Saquinavir

Name: Saquinavir

Saquinavir Interactions

Tell your healthcare provider about all the medicines you take, including prescriptions and non-prescriptions medicines, vitamins and herbal supplements. Saquinavir and other medicines may affect each other causing side effects. Do not start taking a new medicine without talking with your healthcare provider or pharmacist. Your healthcare provider can tell you if it is safe to take saquinavir with other medicines.

Taking saquinavir with certain other medicines can cause serious problems or life threatening reactions.

Medicines you should not take with saquinavir and Norvir include:

  • alfuzosin (Uroxatral)
  • anti-infectives: clarithromycin (Biaxin), erythromycin, halofantrine, pentamidine (Pentam)
  • atazanavir (Reyataz)
  • tacrolimus (Prograf)
  • chlorpromazine
  • clozapine (Clozaril)
  • haloperidol (Haldol)
  • mesoridazine
  • phenothiazines
  • thioridazine
  • ziprasidone (Geodon)
  • CYP3A4 substrates: dapsone, disopyramide (Norpace), quinine
  • cobicistat (Tybost)
  • amiodarone (Cordarone, Pacerone)
  • dofetilide (Tikosyn)
  • flecainide (Tambocor)
  • lidocaine
  • propafenone (Rhythmol)
  • quinidine
  • trazodone (Oleptro)
  • rifampin (Rifadin, Rifamate, Rifater, Rimactane)
  • Ergot containing medicines, including:
    • dihydroergotamine mesylate (DHE 45, Embolex, Migranal)
    • ergonovine, ergonovine and methylergonovine (Ergotrate, Methergine), ergotamine and methylergonovine
    • ergotamine tartrate (Cafergot, Migergot, Ergomar, Ergostate, Medihaler Ergotamine, Wigraine, Wigrettes)
  • lovastatin (Mevacor)
  • simvastatin (Zocor)
  • pimozide (Orap)
  • sildenafil (Revatio)
  • triazolam (Halcion)
  • midazolam hydrochloride oral syrup

The following medicines may increase blood levels and side effects of saquinavir when taken with saquinavir and Norvir:

  • delavirdine (Rescriptor)
  • omeprazole (Prilosec)
  • indinavir (Crixivan)

Saquinavir and Norvir may not work as well when taken together with the following medicines, herbal products, or dietary supplements:

  • efavirenz (Sustiva)
  • nevirapine (Viramune)
  • tipranavir (Aptivus)
  • ritonavir (Norvir)
  • Anticonvulsants such as carbamazepine (Carbatrol, Tegretol), phenobarbital, and phenytoin (Dilantin)
  • dexamethasone
  • garlic capsules, an herbal product sold as a dietary supplement
  • the herbal supplement St. John's wort (Hypericum perforatum) or products containing St. John's wort

Your healthcare provider may need to monitor your therapy more closely if you take saquinavir and Norvir with the following medicines:

  • medicines for erectile problems, such as tadalafil (Cialis), vardenafil (Levitra), or sildenafil citrate (Viagra)
  • a blood thinner medicine such as warfarin (Coumadin, Jantoven)
  • Antidepressants such as trazodone (Desyrel), amitriptyline (Elavil), or imipramine (Tofranil)
  • Benzodiazepines used as sedatives or sleeping pills such as alprazolam (Xanax), clorazepate (Tranxene), diazepam (Valium), and flurazepam (Dalmane)
  • atorvastatin (Lipitor) used for lowering cholesterol
  • Calcium channel blockers used for treatment of high blood pressure or heart disease, such as diltiazem (Cardizem, Cartia XT, Dilacor XR, Diltzac, Taztia XT, Tiazac), felodipine (Plendil), nifedipine (Procardia), nicardipine (Cardene), nimodipine (Nimotop), verapamil-containing medications (such as Calan, Verelan), amlodipine-containing medications (such as Caduet, Norvasc), nisoldipine (Sular), and isradipine (Dynacirc)
  • ketoconazole (Nizoral) and itraconazole (Sporanox) used to treat fungal infections
  • Medicines to prevent organ transplant rejection: cyclosporine (Sandimmune), cyclosporine (Neoral), sirolimus (Rapamune)
  • fluticasone propionate (Flonase, Flovent, Advair), given by nose or inhaled to treat allergic symptoms or asthma
  • digoxin (Lanoxin) used to treat heart rhythm problems or other heart conditions
  • bosentan (Tracleer) and tadalafil (Adcirca) used to treat pulmonary arterial hypertension
  • medicines for gout, such as colchicine (Colcrys)
  • Oral contraceptives containing ethinyl estradiol used for preventing pregnancy
  • Methadone
  • rifabutin (Mycobutin)

If you are not sure if you take a medicine above, ask your healthcare provider or pharmacist.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Saquinavir Precautions

Saquinavir may cause serious side effects including:

  • Interactions with other medicines. It is important to know the medicines that should not be taken with saquinavir. See "Saquinavir Interactions".
  • Changes in your heart rhythm and the electrical activity of your heart. These changes may be seen on an EKG (electrocardiogram) and can lead to serious heart problems. Your risk for these problems may be higher if you:
    • already have a history of abnormal heart rhythm, including Congenital Long QT Syndrome, or other types of heart disease.
    • take other medicines that can affect your heart rhythm while you take saquinavir.

Tell your healthcare provider right away if you have any of these symptoms while taking saquinavir:

  • dizziness
  • lightheadedness
  • fainting
  • sensation of abnormal heartbeats

Do not take saquinavir if:

  • you are taking certain medicines. See "Saquinavir Interactions".
  • your healthcare provider has told you that you have a condition called Congenital Long QT Syndrome.
  • your healthcare provider has told you that you have complete AV (atrioventricular) block and you do not have a pacemaker or you are at risk for complete AV block.
  • your healthcare provider has told you that you have low potassium or low magnesium in your blood.
  • you have severe liver problems.
  • you have had a severe allergic reaction to saquinavir or any of the ingredients in saquinavir.

Saquinavir Food Interactions

Grapefruit and grapefruit juice may interact with saquinavir and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Saquinavir and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category B. Experience in pregnant women is limited. Saquinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the unborn baby.

If you take saquinavir during pregnancy, talk with your healthcare provider about how you can take part in an antiretroviral pregnancy registry. The purpose of the pregnancy registry is to collect information about the health of you and your baby.

What other drugs will affect saquinavir?

Many drugs can interact with saquinavir, and some drugs should not be used together. Tell your doctor about all your current medicines and any you start or stop using, especially:

  • any other antiviral medicines to treat hepatitis or HIV;

  • colchicine;

  • dexamethasone or fluticasone (Flonase, Advair);

  • fusidic acid;

  • fentanyl or methadone;

  • omeprazole (Prilosec);

  • sildenafil (Viagra) and other erectile dysfunction medicines;

  • warfarin (Coumadin, Jantoven);

  • an antibiotic or antifungal medicine;

  • an herbal supplement, especially garlic or St. John's wort;

  • cholesterol medication;

  • heart or blood pressure medication;

  • medicine to prevent organ transplant rejection;

  • medicine to treat pulmonary arterial hypertension;

  • a sedative such as Valium, or other medicines to treat anxiety or mental illness; or

  • seizure medicine.

