Saquinavir mesilate

Saquinavir mesilate Uses, Dosage, Side Effects, Food Interaction and all others data.

Saquinavir mesilate 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. Saquinavir mesilate 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.

Saquinavir mesilate inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

Saquinavir mesilate exerts its antiviral activity by inhibiting an enzyme critical for the HIV-1 viral lifecycle. Like other protease inhibitors, saquinavir has a propensity for participating in drug interactions - use caution when administering saquinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common. Saquinavir mesilate is known to increase the QTc-interval in otherwise healthy individuals, and should therefore be used with caution in patients maintained on other QTc-prolonging medications or for whom prolongation of the QTc-interval may be of particular consequence (e.g. patients with pre-existing heart disease). Careful and regular monitoring of patient bloodwork is recommended, as saquinavir has been associated with the development of metabolic complications (e.g. diabetes mellitus, hyperlipidemia) and worsening of pre-existing liver disease.

Trade Name Saquinavir mesilate
Availability Prescription only
Generic Saquinavir
Saquinavir Other Names Saquinavir
Related Drugs Biktarvy, Truvada, tenofovir, ritonavir, zidovudine, abacavir, emtricitabine, Complera, Atripla, Stribild
Type
Formula C38H50N6O5
Weight Average: 670.8408
Monoisotopic: 670.38426874
Protein binding

Saquinavir is approximately 98% plasma protein-bound independent of serum concentration.

Groups Approved, Investigational
Therapeutic Class Anti-viral drugs
Manufacturer
Available Country Russia
Last Updated: September 19, 2023 at 7:00 am
Saquinavir mesilate
Saquinavir mesilate

Uses

Saquinavir mesilate is an HIV-1 protease inhibitor used for the treatment of HIV1 infection in combination with ritonavir and other antiretroviral agents in adults (over the age of 16 years)

Saquinavir mesilate is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection

How Saquinavir mesilate works

The HIV lifecycle is comprised of 3 distinct stages: assembly, involving creation and packaging of essential viral components; budding, wherein the viral particle crosses the host cell plasma membrane and forms a lipid envelope; and maturation, wherein the viral particle alters its structure and becomes infectious. At the center of this lifecycle is the Gag polyprotein which, along with the products of its proteolysis, coordinate these stages and function as the major structural proteins of the virus. The HIV-1 protease enzyme, a dimeric aspartic protease, is the enzyme responsible for cleaving the Gag polyprotein and thus plays a critical role in many aspects of the HIV viral lifecycle.

Saquinavir mesilate is an inhibitor of the HIV-1 protease enzyme. Its design is based on the "peptidomimetic" principle, wherein the molecule contains a hydroxyethylene scaffold that mimics the normal peptide linkage (cleaved by HIV protease) but which itself cannot be cleaved. By preventing HIV-1 protease activity, and thus the proteolysis of the Gag polyprotein, saquinavir results in the production of immature, non-infectious viral particles.

Dosage

Saquinavir mesilate dosage

Saquinavir mesilate must be administered in combination with ritonavir.

Adults (over the age of 16 years): Saquinavir mesilate 1000 mg twice daily (5x200 mg capsules or 2x500 mg tablets) in combination with ritonavir 100 mg twice daily.

Saquinavir mesilate and ritonavir should be taken within 2 hours after a meal.

Side Effects

The most common adverse reactions are nausea, vomiting, diarrhea, fatigue, pneumonia, lipodystrophy and abdominal pain

Toxicity

The oral LD50 of saquinavir in both rats and mice is >5 g/kg. Data regarding overdose with saquinavir are limited. No acute toxicities or sequelae were noted in a patient ingesting 8 grams of saquinavir as a single dose, and a second subject ingesting 2.4 grams as a single dose experienced throat pain that lasted for 6 hours and subsequently resolved. Treatment of overdose should consist of symptomatic and supportive measures. Dialysis is unlikely to be of benefit given saquinavir's extensive protein-binding.

Interaction

Saquinavir mesilate/ritonavir is a potent inhibitor of CYP3A, significantly increasing the exposure of drugs primarily metabolized by CYP3A.

