Category Archive Drugs A-Z

Mechanism Of Actions

Scopolamine Hydrobromide is the hydrobromide salt form of scopolamine, a tropane alkaloid derived from plants of the nightshade family (Solanaceae), specifically Hyoscyamus niger and Atropa belladonna, with anticholinergic, antiemetic and antivertigo properties. Structurally similar to acetylcholine, scopolamine antagonizes acetylcholine activity mediated by muscarinic receptors located on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. The agent is used to cause mydriasis, cycloplegia, to control the secretion of saliva and gastric acid, to slow gut motility, and prevent vomiting.

Indications of Hyoscine Hydrobromide

Dosage by tablet strength

How to take tablets for excess saliva

• These tablets are available on prescription only. They can be taken by adults and children aged 12 years or older.
• The usual dose is 1 tablet (300 micrograms), 3 times a day.

How to use patches for excess saliva

Adults and children aged 10 years or older:

• Stick a patch to the skin behind the ear.
• Leave the patch on for 72 hours (3 days).
• After 72 hours, remove the patch.
• Stick a new patch behind the other ear.
• After 72 hours, remove the patch.
• Repeat the process.

Occasionally a doctor may prescribe patches for a child under the age of 9 years. In this case, they’ll use your child’s weight to work out what size patch to use. They may only need to use half a patch.

How to use patches for travel sickness

Patches are suitable for adults and children aged 10 years or older.

• Stick a patch to the skin behind the ear 5 to 6 hours before the start of your journey (or the evening before you travel).
• Remove the patch at the end of your journey.
• For long journeys, you can keep the patch on for up to 72 hours (3 days).
• If you’re still traveling after 72 hours, remove the first patch and stick a new patch behind the other ear. You can keep this on for another 72 hours if needed.

Oral
Gastrointestinal tract spasm, Genitourinary spasm

• Adult: As hyoscine butyl bromide: 20 mg 4 times daily.
• Child: As hyoscine butyl bromide: 6-11 years 10 mg tid; ≥12 years Same as adult dose.

Oral
Prophylaxis of motion sickness

• Adult: As hyoscine hydrobromide: Initially, 0.15-0.3 mg 20-30 minutes before a journey, repeat 6 hourly if needed, up to max 3 doses in 24 hours. Max: 0.9 mg daily.
• Child: As hyoscine hydrobromide: 3-4 years Initially, 0.075 mg, repeated once if needed. Max: 0.15 mg daily; >4-10 years 0.075-0.15 mg, repeat 6 hourly if needed. Max: 0.45 mg daily; >10 years 0.15-0.30 mg, repeat 6 hourly if needed. Max: 0.9 mg daily. All doses should be given 20-30 minutes before a journey.

Oral
IBS (irritable bowel syndrome)

• Adult: As hyoscine butyl bromide: Initially, 10 mg tid, may increase up to 20 mg 4 times daily if needed.
• Child: As hyoscine butyl bromide: 6-11 years 10 mg tid; ≥12 years Same as adult dose.

Parenteral
Motion sickness, Nausea, and vomiting, Vertigo

• Adult: As hyoscine hydrobromide: 0.2 mg as a single dose via IM or SC inj (may also be given via IV inj if required).
• Child: As hyoscine hydrobromide: 0.006 mg/kg as a single dose via IM or SC inj.

Parenteral
Gastrointestinal tract spasm, Genitourinary spasm

• Adult: As hyoscine butyl bromide: 20 mg via slow IV or IM inj, may be repeated after 30 minutes if needed. Max: 100 mg daily.

Parenteral
Preoperative medication

• Adult: As hyoscine hydrobromide: 0.2-0.6 mg given via IV, IM, or SC inj, 30-60 minutes prior to induction of anesthesia.
• Child: As hyoscine hydrobromide: 0.015 mg/kg given via IM or SC inj, 30-60 minutes prior to induction of anesthesia.

Transdermal
Prophylaxis of motion sickness

• Adult: As hyoscine hydrobromide patch containing 1.5 mg: Apply 1 patch behind the ear, 4-6 hours before a journey or in the evening before the journey.
• Child: >10 years Same as adult dose.

Transdermal
Postoperative nausea and vomiting

• Adult: As hyoscine hydrobromide patch containing 1.5 mg: Apply 1 patch behind the ear on the evening before the surgery or 1 hour before cesarean section. Discard 24 hours after the surgery.
• Child: >10 years Same as adult dose.

Side Effects Of Hyoscine Hydrobromide

References

• Pregnancy and breast-feeding – There isn’t enough reliable information to know if collagen type II is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.
  
• Collagen allergies –People who are allergic to other types of collagen should not use collagen type II. Other collagen products have been associated with allergic reactions.

• Pregnancy and breast-feeding – There isn’t enough reliable information to know if collagen type II is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.
  
• Collagen allergies –People who are allergic to other types of collagen should not use collagen type II. Other collagen products have been associated with allergic reactions.

Tomopenem is a 1-beta-methylcarbapenem antibiotic with broad-spectrum activity against gram-positive and gram-negative bacteria. Tomopenem has a longer half-life than imipenem-cilastatin or meropenem and shows activity against methicillin-resistant S. aureus.