This list is not complete and many other drugs can interact with saquinavir. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you. Not all possible interactions are listed in this medication guide.

Uses for Saquinavir

Treatment of HIV Infection

Treatment of HIV type 1 (HIV-1) infection in adults and adolescents >16 years of age;1 200 201 used in conjunction with low-dose ritonavir (ritonavir-boosted saquinavir) and other antiretrovirals.1 174 179 200 201 300

Do not use saquinavir without a pharmacokinetic enhancer (i.e., low-dose ritonavir).1 200 201 Pharmacokinetic enhancer (pharmacokinetic booster) necessary to improve saquinavir pharmacokinetic profile.1 200 Do not use with the pharmacokinetic enhancer cobicistat.1 (See Interactions under Cautions.)

Ritonavir-boosted saquinavir usually used in PI-based regimens that include a PI and 2 HIV nucleoside reverse transcriptase inhibitors (dual NRTIs).1 200

Experts state ritonavir-boosted saquinavir not recommended for initial treatment regimens in antiretroviral-naive adults and adolescents because of higher pill burden and more severe adverse cardiac effects (prolonged PR and QT intervals requiring ECG monitoring) compared with other available ritonavir-boosted PIs.200 (See Cardiovascular Effects under Cautions.) Experts also state not recommended for initial treatment regimens in antiretroviral-naive pediatric patients because of limited data.201

Use of saquinavir without low-dose ritonavir (unboosted saquinavir) not recommended at any time because of inadequate bioavailability and inferior virologic efficacy.200 201

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure† (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.199

USPHS recommends a 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) as the preferred regimen for PEP following occupational exposures to HIV.199 Ritonavir-boosted saquinavir and 2 NRTIs can be considered an alternative regimen, but use for PEP only with expert consultation.199 Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF; alternatives are tenofovir DF and lamivudine, zidovudine and lamivudine, or zidovudine and emtricitabine.199

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible.199 Do not delay initiation of PEP while waiting for expert consultation.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure† (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada);198 recommended alternative in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.198

CDC states saquinavir is an alternative antiretroviral that can be used in nPEP regimens, but use in such regimens only with expert consultation.198

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals.198 Do not delay initiation of nPEP while waiting for expert consultation.198

Cautions for Saquinavir

Contraindications

  • Hypersensitivity (anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, or any ingredient in the formulation.1

  • Complete AV block without implanted pacemakers and patients at high risk of complete AV block.1

  • Congenital long QT syndrome.1 (See Cardiovascular Effects under Cautions.)

  • Refractory hypokalemia or hypomagnesemia.1 (See Cardiovascular Effects under Cautions.)

  • Concomitant use with drugs that increase saquinavir plasma concentrations and prolong the QT interval.1 (See Cardiovascular Effects under Cautions.)

  • Severe hepatic impairment.1

  • Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events, including alfuzosin, certain antiarrhythmic agents (amiodarone, bepridil [not commercially available in US], dofetilide, flecainide, systemic lidocaine, propafenone, quinidine), certain anti-infectives (atazanavir, clarithromycin, dapsone, erythromycin, halofantrine [not commercially available in US], pentamidine, quinine, rifampin), certain antipsychotics (clozapine, haloperidol, lurasidone, phenothiazines, pimozide, sertindole [not commercially available in US], ziprasidone), cisapride, disopyramide, ergot alkaloids, lovastatin and simvastatin, oral midazolam, sildenafil used for treatment of pulmonary arterial hypertension [PAH], tacrolimus, trazodone, and triazolam.1 200 (See Specific Drugs and Foods under Interactions.)

Warnings/Precautions

Cardiovascular Effects

Ritonavir-boosted saquinavir causes dose-dependent prolongation of PR interval; second- or third-degree AV block reported rarely.1 Patients with underlying structural heart disease, preexisting conduction system abnormalities, cardiomyopathies, and ischemic heart disease may be at increased risk for developing cardiac conduction abnormalities; ECG monitoring recommended in such patients.1 Concomitant use of ritonavir-boosted saquinavir and other drugs that prolong the PR interval (e.g., calcium-channel blocking agents, β-adrenergic blockers, digoxin, atazanavir) not evaluated.1 Use ritonavir-boosted saquinavir with caution in patients receiving other drugs that prolong the PR interval, particularly drugs metabolized by CYP3A; clinical monitoring recommended.1 (See Specific Drugs and Foods under Interactions.)

Ritonavir-boosted saquinavir causes dose-dependent prolongation of QT interval; torsades de pointes reported rarely.1 Perform ECG prior to initiation of ritonavir-boosted saquinavir.1 Do not use in patients with QT interval ≥450 msec.1 Ritonavir-boosted saquinavir may be initiated in those with baseline QT interval <450 msec; however, repeat ECG after approximately 10 days of ritonavir-boosted saquinavir and discontinue the antiretroviral if QT interval is prolonged >20 msec over baseline.1 ECG monitoring recommended if ritonavir-boosted saquinavir is initiated in patients with CHF, bradyarrhythmias, hepatic impairment, and electrolyte abnormalities.1 Correct hypokalemia or hypomagnesemia prior to initiating ritonavir-boosted saquinavir; monitor these electrolytes periodically during therapy.1

Do not use ritonavir-boosted saquinavir concomitantly with drugs that increase saquinavir plasma concentrations and prolong QT interval.1 Manufacturer states that concomitant use of ritonavir-boosted saquinavir and drugs with the potential to increase QT interval should be considered only when no alternative therapy is available and potential benefits outweigh risks.1 Perform ECG prior to initiation of the drugs.1 Do not use such concomitant therapy in patients with QT interval >450 msec.1 If baseline QT interval is <450 msec, repeat ECG after 3–4 days of concomitant therapy.1 If QT interval is prolonged >20 msec over baseline, clinician should use best clinical judgement regarding discontinuing ritonavir-boosted saquinavir and/or the other drug.1 Cardiology consult recommended if drug discontinuation or interruption is being considered on the basis of ECG assessment.1

Interactions

Saquinavir must be used with a pharmacokinetic enhancer (i.e., low-dose ritonavir).1 Failure to administer saquinavir with recommended dosage of low-dose ritonavir may result in inadequate antiretroviral effects.1 200 When ritonavir-boosted saquinavir is used, consider cautions, precautions, contraindications, and drug interactions associated with both saquinavir and low-dose ritonavir.1

Do not use saquinavir with the pharmacokinetic enhancer cobicistat.1 Cobicistat is not interchangeable with low-dose ritonavir and dosage recommendations for concomitant use of saquinavir and cobicistat not established.1

Concomitant use of ritonavir-boosted saquinavir with certain drugs is not recommended or requires particular caution.1 200 (See Specific Drugs and Foods under Interactions.)

