Saquinavir

Dosage Forms & Strengths

capsule

• 200mg

tablet

• 500mg

HIV Infection

1000 mg (with ritonavir 100 mg) PO q12hr, or in combination with ritonavir-enhanced lopinavir

Treatment-naïve patients

• Initial dose: 500 mg PO BID plus ritonavir 100 mg BID x 7 days, THEN increase to 1000mg/100mg PO BID
• This gradual increase is due to potential for increased risk of PR and QT interval prolongation with standard 1000/100-mg BID dose
• Patients with a baseline QT interval <450 msec, an on-treatment ECG is recommended after ~10 days of therapy
• Patients with a QT interval prolongation over pretreatment by >20 msec should discontinue saquinavir/ritonavir therapy

Dosage Forms & Strengths

capsule

• 200mg

tablet

• 500mg

HIV Infection

Indicated in combination with ritonavir and other antiretrovirals (ARTs) for treatment of HIV-1 infection

<16 years: Safety and efficacy not established

≥16 years: 1000 mg (plus ritonavir 100 mg) PO q12hr

For patients already taking ritonavir 100 mg BID as part of their ART regimen, no additional ritonavir is needed

Treatment-naïve patients

• Initial dose: 500 mg PO BID plus ritonavir 100 mg BID x 7 days, THEN increase to 1000mg/100mg PO BID
• This gradual increase is due to potential for increased risk of PR and QT interval prolongation with standard 1000/100-mg BID dose
• Patients with a baseline QT interval <450 msec, an on-treatment ECG is recommended after ~10 days of therapy
• Patients with a QT interval prolongation over pretreatment by >20 msec should discontinue saquinavir/ritonavir therapy

Investigational in treatment-experienced children

• <2 years: Safety and efficacy not established
• ≥2 years, 5 to <15 kg: 50 mg/kg (plus ritonavir 3 mg/kg) PO q12hr 
• ≥2 years, 15-40 kg: 50 mg/kg (plus ritonavir 2.5 mg/kg) PO q12hr
• ≥2 years, ≥40 kg: 50 mg/kg (plus ritonavir 100mg) PO q12hr

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

• throat pain

Taking this medicine will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

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.

Saquinavir is part of the drug class:

• Protease inhibitors

• Take saquinavir exactly as your healthcare provider tells you.
• Saquinavir comes as a 500 mg tablet or a 200 mg capsule.
• Do not change your dose of saquinavir or stop treatment without first talking with your healthcare provider.
• Saquinavir must be used along with ritonavir (Norvir).
• Take saquinavir with meals or up to 2 hours after a meal.
• When your saquinavir supply starts to run low, get more from your doctor or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to ritonavir and become harder to treat.
• Do not miss a dose of saquinavir. It is very important to take your medicine every day. If you skip doses or take less than the prescribed dose the medicine will not work as well, and the virus may become harder to treat.
• If you miss a dose of saquinavir, you should take the next dose as soon as possible. Do not double your dose.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Saquinavir may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with saquinavir. Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

• chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

• cold sores, sores on your genital or anal area;

• rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

• trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Call your doctor at once if you have:

• any type of infection, skin infection, or open sores;

• cough with yellow or green mucus, stabbing chest pain, wheezing, feeling short of breath;

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

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).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Saquinavir in an HIV PI.1 3 6 10 28 51

• Active against HIV-1 and HIV-2.1 6 13 14 21 25 26 27 28 29 30 31 32 48 51

• Inhibits replication of HIV-1 and HIV-2 by interfering with HIV protease.1 2 3 4 5 6 8 9 10 11 13 14 19 21 22 25 26 27 28 48 51 65

• HIV-1 with reduced susceptibility to saquinavir have been selected in vitro and have emerged during therapy with the drug.1 3 6 9 19 31 34 35 37 38 39 70 92

• Varying degrees of cross-resistance occur among HIV PIs.1 9 32 33 51 58 65 66 68 70 209

Adverse events were not observed in animal reproduction studies. Saquinavir has a low level of transfer across the human placenta. Data collected by the antiretroviral pregnancy registry are insufficient to evaluate human teratogenic risk. A small increased risk of preterm birth has been associated with maternal use of protease inhibitor-based combination antiretroviral therapy during pregnancy; however, the benefits of use generally outweigh this risk and protease inhibitors (PIs) should not be withheld if otherwise recommended. Information related to stillbirth, low birth weight, and small for gestational age infants is limited. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Hyperglycemia, new onset of diabetes mellitus, or diabetic ketoacidosis have been reported with PIs; it is not clear if pregnancy increases this risk.

Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should begin as soon as possible after diagnosis. The Health and Human Services (HHS) Perinatal HIV Guidelines do not recommend ritonavir-boosted saquinavir for initial use in antiretroviral-naive pregnant women due to potential toxicity, twice-daily dosing requirements, and limited data in pregnancy; use of saquinavir without ritonavir is not recommended in any patient. Based on available data, dose adjustments are not required in pregnant women. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated. Monitoring during pregnancy is more frequent than in non-pregnant adults; cART should be continued postpartum.

For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s) and expert consultation is recommended; modification of therapy (if needed) and optimization of the woman’s health should be done prior to conception. HIV-infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).

Applies to saquinavir: oral capsule, oral tablet

General

Nausea, vomiting, diarrhea, fatigue, flatulence, and abdominal pain have been reported the most frequently with this drug (plus ritonavir). Additional side effects have been reported during postmarketing experience that were similar to those observed in clinical trials with saquinavir mesylate and saquinavir soft gel capsules alone or in combination with ritonavir.[Ref]

Gastrointestinal

Very common (10% or more): Nausea, diarrhea
Common (1% to 10%): Vomiting, abdominal distension, abdominal pain, upper abdominal pain, constipation, dry mouth, dyspepsia, eructation, flatulence, lip dry, loose stools, increased blood amylase
Uncommon (0.1% to 1%): Pancreatitis
Frequency not reported: Abdominal discomfort, ascites, bucca mucosa ulceration, dysphagia, gastritis, gastrointestinal (GI) hemorrhage, intestinal obstruction, cheilitis, frequent bowel movements, discolored feces, bloodstained feces, gastralgia, GI inflammation, gingivitis, GI ulcer, glossitis, hemorrhoids, melena, painful defecation, parotid disorder, rectal hemorrhage, salivary gland disorder, stomatitis, tooth disorder, abdominal colic, esophageal ulceration, esophagitis, gastroesophageal reflux, infectious diarrhea, pruritus ani, pyrosis, stomach upset, toothache[Ref]

Metabolic

Very common (10% or more): Increased blood cholesterol, increased blood triglycerides, increased low-density lipoprotein
Common (1% to 10%): Diabetes mellitus/hyperglycemia, anorexia, increased appetite
Uncommon (0.1% to 1%): Decreased appetite
Frequency not reported: Dehydration, hypertriglyceridemia, increased alkaline phosphatase, increased LDH, hypoglycemia, hyperlipidemia, appetite disturbance, increased blood glucose, decreased blood glucose, hypercalcemia, hypocalcemia, hyperphosphatemia, hypophosphatemia, hyperkalemia, hypokalemia, hypernatremia, hyponatremia
Postmarketing reports: Ketoacidosis, metabolic abnormalities (e.g., hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperlactatemia)

Antiretroviral therapy:
-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased blood lipid levels, increased glucose levels

Protease inhibitor therapy:
-Postmarketing reports: New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, diabetic ketoacidosis[Ref]

Diabetes mellitus/hyperglycemia was sometimes associated with ketoacidosis during postmarketing experience.

Redistribution/accumulation of body fat has been reported with antiretroviral therapy; causality has not been established.[Ref]

Hematologic

Very common (10% or more): Decreased platelet count
Common (1% to 10%): Anemia, decreased hemoglobin, decreased lymphocyte count, decreased WBC count
Uncommon (0.1% to 1%): Neutropenia
Frequency not reported: Hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia, thrombocytopenia, splenomegaly, dermal bleeding, microhemorrhages

Protease inhibitor therapy:
-Frequency not reported: Increased bleeding (including spontaneous skin hematomas, hemarthrosis) in hemophiliacs[Ref]

