to take immediate steps to make the heat-stable tablet version of lopinavir/ritonavir, marketed as Kaletra, available ... - Doctors Without Borders,
Fighting HIV — Lessons from Brazil May 10, 2006
Instead, the government reached an agreement last year with Abbott almost halving the price of the drug Kaletra (lopinavir–ritonavir), and it continues to ... - New England Journal of Medicine (subscription),
Abbott's New Tablet Formulation Of Anti-HIV Drug Kaletra And ... Apr 28, 2006
Abbott stated that the new tablet formulation of Kaletra would be composed of 200 mg lopinavir and 50 mg ritonavir, compared to the current soft capsule, which ... - Trading Markets,
Starting treatment with Kaletra involves greater risk of increased ... Apr 24, 2006
Individuals taking an antiretroviral regimen containing the protease inhibitor Kaletra (lopinavir/ritonavir) appear to have the highest risk of developing high ... - Aidsmap,
US firm asked to cut price of drug regimen May 1, 2006
...response from the US manufacturer who said Abbot Laboratories would sell the new version of the second-line fixed dose combination lopinavir/ritonavir (LPV/r ... - Bangkok Post,
Gilead Sciences Announces First Quarter 2006 Financial Results Apr 18, 2006
Infections and showed significant reductions in viral load among HIV-positive patients receiving GS 9137 as monotherapy or in combination with ritonavir as a ... - Genetic Engineering News,
Is diabetes a complication of HIV infection? May 7, 2006
...prophylaxis and an anti-HIV drug combination of 200mg FTC (emtricitabine, Emtriva), 300mg tenofovir (Viread) and six capsules of ritonavir-boosted lopinavir ... - Aidsmap,
FDA: Adult HIV Treatment Guidelines Updated May 4, 2006
Tables have been revised to include up-to-date information about drug interactions and about the lopinavir/ritonavir 200/50 mg tablet formulation. ... - PharmaLive.com (press release),
(PRN) - UN Foundation Malaria Prevention Program Featured in ... Apr 28, 2006
...[+]. (PRN) - Abbott's New Tablet Formulation of Kaletra(R) (Lopinavir/Ritonavir) Receives Positive Opinion From the European Medicines Agency ... [+. ... - Bolsamania.com,
Tablet version of Kaletra receives European green light; MSF calls ... Apr 28, 2006
Abbott’s new tablet formulation of Kaletra (lopinavir/ritonavir) has received a positive opinion from the scientific committee of the European Medicines ... - Aidsmap,
GW students rally against drug co. Apr 19, 2006
The protestors demanded Abbot Laboratories provide the new drug, Kaletra (a combination of drugs Lopinavir and Ritonavir), at affordable prices to the global ... - Daily Colonial,
Accurate timing of drug doses improves response to HIV treatment Apr 26, 2006
...do not give any information on how many patients in their study were taking these drugs, or what proportion were taking ritonavir-boosted protease inhibitors. ... - Aidsmap,
Astellas Launches VAPRISOL(R) for the Treatment of Euvolemic ... Apr 26, 2006
The co-administration of VAPRISOL with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir, is also ... - Yahoo! News (press release)
Panacos Reports First Quarter 2006 Financial Results; PA-457 Phase ... Apr 26, 2006
...the Phase 2b trial of PA-457, including two drug interaction trials studying the effects of coadministration of PA-457 with atazanavir and ritonavir, a trial ... - PharmaLive.com (press release),
Other information
Indication
Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.
Pharmacology
Ritonavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Ritonavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Mechanism Of Action
Ritonavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Drug Category
Anti-HIV Agents; HIV Protease Inhibitors; ATC:J05AE03
Brand Names/Synonyms
Abbott 84538; Kaletra; Norvir; Norvir Sec; Ritonavir; Ritonavir [Usan]
Dosage Forms
CAPSULE (100 mg); SOLUTION (80 mg/mL of ritonavir)
Absorption
The absolute bioavailability of ritonavir has not been determined.