Consider potential drug interactions prior to and during use of ritonavir-boosted saquinavir;1 monitor for adverse effects associated with each drug.1

Hyperglycemic Effects

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of HIV PIs; diabetic ketoacidosis has occurred.1 129 131

Monitor blood glucose and initiate or adjust dosage of oral hypoglycemic agent or insulin as needed.1

Hepatic Effects

Exacerbation of chronic liver dysfunction reported in patients with HBV or HCV, cirrhosis, or other underlying liver abnormalities.1 (See Hepatic Impairment under Cautions.)

Hemophilia A and B

Spontaneous bleeding noted with HIV PIs; causal relationship not established.1 80 127

Caution in patients with history of hemophilia type A or B.80 Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.1 80

Hyperlipidemia

Elevated cholesterol and/or triglycerides reported.1 Markedly elevated triglycerides are a risk factor for developing pancreatitis.1

Monitor cholesterol and triglycerides prior to and periodically during ritonavir-boosted saquinavir therapy.1 Manage lipid disorders as clinically appropriate.1 (See HMG-CoA Reductase Inhibitors under Interactions.)

Lactose Intolerance

Each 200-mg capsule contains 63.3 mg of anhydrous lactose; this quantity should not induce specific symptoms of lactose intolerance.1

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.1 144 145 146 147 148 149 150 151 Mechanisms and long-term consequences unknown; causal relationship not established.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]);1 this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution;1 time to onset is variable and can occur many months after initiation of antiretroviral therapy.1

HIV Resistance

Possibility of HIV-1 resistant to saquinavir and possible cross-resistance to other HIV PIs.1 Continued saquinavir therapy following loss of viral suppression may increase likelihood of cross-resistance to other HIV PIs.1

Specific Populations

Pregnancy

Category B.1

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202

Experts state ritonavir-boosted saquinavir not recommended for initial treatment in antiretroviral-naive pregnant women because of limited data, potential toxicities (e.g., prolonged PR and QT intervals requiring ECG monitoring), high pill burden, and need for twice-daily dosing.202

Lactation

Distributed into milk in rats;202 not known whether distributed into human milk.1 202

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 202

Pediatric Use

Dosages of ritonavir-boosted saquinavir that are effective for treatment of HIV-1 infection in children <16 years of age and below threshold for corrected QT (QTc) and PR interval prolongation not identified to date.1

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.1

Use caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Hepatic Impairment

Contraindicated in severe hepatic impairment.1 Although usual dosage can be used in mild or moderate hepatic impairment,1 some experts recommend caution.200

Renal Impairment

Use caution in severe renal impairment.1

Common Adverse Effects

Diarrhea, abdominal discomfort, nausea, vomiting, fatigue.1 51 75

Interactions for Saquinavir

Metabolized by CYP3A.1 83 94

Inhibits CYP3A.1 94

Substrate for P-glycoprotein (P-gp).1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A with possible alteration in metabolism of saquinavir and/or other drug.1 51 83 94

Drugs Affecting or Affected by P-gp Transport

Potential pharmacokinetic interaction with drugs that are inhibitors, inducers, or substrates of P-gp with possible alteration in pharmacokinetics of saquinavir and/or other drug.1

Drugs that Prolong the QT or PR Interval

Dose-dependent prolongation of QT and PR intervals has been reported in individuals receiving ritonavir-boosted saquinavir; additive effects on QT and/or PR interval prolongation may occur if ritonavir-boosted saquinavir is used concomitantly with other drugs known to have similar effects.1 Concomitant use with other drugs known to prolong QT and/or PR intervals (e.g., class IA and class III antiarrhythmic agents, neuroleptics, phosphodiesterase type 5 inhibitors if used for PAH, some antidepressants, some anti-infectives, some antihistamines) not recommended.1 119 (See Cardiovascular Effects under Cautions.)

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Alfentanil, fentanyl

Alfentanil, fentanyl: Possible increased opiate concentrations and accentuated alfentanil- or fentanyl-associated adverse effects (e.g., respiratory depression, apnea, bradycardia)1 200

Fentanyl: Monitor clinically, especially for potentially fatal respiratory depression200

Alfuzosin

Possible increased alfuzosin concentrations; may result in hypotension1

Concomitant use contraindicated1 200

Antiarrhythmic agents (amiodarone, disopyramide, dofetilide, dronedarone, flecainide, ibutilide, systemic lidocaine, propafenone, quinidine, sotalol)

Amiodarone, disopyramide, dofetilide, dronedarone, flecainide, systemic lidocaine, propafenone, quinidine: Possible increased antiarrhythmic agent concentrations; potential for serious or life-threatening effects (e.g., cardiac arrhythmias)1

Ibutilide, sotalol: Possible additive QT and/or PR interval prolongation1

Amiodarone, disopyramide, dofetilide, flecainide, systemic lidocaine, propafenone, quinidine: Concomitant use contraindicated1

Dronedarone: Experts state concomitant use with ritonavir-boosted saquinavir contraindicated200

Ibutilide, sotalol: Concomitant use not recommended1

Anticoagulants, oral

Apixaban: Increased apixaban concentrations expected200

Dabigatran: Possible increased dabigatran concentrations200

Edoxaban, rivaroxaban: Increased anticoagulant concentrations200

Warfarin: Possible altered warfarin concentrations1 200

Apixaban, edoxaban, rivaroxaban: Avoid concomitant use200

Dabigatran: Dosage adjustments not needed in patients with Clcr >50 mL/minute;200 avoid concomitant use in those with Clcr <50 mL/minute200

Warfarin: Monitor INR, especially when initiating or discontinuing ritonavir-boosted saquinavir;1 200 adjust warfarin dosage as needed1 200

Anticonvulsants (carbamazepine, ethosuximide, lamotrigine, phenobarbital, phenytoin)

Carbamazepine: Possible decreased saquinavir concentrations and increased carbamazepine concentrations1 200

Ethosuximide: Possible increased ethosuximide concentrations200

Lamotrigine: Possible decreased lamotrigine concentrations200

Phenobarbital: Possible decreased saquinavir concentrations1 200

Phenytoin: Possible decreased saquinavir concentrations and decreased phenytoin concentrations200

Carbamazepine, phenobarbital, phenytoin: Concomitant use not recommended;1 experts state consider alternative anticonvulsant;200 if used concomitantly, monitor anticonvulsant and saquinavir concentrations and assess virologic response200

Ethosuximide: Monitor for ethosuximide-associated adverse effects200

Lamotrigine: Increased lamotrigine dosage may be needed;200 consider monitoring lamotrigine concentrations;200 consider alternative anticonvulsant200

Antidepressants, SSRIs

Citalopram, escitalopram, fluoxetine, paroxetine, sertraline: Data not available regarding concomitant use with ritonavir-boosted saquinavir200

