Meropenem - Indications, Side Effects, Dose Administration, Precautions, and Drug Interactions

Overview:

Meropenem is a broad-spectrum antibacterial carbapenem antibiotic. It is active against both gram-negative and positive bacteria. It works by entering the bacterial cell wall and interfering with cell wall synthesis. It can be used for a child patient who is three months old and older and for adults too. But Meropenem is only given by intravenous route.

What Are the Indications of Meropenem?

• It is indicated for complicated skin and skin structure infections, especially in adult and pediatric patients who are three months old or older than three.

• It is also indicated for complicated intra-abdominal infections.

• Bacterial meningitis in pediatric patients who are three or older.

• It also decreases the development of drug resistance. It provides the effectiveness of Meropenem and other bacterial infection, but it should be used only in the cases of strongly suspected bacteria.

Dosage and Administration:

Dosage Strength: 500 mg.

Dosage Routes: Intravenous infusion.

Administration: It is given 500 mg every eight hours by intravenous infusion over 15 to 30 minutes for skin infections in adults.

• It is given one gram every eight hours by intravenous infusion over 15 to 30 minutes for intra-abdominal infections in adult patients.

• If Pseudomonas aeruginosa has caused the infection, then one gram dose every eight hours is given.

• And one gram every eight hours in the intravenous bolus injection 5mL to 20 mL dose is given in three to five minutes in adult cases.

• The dose is reduced in cases of renal impairments.

The Recommended Dosage for Meropenem Injections in Renal Impairment Cases

The Recommended Dosage for Meropenem Injections for Pediatric Patients 3 Months Old or Older

The Recommended Dosage for Meropenem Injection in Pediatric Patients Who Are Less Than 3 Months Old and Have a Normal Renal Function

Contraindication:

• If the patient has a hypersensitivity reaction.

• If the patient has an anaphylactic reaction to beta-lactams.

What Are the Warning and Precautions for the Drug?

• Hypersensitivity Reaction: Some patients have received serious and fatal hypersensitivity reactions after getting Meropenem reactions. So, it is important to notice and observe the patient if they have a hypersensitivity reaction on taking Penicillin or Beta lactams and Cephalosporins.

• Seizures: Seizures and altered central nervous system functioning have been reported in some of the patients in clinical studies. If such cases occur, the patient should be treated with anti-convulsant medications.

• Drug Interactions: When the injection of Meropenem is delivered with Valproic acid or Divalproex sodium, it decreases the serum concentration of the Valproic acid. It increases the chances of seizures in the patients.

• Clostridium Difficile-Associated Diarrhea: Clostridium difficile-associated diarrhea has also been reported in cases after the use of Meropenem antibacterial injections. While treating with antibacterial agents changes the flora of the colon, which increases the growth of Clostridium difficile and produces high levels of toxins A and B.

• Drug-Resistance Development: There are chances of the development of drug resistance after the use of Meropenem.

• Overgrowth of the Non-Susceptible Bacteria: If using Meropenem is done, then an overgrowth of non-susceptible bacteria will occur. The chances of development of superinfection can occur during therapy.

• Thrombocytopenia: If the patient has renal impairments, then they also have thrombocytopenia.

• Development of Motor Impairments: Adverse effects can occur in some cases, like seizures, paresthesia, motor impairments, delirium, and headaches.

Adverse Effects:

• Headache.

• Nausea.

• Vomiting.

• Diarrhea.

• Anemia.

• Rashes.

• Constipation.

Special Considerations:

• Renal Impairment Patients: Patients whose creatinine clearance is less than 50 mL/min then it requires a dosage adjustment.

• Hepatic Impairment Patients: Meropenem injections are given in this patient as there are no effects on liver diseases with the pharmacokinetics of Meropenem.

• Geriatric Patients: Meropenem is used in patients who but renal impaired and have shown reduced plasma clearance than other healthy older patients. But the studies performed have shown safety and effectiveness equally as in younger adults.

• Pediatrics: Child patients older than three months can also have the Meropenem injection. It is completely safe and effective in child patients. the child who suffers from skin structure infections, intra-abdominal infections, and meningitis are given Meropenem.

• Pregnancy: Meropenem injections in pregnant women had no adequate results. So, the cautious use of Meropenem injections is done in cases of pregnancy.

• Nursing Mothers: The use of Meropenem injections has shown results in excretion in human milk. So, the Cautious use of Meropenem is done in nursing mothers.

For Patients:

What Is the Use of Meropenem?

Meropenem is used to treat skin infections, intra-abdominal infections, and meningitis, all caused by bacteria. It can be used in adults and children over three months of age and older. Meropenem is delivered in the form of injections and is also termed antibiotics. They mainly work by killing the bacteria that are causing the infection. These Meropenem injections are mainly for the strongly suspected bacteria, not for cold and cough cases. If these are used in small cases, they can resist the treatment and increase the chances of developing infections.

