ISENTRESS RALTEGRAVIR 400 mg Tablet, Film Coated, 6-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Raltegravir is used to treat human immunodeficiency virus (HIV) infection. Raltegravir is in a class of medications called HIV integrase inhibitors. It works by decreasing the amount of HIV in the blood. Although raltegravir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses. Taking these medications and making other lifestyle changes may decrease the risk of transmitting (spreading) the HIV virus to other people.
Read the full MedlinePlus article ↗- Raltegravir blocks an enzyme called integrase that HIV-1 uses to embed itself in your DNA. Without that step, the virus can't make copies of itself. The reason you need it alongsid...
- What exactly does raltegravir do — and why do I have to take other HIV medicines with it?
- It depends on the form you're taking. The good news is that all forms of raltegravir can be taken with or without food. That said, food does affect how much of the drug gets absorb...
- Does it matter what I eat when I take it?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Raltegravir — tap one for details:
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 1P9D0Z171K
BHT is a synthetic antioxidant that prevents fats and oils in medicines from breaking down and becoming rancid. It helps keep the product stable and effective during storage.
-
UNII L11K75P92J
A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
-
UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
-
UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
-
UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
-
UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII TUF2IVW3M2
Poloxamer 407 is a synthetic polymer made from ethylene oxide and propylene oxide. In medicines, it acts as a thickener, emulsifier, and solubilizer to help mix ingredients and create the right texture.
-
UNII G2M7P15E5P
Polyethylene glycol 3350 is a synthetic polymer used as a solvent, humectant, and thickening agent in medicines. It helps dissolve other ingredients, retain moisture in the product, and achieve the desired consistency.
-
UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
-
UNII 7CV7WJK4UI
Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.
-
UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
-
UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
14 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $34.00 | $204.02 / 6 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Isentress 400 mg 00006-0227-61 | Merck | 60 tablets | $34.543 | — | Availability likely | — |
| Isentress 400 mg 50090-1085-00 | A-S | 60 tablets | — | — | FDA listed | — |
| Isentress 400 mgthis 68071-2113-06 | NuCare | 6 tablets | — | — | FDA listed | — |
| Isentress 400 mg 71205-0777-14 | Proficient | 14 tablets | — | — | FDA listed | — |
| Raltegravir 400 mg 31722-0584-60 | Camber | 60 tablets | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 7754731 ↗ | Drug substance | U-257 | Mar 11, 2029 |
| US 7754731 ↗ | Drug substance | U-257 | Mar 11, 2029 |
| US 8852632 ↗ | Drug substance | U-257 | Jan 28, 2028 |
| US 8771733 ↗ | Drug substance | U-257 | Jun 2, 2030 |
| US 8771733 ↗ | Drug substance | U-257 | Jun 2, 2030 |
| US 10772888 ↗ | Method of use | U-1663 | Mar 30, 2032 |
| US 9649311 ↗ | Drug product | — | Oct 21, 2030 |
| US 7754731*PED ↗ | Drug product | — | Sep 11, 2029 |
| US 9649311*PED ↗ | Drug product | — | Apr 21, 2031 |
| US 7754731*PED ↗ | Drug product | — | Sep 11, 2029 |
Is there a generic version of ISENTRESS 400 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68071-2113-06 You're viewing this | 6 TABLET, FILM COATED in 1 BOTTLE (68071-2113-6) | 2017-01-25 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ISENTRESS® is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in patients 4 weeks of age and older. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response [see Clinical Studies (14) ] . ISENTRESS is a human immunodeficiency virus integrase strand transfer inhibitor (HIV-1 INSTI) indicated: In combination with other antiretroviral agents for the treatment of HIV-1 infection in patients 4 weeks of age and older ( 1 ).
The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response ( 14 ).
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION ISENTRESS can be administered with or without food ( 2.1 ). Do not substitute ISENTRESS chewable tablets or ISENTRESS for oral suspension for the ISENTRESS 400 mg film-coated tablet. See specific dosing guidance for chewable tablets and the formulation for oral suspension ( 2.1 ).