Fluvoxamine: Possible altered saquinavir and ritonavir concentrations200

Citalopram, escitalopram, fluoxetine, paroxetine, sertraline: Titrate SSRI dosage based on clinical response200

Fluvoxamine: Consider alternative therapy200

Antidepressants, tricyclic or tetracyclic

Amitriptyline, clomipramine, desipramine, imipramine, maprotiline, nortriptyline: Increased antidepressant concentrations expected1 200

In patients receiving ritonavir-boosted saquinavir, titrate antidepressant dosage based on clinical assessment and/or plasma concentrations;1 200 use lowest possible antidepressant dosage200

Antifungals, azoles

Fluconazole: Data not available regarding concomitant use with ritonavir-boosted saquinavir200

Isavuconazonium (prodrug of isavuconazole): Possible increased isavuconazole concentrations and altered saquinavir concentrations200

Itraconazole: Possible pharmacokinetic interaction may affect both drugs200

Ketoconazole: Increased ketoconazole concentrations and AUC;1 saquinavir pharmacokinetics not affected1

Posaconazole: Possible increased posaconazole and saquinavir concentrations200

Voriconazole: Possible decreased voriconazole concentrations200

Fluconazole: Some experts state dosage adjustments not needed200

Isavuconazonium: Consider monitoring isavuconazole concentrations;200 monitor for saquinavir-associated adverse effects and virologic efficacy200

Itraconazole: Manufacturer states itraconazole dosage >200 mg daily not recommended with ritonavir-boosted saquinavir;1 experts state consider monitoring itraconazole concentrations to guide dosage adjustments; do not exceed itraconazole dosage of 200 mg daily unless plasma concentrations used to guide dosage200

Ketoconazole: Ketoconazole dosage >200 mg daily not recommended with ritonavir-boosted saquinavir1

Posaconazole: Consider monitoring posaconazole concentrations;200 monitor for saquinavir-associated adverse effects200

Voriconazole: Concomitant use not recommended unless potential benefits outweigh risks;200 if used concomitantly, consider monitoring voriconazole concentrations and adjust dosage accordingly200

Antimycobacterials (bedaquiline, rifabutin, rifampin, rifapentine)

Bedaquiline: Possible increased bedaquiline concentrations;200 clinical importance unknown200

Rifabutin: If used with ritonavir-boosted saquinavir, increased concentrations of rifabutin and its active metabolite;1 96 slightly decreased saquinavir concentrations;1 96 no change in ritonavir concentrations96

Rifampin: If used with ritonavir-boosted saquinavir, markedly decreased saquinavir AUC (80%)1 200 and increased incidence of hepatotoxicity (markedly increased serum transaminases)1 173 200

Rifapentine: Possible decreased saquinavir concentrations200

Bedaquiline: Use concomitantly with ritonavir-boosted saquinavir with caution and only if potential benefits outweigh risks;200 monitor for QTc interval prolongation and liver dysfunction200

Rifabutin: If used concomitantly with ritonavir-boosted saquinavir, saquinavir manufacturer states use usual dosage of ritonavir-boosted saquinavir and decrease rifabutin dosage by at least 75% (i.e., maximum rifabutin dosage of 150 mg every other day or 150 mg 3 times weekly);1 some experts recommend rifabutin dosage of 150 mg once daily or 300 mg 3 times weekly;200 increase monitoring for antimycobacterial effects and adverse events1 96 200 and consider monitoring plasma rifabutin concentrations1 200

Rifampin: Concomitant use contraindicated1 173 200

Rifapentine: Concomitant use not recommended200

Antipsychotics (clozapine, haloperidol, lurasidone, phenothiazines, pimozide, quetiapine, sertindole, ziprasidone)

Clozapine, haloperidol, lurasidone, pimozide, risperidone, sertindole, ziprasidone: Potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias)1 200

Phenothiazines (chlorpromazine, fluphenazine, mesoridazine, perphenazine, prochlorperazine, thioridazine): Potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias)1 200

Quetiapine: Increased quetiapine concentrations expected1 200

Clozapine, haloperidol, lurasidone, pimozide, risperidone, sertindole, ziprasidone: Concomitant use contraindicated1 200

Phenothiazines (chlorpromazine, fluphenazine, mesoridazine, perphenazine, prochlorperazine, thioridazine): Concomitant use contraindicated1 200

Quetiapine: Consider alternative antiretroviral;1 if ritonavir-boosted saquinavir necessary in patient receiving stable quetiapine dosage, reduce quetiapine dosage to one-sixth of original dosage and monitor for quetiapine efficacy and adverse effects;1 200 if quetiapine necessary in patient receiving ritonavir-boosted saquinavir, experts state initiate using lowest quetiapine dosage and titrate as needed200

Atazanavir

Increased saquinavir concentrations and AUC;1 no change in atazanavir concentrations1

Potential for serious and/or life-threatening cardiac arrhythmias1

Concomitant use contraindicated1

Avanafil

Possible increased avanafil concentrations and AUC188

Do not use concomitantly188 200

β-adrenergic blocking agents (atenolol, labetalol, metoprolol, nadolol, sotalol, timolol)

Metoprolol, timolol: Possible increased concentrations of the β-blocker200

Decreased β-blocker dosage may be needed;200 adjust based on clinical response;200 consider use of certain β-blockers not metabolized by CYP isoenzymes (e.g., atenolol, labetalol, nadolol, sotalol)200

Benzodiazepines

Alprazolam, clonazepam, clorazepate, diazepam, flurazepam: Increased benzodiazepine concentrations1 200

Midazolam or triazolam: Increased benzodiazepine concentrations;1 200 potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1

Lorazepam, oxazepam, temazepam: No data, but may have less potential for pharmacokinetic interaction with HIV PIs compared with other benzodiazepines200

Alprazolam, clonazepam, clorazepate, diazepam, flurazepam: Clinical importance of interaction unknown;1 decreased benzodiazepine dosage may be needed;1 monitor for benzodiazepine-associated adverse effects1

Alprazolam or diazepam: Consider using a benzodiazepine with less potential for pharmacokinetic interaction (lorazepam, oxazepam, temazepam)200

Oral midazolam or triazolam: Concomitant use contraindicated1 200

Parenteral midazolam: Experts state that a single parenteral midazolam dose can be given with caution in a monitored situation for procedural sedation in patients receiving ritonavir-boosted saquinavir;200 manufacturer states patient should be monitored closely for respiratory depression and/or prolonged sedation and dosage adjustment considered1

Bosentan

Potential for substantially increased bosentan concentrations1

In patients already receiving ritonavir-boosted saquinavir for ≥10 days, initiate bosentan using a dosage of 62.5 mg once daily or every other day based on individual tolerability1 200

In patients receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating ritonavir-boosted saquinavir; after ≥10 days of ritonavir-boosted saquinavir, resume bosentan using a dosage of 62.5 mg once daily or every other day based on individual tolerability1 200