Increased bleeding (including spontaneous skin hematomas and hemarthrosis) in patients with hemophilia type A and B has been associated with protease inhibitors. In many of the reported cases, treatment with protease inhibitors was continued or restarted and some patients required additional factor VIII. A causal relationship between protease inhibitor therapy and these episodes has not been established.[Ref]

Hepatic

Very common (10% or more): Elevated ALT, elevated AST
Common (1% to 10%): Increased blood bilirubin
Uncommon (0.1% to 1%): Hepatitis, jaundice
Frequency not reported: Chronic active hepatitis, hepatomegaly, hyperbilirubinemia, portal hypertension, elevated GGT, hepatosplenomegaly, severe cutaneous reaction associated with increased liver function tests, increased transaminase levels, exacerbation of chronic liver disease with grade 4 elevated liver function tests, worsening liver disease, severe hepatocellular toxicity (presenting as increased hepatic transaminases), sclerosing cholangitis, cholelithiasis, liver enzyme disorder[Ref]

There have been reports of worsening liver disease in patients with underlying hepatitis B or C, cirrhosis, chronic alcoholism, and/or other underlying liver abnormalities.

Severe hepatocellular toxicity (which presented as increased hepatic transaminases) occurred in healthy subjects exposed to this drug (plus ritonavir) and rifampin. Transaminases increased up to more than 20-fold the upper limit of normal in some patients and were associated with GI symptoms (including abdominal pain, gastritis, nausea, vomiting). Clinical symptoms resolved and hepatic transaminases returned to normal after all 3 drugs were stopped.[Ref]

Cardiovascular

Rare (less than 0.1%): Second or third degree atrioventricular block
Frequency not reported: QT interval prolongation, PR interval prolongation, heart murmur, hypertension, hypotension, thrombophlebitis, vasoconstriction/peripheral vasoconstriction, cyanosis, heart rate disorder, heart valve disorder, vein distension
Postmarketing reports: Torsades de pointes (rarely)[Ref]

This drug (plus ritonavir) showed a dose-dependent prolongation of the QT and PR intervals.[Ref]

Other

Common (1% to 10%): Fatigue, fever/pyrexia, asthenia/weakness, increased fat tissue, malaise
Uncommon (0.1% to 1%): Mucosal ulceration
Frequency not reported: Chest pain, edema, wasting syndrome, intoxication, increased weight, mucosal damage, retrosternal pain, shivering, generalized weakness, earache, ear pressure, otitis, abscess, bacterial infection, candidiasis, herpes simplex, herpes zoster, mycotic infection, staphylococcal infections, decreased weight, external parasites, cellulitis, molluscum contagiosum, moniliasis

Antiretroviral therapy:
-Frequency not reported: Increased weight[Ref]

Respiratory

Common (1% to 10%): Pneumonia, bronchitis, influenza, sinusitis, dyspnea
Frequency not reported: Cough, epistaxis, hemoptysis, laryngitis, pharyngitis, respiratory disorder, rhinitis, upper respiratory tract infection, angina tonsillaris, pulmonary disease[Ref]

Dermatologic

Common (1% to 10%): Acquired lipodystrophy, rash, pruritus, dry skin, eczema, alopecia, lipoatrophy
Uncommon (0.1% to 1%): Stevens-Johnson syndrome, bullous dermatitis
Frequency not reported: Acne, drug eruption, erythema, severe cutaneous reaction associated with increased liver function tests, increased sweating, urticaria, dermatitis, bullous dermatitis skin eruption (including with polyarthritis), folliculitis, furunculosis, hair changes, hot flushes, maculopapular rash, photosensitivity reaction, seborrheic dermatitis, skin disorder, skin nodule, skin pigment changes, skin ulceration, verruca, xeroderma, exanthema, nail disorders, night sweats, psoriasis
Postmarketing reports: Lipodystrophy (including loss of peripheral and facial subcutaneous fat, increased intraabdominal and visceral fat, breast hypertrophy, dorsocervical fat accumulation [buffalo hump])[Ref]