How Is Meropenem Injection Used?

Meropenem injection comes in the form of powder mixed with liquid, which is injected intravenously into the veins. It is given every eight hours, but the length of the treatment and the type of infection is decided by the doctor based on how the patient responds to the medications. The doctors, who decide according to the patient's response, can change the form of the medicine to an oral route instead of an injection. The patient may have a Meropenem injection in the hospital or even at home after understanding its terms of usage. The patient can feel better in the initial days of Meropenem injections. If the patient does not complete the dose course as recommended, then the chances of bacterial development or antibiotic resistance chances are more.

What Are the Precautions Taken While Using Meropenem Injections?

The precautions include

• The patient should inform the doctor if the patient is allergic to Meropenem or any other beta-lactam, Cephalosporin, or Penicillin-resistant.

• The patient should inform the doctor if the patient is taking any other medications, vitamins, or nutritional supplements.

• The patient should also inform the patient about valproic acid or any Probenecid.

• They should inform the concerned doctor if any side effects like seizures, thrombocytopenia, or kidney diseases develop.

• Informing the doctor if the patient is pregnant or planning to get pregnant so that the doctor can recommend the dose and any other ways to control the pregnancy.

• Informing the doctor about breastfeeding is also important.

• Meropenem injection can cause altered mental alertness, so the patient should avoid work that requires any mental attention, like driving.

What Are the Special Dietary Instructions That Follow With Meropenem Injections?

The patient should continue the regular diet unless the doctor recommends any supplementary diet.

What Are the Side Effects of Meropenem Injections?

Side effects are

• Headache.

• Diarrhea.

• Constipation.

• Nausea.

• Vomiting.

• Pain.

• Pain with swelling over the site of injection.

• Tinglingness.

• Staying asleep.

• Sore throat.

• Sometimes, sores in the mouth.

There are some side effects that can be serious; if such effects are experienced by the patient, then the patient requires immediate medical attention. Some of these serious types of side effects are

• Seizures.

• Severe diarrhea, which includes watery or bloody stools.

• Hives.

• Itchiness.

• Flushing.

• Rashes.

• Swelling at face, eyes, and lips.

• Difficulty breathing and swallowing.

• Pale skin.

• Fast, irregular heartbeat.

• Shortness of breath.

• Fever.

• Signs of infection.

For Doctors:

Meropenem Injections:

Meropenem injections are sterile, which is pyrogen-free, and carbapenem antibacterial injections are delivered intravenously. It has a chemical name as (4R,5S,6S)-3- [[(3S,5S)-5-(Dimethylcarbamoyl carbamoyl oyl)-3-pyrrolidinyl]thio]-6- [(1R)-1-hydroxyethyl]-4­ methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid trihydrate with a molecular weight of 437.52 and empirical formula of C17H25N3O5S•3H2O.

It is available in white to yellow crystalline powder, whose color changes from colorless to yellow with its concentration. It has a pH between 7.3 to 8.3. It can be soluble in a 5% monobasic potassium phosphate solution, with slight soluble in hydrated ethanol but insoluble in acetone or ether.

What Is the Clinical Pharmacology of Meropenem?

Pharmacokinetics:

• Mechanism of Actions: The action of Meropenem is bactericidal that is by inhibiting cell wall synthesis. The Meropenem goes through the cell wall of the gram-positive and gram-negative bacteria to reach the Penicillin-binding protein, which is their target. The Meropenem further binds to the penicillin-binding protein of E.coli and P. aeruginosa, and Staphylococcus aureus.

• Plasma Concentrations: When intravenous injections are delivered, the plasma centration that reaches to peak in 30 minutes is 23 mcg/mL for 500 mg dosage and 49 mcg/mL for one gram dose. An intravenous bolus injection of Meropenem in 5 minutes reaches the peak plasma in 45 mcg/mL for 500 mg dosage and 112 mcg/mL for one gram dose. After delivering the injection, the plasma concentration reduces to 1 mcg/mL after six hours of administration.

• Distribution: The plasma binding proteins is 2 %.

• Metabolism: One metabolite of Meropenem is seen, which is also in a microbiologically inactive state.

• Excretion: The elimination of Meropenem is nearly one hour. It is excreted unchanged by the kidneys. And nearly about 70 % is excreted in 12 hours, 2 % in fecal, and the remaining 28 % in one metabolite state, which is met by a biologically inactive metabolite.

Nonclinical Toxicology:

Carcinogenesis: Studies for the carcinogenesis effect of Meropenem have not been performed.

Mutagenesis: The studies were performed on animals (hamsters or mice) to check the mutation effects of Meropenem, but no evidence was found in these tests.

Impairment of Fertility: There were no reproductive toxicity effects seen in the animals (monkeys) in the studies performed.