Buspirone

Increased buspirone concentrations expected200

Use concomitantly with caution;200 use low buspirone dosage and titrate based on clinical response200

Calcium-channel blocking agents

Possible increased concentrations of the calcium-channel blocking agent (e.g., amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil)1 200

Use concomitantly with caution;1 200 monitor closely and adjust dosage of calcium-channel blocking agent based on clinical response and toxicities200

Cisapride

Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1 200

Cobicistat

Concomitant use of saquinavir with cobicistat not recommended;1 dosage recommendations not established1

Concomitant use of ritonavir-boosted saquinavir and cobicistat not recommended due to similar effects of cobicistat and ritonavir on CYP3A1

Colchicine

Possible increased colchicine concentrations and AUC1 200

Patients with renal or hepatic impairment: Avoid concomitant use of colchicine and ritonavir-boosted saquinavir1

Colchicine for treatment of gout flares: In those receiving ritonavir-boosted saquinavir, use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later and repeat dose no earlier than 3 days later1 200

Colchicine for prophylaxis of gout flares: In those receiving ritonavir-boosted saquinavir, decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 mg once daily1 200

Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving ritonavir-boosted saquinavir, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily)1 200

Corticosteroids (beclomethasone, budesonide, dexamethasone, fluticasone, methylprednisolone, prednisolone, prednisone, triamcinolone)

Beclomethasone (orally inhaled, intranasal): Clinically important pharmacokinetic interactions not expected200

Budesonide or fluticasone (orally inhaled, intranasal): Increased corticosteroid concentrations;200 may result in adrenal insufficiency or Cushing's syndrome200

Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations;200 may result in adrenal insufficiency or Cushing's syndrome200

Budesonide, prednisone (systemic): Increased corticosteroid concentrations;200 may result in adrenal insufficiency or Cushing's syndrome; budesonide (systemic) may decrease saquinavir concentrations and virologic efficacy1 200

Dexamethasone (systemic): Possible decreased saquinavir concentrations1 200

Budesonide or fluticasone (orally inhaled, intranasal): Do not use concomitantly unless potential benefits of intranasal or inhaled corticosteroid outweigh risks of systemic corticosteroid adverse effects;1 200 consider alternative (e.g., beclomethasone);200 if concomitant use with fluticasone necessary, reduce fluticasone dosage and monitor for local and systemic effects1

Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Do not use concomitantly; consider alternative nonsteroidal therapies; if intra-articular corticosteroid required, use alternative antiretroviral that does not alter CYP3A activity (e.g., dolutegravir, raltegravir)200

Budesonide, prednisone (systemic): Use concomitantly with caution only when potential benefits outweigh risks of systemic corticosteroid adverse effects200

Dexamethasone (systemic): Concomitant use not recommended;1 consider alternative corticosteroid for long-term therapy200

Daclatasvir

Possible increased daclatasvir concentrations178 200

If used concomitantly, use daclatasvir dosage of 30 mg once daily178 200

Dapsone

Possible serious and/or life-threatening cardiac arrhythmias1

Concomitant use contraindicated1

Darunavir

Decreased darunavir concentrations and AUC and no effect on saquinavir concentrations and AUC with darunavir 400 mg, ritonavir 100 mg, and saquinavir 1 g twice daily204

No in vitro evidence of antagonistic antiretroviral effects204

Appropriate dosages for concomitant use with respect to safety and efficacy not established;200 204 concomitant use of ritonavir-boosted darunavir and saquinavir not recommended204

Delavirdine

Possible increased saquinavir concentrations and AUC;1 212 no clinically important effect on delavirdine pharmacokinetics212

Concomitant use with ritonavir-boosted saquinavir not evaluated1

Concomitant use not recommended;1 if concomitant use required, frequently monitor liver function1

Didanosine

In vitro evidence of additive or synergistic antiretroviral effects1 2 14 29 30 47 69

Digoxin

Ritonavir-boosted saquinavir: Increased digoxin concentrations1

Use concomitantly with caution; monitor digoxin concentrations; may need to reduce digoxin dose1 200

Dolutegravir

Specific data regarding concomitant use not available200

Some experts state dosage adjustments not needed200

Efavirenz

Decreased saquinavir plasma concentrations and AUC;1 200 213 decreased efavirenz concentrations1 213

In vitro evidence of additive antiretroviral effects213

Manufacturer of saquinavir states concomitant use not recommended;1 appropriate dosages for concomitant use with respect to safety and efficacy not established1

Some experts recommend using usual dosage of ritonavir-boosted saquinavir (saquinavir 1 g and ritonavir 100 mg twice daily) with efavirenz200

Elbasvir and grazoprevir

Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Possible increased risk of elevated ALT concentrations due to substantially increased grazoprevir concentrations177 200

Elbasvir/grazoprevir: Concomitant use contraindicated177 200

Elvitegravir

Cobicistat-boosted elvitegravir: Possible altered elvitegravir, cobicistat, and/or saquinavir concentrations if used with ritonavir-boosted saquinavir200

Cobicistat-boosted elvitegravir: Do not use concomitantly with ritonavir-boosted saquinavir200

Emtricitabine

In vitro evidence of additive or synergistic antiretroviral effects218

Enfuvirtide

No clinically important interactions reported1

Eplerenone

Increased eplerenone concentrations expected200

Experts state concomitant use contraindicated200

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)1

Concomitant use contraindicated1 200

If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving saquinavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible202

Estrogens/progestins

Hormonal contraceptives: Possible decreased ethinyl estradiol concentrations1

Etonogestrel-releasing subdermal implants, transdermal ethinyl estradiol and norelgestromin: Data not available200

Alternative or additional contraceptive measures should be used when estrogen-based oral contraceptive is used concomitantly with ritonavir-boosted saquinavir1 200

Etonogestrel-releasing subdermal implants, transdermal ethinyl estradiol and norelgestromin: Consider alternative or additional method of contraception or alternative antiretroviral200

Etravirine

Ritonavir-boosted saquinavir: Decreased etravirine concentrations and AUC; no change in saquinavir concentrations and AUC200 214

No in vitro evidence of antagonistic antiretroviral effects214

Dosage adjustments not needed200 214

Decrease in systemic exposure to etravirine similar to that in patients receiving etravirine in conjunction with ritonavir-boosted darunavir (a combination found to be safe and effective)200 214

Flibanserin

Increased flibanserin concentrations expected200

Experts state concomitant use contraindicated200

Fosamprenavir

No clinically important pharmacokinetic interactions with ritonavir-boosted saquinavir1

In vitro evidence of synergistic antiretroviral effects205

Appropriate dosages for concomitant use with respect to safety and efficacy not established205

Fusidic Acid

Possible increased saquinavir, ritonavir, and fusidic acid concentrations;1 possible increased risk of saquinavir- and fusidic acid-associated adverse effects1