Coadministration of Saquinavir mesilate/ritonavir with drugs that induce CYP3A may result in decreased plasma concentrations of saquinavir and reduced efficacy.

Certain drugs or drug classes should not be coadministered with Saquinavir mesilate/ritonavir based on drug interaction studies or predicted drug interactions

Food Interaction

  • Avoid grapefruit products. Co-administration with grapefruit-containing products inhibits the metabolism of saquinavir.
  • Take after a meal.

[Moderate] ADJUST DOSING INTERVAL: Food significantly increases the absorption of saquinavir.

MONITOR: Coadministration with grapefruit juice may increase the plasma concentrations of saquinavir.

The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

In eight healthy volunteers, ingestion of 400 mL of grapefruit juice prior to administration of a 600 mg dose of saquinavir mesylate increased the area under the plasma concentration-time curve and oral bioavailability of saquinavir by 50% and 100%, respectively, compared to water; however, the increase is not considered clinically relevant.

A high degree of intersubject variability in the grapefruit juice effect was also observed.

The extent to which this interaction may occur with the saquinavir free base soft gelatin capsule is unknown.

However, the saquinavir soft gelatin capsule formulation is no longer commercially available.

MANAGEMENT: Saquinavir mesilate mesylate should be taken with meals or within 2 hours after eating to enhance bioavailability.

Patients should be advised to avoid the consumption of large amounts of grapefruit and grapefruit juice during saquinavir therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation.

Saquinavir mesilate Cholesterol interaction

[Moderate] Hyperlipidemia has been observed in 10% of patients receiving ritonavir during clinical trials.

Increases of 30% to 40% from baseline have been reported for total cholesterol and 200% to 300% or more for triglycerides.

These effects have also been reported during postmarketing experience with other protease inhibitors (PIs) but may be the most dramatic with ritonavir.

The clinical significance of these elevations is unclear.

Severe hyperlipidemia is known to sometimes cause pancreatitis.

In addition, some patients have reportedly developed symptomatic atherosclerosis and coronary artery disease after initiating PI treatment.

Patients with preexisting hyperlipidemia may require closer monitoring during PI therapy, and adjustments made accordingly in their lipid-lowering regimen.

PI therapy should be administered cautiously in patients with coronary artery disease or a history of ischemic heart disease.

Volume of Distribution

The steady-state volume of distribution of saquinavir is approximately 700 L, suggesting extensive distribution into tissues.

Elimination Route

The absolute bioavailability of orally administered saquinavir is only ~4%, thought to be a consequence of incomplete absorption and extensive first-pass metabolism. It is co-administered with ritonavir, another protease inhibitor and a potent inhibitor of the enzymes responsible for saquinavir's first-pass metabolism, in order to dramatically boost its serum concentrations and, by extension, its therapeutic efficacy. Following administration of saquinavir 1000mg twice daily with ritonavir 100mg twice daily the AUC24h at steady-state was 39026 ng.h/mL.

Clearance

The systemic clearance of saquinavir is approximately 1.14 L/h/kg following intravenous administration.

Elimination Route

The primary means of elimination of saquinavir appears to be extensive hepatic metabolism followed by fecal excretion of both the parent drug and metabolic products. Following the administration of radiolabeled saquinavir (both orally and intravenously), approximately 81-88% of radioactivity is recovered in the feces within 5 days of dosing while only 1-3% is recovered in the urine. Mass balance studies indicate that only 13% of orally-administered plasma radioactivity is attributed to unchanged parent drug, with the remainder comprising metabolic products of saquinavir's hepatic metabolism. In contrast, intravenous administration resulted in approximately 66% of the circulating plasma radioactivity being attributed to unchanged parent drug, suggesting a high degree of first-pass metabolism with oral administration.

Pregnancy & Breastfeeding use

Pregnancy: Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: Do not breastfeed if HIV-1-infected mothers are receiving Saquinavir mesilate therapy.

Contraindication

Patients with congenital or documented acquired QT prolongation, patients with refractory hypokalemia or hypomagnesemia, or those on concomitant therapy with other drugs that prolong the QT interval.

