Rapivab peramivir 600 mg/60mL Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Neuraminidase inhibitors class.
Where does this data come from?
🏭 Manufacturer & labeler
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🩺 Clinical
- Rapivab works by blocking an enzyme the flu virus uses to spread inside your body. Unlike oral flu medications such as oseltamivir (Tamiflu), Rapivab is given as a single one-time...
- What exactly does Rapivab do, and how is it different from other flu treatments?
- No — Rapivab is designed as a single dose. You receive one IV infusion over about 15 to 30 minutes, and that's it. There's no follow-up dose needed. The key is getting it early, wi...
- The most common side effect is diarrhea, which is generally mild. Some lab values — like blood sugar, a liver enzyme, and a muscle enzyme — can go up slightly, but these are usuall...
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🧪 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.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
4 inactive ingredients listed in the exact product block matched to this NDC.
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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
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💲 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 mL | 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 · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Rapivab 600 mg/60mLthis 72769-0181-03 | BioCryst | 3 vials | — | — | Discontinued | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
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 10391075 ↗ | Method of use | U-2622 | Feb 12, 2027 |
| US 8778997 ↗ | Method of use | U-2622 | May 7, 2027 |
| US 8778997 ↗ | Method of use | U-1627 | May 7, 2027 |
| US 10391075 ↗ | Method of use | U-3069 | Feb 12, 2027 |
| US 8778997 ↗ | Method of use | U-3069 | May 7, 2027 |
Is there a generic version of RAPIVAB 200 MG/20 ML VIAL?
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72769-0181-03 You're viewing this | 3 VIAL, GLASS in 1 CARTON (72769-181-03) / 20 mL in 1 VIAL, GLASS (72769-181-01) | 2014-12-20 | Inactivated by FDA |
🧭 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 | — Not published for this NDC No photo available yet for this listing. |
| 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. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE RAPIVAB is indicated for the treatment of acute uncomplicated influenza in patients 6 months and older who have been symptomatic for no more than 2 days. RAPIVAB is an influenza virus neuraminidase inhibitor indicated for the treatment of acute uncomplicated influenza in patients 6 months and older who have been symptomatic for no more than two days. ( 1 ) Limitations of Use : Efficacy based on clinical trials in which the predominant influenza virus type was influenza A; a limited number of subjects infected with influenza B virus were enrolled.
( 1 ) Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use. ( 1 ) Efficacy could not be established in patients with serious influenza requiring hospitalization. ( 1 ) Limitations of Use : Efficacy of RAPIVAB is based on clinical trials of naturally occurring influenza in which the predominant influenza infections were influenza A virus; a limited number of subjects infected with influenza B virus were enrolled.
Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs.
Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use RAPIVAB [see Microbiology (12.4) ]. The efficacy of RAPIVAB could not be established in patients with serious influenza requiring hospitalization [see Clinical Studies (14.3) ].
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Administer RAPIVAB as a single dose within 2 days of onset of influenza symptoms ( 2.1 ) Administer RAPIVAB by intravenous infusion for a minimum of 15 minutes ( 2.1 ) Recommended Dosage Single Dose Adults and adolescents (13 years and older) 600 mg Pediatric patients (6 months to 12 years of age) 12 mg/kg (up to 600 mg) Recommended Dosage Adjustments in Patients with Altered Creatinine Clearance Creatinine Clearance (mL/min) ≥50 30-49 10-29 a Up to maximum dose of 600 mg. Adults and adolescents (13 years and older) 600 mg 200 mg 100 mg Pediatric patients a (2 to 12 years of age) 12 mg/kg 4 mg/kg 2 mg/kg No recommendation for dosage adjustment can be made for pediatric patients 6 months to less than 2 years of age with creatinine clearance less than 50 mL/min ( 2.2 ) Hemodialysis: Administer after dialysis ( 2.2 ) RAPIVAB must be diluted prior to administration ( 2.3 ) See the Full Prescribing Information for drug compatibility information ( 2.4 )
2.1Dosage in Acute Uncomplicated Influenza Administer RAPIVAB within 2 days of onset of symptoms of influenza. Adults and Adolescents (13 years of age and older) The recommended dosage of RAPIVAB in adult and adolescent patients 13 years of age and older with acute uncomplicated influenza is a single 600 mg dose, administered via intravenous infusion for 15 to 30 minutes. Pediatric Patients (6 months to 12 years of age) The recommended dosage of RAPIVAB in pediatric patients 6 months to 12 years of age with acute uncomplicated influenza is a single 12 mg/kg dose (up to a maximum dose of 600 mg), administered via intravenous infusion for 15 to 30 minutes.