Concomitant use not recommended1

Garlic

Garlic supplements: Decreased saquinavir plasma concentrations and AUC1 61

Data not available on concomitant use with ritonavir-boosted saquinavir1

Garlic supplements: Do not use in patients receiving ritonavir-boosted saquinavir1 61 200

Grapefruit juice

Oral bioavailability of saquinavir increased103

Halofantrine

Potential for serious and/or life-threatening cardiac arrhythmias1

Concomitant use contraindicated1

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, simvastatin: Decreased clearance and increased concentrations of statins with potential for increased risk of myopathy and/or rhabdomyolysis1 186 200

Pravastatin: If used with ritonavir-boosted saquinavir, decreased pravastatin AUC200

Atorvastatin: Carefully titrate atorvastatin dosage using lowest necessary dosage; do not exceed atorvastatin dosage of 20 mg daily186 200

Lovastatin: Concomitant use contraindicated1 200

Pitavastatin: Experts state dosage adjustments not needed200

Pravastatin: Experts state dosage adjustments not needed 200

Rosuvastatin: Carefully titrate rosuvastatin dosage using lowest necessary dosage; monitor for toxicities200

Simvastatin: Concomitant use contraindicated1 200

Immunosuppressive agents (cyclosporine, everolimus, sirolimus, tacrolimus)

Cyclosporine, everolimus, sirolimus: Increased immunosuppressive agent concentrations expected1 155 200

Cyclosporine, everolimus, sirolimus: Monitor immunosuppressive agent concentrations;1 200 some experts state initiate immunosuppressive agent with adjusted dosage to account for potential increased concentrations,200 monitor for toxicities,200 consult specialist if needed200

Tacrolimus: Concomitant use contraindicated1 200

Indinavir

Increased saquinavir concentrations;1 may result in nephrolithiasis1

Data not available on concomitant use with ritonavir-boosted saquinavir1

Concomitant use not recommended;1 appropriate dosages for concomitant use with respect to safety and efficacy not established1

Ivabradine

Increased ivabradine concentrations expected200

Experts state concomitant use contraindicated200

Lamivudine

In vitro evidence of additive or synergistic antiretroviral effects1 2 14 29 30 47 69

 

Ledipasvir and sofosbuvir

Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): Clinically important pharmacokinetic interactions not expected200

Concomitant use of ledipasvir/sofosbuvir and HIV antiretroviral regimen that includes ritonavir-boosted saquinavir and tenofovir DF: Possible increased tenofovir concentrations200

Ledipasvir/sofosbuvir: Dosage adjustments not needed200

Concomitant use of ledipasvir/sofosbuvir and HIV antiretroviral regimen that includes ritonavir-boosted saquinavir and tenofovir DF: Experts state consider alternative HCV treatment or an alternative antiretroviral regimen;200 if concomitant use necessary, monitor for tenofovir-associated adverse effects200

Lopinavir

Fixed combination of lopinavir and ritonavir (lopinavir/ritonavir): Increased saquinavir concentrations;207 potential additive effects on QT and/or PR interval prolongation1

Saquinavir concentrations achieved with a regimen of saquinavir 1 g twice daily with lopinavir 400 mg/ritonavir 100 mg twice daily are similar to those with ritonavir-boosted saquinavir (saquinavir 1 g and ritonavir 100 mg twice daily)1 189

In vitro evidence of additive to synergistic antiretroviral effects1 207

Use concomitantly with caution1

If used concomitantly, recommended dosage is saquinavir 1 g twice daily with lopinavir 400 mg/ritonavir 100 mg twice daily1 207

Once-daily regimen of lopinavir/ritonavir not studied in conjunction with saquinavir207

Macrolides (clarithromycin, erythromycin)

Clarithromycin: Increased saquinavir and clarithromycin AUC; decreased 14-hydroxyclarithromycin AUC;1 200 potential serious and/or life-threatening cardiac arrhythmias1

Erythromycin: Potential serious and/or life-threatening cardiac arrhythmias1

Clarithromycin: Concomitant use contraindicated;1 200 consider alternative macrolide (e.g., azithromycin);200

Erythromycin: Concomitant use contraindicated1

Maraviroc

Ritonavir-boosted saquinavir: Increased maraviroc concentrations and AUC1 200 224

No in vitro evidence of antagonistic antiretroviral effects224

Ritonavir-boosted saquinavir: Recommended dosage of maraviroc is 150 mg twice daily1 200

Mefloquine

Low-dose ritonavir: Decreased ritonavir concentrations and AUC;200 no effect on mefloquine concentrations200

Ritonavir-boosted saquinavir: Data not available200

Ritonavir-boosted saquinavir: Use concomitantly with caution200

Methadone

Decreased methadone concentrations with ritonavir-boosted saquinavir1 200

Potential for additive QT and/or PR interval prolongation1

Use concomitantly with caution;1 monitor closely for opiate withdrawal and increase methadone dosage as clinically indicated1 200

Nefazodone

Possible increased saquinavir concentrations1

Monitor for saquinavir-associated adverse effects1

Nelfinavir

Increased saquinavir concentrations and increased nelfinavir concentrations208

In vitro evidence of additive antiretroviral effects208

Concomitant use not recommended1

Nevirapine

Decreased saquinavir concentrations and AUC;1 200 nevirapine concentrations not affected200

Concomitant use with ritonavir-boosted saquinavir not evaluated1

In vitro evidence of additive or synergistic antiretroviral effects1

Concomitant use not recommended;1 appropriate dosages for concomitant use with respect to safety and efficacy not established1 200

Ombitasvir, paritaprevir, and ritonavir

Fixed combination of ombitasvir, paritaprevir, and ritonavir with or without dasabuvir: Concomitant use contraindicated200

Pentamidine

Possible serious and/or life-threatening cardiac arrhythmias1 200

Concomitant use contraindicated1 200

Proton-pump inhibitors

Omeprazole with ritonavir-boosted saquinavir: Increased saquinavir concentrations1

Caution advised if ritonavir-boosted saquinavir used with a proton-pump inhibitor;1 monitor for saquinavir toxicities (GI symptoms, increased triglycerides, deep-vein thrombosis, QT-interval prolongation)1 200

Quinine

Possible serious and/or life-threatening cardiac arrhythmias1

Concomitant use contraindicated1

Quinupristin and dalfopristin

Fixed combination of quinupristin and dalfopristin (quinupristin/dalfopristin): Possible increased saquinavir concentrations1

Quinupristin/dalfopristin: Use concomitantly with caution;1 monitor for saquinavir-associated adverse effects1

Raltegravir

Specific data regarding concomitant use not available200

In vitro evidence of additive to synergistic antiretroviral effects225

Experts state dosage adjustments not needed if raltegravir used concomitantly with ritonavir-boosted saquinavir200

Ranolazine

Experts state concomitant use contraindicated200

Rilpivirine

Ritonavir-boosted saquinavir: Possible increased rilpivirine concentrations; not expected to affect saquinavir concentrations226

