Invirase Information
Invirase (Saquinavir)
Invirase (Saquinavir) Dosage And Administration
Invirase (Saquinavir) must be used in combination with ritonavir, because it significantly inhibits saquinavir's metabolism to provide increased plasma saquinavir levels.
Invirase (Saquinavir) Dosage Forms And Strengths
Capsules: 200 mg Film-coated tablets: 500 mg
Invirase (Saquinavir) Contraindications
Invirase (Saquinavir) is contraindicated in patients with clinically significant hypersensitivity (e.g., anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, saquinavir mesylate, or any of its ingredients including ritonavir.
Invirase (Saquinavir) when administered with ritonavir is contraindicated in patients with severe hepatic impairment.
Coadministration of Invirase (Saquinavir) /ritonavir is contraindicated with drugs that are CYP3A substrates for which increased plasma levels may result in serious or life-threatening reactions. These drugs and potentially related adverse events are listed in .
Invirase (Saquinavir) Warnings And Precautions
If a serious or severe toxicity occurs during treatment with Invirase (Saquinavir) , Invirase (Saquinavir) should be interrupted until the etiology of the event is identified or the toxicity resolves. At that time, resumption of treatment with full-dose Invirase (Saquinavir) may be considered. For antiretroviral agents used in combination with Invirase (Saquinavir) , physicians should refer to the complete product information for these drugs for dose adjustment recommendations and for information regarding drug-associated adverse reactions.
Invirase (Saquinavir) Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The original Invirase (Saquinavir) safety database consisted of a total of 574 patients who received saquinavir 600 mg alone or in combination with ZDV or ddC. Combination dosing with ritonavir is based on 352 HIV-1 infected patients and 166 healthy subjects who received various combinations of either saquinavir (hard gel or soft-gel capsules) with ritonavir.
The recommended dose of Invirase (Saquinavir) is 1000 mg twice daily co-administered with ritonavir 100 mg twice daily, in combination with other antiretroviral agents. lists grade 2, 3 and 4 adverse events that occurred in ≥2% of patients receiving saquinavir soft gel capsules with ritonavir (1000/100 mg bid).
Limited experience is available from three studies investigating the pharmacokinetics of the Invirase (Saquinavir) 500 mg film-coated tablet compared to the Invirase (Saquinavir) 200 mg capsule in healthy volunteers (n=140). In two of these studies saquinavir was boosted with ritonavir; in the other study, saquinavir was administered as single drug. The Invirase (Saquinavir) tablet and the capsule formulations were similarly tolerated. The most common adverse events were gastrointestinal disorders (such as diarrhea). Similar bioavailability was demonstrated and no clinically significant differences in saquinavir exposures were seen. Thus, similar safety profiles are expected between the two Invirase (Saquinavir) formulations.
In a study investigating the drug-drug interaction of rifampin 600 mg/day daily and Invirase (Saquinavir) 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted Invirase (Saquinavir) ) involving 28 healthy volunteers, 11 of 17 healthy volunteers (65%) exposed concomitantly to rifampin and ritonavir-boosted Invirase (Saquinavir) developed severe hepatocellular toxicity which presented as increased hepatic transaminases. In some subjects, transaminases increased up to >20-fold the upper limit of normal and were associated with gastrointestinal symptoms, including abdominal pain, gastritis, nausea, and vomiting. Following discontinuation of all three drugs, clinical symptoms abated and the increased hepatic transaminases normalized .
Invirase (Saquinavir) Drug Interactions
Drug interaction studies have been completed with both Invirase (Saquinavir) and saquinavir soft gel capsules. Observations from drug interaction studies with saquinavir soft gel capsules may not be predictive for Invirase (Saquinavir) /ritonavir.
Based on the finding of dose-dependent prolongations of QT and PR intervals in healthy volunteers receiving Invirase (Saquinavir) /ritonavir, additive effects on QT and/or PR interval prolongation may occur with certain members of the following drug classes: antiarrhythmics class IA or class III, neuroleptics, antidepressive agents, PDE5 inhibitors (when used for pulmonary arterial hypertension), antimicrobials, antihistaminics and others. This effect might lead to an increased risk of ventricular arrhythmias, notably torsades de pointes. Therefore, concurrent administration of these agents with Invirase (Saquinavir) /ritonavir is contraindicated .