Adults 400 mg film-coated tablet orally, twice daily ( 2.2 ). During coadministration with rifampin in adults, 800 mg twice daily ( 2.1 ). Children and Adolescents If at least 25 kg: One 400 mg film-coated tablet orally, twice daily.
If unable to swallow a tablet, consider the chewable tablet, as specified in Table 1 ( 2.3 ). If at least 3 kg to less than 25 kg: Weight based dosing, as specified in Table 2. For patients weighing between 11 and 20 kg, either the chewable tablet or the formulation for oral suspension can be used, as specified in Table 2 ( 2.3 ).
2.1General Dosing Recommendations ISENTRESS Film-Coated Tablets, Chewable Tablets and For Oral Suspension can be administered with or without food [see Clinical Pharmacology (12.3) ] . Because the formulations are not bioequivalent, do not substitute ISENTRESS chewable tablets or ISENTRESS for oral suspension for the ISENTRESS 400 mg film-coated tablet. See specific dosing guidance for chewable tablets and the formulation for oral suspension.
During coadministration of ISENTRESS 400 mg film-coated tablets with rifampin, the recommended dosage of ISENTRESS is 800 mg twice daily in adults. There are no data to guide co-administration of ISENTRESS with rifampin in patients below 18 years of age [see Drug Interactions (7.2) ] . Maximum dose of chewable tablets is 300 mg twice daily.
Maximum dose of oral suspension is 100 mg twice daily. Each single-use packet for oral suspension contains 100 mg of raltegravir which is suspended in 5 mL of water giving a final concentration of 20 mg/mL.
2.2Adults For the treatment of adult patients with HIV-1 infection, the dosage of ISENTRESS is one 400 mg film-coated tablet administered orally, twice daily.
2.3Pediatrics If at least 25 kg: One 400 mg film-coated tablet orally, twice daily. If unable to swallow a tablet, consider the chewable tablet, as specified in Table 1. Table 1: Alternative Dose The weight-based dosing recommendation for the chewable tablet is based on approximately 6 mg/kg/dose twice daily [see Clinical Pharmacology (12.3)] . with ISENTRESS Chewable Tablets for Pediatric Patients Weighing at Least 25 kg Body Weight (kg) Dose Number of Chewable Tablets 25 to less than 28 150 mg twice daily 1.5 × 100 mg The 100 mg chewable tablet can be divided into equal halves. twice daily 28 to less than 40 200 mg twice daily 2 × 100 mg twice daily At least 40 300 mg twice daily 3 × 100 mg twice daily If at least 4 weeks of age and weighing at least 3 kg to less than 25 kg: Weight based dosing, as specified in Table 2.
For patients weighing between 11 and 20 kg, either the chewable tablet or oral suspension can be used, as specified in Table 2. Patients can remain on the oral suspension as long as their weight is below 20 kg. Refer to Table 2 for appropriate dosing [see Clinical Studies (14.3) ] .
Table 2: Recommended Dose The weight-based dosing recommendation for the chewable tablet and oral suspension is based on approximately 6 mg/kg/dose twice daily [see Clinical Pharmacology (12.3)] . for ISENTRESS For Oral Suspension and Chewable Tablets in Pediatric Patients Weighing Less than 25 kg Body Weight (kg) Volume (Dose) of Suspension to be Administered Number of Chewable Tablets 3 to less than 4 1 mL (20 mg) twice daily 4 to less than 6 1.5 mL (30 mg) twice daily 6 to less than 8 2 mL (40 mg) twice daily 8 to less than 11 3 mL (60 mg) twice daily 11 to less than 14 For weight between 11 and 20 kg either formulation can be used.
Note: The chewable tablets are available as 25 mg and 100 mg tablets. 4 mL (80 mg) twice daily 3 × 25 mg twice daily 14 to less than 20 5 mL (100 mg) twice daily 1 × 100 mg twice daily 20 to less than 2…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Film-coated Tablets 400 mg pink, oval-shaped, film-coated tablets with "227" on one side. Chewable Tablets 100 mg pale orange, oval-shaped, orange-banana flavored, chewable tablets scored on both sides and imprinted on one face with the Merck logo and "477" on opposite sides of the score. 25 mg pale yellow, round, orange-banana flavored, chewable tablets with the Merck logo on one side and "473" on the other side.