Overdosage:

The studies on the rates with the higher doses of Meropenem injections, which ranged from nearly 2200 mg/kg to 4000 mg/kg, revealed effects such as ataxia, dyspnea, and convulsions. However, even the studies performed as 2 grams intravenously given in every eight hours have shown no adverse effects on patients with renal impairment. Hence the adverse reactions related to overdosage of Meropenem are generally mild according to severity point and can be resolved on dose reduction or withdrawal. In a healthy patient, rapid renal excretion can take place to eliminate the Meropenem from the body.

How Does Meropenem Interacts With Other Drug?

• Probenecid: When the patient co-administered the Meropenem with Probenecid, then there was an increased plasma concentration of Meropenem.

• Valproic Acid: The co-administration of Valproic acid with Meropenem decreases the therapeutic requirement of the Valproic acid for its beneficial use and even increases the chances of seizures. If in case, they are co-administered, then anticonvulsive therapy is started along with it.

Adverse Reactions:

Local Reactions:

• Inflammation.

• Thrombophlebitis.

• Pain at the site.

• Edema at the injection site.

• Reaction at the site.

Systemic Reaction:

• Body: Abdominal pain, chest pain, fever, back pain, chills, and pelvic pains.

• Cardiovascular System: Heart failure, heart arrest, tachycardia, hypertension, hypotension, syncope, and pulmonary embolus.

• Digestive System: Anorexia, jaundice, flatulence, ileus, and hepatic failure.

• Lymphatic System: Anemia and hypervolemia.

• Nutritional: Peripheral edema and hypoxia.

• Nervous System: Insomnia, delirium, confusion, seizures, nervousness, paresthesia, hallucinations, anxiety, and depression.

• Respiratory System: Dyspnea, pleural effusion, asthma, cough, lung edema.

• Skin: urticaria, sweating, and skin ulcers.

• Urological System: Dysuria, kidney failure, urinary incontinence, and vaginal moniliasis.

Clinical Studies:

• Complicated Skin and Skin Structure Infections: Randomized, multi-center, double-blind trials were performed on the population of the United States, South Africa, and Canada. The study was performed on 510 patients with 500 mg of the Meropenem intravenous dose, which is given every eight hours, and 527 patients with Imipenem-Cilastin 500 mg dose intravenously every eight hours. All such patients have complicated skin and skin structure infections. Among these populations selected, 37 % have diabetes, 12 % have peripheral vascular disease, and 67 % have surgical intervention. However, 261 patients were evaluated for Meropenem, and 287 were evaluated for Imipenem-Cilastatin. The success rates in patients were 86 % with the Meropenem dose and 83 % with Imipenem-Cilastatin. The patient who discontinued the treatment because of the development of the adverse effects was nearly 2.5 %.

• Intra-Abdominal Infections: Controlled studies were performed in the United States with Meropenem compared to Clindamycin or Tobramycin. However, Europe has conducted three studies along with Meropenem. The use of Imipenem, Meropenem, and Cefotaxime or Metronidazole was taken. The usage of this different drug has a different microbiological eradication rate. Meropenem causes 67% eradication, Imipenem 62 %, Cefotaxime 86 %, and Clindamycin 76 %.

• Bacterial Meningitis: 446 patients, including 397 pediatric patients, were present in the four clinical trials and were randomized to Meropenem with 40 mg/kg every eight hours or Cefotaxime used compared to it. All the patients suffer from bacterial meningitis. The patients who were not cured five to seven weeks post-completion of the visits have moderate to the severe motor, with behavior or developmental deficits and hearing deficits greater than 60 decibels. In ears or blindness. Of if the patient requires surgical drainage or if the patient requires other antibacterial drugs to complete the dose. Among those patients, five patients were not cured, three from the Cefoxamine group and two from the Meropenem group. Most of the patients have been performing hearing tests. Almost 61 % of patients have no hearing loss, 20 % have a 20 to 40 decibel of loss, and greater than 40 to 60 decibel was seen in 8 % and less than 60 decibels in 9 % of patients.

How Is Meropenem Supplied?

It comes in 20 mL, and 30 mL injection vials containing Meropenem delivered 500 mg intravenously. The dry powder form is stored at a room temperature of 20 to 25 degrees Celsius.

Patient Information:

• Instruct the patient about the usage of Meropenem and that it is used only for antibacterial use but not for antiviral use.

• The use of Meropenem for other non-susceptible bacterial infections can cause drug resistance. And the loss of effectiveness.

• Diarrhea can be suffered post-treatment with Meropenem. If such side effects are seen, then discontinue the drug.

• If the patient takes Valproic acid or Probenecid, their co-administration is inhibited with Meropenem.

• The patient should be instructed about the adverse effects like seizures, paresthesia, headaches, delirium, and motor impairment.