Invirase (Saquinavir) Use In Specific Populations
The Centers for Disease Control and Prevention recommend that HIV
infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV.
mothers should be instructed not to breast-feed if they are receiving Invirase (Saquinavir) .
Invirase (Saquinavir) Overdosage
There is limited experience of overdose with saquinavir.
No acute toxicities or sequelae were noted in 1 patient who ingested 8 grams of Invirase (Saquinavir) as a single dose. The patient was treated with induction of emesis within 2 to 4 hours after ingestion. A second patient ingested 2.4 grams of Invirase (Saquinavir) in combination with 600 mg of ritonavir and experienced pain in the throat that lasted for 6 hours and then resolved. In an exploratory Phase II study of oral dosing with Invirase (Saquinavir) at 7200 mg/day (1200 mg q4h), there were no serious toxicities reported through the first 25 weeks of treatment.
Treatment of overdose with saquinavir should consist of general supportive measures including monitoring of vital signs and ECG and observations of the patient's clinical status. Since saquinavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
Invirase (Saquinavir) Description
Invirase (Saquinavir) brand of saquinavir mesylate is an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease.
The chemical name for saquinavir mesylate is N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide methanesulfonate with a molecular formula CHNO∙CHOS and a molecular weight of 766.96. The molecular weight of the free base is 670.86. Saquinavir mesylate has the following structural formula:
Saquinavir mesylate is a white to off-white, very fine powder with an aqueous solubility of 2.22 mg/mL at 25°C.
Invirase (Saquinavir) is available as light brown and green, opaque hard gelatin capsules for oral administration in a 200-mg strength (as saquinavir free base). Each capsule also contains the inactive ingredients lactose, microcrystalline cellulose, povidone K30, sodium starch glycolate, talc, and magnesium stearate. Each capsule shell contains gelatin and water with the following dye systems: red iron oxide, yellow iron oxide, black iron oxide, FD&C Blue #2, and titanium dioxide.
Invirase (Saquinavir) is also available as a light orange to greyish- or brownish-orange, oval cylindrical, biconvex film-coated tablet for oral administration in a 500-mg strength (as saquinavir free base). Each tablet also contains the inactive ingredients lactose, microcrystalline cellulose, povidone K30, croscarmellose sodium, and magnesium stearate. Each film coat contains hypromellose, titanium dioxide, talc, iron oxide yellow, iron oxide red, and triacetin.
Invirase (Saquinavir) Clinical Pharmacology
QTcS interval was evaluated in a randomized, placebo and active (moxifloxacin 400 mg once daily) controlled crossover study in 59 healthy adults, with ECG measurements on Day 3. The maximum mean (95% upper confidence bound) differences in QTcS interval from placebo after baseline-correction were 18.9 (22.0) and 30.2 (33.4) ms for 1000/100 mg twice daily and supratherapeutic 1500/100 mg twice daily of Invirase (Saquinavir) /ritonavir, respectively. There is a delayed effect between QTc interval change and drug concentrations, with the maximum placebo-adjusted baseline-corrected QTcS observed at about 12-20 h post-dose. Invirase (Saquinavir) /ritonavir 1500/100 mg twice daily resulted in a Day 3 mean Cmax of Invirase (Saquinavir) approximately 1.4-fold higher than the mean C observed on Day 3 with the approved therapeutic dose in healthy volunteers (within the same study). QTcS in this study was QT/RR for males and QT/RR for females, which are similar to Fridericia's correction (QTcF=QT/RR).
PR and QRS interval prolongations were also noted in subjects receiving Invirase (Saquinavir) /ritonavir in the same study on Day 3. The maximum mean (95% upper confidence bound) difference from placebo in the PR interval after baseline-correction were 28.6 (31.6) and 38.4 (41.4) ms for 1000/100 mg twice daily and supratherapeutic 1500/100 mg twice daily saquinavir/ritonavir respectively. The maximum mean (95% upper confidence bound) difference from placebo in QRS interval after baseline correction were 2.9 (3.9) and 4.4 (5.3) ms for 1000/100 mg twice daily and supratherapeutic 1500/100 mg twice daily Invirase (Saquinavir) /ritonavir respectively. In this study using healthy subjects, PR interval prolongation of >200 ms was also observed in 40% and 47% of subjects receiving Invirase (Saquinavir) /ritonavir 1000/100 mg bid and 1500/100 mg bid, respectively, on Day 3. Three (3%) of subjects in the active control moxifloxacin arm and 5% in the placebo arm experienced PR prolongation of >200 ms.