Interactions
-->Interactions for Ritonavir:
Ritonavir has been found to be an inhibitor of cytochrome P450 3A (CYP3A) both in vitro and in vivo
(Table 2). Agents that are extensively metabolized by CYP3A and have high first pass metabolism appear to be the most
susceptible to large increases in AUC (>3-fold) when co-administered with ritonavir. Ritonavir also inhibits
CYP2D6 to a lesser extent. Co-administration of substrates of CYP2D6 with ritonavir could result in increases (up to
2-fold) in the AUC of the other agent, possibly requiring a proportional dosage reduction. Ritonavir also appears to
induce CYP3A as well as other enzymes, including glucuronosyl transferase, CYP1A2, and possibly CYP2C9.
Drugs that are contraindicated specifically due to the expected magnitude of interaction and potential for serious
adverse events are listed both in CONTRAINDICATIONS Table 3 and under Contraindicated Drugs in Table
4.
Those drug interactions that have been established based on drug interaction studies are listed with the
pharmacokinetic results in CLINICAL PHARMACOLOGY , Table 2. The clinical recommendations based on the results
of these studies are listed in Table 4 Established Drug Interactions: Alteration in Dose or Regimen Recommended
Based on Drug Interaction Studies.
A systematic review of over 200 medications prescribed to HIV-infected patients was performed to identify
potential drug interactions with ritonavir. 2 There are a number of agents in which CYP3A or CYP2D6
partially contribute to the metabolism of the agent. In these cases, the magnitude of the interaction and therapeutic
consequences cannot be predicted with any certainty.
When co-administering ritonavir with calcium channel blockers, immunosuppressants, some HMG-CoA reductase
inhibitors, some steroids, or other substrates of CYP3A, or most antidepressants, certain antiarrhythmics, and some
narcotic analgesics which are partially mediated by CYP2D6 metabolism, it is possible that substantial increases in
concentrations of these other agents may occur, possibly requiring a dosage reduction (>50%); examples are listed
in Table 4 Predicted Drug Interactions: Use With Caution, Dose Decrease May be Needed.
When co-administering ritonavir with any agent having a narrow therapeutic margin, such as anticoagulants,
anticonvulsants, and antiarrhythmics, special attention is warranted. With some agents, the metabolism may be
induced, resulting in decreased concentrations.
Table 4
Drug Interactions With NORVIR
CONTRAINDICATED DRUGS
(Same as Table 3)
|
DRUGS THAT ARE CONTRAINDICATED WITH
NORVIR USE
|
|
Drug Class
|
Drugs Within Class That Are
CONTRAINDICATED With NORVIR
|
|
Antiarrhythmics
|
amiodarone, bepridil, flecainide, propafenone, quinidine
|
|
Antihistamines
|
astemizole, terfenadine
|
|
Antimigraine
|
dihydroergotamine, ergotamine
|
|
Sedative/hypnotics
|
midazolam, triazolam
|
|
GI motility agent
|
cisapride
|
|
Neuroleptic
|
pimozide
|
Established Drug Interactions: Alteration in Dose or
Regimen Recommended Based
on Drug Interaction Studies
|
Drug Name
|
Effect
|
Clinical Comment
|
|
Clarithromycin
|
up clarithromycin
concentration
|
For patients with renal impairment the following dosage adjustments should be considered:
· For patients with CL CR 30 to 60 mL/min the dose of clarithromycin should be reduced
by 50%.
· For patients with CL CR < 30 mL/min the dose of clarithromycin should be decreased
by 75%.
No dose adjustment for patients with normal renal function is necessary.