For Oral Suspension 100 mg white to off-white, banana flavored, granular powder that may contain yellow or beige to tan particles in a child resistant single-use foil packet. Film-Coated Tablets: 400 mg ( 3 ). Chewable Tablets: 100 mg scored and 25 mg ( 3 ).
For Oral Suspension: Single-use packet of 100 mg ( 3 ).
⛔ Contraindications ▾
4 CONTRAINDICATIONS None None ( 4 ).
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Severe, potentially life-threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis. Immediately discontinue treatment with ISENTRESS and other suspect agents if severe hypersensitivity, severe rash, or rash with systemic symptoms or liver aminotransferase elevations develops and monitor clinical status, including liver aminotransferases closely ( 5.1 ).
Monitor for Immune Reconstitution Syndrome ( 5.2 ). Inform patients with phenylketonuria that the 100 mg and 25 mg chewable tablets contain phenylalanine ( 5.3 ).
5.1Severe Skin and Hypersensitivity Reactions Severe, potentially life-threatening, and fatal skin reactions have been reported. These include cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure.
Discontinue ISENTRESS and other suspect agents immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema). Clinical status including liver aminotransferases should be monitored and appropriate therapy initiated. Delay in stopping ISENTRESS treatment or other suspect agents after the onset of severe rash may result in a life-threatening reaction.
5.2Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including ISENTRESS. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia, tuberculosis), which may necessitate further evaluation and treatment. Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
5.3Phenylketonurics ISENTRESS Chewable Tablets contain phenylalanine, a component of aspartame. Each 25 mg ISENTRESS Chewable Tablet contains approximately 0.05 mg phenylalanine. Each 100 mg ISENTRESS Chewable Tablet contains approximately 0.10 mg phenylalanine. Phenylalanine can be harmful to patients with phenylketonuria.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 practice. The most common adverse reactions of moderate to severe intensity (≥2%) are insomnia, headache, dizziness, nausea and fatigue ( 6.1 ). Creatine kinase elevations were observed in subjects who received ISENTRESS.
Myopathy and rhabdomyolysis have been reported. Use with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medications known to cause these conditions and patients with a history of rhabdomyolysis, myopathy or increased serum creatine kinase ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Treatment-Naïve Adults The following safety assessment of ISENTRESS in treatment-naïve subjects is based on the randomized double-blind active controlled study of treatment-naïve subjects, STARTMRK (Protocol 021) with ISENTRESS 400 mg twice daily in combination with a fixed dose of emtricitabine 200 mg (+) tenofovir 300 mg, (N=281) versus efavirenz (EFV) 600 mg at bedtime in combination with emtricitabine (+) tenofovir, (N=282). During double-blind treatment, the total follow-up for subjects receiving ISENTRESS 400 mg twice daily + emtricitabine (+) tenofovir was 1104 patient-years and 1036 patient-years for subjects receiving efavirenz 600 mg at bedtime + emtricitabine (+) tenofovir.
In Protocol 021, the rate of discontinuation of therapy due to adverse events was 5% in subjects receiving ISENTRESS + emtricitabine (+) tenofovir and 10% in subjects receiving efavirenz + emtricitabine (+) tenofovir. The clinical adverse drug reactions (ADRs) listed below were considered by investigators to be causally related to ISENTRESS + emtricitabine (+) tenofovir or efavirenz + emtricitabine (+) tenofovir. Clinical ADRs of moderate to severe intensity occurring in ≥2% of treatment-naïve subjects treated with ISENTRESS are presented in Table 3.