2.2Dosing in Patients with Renal Impairment Significantly increased drug exposures were observed when RAPIVAB was administered to adult subjects with renal dysfunction [see Clinical Pharmacology (12.3) ] . Therefore, the RAPIVAB dosage should be reduced for patients with baseline creatinine clearance below 50 mL/min using the recommendations in Table 1 and Table 2. No dosage adjustment is required for single administration of RAPIVAB in patients with creatinine clearance of 50 mL/min or higher [see Clinical Pharmacology (12.3) ] .
In patients with chronic renal impairment maintained on hemodialysis, RAPIVAB should be administered after dialysis at a dose adjusted based on renal function (Table 1 and Table 2) [see Clinical Pharmacology (12.3) ] . Table 1. Dosage Adjustment for Adults and Adolescents (13 Years and Older) with Altered Creatinine Clearance Creatinine Clearance a (mL/min) ≥50 30 to 49 10 to 29 a Calculated using the Cockcroft and Gault equation.
Recommended Dose (mg) 600 mg 200 mg 100 mg Table 2. Dosage Adjustment for Pediatric Patients (2 to 12 Years of Age) with Altered Creatinine Clearance Creatinine Clearance a (mL/min) ≥50 30 to 49 10 to 29 a Calculated using the Cockcroft and Gault equation. b Up to maximum dose of 600 mg. Recommended Dose (mg/kg) b 12 mg/kg 4 mg/kg 2 mg/kg No data are available to inform a recommendation for dosage adjustment with RAPIVAB in pediatric patients 6 months to less than 2 years of age with creatinine clearance less than 50 mL/min [see Use in Specific Populations (8.4 , 8.6) , Clinical Pharmacology (12.3) ] .
2.3Preparation of RAPIVAB for Intravenous Infusion Use aseptic technique during the preparation of RAPIVAB to prevent inadvertent microbial contamination. There is no preservative or bacteriostatic agent present in the solution. Follow the steps below to prepare a diluted solution of RAPIVAB: (a) Do not use if seal over bottle opening is broken or missing.
(b) Visually inspect RAPIVAB for particulate matter and discoloration prior to administration. (c) Dilute an appropriate dose of RAPIVAB 10 mg/mL solution [see Dosage and Administration (2.1 , 2.2) ] in 0.9% or 0.45% sodium chloride, 5% dextrose, or lactated Ringer's. The maximum infusion volume is provided in Table 3.
The final concentration of diluted RAPIVAB for administration should be between 1…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Each vial of RAPIVAB injection contains 200 mg per 20 mL (10 mg per mL) as a clear, colorless solution [see How Supplied/Storage and Handling (16) ]. Injection: 200 mg in 20 mL (10 mg/mL) in a single-use vial ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS RAPIVAB is contraindicated in patients with known serious hypersensitivity or anaphylaxis to peramivir or any component of the product. Severe allergic reactions have included anaphylaxis, erythema multiforme, and Stevens-Johnson syndrome [see Warnings and Precautions (5.1) ] . Patients with known serious hypersensitivity or anaphylaxis to peramivir or any component of RAPIVAB ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Cases of anaphylaxis and serious skin/hypersensitivity reactions such as Stevens-Johnson syndrome and erythema multiforme have occurred with RAPIVAB. Discontinue RAPIVAB and initiate appropriate treatment if anaphylaxis or serious skin reaction occurs or is suspected. ( 5.1 ) Neuropsychiatric events: Patients with influenza may be at an increased risk of hallucinations, delirium, and abnormal behavior early in their illness.
Monitor for signs of abnormal behavior. ( 5.2)
5.1Serious Skin/Hypersensitivity Reactions Rare cases of serious skin reactions, including erythema multiforme, have been reported with RAPIVAB in clinical studies and in postmarketing experience. Cases of anaphylaxis and Stevens-Johnson syndrome have been reported in postmarketing experience with RAPIVAB. Discontinue RAPIVAB and institute appropriate treatment if anaphylaxis or a serious skin reaction occurs or is suspected.
The use of RAPIVAB is contraindicated in patients with known serious hypersensitivity or anaphylaxis to RAPIVAB [see Contraindications (4) , Adverse Reactions (6.2) ].