|
|
Desipramine
|
up desipramine concentration
|
Dosage reduction and concentration monitoring of desipramine is recommended
|
|
Didanosine
|
|
Dosing of didanosine and ritonavir should be separated by 2.5 hours to avoid formulation incompatibility
|
|
Disulfiram/Metronidazole
|
|
Ritonavir formulations contain alcohol, which can produce disulfiram-like reactions when co-administered
with disulfiram or other drugs that produce this reaction (e.g., metronidazole)
|
|
Indinavir
|
up indinavir concentration
|
Appropriate doses for this combination, with respect to efficacy and safety, have not been established
|
|
Ketoconazole
|
up ketoconazole concentration
|
High doses of ketoconazole (>200 mg/day) are not recommended
|
|
Meperidine
|
down meperidine concentration/
up normeperidine
concentration (metabolite)
|
Dosage increase and long-term use of meperidine with ritonavir are not recommended due to the increased
concentrations of the metabolite normeperidine which has both analgesic activity and CNS stimulant
activity (e.g., seizures)
|
|
Methadone
|
down methadone concentration
|
Dosage increase of methadone may be considered
|
|
Oral Contraceptives
|
down ethinyl estradiol
concentration
|
Dosage increase or alternate contraceptive measures should be considered
|
|
Rifabutin
|
up rifabutin and rifabutin
metabolite concentration
|
Dosage reduction of rifabutin by at least three-quarters of the usual dose of 300 mg/day is recommended
(e.g., 150 mg every other day or three times a week). Further dosage reduction may be necessary
|
|
Rifampin
|
down ritonavir concentration
|
Alternate antimycobacterial agents such as rifabutin should be considered
|
|
Saquinavir
|
up saquinavir concentration
|
When used in combination therapy for up to 24 weeks, doses of 400 mg b.i.d. of ritonavir and saquinavir
were better tolerated than the higher doses of the combination. Saquinavir plasma concentrations achieved
with Invirase® (saquinavir mesylate) (400 mg b.i.d.) and ritonavir (400 mg b.i.d.) are similar to
those achieved with Fortovaseô (saquinavir) (400 mg b.i.d.) and ritonavir (400 mg b.i.d.)
|
|
Sildenafil
|
up sildenafil concentration
|
Sildenafil should not exceed a maximum single dose of
25 mg in a 48-hour period in patients receiving concomitant ritonavir therapy
|
|
Theophylline
|
down theophylline concentration
|
Increased dosage of theophylline may be required; therapeutic monitoring should be considered
|
|
Predicted Drug Interactions: Use With Caution, Dose
Decrease of Coadministered Drug May Be Needed
|
Examples of Drugs in Which Plasma Concentrations May Be Increased
By Co-Administration With NORVIR |
|
Drug Class
|
Examples of Drugs
|
|
Analgesics, narcotic
|
tramadol, propoxyphene
|
|
Antiarrhythmics
|
disopyramide, lidocaine, mexilitine
|
|
Anticonvulsants
|
carbamazepine, clonazepam, ethosuximide
|
|
Antidepressants
|
bupropion, nefazodone, selective serotonin reuptake inhibitors (SSRIs), tricyclics
|
|
Antiemetics
|
dronabinol
|
|
Antiparasitics
|
quinine
|
|
(beta)-blockers
|
metoprolol, timolol
|
|
Calcium channel blockers
|
diltiazem, nifedipine, verapamil
|
|
Hypolipidemics, HMG CoA reductase inhibitors 1
|
atorvastatin, cerivastatin, lovastatin, simvastatin
|
|
Immunosuppressants
|
cyclosporine, tacrolimus
|
|
Neuroleptics
|
perphenazine, risperidone, thioridazine
|
|
Sedative/hypnotics
|
clorazepate, diazepam, estazolam, flurazepam, zolpidem
|
|
Steroids
|
dexamethasone, prednisone
|
|
Stimulants
|
methamphetamine
|
|
1 Coadministration with lovastatin and simvastatin is not recommended.
|
|
Predicted Drug Interactions: Use With Caution, Dose Increase of Coadministered Drug May Be Needed
|
|
Examples of Drugs in Which Plasma Concentrations
May Be Decreased By Co-Administration
With NORVIR
|
|
Anticoagulants
|
warfarin
|
|
Anticonvulsants
|
phenytoin, divalproex, lamotrigine
|
|
Antiparasitics
|
atovaquone
|
Post-Marketing Experience with Drugs Listed in Table 4
Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide,
mexiletine, nefazodone, fluoxetine, and beta blockers. The possibility of drug interaction cannot be excluded.
Chemical IUPAC Name
1,3-thiazol-5-ylmethyl [3-hydroxy-5-[3-methyl-2-[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino-butanoyl]amino-1,6-diphenyl-hexan-2-yl]aminoformate
Chemical Formula
C37H48N6O5S2
Half Life
3-5 hours
Drug Type
Approved Drug
# Accession No
APRD00312
CAS Registry Number
155213-67-5
