Ofirmev

Name: Ofirmev

Commonly used brand name(s)

In the U.S.

  • Ofirmev

Available Dosage Forms:

  • Solution

Therapeutic Class: Analgesic

Uses For Ofirmev

Acetaminophen injection is used together with other medicines (eg, narcotic pain relievers) to relieve moderate to severe pain.

Acetaminophen is used to relieve mild to moderate pain and reduce fever in patients. It does not become habit-forming when taken for a long time. Acetaminophen may cause unwanted effects when taken in large doses, including liver damage.

This medicine is available only with your doctor's prescription.

Proper Use of Ofirmev

A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed in one of your veins. The medicine must be injected slowly over 15 minutes.

Your doctor will give you a few doses of this medicine until your condition improves, and then switch you to an oral medicine that works the same way. If you have any concerns about this, talk to your doctor.

What are some things I need to know or do while I take Ofirmev?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
  • Avoid other sources of acetaminophen. Check labels closely. Too much acetaminophen may cause problems.
  • Call your doctor right away if you take more than 4,000 mg (milligrams) of acetaminophen in a day, even if you feel well.
  • Talk with your doctor before you drink alcohol.
  • If you are taking warfarin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with Ofirmev.
  • This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
  • Different brands of Ofirmev may have different doses for children. Talk with the doctor before giving this medicine to a child.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Ofirmev while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Ofirmev or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Ofirmev (acetaminophen injection). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Dosage Forms and Strengths

Ofirmev is a sterile, clear, colorless, non-pyrogenic, preservative free, isotonic formulation of acetaminophen intended for intravenous infusion. Each 100 mL glass vial or 100 mL bag contains 1000 mg acetaminophen (10 mg/mL).

Warnings and Precautions

Hepatic Injury

Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death [see Overdosage (10)]. Do not exceed the maximum recommended daily dose of acetaminophen [see Dosage and Administration (2)]. The maximum recommended daily dose of acetaminophen includes all routes of acetaminophen administration and all acetaminophen-containing products administered, including combination products.

Use caution when administering acetaminophen in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss), or severe renal impairment (creatinine clearance ≤ 30 mL/min) [see Use in Specific Populations (8.6, 8.7)].

Serious Skin Reactions

Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Risk of Medication Errors

Take care when prescribing, preparing, and administering Ofirmev (acetaminophen) Injection in order to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

  • the dose in milligrams (mg) and milliliters (mL) is not confused;
  • the dosing is based on weight for patients under 50 kg;
  • infusion pumps are properly programmed; and
  • the total daily dose of acetaminophen from all sources does not exceed maximum daily limits [see Dosage and Administration (2)].

Allergy and Hypersensitivity

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, and pruritus. There were infrequent reports of life-threatening anaphylaxis requiring emergent medical attention. Discontinue Ofirmev immediately if symptoms associated with allergy or hypersensitivity occur. Do not use Ofirmev in patients with acetaminophen allergy.

Use in specific populations

Pregnancy

Risk Summary

Published epidemiological studies with oral acetaminophen use during pregnancy have not reported a clear association with acetaminophen use and birth defects, miscarriage, or adverse maternal or fetal outcomes [see Data]. Animal reproduction studies have not been conducted with IV acetaminophen. Reproductive and developmental studies in rats and mice from the published literature identified adverse events at clinically relevant doses with acetaminophen. Treatment of pregnant rats with doses of acetaminophen approximately equal to the maximum human daily dose (MHDD) showed evidence of fetotoxicity and increases in bone variations in the fetuses. In another study, necrosis was observed in the liver and kidney of both pregnant rats and fetuses at doses approximately equal to the MHDD. In mice and rats treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproductive capacity were reported. In mice, a reduction in number of litters of the parental mating pair was observed as well as retarded growth, abnormal sperm in their offspring and reduced birth weight in the next generation. In rats, female fertility was decreased following in utero exposure to acetaminophen [see Data].

The estimated background risk of major birth defects and miscarriages 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 2-4% and 15-20%, respectively.

Data

Human Data

The results from a large population-based prospective cohort, including data from 26,424 women with live born singletons who were exposed to oral acetaminophen during the first trimester, indicate no increased risk for congenital malformations, compared to a control group of unexposed children. The rate of congenital malformations (4.3%) was similar to the rate in the general population. A population-based, case-control study from the National Birth Defects Prevention Study showed that 11,610 children with prenatal exposure to acetaminophen during the first trimester had no increased risk of major birth defects compared to 4,500 children in the control group. Other epidemiological data showed similar results. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including recall bias.

Animal Data

Studies in pregnant rats that received oral acetaminophen during organogenesis at doses up to 0.85 times the maximum human daily dose (MHDD = 4 grams/day, based on a body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose‑related increase in bone variations (reduced ossification and rudimentary rib changes). Offspring had no evidence of external, visceral, or skeletal malformations. When pregnant rats received oral acetaminophen throughout gestation at doses of 1.2 times the MHDD (based on a body surface area comparison), areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses. These effects did not occur in animals that received oral acetaminophen at doses 0.3 times the MHDD, based on a body surface area comparison.