Table 3: Adverse Drug Reactions Includes adverse experiences considered by investigators to be at least possibly, probably, or definitely related to the drug. of Moderate to Severe Intensity Intensities are defined as follows: Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating with inability to work or do usual activity). Occurring in ≥2% of Treatment-Naïve Adult Subjects Receiving ISENTRESS (240 Week Analysis) System Organ Class, Preferred Term Randomized Study Protocol 021 ISENTRESS 400 mg Twice Daily + Emtricitabine (+) Tenofovir (n = 281) Efavirenz 600 mg At Bedtime + Emtricitabine (+) Tenofovir (n = 282) n = total number of subjects per treatment group Gastrointestinal Disorders Nausea 3% 4% General Disorders and Administration Fatigue 2% 3% Nervous System Disorders Headache 4% 5% Dizziness 2% 6% Psychiatric Disorders Insomnia 4% 4% Laboratory Abnormalities The percentages of adult subjects treated with ISENTRESS 400 mg twice daily or efavirenz in Protocol 021 with selected Grades 2 to 4 laboratory abnormalities that represent a worsening Grade from baseline are presented in Table 4.
Table 4: Selected Grade 2 to 4 Laboratory Abnormalities Reported in Treatment-Naïve Subjects (240 Week Analysis) Randomized Study Protocol 021 Laboratory Parameter Preferred Term (Unit) Limit ISENTRESS 400 mg Twice Daily + Emtricitabine (+) Tenofovir (N = 281) Efavirenz 600 mg At Bedtime + Emtricitabine (+) Tenofovir (N = 282) ULN = Upper limit of normal range Hematology Absolute neutrophil count (10 3 /µL) Grade 2 0.75 - 0.999 3% 5% Grade 3 0.50 - 0.749 3% 1% Grade 4 <0.50 1% 1% Hemoglobin (gm/dL) Grade 2 7.5 - 8.4 1% 1% Grade 3 6.5 - 7.4 1% 1% Grade 4 <6.5 <1% 0% Platelet count…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Coadministration of ISENTRESS and other drugs may alter the plasma concentration of raltegravir. The potential for drug-drug interactions must be considered prior to and during therapy ( 7 ). Coadministration of ISENTRESS with drugs that are strong inducers of UGT1A1, such as rifampin, may result in reduced plasma concentrations of raltegravir ( 2.1 , 7.2 ).
7.1Effect of Raltegravir on the Pharmacokinetics of Other Agents Raltegravir does not inhibit (IC 50 >100 µM) CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A in vitro . Moreover, in vitro , raltegravir did not induce CYP1A2, CYP2B6 or CYP3A4. A midazolam drug interaction study confirmed the low propensity of raltegravir to alter the pharmacokinetics of agents metabolized by CYP3A4 in vivo by demonstrating a lack of effect of raltegravir on the pharmacokinetics of midazolam, a sensitive CYP3A4 substrate.
Similarly, raltegravir is not an inhibitor (IC 50 >50 µM) of UGT1A1 or UGT2B7, and raltegravir does not inhibit P-glycoprotein-mediated transport. Based on these data, ISENTRESS is not expected to affect the pharmacokinetics of drugs that are substrates of these enzymes or P-glycoprotein (e.g., protease inhibitors, NNRTIs, opioid analgesics, statins, azole antifungals, proton pump inhibitors and anti-erectile dysfunction agents).
7.2Effect of Other Agents on the Pharmacokinetics of Raltegravir Raltegravir is not a substrate of cytochrome P450 (CYP) enzymes. Based on in vivo and in vitro studies, raltegravir is eliminated mainly by metabolism via a UGT1A1-mediated glucuronidation pathway. Coadministration of ISENTRESS with drugs that inhibit UGT1A1 may increase plasma levels of raltegravir and coadministration of ISENTRESS with drugs that induce UGT1A1, such as rifampin, may reduce plasma levels of raltegravir.
The impact of other inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown. Selected drug interactions are presented in Table 8 [see Clinical Pharmacology (12.3) ] . Table 8: Selected Drug Interactions in Adults Concomitant Drug Class: Drug Name Effect on Concentration of Raltegravir Clinical Comment Metal-Containing Antacids aluminum and/or magnesium-containing antacids ↓ Coadministration or staggered administration of aluminum and/or magnesium hydroxide-containing antacids and ISENTRESS is not recommended.
Other Agents rifampin ↓ The recommended dosage of ISENTRESS is 800 mg twice daily during coadministration with rifampin. There are no data to guide co-administration of ISENTRESS with rifampin in patients below 18 years of age [see Dosage and Administration (2.1) ].
