saquinavir

American Heritage Dictionary:

sa·quin·a·vir

(sə-kwĭn'ə-vîr) pronunciation

n.
A protease-inhibiting drug usually used in combination with other drugs to suppress the replication of HIV.

[saquin- (perhaps alteration of (i)soquin(oline) : ISO- + QUINOLINE) + A(NTI)VIR(AL).]

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Saquinavir

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Brand names: Fortovase®, Invirase®

Chemical formula:

Drug Forms:

Saquinavir Mesylate Oral tablet (below)
Saquinavir Mesylate Oral capsule

Espa�ol:

Mesilato de saquinavir, Tableta oral
Mesilato de saquinavir, Cápsula oral

Saquinavir Mesylate Oral tablet

What is this medicine?

SAQUINAVIR (sa KWIN a veer) is an antiretroviral medicine. It is used with other medicines to treat HIV. This medicine is not a cure for HIV. It will not stop the spread of HIV to others.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•diabetes
•heart disease
•hemophilia
•history of irregular heartbeat
•history of low levels of calcium, magnesium, or potassium in the blood
•liver disease
•an unusual or allergic reaction to saquinavir, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Take this medicine with food. Take this medicine with ritonavir at regular intervals. Do not take your medicine more often than directed. For your anti-HIV therapy to work as well as possible, take each dose exactly as prescribed. Do not skip doses or stop your medicine even if you feel better. Skipping doses may make the HIV virus resistant to this medicine and other medicines. Do not stop taking except on your doctor's advice.

A special MedGuide will be given to you by the pharmacist with each prescription and refill. Be sure to read this information carefully each time.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

Try not to miss an appointment. Call your prescriber or health care professional for advice if you miss a dose.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•alfuzosin
•arsenic trioxide
•certain medicines for cholesterol like cerivastatin, lovastatin, simvastatin
•chloroquine
•cisapride
•clarithromycin
•droperidol
•erythromycin
•garlic supplements
•haloperidol
•medicines for headaches like dihydroergotamine, ergonovine, ergotamine, methylergonovine
•medicines for irregular heart beat like amiodarone, disopyramide, dofetilide, flecainide, ibutilide, lidocaine, procainamide, propafenone, sotalol, quinidine
•methadone
•midazolam
•pentamidine
•pimozide
•ranolazine
•red yeast rice
•rifampin
•rifapentine
•sildenafil
•St. John's wort
•thioridazine
•trazodone
•triazolam
•ziprasidone

This medicine may also interact with the following medications:
•atorvastatin
•certain medicines for blood pressure, heart disease, irregular heart beat
•cyclosporine
•dexamethasone
•female hormones, like estrogens or progestins and birth control pills, patches, rings, or injections
•fluticasone
•medicines for depression, anxiety, or psychotic disturbances
•medicines for diabetes
•medicines for erectile dysfunction
•medicines for fungal infections like ketoconazole and itraconazole
•medicines for seizures like carbamazepine, phenobarbital, phenytoin
•medicines for stomach problems like esomeprazole, omeprazole, pantoprazole, rabeprazole, ranitidine
•other medicines for HIV
•rapamycin
•rifabutin
•tacrolimus
•warfarin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular check ups. Discuss any new symptoms with your doctor. You will need to have important blood work done while on this medicine.

HIV is spread to others through sexual or blood contact. Talk to your doctor about how to stop the spread of HIV.

Birth control pills may not work properly while you are taking this medicine. Talk to your doctor about using an extra method of birth control. Women who can still have children must use a reliable form of barrier contraception, like a condom or diaphragm.

This medicine may affect blood sugar levels. If you have diabetes, check with your doctor or health care professional before you change your diet or the dose of your diabetic medicine.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•fast, irregular heartbeat
•feeling faint or lightheaded, falls
•unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•diarrhea
•increased hunger or thirst
•increased urination
•nausea, vomiting
•stomach pain
•weight gain around waist, back, or thinning of face, arms, legs

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store tightly closed at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from moisture. Throw away any unused medicine after the expiration date.

Last updated: 10/13/2005 2:50:00 PM

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Oxford A-Z of Medicinal Drugs:

saquinavir

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A protease inhibitor (see antiviral drugs), similar to indinavir, used in combination with other antiretrovirals for the treatment of HIV disease. It is available as capsules on prescription only.

Side effects:
include diarrhoea, dry mouth, abdominal discomfort, nausea, headache, peripheral neuropathy (causing tingling and numbness in the limbs), breathlessness, increased appetite, loss of hair, and rashes.