No in vitro evidence of antagonistic antiretroviral effects226

Ritonavir-boosted saquinavir: Dosage adjustments not needed 200

Ritonavir

Substantially increased saquinavir concentrations when saquinavir 1 g twice daily used with low-dose ritonavir (100 mg twice daily)1

Concomitant low-dose ritonavir used as a pharmacokinetic enhancer (pharmacokinetic booster) for therapeutic advantage (ritonavir-boosted saquinavir)1 200

Ritonavir-boosted saquinavir causes dose-dependent prolongation of QT and PR intervals; torsades de pointes and complete heart block reported1 119

Recommended dosage is saquinavir 1 g twice daily with ritonavir 100 mg twice daily1 200 209

Monitor ECG and electrolytes prior to and during therapy with ritonavir-boosted saquinavir1 (see Cardiovascular Effects under Cautions)

St. John’s wort (Hypericum perforatum)

Possible decreased saquinavir concentrations;1 162 163 206 potential loss of virologic response and development of resistance1

Do not use concomitantly1 200

Salmeterol

Possible increased salmeterol concentrations and increased risk of QT interval prolongation, palpitations, or sinus tachycardia1 200

Concomitant use not recommended1 200

Sildenafil

Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection)1 200

Sildenafil for treatment of erectile dysfunction: Use caution and reduce sildenafil dosage (do not exceed 25 mg every 48 hours); closely monitor for adverse effects1 200

Sildenafil for treatment of PAH: Concomitant use contraindicated;1 200 safe and effective dosage for concomitant use not established1 200

Simeprevir

Possible altered (increased or decreased) simeprevir concentrations187

Concomitant use not recommended187 200

Stavudine

In vitro evidence of additive or synergistic antiretroviral effects1 2 14 29 30 47 69

Suvorexant

Increased suvorexant concentrations expected200

Experts state concomitant use not recommended200

Tadalafil

Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection)1 200

Tadalafil for treatment of erectile dysfunction: Use initial tadalafil dosage of 5 mg; do not exceed a single dose of 10 mg in 72 hours; monitor closely for adverse effects1 200

Tadalafil for treatment of benign prostatic hyperplasia: Do not exceed tadalafil dosage of 2.5 mg once daily200

Tadalafil (Adcirca) for treatment of PAH: In patients already receiving ritonavir-boosted saquinavir for ≥1 week, use initial tadalafil dosage of 20 mg once daily and increase dosage to 40 mg once daily based on individual tolerability1 200

Avoid use of tadalafil (Adcirca) for treatment of PAH during initiation of ritonavir-boosted saquinavir therapy;1 200 in patients receiving tadalafil for treatment of PAH, discontinue tadalafil for at least 24 hours before starting ritonavir-boosted saquinavir; tadalafil can be restarted after ≥1 week of ritonavir-boosted saquinavir therapy using initial tadalafil dosage of 20 mg once daily and increasing dosage to 40 mg once daily based on individual tolerability1 200

If tadalafil is used for treatment of benign prostatic hyperplasia, do not exceed tadalafil dosage of 2.5 mg once daily200

Tenofovir

No clinically important change in saquinavir or tenofovir concentrations or AUC with saquinavir 1 g twice daily and ritonavir 100 mg twice daily with tenofovir 300 mg once daily1 221

In vitro evidence of additive or synergistic antiretroviral effects against HIV-1221

Dosage adjustments not needed with ritonavir-boosted saquinavir221

Ticagrelor

Increased ticagrelor concentrations expected200

Avoid concomitant use200

Tipranavir

Decreased saquinavir concentrations and AUC1

Concomitant use not recommended1

Trazodone

Increased trazodone concentrations expected;1 200 increased risk of potentially life-threatening cardiac arrhythmias1

Concomitant use contraindicated1 200

Vardenafil

Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection)1 200

Vardenafil for treatment of erectile dysfunction: Use caution; do not exceed vardenafil dosage of 2.5 mg in 72 hours; monitor closely for adverse effects1 200

Vincamine (not available in US)

Possible increased vincamine concentrations;1 possible increased risk for cardiac arrhythmias1

Use concomitantly with caution;1 monitor for vincamine-associated adverse effects1

Vorapaxar

Increased vorapaxar concentrations expected200

Avoid concomitant use200

Zidovudine

In vitro evidence of additive or synergistic antiretroviral effects1 2 14 29 30 47 69

 

Zolpidem

Possible increased zolpidem concentrations200

Experts state initiate zolpidem at low dosage;200 dosage reduction may be needed200

Advice to Patients

  • Saquinavir medication guide must be provided to the patient each time the drug is dispensed;1 importance of patient reading the medication guide prior to initiating saquinavir therapy and each time prescription is refilled.1

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.1 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1

  • Importance of using in conjunction with other antiretroviralsnot for monotherapy.1

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.1

  • Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to acquired immunodeficiency syndrome (AIDS) and death.203

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.1 200

  • Importance of taking within 2 hours of a meal, not on an empty stomach.1

  • Advise patients that ECG changes (PR and/or QT interval prolongation) have occurred;1 importance of consulting clinician if symptoms such as dizziness, lightheadedness, fainting, or sensation of abnormal heartbeats occur.1

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (e.g., St. John’s wort), and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise HIV-infected women not to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Uses For saquinavir

Saquinavir is used together with ritonavir (Norvir®) and other medicines for the treatment of human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Saquinavir will not cure or prevent HIV infection or AIDS. It helps keep HIV from reproducing and slows the destruction of the immune system. This may help delay problems related to AIDS or HIV disease from occurring. Saquinavir will not keep you from spreading HIV to other people.

saquinavir is available only with your doctor's prescription.

saquinavir Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Chest pain
  • cough
  • fever or chills
  • increased amount of fat in the upper back and neck, or around the chest and stomach area
  • loss of fat from the legs, arms, and face
  • sneezing
  • sore throat
  • tightness in the chest
  • troubled breathing
Less common
  • Blurred vision
  • cough-producing mucus
  • diarrhea
  • dry mouth
  • flushed, dry skin
  • fruit-like breath odor
  • general feeling of discomfort or illness
  • headache
  • increased hunger
  • increased thirst
  • increased urination
  • joint pain
  • loss of appetite
  • loss of consciousness
  • muscle aches and pains
  • nausea
  • runny nose
  • shivering
  • skin rash
  • sore throat
  • stomachache
  • sweating
  • trouble sleeping
  • unexplained weight loss
  • unusual tiredness or weakness
  • vomiting
Rare
  • Burning or prickling sensation
  • confusion
  • dehydration
  • dry or itchy skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common
  • Acid or sour stomach
  • back pain
  • belching
  • bloated or full feeling
  • change in taste
  • decreased interest in sexual intercourse
  • difficulty having a bowel movement (stool)
  • discouragement
  • excess air or gas in the stomach or intestines
  • fear
  • feeling sad or empty
  • headache
  • heartburn
  • inability to have or keep an erection
  • indigestion
  • irritability
  • lack of appetite
  • loss in sexual ability, desire, drive, or performance
  • loss of interest or pleasure
  • mouth ulcers
  • nervousness
  • pain or tenderness around the eyes and cheekbones
  • passing gas
  • skin rash, encrusted, scaly, and oozing
  • skin warts
  • stomach upset, discomfort, or pain
  • stuffy nose
  • tiredness
  • trouble concentrating
  • weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Invirase: 200 mg