7.3Drugs without Clinically Significant Interactions with ISENTRESS In drug interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of the following: hormonal contraceptives, methadone, lamivudine, tenofovir, etravirine, darunavir/ritonavir, or boceprevir. Moreover, atazanavir, atazanavir/ritonavir, boceprevir, calcium carbonate antacids, darunavir/ritonavir, efavirenz, etravirine, omeprazole, or tipranavir/ritonavir did not have a clinically meaningful effect on the pharmacokinetics of raltegravir.
No dose adjustment is required when ISENTRESS is coadministered with these drugs.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: ISENTRESS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus ( 8.1 ). Nursing Mothers: Breastfeeding is not recommended while taking ISENTRESS ( 8.3 ).
8.1Pregnancy Pregnancy Category C ISENTRESS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. In addition, there have been no pharmacokinetic studies conducted in pregnant patients.
Developmental toxicity studies were performed in rabbits (at oral doses up to 1000 mg/kg/day) and rats (at oral doses up to 600 mg/kg/day). The reproductive toxicity study in rats was performed with pre-, peri-, and postnatal evaluation. The highest doses in these studies produced systemic exposures in these species approximately 3- to 4-fold the exposure at the recommended human dose.
In both rabbits and rats, no treatment-related effects on embryonic/fetal survival or fetal weights were observed. In addition, no treatment-related external, visceral, or skeletal changes were observed in rabbits. However, treatment-related increases over controls in the incidence of supernumerary ribs were seen in rats at 600 mg/kg/day (exposures 3-fold the exposure at the recommended human dose).
Placenta transfer of drug was demonstrated in both rats and rabbits. At a maternal dose of 600 mg/kg/day in rats, mean drug concentrations in fetal plasma were approximately 1.5- to 2.5-fold greater than in maternal plasma at 1 hour and 24 hours postdose, respectively. Mean drug concentrations in fetal plasma were approximately 2% of the mean maternal concentration at both 1 and 24 hours postdose at a maternal dose of 1000 mg/kg/day in rabbits.
Antiretroviral Pregnancy Registry To monitor maternal-fetal outcomes of pregnant patients exposed to ISENTRESS, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
8.3Nursing Mothers Breastfeeding is not recommended while taking ISENTRESS. In addition, it is recommended that HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1. It is not known whether raltegravir is secreted in human milk.
However, raltegravir is secreted in the milk of lactating rats. Mean drug concentrations in milk were approximately 3-fold greater than those in maternal plasma at a maternal dose of 600 mg/kg/day in rats. There were no effects in rat offspring attributable to exposure of ISENTRESS through the milk.
8.4Pediatric Use The safety, tolerability, pharmacokinetic profile, and efficacy of ISENTRESS were evaluated in HIV-1 infected infants, children and adolescents 4 weeks to 18 years of age in an open-label, multicenter clinical trial, IMPAACT P1066 [see Clinical Pharmacology (12.3) and Clinical Studies (14.3) ] . The safety profile was comparable to that observed in adults [see Adverse Reactions (6.1) ] . See Dosage and Administration (2.3) for dosing recommendations for children 4 weeks of age and older.
The safety and dosing information for ISENTRESS have not been established in infants less than 4 weeks of age.
8.5Geriatric Use Clinical studies of ISENTRESS did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
8.6Use in Patients with Hepatic Impairment No clinically important pharmacokinetic differences between subjects with moderate hepatic impairment and healthy subjects were observed. No dosage adjustment is necessary for patients with mild to moderate hepa…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category C ISENTRESS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. In addition, there have been no pharmacokinetic studies conducted in pregnant patients.
Developmental toxicity studies were performed in rabbits (at oral doses up to 1000 mg/kg/day) and rats (at oral doses up to 600 mg/kg/day). The reproductive toxicity study in rats was performed with pre-, peri-, and postnatal evaluation. The highest doses in these studies produced systemic exposures in these species approximately 3- to 4-fold the exposure at the recommended human dose.
In both rabbits and rats, no treatment-related effects on embryonic/fetal survival or fetal weights were observed. In addition, no treatment-related external, visceral, or skeletal changes were observed in rabbits. However, treatment-related increases over controls in the incidence of supernumerary ribs were seen in rats at 600 mg/kg/day (exposures 3-fold the exposure at the recommended human dose).
