Perofen 400

Perofen 400 is a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). It is a racemic mixture of [+]S- and [-]R-enantiomers.

The chemical name for Perofen 400 is (±)-2-(4-isobutylphenyl) propionic acid. It has a molecular weight of 206.28 and a molecular formula of C₁₃H₁₈O₂.

Perofen 400 is a colorless, crystalline stable solid, with a melting point of 75-77°C. It is relatively insoluble in water but readily soluble in most organic solvents. Perofen 400 has a pKa of 4.43±0.03 and an n-octanol/water partition coefficient of 11.7 at pH 7.4.

Perofen 400 has shown analgesic, anti-inflammatory and antipyretic activity in both animal and human studies. These properties provide symptomatic relief of inflammation and pain.

Carefully consider the potential benefits and risks of Perofen 400

Oral Suspension and other treatment options before deciding to use Perofen 400. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

In Pediatric Patients, Perofen 400

Oral Suspension is indicated:

• For reduction of fever in patients aged 6 months up to 2 years of age.
• For relief of mild to moderate pain in patients aged 6 months up to 2 years of age.
• For relief of signs and symptoms of juvenile arthritis.

In Adults, Perofen 400

Oral Suspension is indicated:

• For treatment of primary dysmenorrhea.
• For relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis.

Since there have been no controlled trials to demonstrate whether there is any beneficial effect or harmful interaction with the use of Perofen 400 in conjunction with aspirin, the combination cannot be recommended.

Perofen 400 is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain, and helps to relieve symptoms of arthritis (osteoarthritis, rheumatoid arthritis, or juvenile arthritis), such as inflammation, swelling, stiffness, and joint pain. Perofen 400 does not cure arthritis and will help you only as long as you continue to take it.

In addition, Perofen 400 can be used to treat fever, menstrual cramps, and other conditions as determined by your doctor.

Perofen 400 is available both over-the-counter (OTC) and with your doctor's prescription.

Recommended Dose

A course of therapy is three doses of Perofen 400 administered intravenously (administration via an umbilical arterial line has not been evaluated). An initial dose of 10 mg per kilogram is followed by two doses of 5 mg per kilogram each, after 24 and 48 hours. All doses should be based on birth weight. If anuria or marked oliguria (urinary output < 0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of Perofen 400, no additional dosage should be given until laboratory studies indicate that renal function has returned to normal. If the ductus arteriosus closes or is significantly reduced in size after completion of the first course of Perofen 400, no further doses are necessary. If during continued medical management the ductus arteriosus fails to close or reopens, then a second course of Perofen 400, alternative pharmacological therapy, or surgery may be necessary.

Directions For Use

For intravenous administration only.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use Perofen 400 if particulate matter is observed.

After the first withdrawal from the vial, any solution remaining must be discarded because Perofen 400 contains no preservative.

For administration, Perofen 400 should be diluted to an appropriate volume with dextrose or saline. Perofen 400 should be prepared for infusion and administered within 30 minutes of preparation and infused continuously over a period of 15 minutes. The drug should be administered via the IV port that is nearest the insertion site. After the first withdrawal from the vial, any solution remaining must be discarded because Perofen 400 contains no preservative.

Since Perofen 400 is potentially irritating to tissues, it should be administered carefully to avoid extravasation.

Perofen 400 should not be simultaneously administered in the same intravenous line with Total

Parenteral Nutrition (TPN). If necessary, TPN should be interrupted for a 15-minute period prior to and after drug administration. Line patency should be maintained by using dextrose or saline.

How supplied

Dosage Forms And Strengths

10 mg/mL as a clear sterile preservative-free solution of the L-lysine salt of Perofen 400 in a 2 mL single-use vial.

Perofen 400 (Perofen 400 lysine) Injection is dispensed in clear glass single-use vials, each containing 2 mL of sterile solution (NDC 55292-122-52). The solution is not buffered and contains no preservatives. Each milliliter contains 17.1 mg/mL (±)-Perofen 400 L-lysine [equivalent to 10 mg/mL (±)-Perofen 400] dissolved in Water for Injection, USP. Perofen 400 is supplied in a carton containing 3 single-use vials.

Storage And Handling

Store at 20-25°C (68-77°F); excursions permitted 15-30°C (59-86°F). Protect from light. Store vials in carton until contents have been used.

Manufactured by: AAIPharma Services, Charleston, SC 29405, U.S.A. For: Recordati Rare Diseases Inc. Lebanon, NJ 08833, U.S.A. Revised: October 2015

See also:
What is the most important information I should know about Perofen 400?

This medicine may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term. Do not use Perofen 400 just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Get emergency medical help if you have chest pain, weakness, shortness of breath, slurred speech, or problems with vision or balance.

This medicine may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are taking Perofen 400, especially in older adults.

Call your doctor at once if you have symptoms of stomach bleeding such as black, bloody, or tarry stools, or coughing up blood or vomit that looks like coffee grounds.

Do not take more of this medication than is recommended. An overdose of Perofen 400 can cause damage to your stomach or intestines. Use only the smallest amount of Perofen 400 needed to get relief from your pain, swelling, or fever.

Use Perofen 400 capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Perofen 400 capsules comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Perofen 400 capsules refilled.
• Take Perofen 400 capsules by mouth with or without food. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach or bowel problems (eg, bleeding, ulcers). Talk with your doctor or pharmacist if you have persistent stomach upset.
• Swallow Perofen 400 capsules whole. Do not break, crush, or chew before swallowing.
• Take Perofen 400 capsules with a full glass of water (8 oz/240 mL) as directed by your doctor.
• If you miss a dose of Perofen 400 capsules and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose. Go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about the proper use of Perofen 400 capsules.