Nervous system

Common (1% to 10%): Headache, paresthesia, peripheral neuropathy, dizziness, dysgeusia/taste alteration
Uncommon (0.1% to 1%): Somnolence, convulsions
Frequency not reported: Abnormal coordination, hypoesthesia, intracranial hemorrhage (sometimes leading to death), tremor, loss of consciousness, syncope, tinnitus, dysarthria, dysesthesia, ataxia, extremity numbness, face numbness, facial pain, hyperesthesia, hyperreflexia, hyporeflexia, lethargy, lightheadedness, paresis, poliomyelitis, progressive multifocal leukoencephalopathy, seizures, spasms, decreased hearing, stroke, myelopolyradiculoneuritis, prickly sensation[Ref]

Psychiatric

Common (1% to 10%): Decreased libido, sleep disorder
Frequency not reported: Anxiety/anxiety attack, confusion/confusional state, depression, insomnia, libido disorder, psychotic disorder/psychosis, suicide attempt, agitation, amnesia, euphoria, excessive dreaming, hallucination, irritability, overdose effect, psychic disorders, reduced intellectual ability, speech disorder[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, muscle spasms
Frequency not reported: Arthralgia, myalgia, polyarthritis, elevated blood creatine phosphokinase, arthritis, muscle cramps, musculoskeletal pain, musculoskeletal disorders, stiffness, tissue changes, trauma, leg cramps

Combination antiretroviral therapy:
-Frequency not reported: Osteonecrosis

Protease inhibitor therapy:
-Rare (less than 0.1%): Rhabdomyolysis
-Frequency not reported: Increased creatine phosphokinase, myalgia, myositis[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity
Frequency not reported: Allergic reaction, drug fever[Ref]

Renal

Common (1% to 10%): Increased blood creatinine
Uncommon (0.1% to 1%): Renal impairment
Frequency not reported: Nephrolithiasis, acute renal insufficiency[Ref]

Ocular

Uncommon (0.1% to 1%): Visual impairment
Frequency not reported: Blepharitis, dry eye syndrome, eye irritation, visual disturbance, xerophthalmia, chalazion, cytomegalovirus retinitis[Ref]

Immunologic

Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)[Ref]

Genitourinary

Frequency not reported: Enlarged prostate, pelvic pain, vaginal discharge, micturition disorder, urinary tract infection, epididymitis, impotence, menstrual disorder, menstrual irregularity, nocturia, penis disorder, renal calculus, renal colic, urinary tract bleeding[Ref]

Oncologic

Frequency not reported: Acute myeloid leukemia, papillomatosis, skin papilloma, tumor[Ref]

Endocrine

Frequency not reported: Hyperprolactinemia, increased thyroid stimulating hormone[Ref]

Some side effects of saquinavir may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Standard dose: Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Therapy-naive patients (starting therapy with saquinavir/ritonavir):
-The first 7 days: Saquinavir 500 mg plus ritonavir 100 mg orally twice a day
-After 7 days: Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Patients switching immediately (no washout period) from another ritonavir-containing regimen or from a NNRTI-based regimen (excluding delavirdine, rilpivirine): Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Patients switching from a regimen containing delavirdine or rilpivirine:
-The first 7 days: Saquinavir 500 mg plus ritonavir 100 mg orally twice a day
-After 7 days: Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Use: In combination with ritonavir and other antiretrovirals, for the treatment of HIV-1 infection

16 years or older:
Standard dose: Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Therapy-naive patients (starting therapy with saquinavir/ritonavir):
-The first 7 days: Saquinavir 500 mg plus ritonavir 100 mg orally twice a day
-After 7 days: Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Patients switching immediately (no washout period) from another ritonavir-containing regimen or from a NNRTI-based regimen (excluding delavirdine, rilpivirine): Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Patients switching from a regimen containing delavirdine or rilpivirine:
-The first 7 days: Saquinavir 500 mg plus ritonavir 100 mg orally twice a day
-After 7 days: Saquinavir 1000 mg plus ritonavir 100 mg orally twice a day

Comments:
-Doses that are both reliably effective and safe (i.e., below levels of concern for QT and PR interval prolongation) could not be established for pediatric patients younger than 16 years.

Use: In combination with ritonavir and other antiretrovirals, for the treatment of HIV-1 infection

Mild or moderate liver dysfunction: No adjustment recommended.

When used with ritonavir:
-Severe liver dysfunction: Contraindicated