Placenta transfer of drug was demonstrated in both rats and rabbits. At a maternal dose of 600 mg/kg/day in rats, mean drug concentrations in fetal plasma were approximately 1.5- to 2.5-fold greater than in maternal plasma at 1 hour and 24 hours postdose, respectively. Mean drug concentrations in fetal plasma were approximately 2% of the mean maternal concentration at both 1 and 24 hours postdose at a maternal dose of 1000 mg/kg/day in rabbits.
Antiretroviral Pregnancy Registry To monitor maternal-fetal outcomes of pregnant patients exposed to ISENTRESS, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety, tolerability, pharmacokinetic profile, and efficacy of ISENTRESS were evaluated in HIV-1 infected infants, children and adolescents 4 weeks to 18 years of age in an open-label, multicenter clinical trial, IMPAACT P1066 [see Clinical Pharmacology (12.3) and Clinical Studies (14.3) ] . The safety profile was comparable to that observed in adults [see Adverse Reactions (6.1) ] . See Dosage and Administration (2.3) for dosing recommendations for children 4 weeks of age and older.
The safety and dosing information for ISENTRESS have not been established in infants less than 4 weeks of age.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of ISENTRESS did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
10 OVERDOSAGE No specific information is available on the treatment of overdosage with ISENTRESS. Doses as high as 1600-mg single dose and 800-mg twice-daily multiple doses were studied in healthy volunteers without evidence of toxicity. Occasional doses of up to 1800 mg per day were taken in the clinical studies of HIV-1 infected subjects without evidence of toxicity.
In the event of an overdose, it is reasonable to employ the standard supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy if required. The extent to which ISENTRESS may be dialyzable is unknown.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Raltegravir is an HIV-1 antiviral drug [see Microbiology (12.4) ] .
12.2Pharmacodynamics In a monotherapy study raltegravir (400 mg twice daily) demonstrated rapid antiviral activity with mean viral load reduction of 1.66 log 10 copies/mL by Day 10. In the randomized, double-blind, placebo-controlled, dose-ranging trial, Protocol 005, and Protocols 018 and 019, antiviral responses were similar among subjects regardless of dose. Effects on Electrocardiogram In a randomized, placebo-controlled, crossover study, 31 healthy subjects were administered a single oral supratherapeutic dose of raltegravir 1600 mg and placebo.
Peak raltegravir plasma concentrations were approximately 4-fold higher than the peak concentrations following a 400 mg dose. ISENTRESS did not appear to prolong the QTc interval for 12 hours postdose. After baseline and placebo adjustment, the maximum mean QTc change was -0.4 msec (1-sided 95% upper Cl: 3.1 msec).
12.3Pharmacokinetics Adults Absorption Raltegravir (film-coated tablet) is absorbed with a T max of approximately 3 hours postdose in the fasted state. Raltegravir AUC and C max increase dose proportionally over the dose range 100 mg to 1600 mg. Raltegravir C 12hr increases dose proportionally over the dose range of 100 to 800 mg and increases slightly less than dose proportionally over the dose range 100 mg to 1600 mg.
With twice-daily dosing, pharmacokinetic steady state is achieved within approximately the first 2 days of dosing. There is little to no accumulation in AUC and C max . The average accumulation ratio for C 12hr ranged from approximately 1.2 to 1.6.
The absolute bioavailability of raltegravir has not been established. Based on a formulation comparison study in healthy adult volunteers, the chewable tablet and oral suspension have higher oral bioavailability compared to the 400 mg film-coated tablet. In subjects who received 400 mg twice daily alone, raltegravir drug exposures were characterized by a geometric mean AUC 0-12hr of 14.3 µM∙hr and C 12hr of 142 nM.
Considerable variability was observed in the pharmacokinetics of raltegravir. For observed C 12hr in Protocols 018 and 019, the coefficient of variation (CV) for inter-subject variability = 212% and the CV for intra-subject variability = 122%. Effect of Food on Oral Absorption ISENTRESS may be administered with or without food.