5.2Neuropsychiatric Events Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur in uncomplicated influenza as well. There have been postmarketing reports of delirium and abnormal behavior leading to injury in patients with influenza who were receiving neuraminidase inhibitors, including RAPIVAB.
Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of RAPIVAB to these events has not been established.
Patients with influenza should be closely monitored for signs of abnormal behavior.
5.3Risk of Bacterial Infections There is no evidence for efficacy of RAPIVAB in any illness caused by agents other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. RAPIVAB has not been shown to prevent such complications.
Prescribers should be alert to the potential for secondary bacterial infections and treat with antibiotics as appropriate.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Serious skin and hypersensitivity reactions [see Warnings and Precautions (5.1) ] Neuropsychiatric events [see Warnings and Precautions (5.2) ] Most common adverse reaction (incidence >2%) is diarrhea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience 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. Adverse Reactions in Adults (18 years of age and older) In 5 randomized, double-blind, controlled trials, 1,399 subjects with acute uncomplicated influenza received a single dose of RAPIVAB, administered intravenously or intramuscularly, at doses up to 600 mg.
Among the 664 subjects receiving RAPIVAB 600 mg (intravenous or intramuscular), the most commonly observed adverse reaction was diarrhea, occurring at a rate of 8% versus 7% in subjects receiving placebo. No subject receiving RAPIVAB 600 mg experienced a serious adverse event and <1% discontinued study because of an adverse reaction. Clinically significant laboratory abnormalities (DAIDS Grades 2 to 4) listed in Table 4 occurred more frequently in subjects treated with RAPIVAB 600 mg (intravenous or intramuscular) than placebo.
Only events occurring at ≥2% are included. Table 4: Laboratory Abnormalities Occurring in ≥2% of Subjects Treated with RAPIVAB 600 mg Laboratory Parameter Abnormality a RAPIVAB 600 mg Placebo a Frequencies based on treatment-emergent laboratory abnormalities. Alanine Aminotransferase (>2.5 × ULN) (n = 654) 3% (n = 430) 2% Serum Glucose (>160 mg/dL) (n = 660) 5% (n = 433) 3% Creatine Phosphokinase (≥6.0 × ULN) (n = 654) 4% (n = 431) 2% Neutrophils (<1.000 ×10 9 /L) (n = 654) 8% (n = 430) 6% In a subset of subjects with serious influenza requiring hospitalization treated with RAPIVAB 600 mg as monotherapy (n = 101), the following adverse reactions were also reported more frequently with RAPIVAB as compared to placebo: constipation (4% versus 2%), insomnia (3% versus 0%), AST increased (3% versus 2%), and hypertension (2% versus 0%).
Adverse Reactions in Adolescent and Pediatric Subjects (6 months to 17 years of age) Assessment of adverse reactions is based on a randomized, active-controlled study in which 130 adolescent and pediatric subjects ages 6 months to 17 years of age with acute uncomplicated influenza received open-label treatment with a single dose of RAPIVAB (n = 107), or 5 days of treatment with oseltamivir (n = 23) [see Use in Specific Populations (8.4) , Clinical Studies (14.2) ] . The safety profile of RAPIVAB in subjects 6 months to 17 years of age was generally similar to that observed in adults.
The only adverse reaction reported in pediatric subjects treated with RAPIVAB (occurring in ≥2% of subjects) and not reported in adults was vomiting (3% versus 9% for oseltamivir). The only clinically significant laboratory abnormality (DAIDS Grade 2) occurring in ≥2% of pediatric subjects treated with RAPIVAB (and not previously reported in adults) was proteinuria by dipstick analysis (3% versus 0% for oseltamivir).
6.2Postmarketing Experience The following additional adverse reactions have been identified during postapproval use of RAPIVAB. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Dermatologic: Stevens-Johnson syndrome, exfoliative dermatitis, rash [see Warnings and Precautions (5.1) ] .
General Disorders and Administration Site Conditions: Anaphylactic/anaphylactoid reactions [see Warnings and Precautions (5.1) ] . Psychiatric: Abnormal…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS This section describes clinically relevant drug interactions with RAPIVAB. Drug-drug interaction studies are described elsewhere in the labeling [see Clinical Pharmacology (12.3) ]. Live attenuated influenza vaccine (LAIV), intranasal: Avoid use of LAIV within 2 weeks before or 48 hours after administration of RAPIVAB, unless medically indicated ( 7.1 )
7.1Influenza Vaccines Inactivated influenza vaccine can be administered at any time relative to use of RAPIVAB. For live attenuated influenza vaccine (LAIV), antiviral drugs may inhibit viral replication and thus may reduce vaccine efficacy. The concurrent use of RAPIVAB with LAIV intranasal has not been evaluated.