Saquinavir mesilate is contraindicated in patients with complete atrioventricular (AV) block without implanted pacemakers, or patients who are at high risk of complete AV block.

Saquinavir mesilate is contraindicated in patients with clinically significant hypersensitivity (e.g., anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, saquinavir mesylate, or any of its ingredients

Saquinavir mesilate when administered with ritonavir is contraindicated in patients with severe hepatic impairment.

Coadministration of Saquinavir mesilate/ritonavir with CYP3A substrates for which increased plasma levels may result in serious or life-threatening reactions.

Coadministration of Saquinavir mesilate/ritonavir with rifampin due to the risk of severe hepatotoxicity.

Special Warning

Pediatric Use: Pediatric dose recommendations that are both reliably effective and below thresholds of concern with respect to QT and PR prolongation could not be determined

Geriatric Use: Caution should be exercised due to greater frequency of decreased hepatic, renal or cardiac function in elderly population.

Impaired Renal Function: No initial dose adjustment is necessary for patients with renal impairment.

Impaired Hepatic Function: No dose adjustment is necessary for patients with mild or moderate hepatic impairment.

Storage Condition

The capsules and tablets should be stored at 25 degree C

Innovators Monograph

You find simplified version here Saquinavir mesilate

Saquinavir mesilate contains Saquinavir see full prescribing information from innovator Saquinavir mesilate Monograph, Saquinavir mesilate MSDS, Saquinavir mesilate FDA label

FAQ

What is Saquinavir mesilate used for?

Saquinavir mesilate is used in combination with ritonavir and other medications to treat human immunodeficiency virus (HIV) infection.Saquinavir mesilate is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood.

How safe is Saquinavir mesilate?

We evaluated Saquinavir mesilate an orally active, selective inhibitor of HIV proteinase.

What are the common side effects of Saquinavir mesilate?

Common side effects may include: nausea, vomiting, diarrhea, stomach pain; tired feeling; or. changes in the shape or location of body fat especially in your arms, legs, face, neck, breasts, and waist.

When do I take Saquinavir mesilate?

Saquinavir mesilate is usually taken at the same time as ritonavir  two times a day within 2 hours after a full meal.

Is Saquinavir mesilate safe during pregnancy?

Saquinavir mesilate should not be used during pregnancy.

Is Saquinavir mesilate safe during breastfeeding?

Breastfeeding is not recommended during use of this drug; if replacement feeding is not an option, a different drug may be preferred.

What is the mechanism of Saquinavir mesilate?

Saquinavir mesilate is a peptide-like substrate analogue that binds to the protease active site and inhibits the activity of the enzyme. Saquinavir mesilate inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature noninfectious virus particles.

Who should not take Saquinavir mesilate?

The following conditions are contraindicated with Saquinavir mesilate. Check with your physician if you have any of the following:
Conditions:

  • diabetes
  • high cholesterol
  • high amount of triglyceride in the blood
  • low amount of magnesium in the blood
  • low amount of potassium in the blood
  • hemophilia
  • alcoholism
  • a low supply of oxygen rich blood to the heart
  • cardiomyopathy, a disease of the heart muscle
  • complete heart block
  • second degree atrioventricular heart block
  • torsades de pointes, a type of abnormal heart rhythm
  • prolonged QT interval on EKG
  • abnormal EKG with QT changes from birth
  • hardening of the liver
  • liver problems
  • a mother who is producing milk and breastfeeding
  • structural disorder of heart

What happen If I missed Saquinavir mesilate?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Can I take Saquinavir mesilate for a long time?

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not stop using this medicine without checking first with your doctor.

Can I take Saquinavir mesilate without food?

It is important that this medicine be taken with food. Take it within 2 hours after a meal.

What should I avoid while taking Saquinavir mesilate?

Using Saquinavir mesilate will not prevent your disease from spreading. Do not have unprotected sex or share razors or toothbrushes. Ask your doctor how to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe.


Can I take overdose of Saquinavir mesilate?

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.
If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

*** Taking medicines without doctor's advice can cause long-term problems.
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