Raltegravir was administered without regard to food in the pivotal safety and efficacy studies in HIV-1-infected patients. The effect of consumption of low-, moderate- and high-fat meals on steady-state raltegravir pharmacokinetics was assessed in healthy volunteers administered the 400 mg film-coated tablet. Administration of multiple doses of raltegravir following a moderate-fat meal (600 Kcal, 21 g fat) did not affect raltegravir AUC to a clinically meaningful degree with an increase of 13% relative to fasting.
Raltegravir C 12hr was 66% higher and C max was 5% higher following a moderate-fat meal compared to fasting. Administration of raltegravir following a high-fat meal (825 Kcal, 52 g fat) increased AUC and C max by approximately 2-fold and increased C 12hr by 4.1-fold. Administration of raltegravir following a low-fat meal (300 Kcal, 2.5 g fat) decreased AUC and C max by 46% and 52%, respectively; C 12hr was essentially unchanged.
Food appears to increase pharmacokinetic variability relative to fasting. Administration of the chewable tablet with a high fat meal led to an average 6% decrease in AUC, 62% decrease in C max , and 188% increase in C 12hr compared to administration in the fasted state. Administration of the chewable tablet with a high fat meal does not affect raltegravir pharmacokinetics to a clinically meaningful degree and the chewable tablet can be administered without regard to food.
The effect of food on the formulation for oral suspension was not studied. Distribution Raltegravir is approximately 83% bound to human plasma protein ove…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Raltegravir is an HIV-1 antiviral drug [see Microbiology (12.4) ] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING ISENTRESS tablets 400 mg are pink, oval-shaped, film-coated tablets with "227" on one side. They are supplied as follows: NDC 68071-2113-6 bottles of 6 Storage and Handling 400 mg Film-coated Tablets, Chewable Tablets and For Oral Suspension Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F). See USP Controlled Room Temperature.
Chewable Tablets Store in the original package with the bottle tightly closed. Keep the desiccant in the bottle to protect from moisture. For Oral Suspension Store in the original container.
Do not open foil packet until ready for use.
📦 Storage and Handling ▾
Storage and Handling 400 mg Film-coated Tablets, Chewable Tablets and For Oral Suspension Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F). See USP Controlled Room Temperature. Chewable Tablets Store in the original package with the bottle tightly closed. Keep the desiccant in the bottle to protect from moisture. For Oral Suspension Store in the original container. Do not open foil packet until ready for use.
📋 Description ▾
11 DESCRIPTION ISENTRESS contains raltegravir potassium, a human immunodeficiency virus integrase strand transfer inhibitor. The chemical name for raltegravir potassium is N -[(4-Fluorophenyl) methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]ethyl]-6-oxo-4-pyrimidinecarboxamide monopotassium salt. The empirical formula is C 20 H 20 FKN 6 O 5 and the molecular weight is 482.51.
The structural formula is: Raltegravir potassium is a white to off-white powder. It is soluble in water, slightly soluble in methanol, very slightly soluble in ethanol and acetonitrile and insoluble in isopropanol. Each 400 mg film-coated tablet of ISENTRESS for oral administration contains 434.4 mg of raltegravir (as potassium salt), equivalent to 400 mg of raltegravir free phenol and the following inactive ingredients: calcium phosphate dibasic anhydrous, hypromellose 2208, lactose monohydrate, magnesium stearate, microcrystalline cellulose, poloxamer 407 (contains 0.01% butylated hydroxytoluene as antioxidant), sodium stearyl fumarate.
In addition, the film coating contains the following inactive ingredients: black iron oxide, polyethylene glycol 3350, polyvinyl alcohol, red iron oxide, talc and titanium dioxide. Each 100 mg chewable tablet of ISENTRESS for oral administration contains 108.6 mg of raltegravir (as potassium salt), equivalent to 100 mg of raltegravir free phenol and the following inactive ingredients: ammonium hydroxide, crospovidone, ethylcellulose 20 cP, fructose, hydroxypropyl cellulose, hypromellose 2910/6cP, magnesium stearate, mannitol, medium chain triglycerides, monoammonium glycyrrhizinate, natural and artificial flavors (orange, banana, and masking that contains aspartame), oleic acid, PEG 400, red iron oxide, saccharin sodium, sodium citrate dihydrate, sodium stearyl fumarate, sorbitol, sucralose and yellow iron oxide.