Tablet, Oral:

Invirase: 500 mg

Contraindications

Hypersensitivity (eg, anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, saquinavir mesylate, or any component of the formulation; congenital QT prolongation, refractory hypokalemia or hypomagnesemia, concomitant use of other medications that both increase saquinavir plasma concentrations and prolong the QT interval; complete AV block (without implanted ventricular pacemaker) or patients at high risk of complete AV block; severe hepatic impairment; coadministration of saquinavir/ritonavir with CYP3A substrates (eg, alfuzosin, amiodarone, atazanavir, bepridil, chlorpromazine, cisapride, clarithromycin, clozapine, dapsone, disopyramide, dofetilide, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), erythromycin, flecainide, halofantrine, haloperidol, lidocaine (systemic), lovastatin, lurasidone, midazolam (oral), pentamidine, phenothiazines, pimozide, propafenone, quinidine, quinine, rifampin, sertindole, sildenafil (when used for pulmonary artery hypertension [eg, Revatio]), simvastatin, tacrolimus, thioridazine, trazodone, triazolam, ziprasidone).

Canadian labeling: Additional contraindications (not in U.S. labeling): Concurrent use with quetiapine, procainamide, sotalol, astemizole, or terfenadine; concurrent use with medications that both increase saquinavir plasma concentrations and prolong the PR interval; acquired QT prolongation

Adverse Reactions

Incidence data for saquinavir soft gel capsule formulation (no longer available) in combination with ritonavir:

10%: Gastrointestinal: Nausea (11%)

1% to 10%:

Cardiovascular: Chest pain

Central nervous system: Fatigue (6%), anxiety, depression, headache, insomnia, pain, paresthesia

Dermatologic: Pruritus (3%), skin rash (3%), eczema (2%), cheilosis (≤2%), xeroderma (≤2%), warts

Endocrine & metabolic: Lipodystrophy (5%), hyperglycemia (3%), change in libido, hypoglycemia, hyperkalemia

Gastrointestinal: Diarrhea (8%), vomiting (7%), abdominal pain (6%), constipation (2%), abdominal distress, decreased appetite, dysgeusia, dyspepsia, flatulence, increased serum amylase, oral mucosa ulcer

Hepatic: Increased serum ALT, increased serum AST, increased serum bilirubin

Infection: Influenza (3%)

Neuromuscular & skeletal: Back pain (2%), increased creatine phosphokinase, weakness

Respiratory: Pneumonia (5%), bronchitis (3%), sinusitis (3%)

Miscellaneous: Fever (3%)

Frequency not defined; reported for hard or soft gel capsule with/without ritonavir:

Cardiovascular: Heart valve disease (including murmur), hypertension, hypotension, peripheral vasoconstriction, prolongation P-R interval on ECG, prolonged Q-T interval on ECG, syncope, thrombophlebitis

Central nervous system: Agitation, amnesia, ataxia, colic, confusion, drowsiness, hallucination, hyperreflexia, hyporeflexia, neuropathy, poliomyelitis, progressive multifocal leukoencephalopathy, psychosis, seizure, speech disturbance

Dermatologic: Alopecia, bullous dermatitis, dermal ulcer, dermatitis, erythema, maculopapular rash, skin photosensitivity, Stevens-Johnson syndrome, urticaria

Endocrine & metabolic: Dehydration, diabetes mellitus, electrolyte disturbance, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased thyroid stimulating hormone level

Gastrointestinal: Bloody stools, dysphagia, esophagitis, gastritis, intestinal obstruction, pancreatitis, stomatitis

Genitourinary: Benign prostatic hypertrophy, hematuria, impotence, urinary tract infection

Hematologic & oncologic: Acute myelocytic leukemia, anemia (including hemolytic), leukopenia, neutropenia, pancytopenia, rectal hemorrhage, splenomegaly, thrombocytopenia

Hepatic: Ascites, hepatic disease (exacerbation), hepatitis, hepatomegaly, hepatosplenomegaly, increased serum alkaline phosphatase, jaundice

Immunologic: Immune reconstitution syndrome

Infection: Infection (bacterial, fungal, viral)

Neuromuscular & skeletal: Arthritis

Ophthalmic: Blepharitis, visual disturbance

Otic: Auditory impairment, otitis, tinnitus

Renal: Nephrolithiasis

Respiratory: Cyanosis, dyspnea, hemoptysis, pharyngitis, upper respiratory tract infection

<1% (Limited to important or life-threatening): Atrioventricular block (second or third degree), autoimmune disease, torsades de pointes

In Summary

Commonly reported side effects of saquinavir include: abdominal distress, diarrhea, and nausea. Other side effects include: vomiting. See below for a comprehensive list of adverse effects.

Other Comments

Administration advice:
-Must use in combination with ritonavir and other antiretrovirals.
-Administer this drug at the same time as ritonavir and within 2 hours after a full meal.
-Do not administer additional ritonavir in patients already using ritonavir (100 mg twice a day) as part of their antiretroviral regimen.
-Patients unable to swallow capsules: (1) Open capsules and place contents into empty container; (2) Add 15 mL of either sugar syrup or sorbitol syrup (for patients with type 1 diabetes or glucose intolerance) OR 3 teaspoons of jam to the capsule contents in the container; (3) Stir with spoon for 30 to 60 seconds; (4) Administer the full amount prepared for each dose; suspensions should be at room temperature before use.

Storage requirements:
-Store at 25C (77F); excursion permitted to 15C to 30C (59F to 86F); close bottle tightly.

General:
-The following should be considered when starting this drug: Twice-daily use of this drug (plus ritonavir) is supported by safety and pharmacokinetic data; efficacy of this drug (plus ritonavir) has not been compared against efficacy of antiretroviral regimens currently considered standard of care; the number of baseline primary protease inhibitor mutations affects virologic response to this drug (plus ritonavir).
-Ritonavir significantly inhibits metabolism of this drug, increasing plasma saquinavir levels; the manufacturer product information for ritonavir should be consulted.
-Cobicistat is not interchangeable with ritonavir to increase systemic exposure of this drug.

Monitoring:
-Cardiovascular: ECG (before starting and during therapy); PR interval (if used with other agents that prolong PR interval)
-Metabolic: Potassium and magnesium (periodically during therapy); cholesterol and triglyceride levels (prior to therapy and periodically thereafter)

Patient advice:
-Read the US FDA-approved patient labeling (Medication Guide).
-Consult healthcare provider if dizziness, lightheadedness, or palpitations occur.

(web3)