In a continuous breeding study, pregnant mice received 0.25, 0.5, or 1.0% acetaminophen via the diet (357, 715, or 1430 mg/kg/day). These doses are approximately 0.43, 0.87, and 1.7 times the MHDD, respectively, based on a body surface area comparison.

Lactation

Risk Summary

There is no information regarding the presence of Ofirmev in human milk, the effects on the breastfed infant, or the effects on milk production. However, limited published studies report that acetaminophen passes rapidly into human milk with similar levels in the milk and plasma. Average and maximum neonatal doses of 1% and 2%, respectively, of the weight-adjusted maternal dose are reported after a single oral administration of 1 gram APAP. There is one well-documented report of a rash in a breast-fed infant that resolved when the mother stopped acetaminophen use and recurred when she resumed acetaminophen use. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Ofirmev and any potential adverse effects on the breastfed infant from Ofirmev or from the underlying maternal condition.

Females and Males of Reproductive Potential

Based on animal data use of acetaminophen may cause reduced fertility in males and females of reproductive potential. It is not known whether these effects on fertility are reversible. Published animal studies reported that oral acetaminophen treatment of male animals at doses that are 1.2 times the MHDD and greater (based on a body surface area comparison) result in decreased testicular weights, reduced spermatogenesis, and reduced fertility. In female animals given the same doses, reduced implantation sites were reported. Additional published animal studies indicate that acetaminophen exposure in utero adversely impacts reproductive capacity of both male and female offspring at clinically relevant exposures [see Nonclinical Toxicology (13.1)].

Pediatric Use

Treatment of Acute Pain

The safety and effectiveness of Ofirmev for the treatment of acute pain in pediatric patients ages 2 years and older is supported by evidence from adequate and well-controlled studies of Ofirmev in adults and safety and pharmacokinetic data from adult and 483 pediatric patients across all age groups [see Dosage and Administration (2.3) and Pharmacokinetics (12.3)].

The effectiveness of Ofirmev for the treatment of acute pain in pediatric patients younger than 2 years of age has not been established.

In patients younger than 2 years, efficacy was not demonstrated in a double-blind, placebo-controlled study of 198 pediatric patients younger than 2 years. Pediatric patients less than 2 years of age, including neonates from 28 to 40 weeks gestational age at birth, were randomized to receive opioid plus acetaminophen or opioid plus placebo. No difference in analgesic effect of intravenous acetaminophen, measured by assessment of reduced need for additional opioid treatment for pain control, was observed.

Treatment of Fever

The safety and effectiveness of Ofirmev for the treatment of fever in pediatric patients, including premature neonates born at ≥ 32 weeks gestational age is supported by adequate and well-controlled studies of Ofirmev in adults, clinical studies in 244 pediatric patients 2 years and older, and safety and pharmacokinetic data from 239 patients younger than 2 years including neonates ≥ 32 weeks gestational age.

Geriatric Use

Of the total number of subjects in clinical studies of Ofirmev, 15% were age 65 and over, while 5% were age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Hepatic Impairment

Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease [see Warnings and Precautions (5.1) and Clinical Pharmacology (12)]. A reduced total daily dose of acetaminophen may be warranted.

Patients with Renal Impairment

In cases of severe renal impairment (creatinine clearance ≤ 30 mL/min), longer dosing intervals and a reduced total daily dose of acetaminophen may be warranted.

Ofirmev Description

 Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent. Its chemical name is N-acetyl-p-aminophenol. Acetaminophen has a molecular weight of 151.16. Its structural formula is:

 Ofirmev injection is a sterile, clear, colorless, non pyrogenic, isotonic formulation of acetaminophen intended for intravenous infusion. It has a pH of approximately 5.5 and an osmolality of approximately 290 mOsm/kg. Each 100 mL contains 1000 mg acetaminophen, USP, 3850 mg mannitol, USP, 25 mg cysteine hydrochloride, monohydrate, USP, and 10.4 mg dibasic sodium phosphate, USP. pH is adjusted with hydrochloric acid and/or sodium hydroxide.

How Supplied/Storage and Handling

NDC 43825-102-01 - Ofirmev (acetaminophen) Injection is supplied in a 100 mL glass vial containing 1000 mg acetaminophen (10 mg/mL) in cartons of 24 vials.

NDC 43825-102-03 - Ofirmev (acetaminophen) Injection is supplied in a 100 mL bag containing 1000 mg acetaminophen (10 mg/mL) in cartons of 24 bags.

Do not remove unit from overwrap until ready for use.

To open, tear outer wrap at the notch and remove solution bag. After removing the outer wrap, check the container for minute leaks by squeezing the solution bag firmly. If leaks are found, discard the solution because the sterility may be impaired. A small amount of moisture may be present inside the outer wrap.

Ofirmev should be stored at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

For single-dose only. The product should be used within 6 hours after opening. Do not refrigerate or freeze.

Manufactured for:
Mallinckrodt Hospital Products Inc.
Hazelwood, MO 63042 USA

Revised: 01/2017

Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals logo and other brands are trademarks of a Mallinckrodt company.

© 2017 Mallinckrodt.

U.S. PATENT NUMBERS:
6,028,222; 6,992,218                                                           

Mallinckrodt™
Pharmaceuticals                                                             

(web3)