Each 25 mg chewable tablet of ISENTRESS for oral administration contains 27.16 mg of raltegravir (as potassium salt), equivalent to 25 mg of raltegravir free phenol and the following inactive ingredients: ammonium hydroxide, crospovidone, ethylcellulose 20 cP, fructose, hydroxypropyl cellulose, hypromellose 2910/6cP, magnesium stearate, mannitol, medium chain triglycerides, monoammonium glycyrrhizinate, natural and artificial flavors (orange, banana, and masking that contains aspartame), oleic acid, PEG 400, saccharin sodium, sodium citrate dihydrate, sodium stearyl fumarate, sorbitol, sucralose and yellow iron oxide.
Each packet of ISENTRESS for oral suspension 100 mg, contains 108.6 mg of raltegravir (as potassium salt), equivalent to 100 mg of raltegravir free phenol and the following inactive ingredients: ammonium hydroxide, banana with other natural flavors, carboxymethylcellulose sodium, crospovidone, ethylcellulose 20 cP, fructose, hydroxypropyl cellulose, hypromellose 2910/6cP, macrogol/PEG 400, magnesium stearate, maltodextrin, mannitol, medium chain triglycerides, microcrystalline cellulose, monoammonium glycyrrhizinate, oleic acid, sorbitol, sucralose and sucrose.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use). General Information Instruct patients to reread patient labeling each time the prescription is renewed. Patients should remain under the care of a physician when using ISENTRESS.
Instruct patients to inform their physician or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens. ISENTRESS is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection such as opportunistic infections. Tell patients that sustained decreases in plasma HIV RNA have been associated with a reduced risk of progression to AIDS and death.
Patients should remain on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses. Advise patients to avoid doing things that can spread HIV-1 infection to others. Do not share needles or other injection equipment.
Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades. Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.
Do not breastfeed. Mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk. Also, it is unknown if ISENTRESS can be passed to the baby through breast milk and whether it could harm the baby.
General Dosing Instructions Instruct patients that if they miss a dose of ISENTRESS, they should take it as soon as they remember. If they do not remember until it is time for the next dose, instruct them to skip the missed dose and go back to the regular schedule. Instruct patients not to double their next dose or take more than the prescribed dose.
Film-Coated Tablets and Chewable Tablets Inform patients that the chewable tablet forms can be chewed or swallowed whole, but the film-coated tablets must be swallowed whole. For Oral Suspension Instruct parents and/or caregivers to read the Instructions for Use before preparing and administering ISENTRESS for oral suspension to pediatric patients. Instruct parents and/or caregivers that ISENTRESS for oral suspension should be administered within 30 minutes of mixing.
Severe and Potentially Life-threatening Rash Inform patients that severe and potentially life-threatening rash has been reported. Advise patients to immediately contact their healthcare provider if they develop rash. Instruct patients to immediately stop taking ISENTRESS and other suspect agents, and seek medical attention if they develop a rash associated with any of the following symptoms as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome, toxic epidermal necrolysis or severe hypersensitivity: fever, generally ill feeling, extreme tiredness, muscle or joint aches, blisters, oral lesions, eye inflammation, facial swelling, swelling of the eyes, lips, mouth, breathing difficulty, and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes, dark or tea colored urine, pale colored stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching or sensitivity on the right side below the ribs).
Inform patients that if severe rash occurs, their physician will closely monitor them, order laboratory tests and initiate appropriate therapy. Rhabdomyolysis Before patients begin ISENTRESS, ask them if they have a history of rhabdomyolysis, myopathy or increased creatine kinase or if they are taking medications known to cause these conditions such as statins, fenofibrate, gemfibrozil or zidovudine. Instruct patients to immediately report to their healthcare provider any unexplained muscle pain, tenderness, or weakness while taking ISENTRESS.
Phenylketonuria Alert patients with phenylketonuria that ISENTRESS Chewable Tablets contain phenylalanine [see Warn…