Because of the potential for interference between these two products, avoid use of LAIV within 2 weeks before or 48 hours after administration of RAPIVAB unless medically indicated.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Limited available data with RAPIVAB use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with influenza in pregnancy [see Clinical Considerations ] . In animal reproduction studies, no adverse developmental effects were observed in rats when peramivir was administered by intravenous bolus injection during organogenesis at the maximum feasible dose, resulting in systemic drug exposures (AUC) approximately 8 times those in humans at the recommended dose.
However, when peramivir was administered to rats by continuous intravenous infusion during the same gestation period, fetal abnormalities of reduced renal papilla and dilated ureters were observed. In rabbits, administration of peramivir during organogenesis at exposures 8 times those in humans at the recommended dose resulted in developmental toxicity (abortion or premature delivery) at a maternally toxic dose [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, stillbirths, birth defects, preterm delivery, low birthweight, and small for gestational age.
Data Animal Data Reproductive toxicity studies have been performed in rats and rabbits. In rats, peramivir was administered once daily by intravenous bolus injection at doses of 200, 400, and 600 mg/kg/day on Gestational Days 6 to 17. No treatment-related fetal toxicities were observed when peramivir was administered by intravenous bolus injection at the maximum feasible dose of 600 mg/kg, resulting in exposures approximately 8 times those in humans at the recommended dose.
Peramivir was also administered by continuous intravenous infusion to rats at daily doses of 50, 400, and 1000 mg/kg/day on Gestational Days 6 to 17. Dose related increases in the incidence of fetal abnormalities of reduced renal papilla and dilated ureters were observed at 400 and 1000 mg/kg/day. The systemic drug exposure in rats at a dose without fetal effects was less than the exposures in humans at the recommended dose.
In rabbits, peramivir was administered once daily by intravenous bolus injection at doses of 25, 50, 100, and 200 mg/kg/day on Gestational Days 7 to 19. Developmental toxicity (abortion or premature delivery) was observed at maternally toxic dose levels (100 and 200 mg/kg/day) resulting in exposures approximately 8 times those in humans at the recommended dose. The exposure in rabbits at doses without developmental toxicity was less than the exposure in humans at the recommended dose.
A pre/post-natal developmental toxicity study was performed in pregnant rats administered peramivir once daily by intravenous infusion at doses of 50, 200, 400, and 600 mg/kg/day on Gestational Day 6 through Lactation Day 20. No significant effects of peramivir on developmental outcomes were observed in nursing pups at up to the highest dose tested.
8.2Lactation Risk Summary There are no data on the presence of RAPIVAB in human milk, the effects on the breastfed infant, or the effects on milk production. Peramivir is present in rat milk [see Data ]. Limited clinical data during lactation preclude a clear determination of the risk of RAPIVAB to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for RAPIVAB and any potential adverse…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Limited available data with RAPIVAB use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with influenza in pregnancy [see Clinical Considerations ] . In animal reproduction studies, no adverse developmental effects were observed in rats when peramivir was administered by intravenous bolus injection during organogenesis at the maximum feasible dose, resulting in systemic drug exposures (AUC) approximately 8 times those in humans at the recommended dose.
However, when peramivir was administered to rats by continuous intravenous infusion during the same gestation period, fetal abnormalities of reduced renal papilla and dilated ureters were observed. In rabbits, administration of peramivir during organogenesis at exposures 8 times those in humans at the recommended dose resulted in developmental toxicity (abortion or premature delivery) at a maternally toxic dose [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, stillbirths, birth defects, preterm delivery, low birthweight, and small for gestational age.
Data Animal Data Reproductive toxicity studies have been performed in rats and rabbits. In rats, peramivir was administered once daily by intravenous bolus injection at doses of 200, 400, and 600 mg/kg/day on Gestational Days 6 to 17. No treatment-related fetal toxicities were observed when peramivir was administered by intravenous bolus injection at the maximum feasible dose of 600 mg/kg, resulting in exposures approximately 8 times those in humans at the recommended dose.