Precautions:
saquinavir should be used with caution by people with impaired kidney or liver function or haemophilia and by pregnant women. It should not be used during breastfeeding.

Interactions with other drugs:
saquinavir interacts with a number of drugs, including those listed below, and it is therefore important to inform a doctor before taking any other medicines with saquinavir.
Antiepileptic drugs: primidone, phenobarbital, phenytoin, and carbamazepine can reduce the plasma concentration (and therefore effectiveness) of saquinavir.
Antimigraine drugs: the toxic effects of ergotamine and methysergide may be increased.
Antipsychotic drugs saquinavir can increase the plasma concentration (and therefore side effects) of pimozide and sertindole, which should therefore not be taken with it.
Antiviral drugs the plasma concentration (and therefore side effects) of maraviroc are increased by saquinavir; ritonavir increases the plasma concentration of saquinavir and tipranavir reduces it.
Ciclosporin: the plasma concentrations of both drugs are increased.
Cilostazol its plasma concentration may be increased and it should not be used with saquinavir.
Midazolam its plasma concentration is increased, causing profound sedation, and it should not be taken with saquinavir.
Ranolazine its plasma concentration may be increased and it should not be used with saquinavir.
Rifampicin and rifabutin: can reduce the plasma concentration (and therefore effectiveness) of saquinavir and should not be used with it.
Statins rosuvastatin and simvastatin should not be taken with saquinavir as this increases the risk of muscle damage.
Tacrolimus its plasma concentration is increased and therefore its dosage may need to be reduced.

Proprietary preparation:
Invirase.

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Oxford Dictionary of Biochemistry:

saquinavir

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a peptidomimetic antiviral drug that contains phenyl and other bulky groups and inhibits HIV protease by binding to its active site.

Previous:	saprophyte, saposin, saporin
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Wikipedia on Answers.com:

Saquinavir

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Saquinavir

Systematic (IUPAC) name
(2S)-N-[(2S,3R)-4-[(3S)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinolin-2-ylformamido)butanediamide
Clinical data
Trade names	Invirase
AHFS/Drugs.com	monograph
MedlinePlus	a696001
Pregnancy cat.	B1 (Australia)
Legal status	?
Pharmacokinetic data
Protein binding	98%
Half-life	9 - 15 houres
Identifiers
CAS number	127779-20-8^Y
ATC code	J05AE01
PubChem	CID 441243
DrugBank	APRD00623
ChemSpider	390016^Y
UNII	L3JE09KZ2F^Y
KEGG	D00429^Y
ChEMBL	CHEMBL114^Y
NIAID ChemDB	AIDSNO:000640
Chemical data
Formula	C₃₈H₅₀N₆O₅
Mol. mass	670.841 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1^Y Key:QWAXKHKRTORLEM-UGJKXSETSA-N^Y
N(what is this?) (verify)

Saquinavir is an antiretroviral drug used in HIV therapy. It falls in the protease inhibitor class. Two formulations have been marketed:

a hard-gel capsule formulation of the mesylate, with trade name Invirase, which requires combination with ritonavir to increase the saquinavir bioavailability;

a soft-gel capsule formulation of saquinavir, with trade name Fortovase.

Both formulations are generally used as a component of highly active antiretroviral therapy (HAART).

Contents

1 History
2 Mode of action
3 Adverse reactions
4 Bioavailability and drug interactions
5 References
6 Further reading

History

Saquinavir was the first protease inhibitor (and sixth antiretroviral) approved by the Food and Drug Administration (FDA). It was approved on December 6, 1995, as Invirase, a poorly-absorbed hard gel capsule which quickly led to viral resistance in many of the pioneer patients. The manufacturer, Roche, and the FDA rushed Invirase to market in light of the dire conditions of the HIV/AIDS epidemic that prevailed at the time and there was a lot of pressure to produce products quickly.^{[citation needed]}

It was approved again on Nov 7, 1997 as Fortovase, a soft gel capsule reformulated for improved bioavailability. Roche announced in May 2005 that, owing to reduction in demand, Fortovase would cease being marketed early in 2006 in favour of Invirase boosted with ritonavir. ^[1]

Mode of action

Saquinavir is a protease inhibitor. Proteases are enzymes that cleave protein molecules into smaller fragments. HIV protease is vital for both viral replication within the cell and release of mature viral particles from an infected cell. Saquinavir inhibits both HIV-1 and HIV-2 proteases.

Adverse reactions

The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including diarrhea, nausea, loose stools & abdominal discomfort. Invirase is better tolerated than Fortovase.