Tomopenem is a 1-beta-methylcarbapenem antibiotic with broad-spectrum activity against gram-positive and gram-negative bacteria. Tomopenem has a longer half-life than imipenem-cilastatin or meropenem and shows activity against methicillin-resistant S. aureus.

Tomopenem (formerly CS-023) is a novel carbapenem with improved activity against diverse hospital pathogens, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), and has a half-life about twice longer than the half-lives of other carbapenems such as imipenem and meropenem. Our objective in this study was to estimate the efficacy of tomopenem in humans by human-simulated exposures in a neutropenic murine thigh infection model against 9 clinical isolates of P. aeruginosa with MICs of 4 to 32 μg/ml and 9 clinical isolates of MRSA with MICs of 4 to 16 μg/ml. Human-simulated dosing regimens in neutropenic mice were designed to approximate the cumulative percentage of a 24-h period that the free drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f%T(MIC)) observed with tomopenem at 750 and 1,500 mg given as a 0.5-h infusion three times a day (TID) in humans. As reported previously, there was no difference between the target values of P. aeruginosa and MRSA required for efficacy (K. Sugihara et al., Antimicrob. Agents Chemother. 54:5298-5302, 2010). Tomopenem at 750 mg showed bactericidal or bacteriostatic effects against 10 of 11 strains of P. aeruginosa and MRSA with MICs of ≤ 8 μg/ml (f%T(MIC) ≥ 41), and tomopenem at 1,500 mg showed bactericidal effects against 16 of 17 strains of P. aeruginosa and MRSA with MICs of ≤ 16 μg/ml (f%T(MIC) ≥ 43). Meropenem at 1,000 mg TID was tested for comparison purposes and showed bactericidal or bacteriostatic effects against 3 of 4 strains of P. aeruginosa with MICs of ≤ 4 μg/ml (f%T(MIC) ≥ 33). From these results, tomopenem is expected to be effective with an f%T(MIC) of over 40 against P. aeruginosa and MRSA strains with MICs of ≤ 8 μg/ml at doses of 750 mg TID and strains with MICs of ≤ 16 μg/ml at doses of 1,500 mg TID.

References

Tebipenem Pivoxil is an orally available pivaloyloxymethyl ester prodrug of tebipenem, a broad-spectrum 1-beta-methylcarbapenem antibiotic with a 1-(1,3-thiazolin-2-yl) azetidin-3-ylthio group at the C-2 position. After oral administration of tebipenem pivoxil, the ester bond is cleaved, releasing active tebipenem.

Tebipenem (brand name Orapenem) is a broad-spectrum orally-administered antibiotic, from the carbapenem subgroup of β-lactam antibiotics. It was developed as a replacement drug to combat bacteria that had acquired antibiotic resistance to commonly used antibiotics. Tebipenem is formulated as the ester tebipenem pivoxil due to the better absorption and improved bioavailability of this form.^[rx] It has performed well in clinical trials for ear infection and looks likely to be further developed in the future.^[rx] It is only marketed in Japan.^[rx] Tebipenem is the first carbapenem whose prodrug form, the pivaloyl ester, is orally available.^[rx]

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr, formerly SPR994) is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) Gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacteriaceae. The safety and pharmacokinetics (PK) of tebipenem were studied after administration of single and multiple ascending oral doses of TBPM-PI-HBr in fed and fasted states. Healthy adults received single oral doses of TBPM-PI-HBr at 100 mg to 900 mg or placebo (n = 108) or multiple doses of 300 mg or 600 mg every 8 h or placebo (n = 16) for 14 days. In the single-ascending-dose (SAD) phase, mean tebipenem plasma concentrations increased in a linear and dose-proportional manner for doses of 100 to 900 mg and were comparable in the fasted and fed states for the 300- and 600-mg doses. In the MAD phase, tebipenem maximum concentration (C_max) was reached within 1.5 h and was dose-proportional on day 1 and higher than dose-proportional (2.7-fold) on day 14. AUC was more than 2-fold greater on day 1 (2.7-fold) and day 14 (2.5-fold) for 600 mg q8h than for 300 mg q8h. Approximately 55% to 60% of tebipenem was recovered in the urine. TBPM-PI-HBr was well tolerated; mild, transient diarrhea was the most commonly reported adverse event. TBPM-PI-HBr provides an orally bioavailable carbapenem option to treat serious infections caused by MDR Enterobacteriaceae and has the potential to decrease the need for intravenous antibiotic therapy in the hospital or outpatient setting. (This study has been registered at ClinicalTrials.gov under identifier NCT03395249.)

Data or information available

References

Panipenem is a broad-spectrum parenteral carbapenem with activity against aerobic, anaerobic, gram-positive, and gram-negative organisms including non-fermenters. Panipenem is often co-administered with betamipron to prevent nephrotoxicity.