Peramivir was also administered by continuous intravenous infusion to rats at daily doses of 50, 400, and 1000 mg/kg/day on Gestational Days 6 to 17. Dose related increases in the incidence of fetal abnormalities of reduced renal papilla and dilated ureters were observed at 400 and 1000 mg/kg/day. The systemic drug exposure in rats at a dose without fetal effects was less than the exposures in humans at the recommended dose.
In rabbits, peramivir was administered once daily by intravenous bolus injection at doses of 25, 50, 100, and 200 mg/kg/day on Gestational Days 7 to 19. Developmental toxicity (abortion or premature delivery) was observed at maternally toxic dose levels (100 and 200 mg/kg/day) resulting in exposures approximately 8 times those in humans at the recommended dose. The exposure in rabbits at doses without developmental toxicity was less than the exposure in humans at the recommended dose.
A pre/post-natal developmental toxicity study was performed in pregnant rats administered peramivir once daily by intravenous infusion at doses of 50, 200, 400, and 600 mg/kg/day on Gestational Day 6 through Lactation Day 20. No significant effects of peramivir on developmental outcomes were observed in nursing pups at up to the highest dose tested.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of RAPIVAB for the treatment of influenza has been established in pediatric patients 6 months to 17 years of age. Use of RAPIVAB for this indication is supported by evidence from adequate and well-controlled trials of RAPIVAB in adults with additional data from Study 305, a randomized, active-controlled trial of 130 adolescent and pediatric subjects with acute uncomplicated influenza who received open-label treatment with a single dose of RAPIVAB or 5 days of treatment with oseltamivir administered within 48 hours of onset of symptoms of influenza [see Dosage and Administration (2.1 , 2.2 , 2.3) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.2) ].
Study 305 included: 13 to 17 years of age: 21 subjects treated with RAPIVAB 600 mg 6 months to 12 years of age: 86 subjects treated with RAPIVAB 12 mg/kg (up to a maximum dose of 600 mg) Safety and effectiveness of RAPIVAB in pediatric patients less than 6 months of age have not been established. No data are available for RAPIVAB use in pediatric patients 6 months to less than 2 years with creatinine clearance <50 mL/min to inform a recommendation for dosage adjustment [see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) ] .
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical trials of RAPIVAB 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 exposures between the elderly and younger subjects [see Clinical Pharmacology (12.3) ].
🆘 Overdosage ▾
10 OVERDOSAGE There is no human experience of acute overdosage with RAPIVAB. Treatment of overdosage with RAPIVAB should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with RAPIVAB. RAPIVAB is cleared by renal excretion and can be cleared by hemodialysis.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Peramivir is an antiviral drug with activity against influenza virus [see Microbiology (12.4) ].
12.2Cardiac Electrophysiology At twice the maximum recommended dose, RAPIVAB did not prolong the QTc interval to any clinically relevant extent.
12.3Pharmacokinetics The pharmacokinetics of RAPIVAB was evaluated in Phase 1 trials in adults. The pharmacokinetic parameters following intravenous administration of RAPIVAB (0.17 to 2 times the recommended dose) showed a linear relationship between dose and exposure parameters (C max and AUC). Following intravenous administration of a single dose of RAPIVAB 600 mg over 30 minutes, a maximum plasma concentration (C max ) of 46,800 ng/mL (46.8 µg/mL) was reached at the end of infusion.
AUC 0-∞ values were 102,700 ng ∙ hr/mL. Distribution In vitro binding of peramivir to human plasma proteins is <30%. Based on a population pharmacokinetic analysis, the central volume of distribution was
12.56L. Metabolism and Elimination Peramivir is not a substrate for cytochrome P450 (CYP) enzymes, does not affect glucuronidation, and is not a substrate or inhibitor of P-glycoprotein mediated transport. Peramivir is not significantly metabolized in humans.
The elimination half-life of RAPIVAB following intravenous administration to healthy subjects of 600 mg as a single dose is approximately 20 hours. The major route of elimination of RAPIVAB is via the kidney. Renal clearance of unchanged peramivir accounts for approximately 90% of total clearance.
Negligible accumulation was observed following multiple doses, either once or twice daily, for up to 10 days. Specific Populations Race: Pharmacokinetics of peramivir was evaluated primarily in Caucasians and Asians. Based on a population pharmacokinetic analysis including race as a covariate, volume of distribution was dependent on weight and Asian race.