Bioavailability and drug interactions

Saquinavir, in the Invirase formulation, has a low and variable oral bioavailability, when given alone. The Fortovase formulation at the standard dosage delivers approximately eightfold more active drug than Invirase, also at the standard dosage.^[2]

In the clinic, it was found that the oral bioavailability of saquinavir in both formulations significantly increases when patients also receive the PI ritonavir. For patients, this has the major benefit that they can take less saquinavir, while maintaining sufficient saquinavir blood plasma levels to efficiently suppress the replication of HIV.

The mechanism behind this welcome observation was not directly known, but later it was determined that ritonavir inhibits the cytochrome P450 3A4 isozyme. Normally, this enzyme metabolizes saquinavir to an inactive form, but with the ritonavir inhibiting this enzyme, the saquinavir blood plasma levels increased considerably. Additionally, ritonavir also inhibits multidrug transporters, although to a much lower extent.

Unlike other protease inhibitors, the absorption of saquinavir seems to be improved by omeprazole.^[3]

References

^ Withdrawal of Fortovase (PDF)
^ Fortovase^TM (saquinavir) soft gelatin capsules. Product information (November 1997)
^ Winston A, Back D, Fletcher C et al. (2006). "Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers". AIDS 20 (10): 1401–6. doi:10.1097/01.aids.0000233573.41597.8a. PMID 16791014.

Nucleoside & Nucleotide (NRTI)	Nucleoside analogues/NARTIs: Abacavir (ABC)°^# • Emtricitabine (FTC)°^# • Lamivudine (3TC)°^# • Didanosine (ddI)^# • Zidovudine (AZT)^# • Apricitabine^† • Stampidine^† • Elvucitabine^† • Racivir^† • Amdoxovir^†• Stavudine (d4T)^# • Zalcitabine (ddC)^◊ • Festinavir^† Nucleotide analogues/NtRTIs: Tenofovir°^# • GS 7340

Non-Nucleoside (NNRTI) (Discovery & development)	(1^st generation) Efavirenz°^# • Nevirapine^# • Loviride^◊ • Delavirdine^◊ • (2^nd generation) diarylpyrimidines (Etravirine, Rilpivirine) • Lersivirine^†

Integrase inhibitors

Raltegravir • Elvitegravir^† • Dolutegravir^† • Globoidnan A (experimental) • MK-2048^† • BI 224436^†

Maturation inhibitors

Bevirimat^† • Vivecon^†

Protease Inhibitors (PI)
(Discovery and development)

1^st generation	Fosamprenavir° • Lopinavir°^# • Nelfinavir^# • Ritonavir^# • Saquinavir^# • Amprenavir^◊ • Indinavir^◊^#

2^nd generation	Atazanavir° • Darunavir • Tipranavir

Combined formulations

Lamivudine/zidovudine • Emtricitabine/tenofovir/efavirenz • Abacavir/lamivudine/zidovudine • Tenofovir/emtricitabine • Lopinavir/ritonavir • Abacavir/lamivudine • Emtricitabine/rilpivirine/tenofovir

Experimental agents

Uncoating inhibitors	TRIM5alpha (gene)

Transcription inhibitors	Tat antagonists

Translation inhibitors	Trichosanthin

Other	Abzyme • Calanolide A • Ceragenin • Cyanovirin-N • Diarylpyrimidines • Epigallocatechin gallate (EGCG) • Foscarnet • Griffithsin • Hydroxycarbamide • Miltefosine • Portmanteau inhibitors • Seliciclib^† • Synergistic enhancers • Tre recombinase • Zinc finger protein transcription factor • KP-1461^† • Cobicistat^†

Failed agents	Dexelvucitabine • Capravirine • Emivirine • Lodenosine • Atevirdine • Brecanavir • Aplaviroc

^#WHO-EM. ^‡Withdrawn from market. Clinical trials: ^†Phase III. ^§Never to phase III °DHHS preferred first-line agent. ^◊Formerly or rarely used agent.

M: VIR

virs(prot)/clss

cutn/syst (hppv/hiva, infl/zost/zoon)/epon

drugJ(dnaa, rnaa, rtva, vacc)

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		Oxford A-Z of Medicinal Drugs. Market University Press. © 2000, 2003, 2010 An A-Z of Medicinal Drugs. All rights reserved. Read more
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saquinavir

sa·quin·a·vir

Saquinavir

saquinavir

saquinavir

Saquinavir

History

Mode of action

Adverse reactions

Bioavailability and drug interactions

References

Further reading