Invirase (Saquinavir) How Supplied/storage And Handling
Invirase (Saquinavir) 200-mg capsules are light brown and green opaque capsules with ROCHE and 0245 imprinted on the capsule shell—bottles of 270 (NDC 0004-0245-15).
Invirase (Saquinavir) 500-mg film-coated tablets are light orange to greyish- or brownish-orange, oval cylindrical, biconvex tablets with ROCHE and SQV 500 imprinted on the tablet face—bottles of 120 (NDC 0004-0244-51).
Invirase (Saquinavir) Patient Counseling Information
A statement to patients and health care providers is included on the product's bottle label:
Patients should be informed that Invirase (Saquinavir) is not a cure for HIV-1 infection and that they may continue to acquire illnesses associated with advanced HIV-1 infection, including opportunistic infections. They should be informed that Invirase (Saquinavir) therapy has not been shown to reduce the risk of transmitting HIV-1 to others through sexual contact or blood contamination.
Invirase (Saquinavir) Fda-approved Medication Guide
Read this Medication Guide before you start taking Invirase (Saquinavir) and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about your treatment with Invirase (Saquinavir) before you start taking it and at regular checkups. You should stay under a healthcare provider's care when taking Invirase (Saquinavir) .
Tell your healthcare provider right away if you have any of these symptoms while taking Invirase (Saquinavir) :
Invirase (Saquinavir) is a prescription anti-HIV medicine used in people 16 years and older. Invirase (Saquinavir) belongs to a class of anti-HIV medicines called protease inhibitors. Invirase (Saquinavir) is used with ritonavir and other anti-HIV medicines to treat people with human immunodeficiency virus (HIV-1) infection. HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).
It is not known if Invirase (Saquinavir) is safe and effective in children younger than 16 years old.
Do not take Invirase (Saquinavir) if:
Invirase (Saquinavir) may not be right for you. Before you take Invirase (Saquinavir) , tell your healthcare provider if you:
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of Invirase (Saquinavir) . For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Genentech at 1-800-835-2555.
Invirase (Saquinavir) does not cure HIV, and it does not prevent you from getting other illness from advanced HIV infections. Invirase (Saquinavir) does not stop you from passing HIV infections to others. Do not share needles, or personal items that can have blood or body fluids on them, like toothbrushes and razor blades. Always practice safer sex by using condoms to lower the chance of sexual contact with semen, vaginal secretions, or blood.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Invirase (Saquinavir) for a condition for which it was not prescribed. Do not give Invirase (Saquinavir) to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about Invirase (Saquinavir) . If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Invirase (Saquinavir) that is written for health professionals.
For more information, go to http://www.gene.com/gene/products/information/Invirase (Saquinavir) or call 1-877-436-3683 (1-877-Genentech).
Active ingredient: saquinavir mesylate
Inactive ingredients:
200 mg Capsule: lactose, microcrystalline cellulose, povidone K30, sodium starch glycolate, talc, and magnesium stearate.
Capsule shell: gelatin and water with the following dye systems: red iron oxide, yellow iron oxide, black iron oxide, FD&C Blue #2, and titanium dioxide.
500 mg Tablet: lactose, microcrystalline cellulose, povidone K30, croscarmellose sodium, and magnesium stearate.
Film coat: hypromellose, titanium dioxide, talc, iron oxide yellow, iron oxide red, and triacetin.
The brands listed are trademarks of their respective owners and are not trademarks of Roche Laboratories, Inc. The makers of these brands are not affiliated with and do not endorse Roche Laboratories, Inc. or its products.
Invirase (Saquinavir) is a registered trademark of Hoffmann-La Roche Inc.
Invirase (Saquinavir)
Invirase (Saquinavir)