No dose adjustment is required based on weight or Asian race. Gender: Peramivir pharmacokinetics was similar in male and female subjects. Pediatric Patients: The pharmacokinetics of peramivir has been evaluated in a study in pediatric subjects 6 months to 17 years of age with acute uncomplicated influenza.
Pharmacokinetic sampling in this study was limited to approximately 3 hours after administration of peramivir. Geometric mean (GM) PK parameters are provided in Table 5. Table 5.
Geometric Mean (%CV) C max and AUC 0-3 by Age Group in Comparison to Adults Age Group GM C max (ng/mL) (%CV) GM AUC 0-3 (ng.h/mL) (%CV) 6 months to <2 years 38,000 (73.7) 46,200 (35.8) 2 to <7 years 47,400 (48.4) 62,700 (39.7) 7 to <13 years 61,200 (53) 76,300 (43.1) 13 to <18 years 51,500 (33) 65,500 (28.1) Healthy Adults (Study 113) 45,700 (21.5) 68,500 (19.1) Peramivir pharmacokinetics in subjects 2 to 17 years of age was similar to adults. In pediatric patients 6 months to less than 2 years of age, the GM AUC 0-3 and C max were lower than that of healthy adult subjects, with GM ratios (90% CI) of 0.68 (0.52 to 0.88) and 0.83 (0.59 to 1.18), respectively.
The difference in exposure is not considered to be clinically significant. Geriatric Patients: Peramivir pharmacokinetics in elderly subjects was similar to non-elderly subjects. Peak concentrations of peramivir after a single 4 mg/kg intravenous dose were approximately 10% higher in elderly subjects when compared to young adults (22,647 vs 20,490 ng/mL, respectively).
Exposure (AUC 0-12 ) to peramivir at steady state was roughly 34% higher in elderly subjects compared to young adults (61,572 vs 46,000 ng∙hr/mL, respectively). Dose adjustment is not required for elderly patients. Patients with Impaired Renal Function: A trial was conducted in adult subjects with various degrees of renal impairment.
When compared to a concurrent cohort with normal renal function, no change in mean C max was observed (6 subjects per cohort). However, mean AUC 0-∞ after a single 2 mg/kg intravenous dose was increased by 28%, by 302%, and by 412%…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Peramivir is an antiviral drug with activity against influenza virus [see Microbiology (12.4) ].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING RAPIVAB injection is a clear, colorless sterile, isotonic solution. Each single-use vial contains 200 mg per 20 mL (10 mg/mL) of peramivir in a clear glass vial (NDC # 72769-181-01). RAPIVAB injection is supplied in cartons containing 3 single-use vials (NDC # 72769-181-03).
Store vials of RAPIVAB injection in original cartons at 20°C to 25°C (68°F to 77°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F). Do not use if seal over bottle opening is broken or missing.
📦 Storage and Handling ▾
Store vials of RAPIVAB injection in original cartons at 20°C to 25°C (68°F to 77°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F). Do not use if seal over bottle opening is broken or missing.
📋 Description ▾
11 DESCRIPTION RAPIVAB (peramivir) is an inhibitor of influenza virus neuraminidase. The chemical name is (1S,2S,3R,4R)-3-[(1S)-1-(acetylamino)-2-ethylbutyl]-4-(carbamimidoylamino)-2-hydroxycyclopentanecarboxylic acid, trihydrate. The chemical formula is C 15 H 28 N 4 O 4 ∙ 3H 2 O , representing a molecular weight of 382.45.
The molecular structure is as follows: RAPIVAB injection is a clear, colorless, sterile, isotonic solution (200 mg per 20 mL) in glass vials fitted with rubber stoppers and royal blue flip-off seals. Each mL contains 10 mg peramivir (on an anhydrous basis) in 0.9% sodium chloride solution. The pH may have been adjusted with sodium hydroxide, USP and/or hydrochloric acid, USP.
The pH is 5.5 to 8.5. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients of the following: There is a risk of severe allergic reactions (including anaphylaxis) or serious skin reactions with RAPIVAB use. Advise patients to seek immediate medical attention if an allergic-like reaction occurs or is suspected [see Warnings and Precautions (5.1) ] . There is a risk of neuropsychiatric events in patients with influenza.
Patients should contact their physician if they experience signs of abnormal behavior after receiving RAPIVAB [see Warnings and Precautions (5.2) ] .