Perofen 400 is used to relieve pain from various conditions such as headache, dental pain, menstrual cramps, muscle aches, or arthritis. It is also used to reduce fever and to relieve minor aches and pain due to the common cold or flu. Perofen 400 is a nonsteroidal anti-inflammatory drug (NSAID). It works by blocking your body's production of certain natural substances that cause inflammation. This effect helps to decrease swelling, pain, or fever.

If you are treating a chronic condition such as arthritis, ask your doctor about non-drug treatments and/or using other medications to treat your pain. See also Warning section.

This form of Perofen 400 is intended for use by children. Do not give this medication to a child younger than 6 months unless directed by the doctor.

Check the ingredients on the label even if you have used the product before. The manufacturer may have changed the ingredients. Also, products with similar names may contain different ingredients meant for different purposes. Taking the wrong product could harm you.

How to use Perofen 400

Read and follow all directions on the product package before using this medication. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor or the package label, usually every 6 to 8 hours as needed. Shake the bottle well before each dose. Carefully measure the dose using the provided dropper/syringe. Do not use a household spoon because you may not get the correct dose. If you have stomach upset while taking this medication, take it with food or milk.

The dosage is based on your medical condition and response to treatment. To reduce your risk of stomach bleeding and other side effects, take this medication at the lowest effective dose for the shortest possible time. Do not increase your dose or take this drug more often than directed by your doctor or the package label.

When Perofen 400 is used by children, the dose is based on the child's weight. Read the package directions to find the proper dose for your child's weight. Consult the pharmacist or doctor if you have questions or if you need help choosing a nonprescription product.

If you are using this drug "as needed" (not on a regular schedule), remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has worsened, the medication may not work as well.

If your condition persists or worsens, or if you think you may have a serious medical problem, get medical help right away. If you are using the nonprescription product to treat yourself or a child for fever or pain, consult the doctor right away if fever worsens or lasts more than 3 days, or if pain worsens or lasts more than 10 days.

See also:
What other drugs will affect Perofen 400?

Coumarin-Type Anticoagulants: Several short-term controlled studies failed to wshow that Perofen 400 significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on coumarin-type anticoagulants. However, because bleeding has been reported when Perofen 400 and other nonsteroidal anti-inflammatory agents have been administered to patients on coumarin-type anticoagulants, the physician should be cautious when administering Perofen 400 to patients on anticoagulants.

Aspirin: Animal studies wshow that aspirin given with nonsteroidal anti-inflammatory agents, including Perofen 400, yields a net decrease in anti-inflammatory activity with lowered blood levels of the non-aspirin drug. Single dose bioavailability studies in normal volunteers have failed to wshow an effect of aspirin on Perofen 400 blood levels. Correlative clinical studies have not been performed.

Methotrexate: Apo-Perofen 400, as well as other nonsteroidal anti-inflammatory drugs, probably reduces the tubular secretion of methotrexate based on in vitro studies in rabbit kidney slices. This may indicate that Perofen 400 could enhance the toxicity of methotrexate. Caution should be used if Perofen 400 is administered concomitantly with methotrexate.

H-2 Antagonists: In studies with human volunteers, co-administration of cimetidine or ranitidine with Perofen 400 had no substantive effect on Perofen 400 serum concentrations.

Furosemide: Clinical studies, as well as random observations, have shown that Perofen 400 can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with Perofen 400, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy.

Lithium: Apo-Perofen 400 produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of eleven normal volunteers. The mean minimum lithium concentration increased 15% and the renal clearance of lithium was decreased by 19% during this period of concomitant drug administration.

This effect has been attributed to inhibition of renal prostaglandin synthesis by Perofen 400. Thus, when Perofen 400 and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparation before use of such concurrent therapy).

See also:
What are the possible side effects of Perofen 400?

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events
• GI Bleeding, Ulceration and Perforation
• Hepatotoxicity
• Hypertension
• Heart Failure and Edema
• Renal Toxicity and Hyperkalemia
• Anaphylactic reactions
• Serious Skin Reactions
• Hematologic Toxicity

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared directly to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adult Population

During clinical development, 560 patients were exposed to Perofen 400, 438 in pain and 122 with fever. In the pain studies, Perofen 400 was started intra-operatively and administered at a dose of 400 mg or 800 mg every six hours for up to three days. In the fever studies, Perofen 400 was administered at doses of 100 mg, 200 mg, or 400 mg every four or six hours for up to 3 days. The most frequent type of adverse reaction occurring with oral Perofen 400 is gastrointestinal.

Pain Studies

The incidence rates of adverse reactions listed in the following table were derived from multi-center, controlled clinical studies in post-operative patients comparing Perofen 400 to placebo in patients also receiving morphine as needed for post-operative pain.

Table 1: Post-operative Patients with Adverse Reactions Observed in ≥ 3% of Patients in any Perofen 400 Treatment Group in Pain Studies*

Fever Studies

Fever studies were conducted in febrile hospitalized patients with malaria and febrile hospitalized patients with varying causes of fever. In hospitalized febrile patients with malaria, the adverse reactions observed in at least two Perofen 400-treated patients included abdominal pain and nasal congestion.

In hospitalized febrile patients (all causes), adverse reactions observed in more than two patients in any given treatment group are presented in the table below.

Table 2: Patients with Adverse Reactions Observed in ≥ 3% of Patients in any Perofen 400 Treatment Group in All-Cause Fever Study

Pediatric Population

A total of 143 pediatric patients ages 6 months and older have received Perofen 400 in controlled clinical trials. The most common adverse reactions (incidence greater than or equal to 2%) in pediatric patients treated with Perofen 400 were infusion site pain, vomiting, nausea, anemia and headache.