Panipenem/betamipron is a carbapenem antibiotic marketed by Daiichi Sankyo Co. of Japan. It was launched in 1993,^[rx] under the brand name Carbenin.^[rx]

It is a combination in which panipenem is the carbapenem antibiotic and betamipron inhibits renal uptake of panipenem^[rx] and so reduces its nephrotoxicity^[rx] (much like the imipenem/cilastatin combination).

The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds.

Data and information not available

• https://pubchem.ncbi.nlm.nih.gov/compound/72015
• https://pubchem.ncbi.nlm.nih.gov/compound/Panipenem-betamipron

Lenapenem is a broad-spectrum, carbapenem antibiotic with bactericidal activity. Lenapenem binds to penicillin-binding proteins (PBPs) located on the bacterial cell wall, thereby inhibiting the final transpeptidation step in the synthesis of peptidoglycan, an essential component of the bacterial cell wall. This inhibition weakens the bacterial cell wall and leads to lytic cell death in a wide range of Gram-positive and Gram-negative aerobic and anaerobic pathogens.

Mechanism of Action

Lenapenem is a broad-spectrum, carbapenem antibiotic with bactericidal activity. Lenapenem binds to penicillin-binding proteins (PBPs) located on the bacterial cell wall, thereby inhibiting the final transpeptidation step in the synthesis of peptidoglycan, an essential component of the bacterial cell wall. This inhibition weakens the bacterial cell wall and leads to lytic cell death in a wide range of Gram-positive and Gram-negative aerobic and anaerobic pathogens.

Data or details information are not available

References

Imipenem is a semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to many beta-lactamases. Similar compounds include meropenem, known for having greater activity against Gram-negative bacteria, and the newer ertapenem which exhibits a longer half-life due to increased binding to plasma proteins.^[rx]Imipenem is commonly used in combination with cilastatin and is now available in a triple-drug product with cilastatin and sulbactam which was recently approved by the FDA. Imipenem was first approved by the FDA in November 1985 as the combination product Primaxin marketed by Merck & Co.^[rx]

Imipenem and cilastatin injection is used to treat certain serious infections that are caused by bacteria, including endocarditis (infection of the heart lining and valves) and respiratory tract (including pneumonia), urinary tract, abdominal (stomach area), gynecological, blood, skin, bone, and joint infections. Imipenem is in a class of medications called carbapenem antibiotics. It works by killing bacteria. Cilastatin is in a class of medications called dehydropeptidase inhibitors. It works by helping imipenem stay active in your body for a longer period of time.

Mechanism of action

Imipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria.^[rx] This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to penicillin-binding proteins (PBPs). In E. coli and selected strains of P. aeruginosa, imipenem has shown to have the highest affinity to PBP-2, PBP-1a, and PBP-1b.^[rx] This inhibition of PBPs prevents the bacterial cell from adding to the peptidoglycan polymer which forms the bacterial cell wall eventually leading to cell death.^[rx]

Imipenem is a beta-lactam antibiotic belongings to the subgroup of carbapenems.^[rx] Imipenem is active against aerobic and anaerobic Gram-positive as well as Gram-negative bacteria including Pseudomonas aeruginosa and Enterococcus. It exerts a bactericidal effect by disrupting cell wall synthesis.

Indications of Imipenem

The spectrum of bacterial susceptibility and resistance

• Acinetobacter anitratus, Acinetobacter calcoaceticus, Actinomyces odontolyticus, Aeromonas hydrophila, Bacteroides distasonis, Bacteroides uniformis, and Clostridium perfringens are generally susceptible to imipenem, while Acinetobacter baumannii, some Acinetobacter spp., Bacteroides fragilis, and Enterococcus faecalis have developed resistance to imipenem to varying degrees. Not many species are resistant to imipenem except Pseudomonas aeruginosa (Oman) and Stenotrophomonas maltophilia.^[rx]

Coadministration with cilastatin

• Imipenem is rapidly degraded by the renal enzyme dehydropeptidase 1 when administered alone, and is almost always coadministered with cilastatin to prevent this inactivation.^[rx]
• Imipenem is indicated, in combination with cilastatin with or without sulbactam, for the treatment of bacterial infections including respiratory, skin, bone, gynecologic, urinary tract, and intra-abdominal as well as septicemia and endocarditis.^[rx]
• Bloodstream Infections
• Bone and Joint Infections
• Complicated Intra-Abdominal Infections
• Complicated Urinary Infection
• Complicated Urinary Tract Infection
• Endocarditis caused by staphylococcus aureus
• Gynecological infection
• Intra-Abdominal Infections
• Lower respiratory tract infection bacterial
• Pyelonephritis
• Skin and Subcutaneous Tissue Bacterial Infections
• Uncomplicated Urinary Tract Infections

Contraindications of Imipenem

• Children less than 30 kg with renal impairment, children with CNS infections (increased seizure risk), known hypersensitivity to local anesthetics of the amide-type, and in patients with severe shock or heart block
• History of seizures,
• Concomitant ganciclovir; risk for generalized seizures,
• Hypersensitivity to penicillins,
• cephalosporins, and other beta-lactams

Dosage of Imipenem

Strengths: 500mg, 750mg

Intramuscular

• 500mg imipenem and 500mg cilastatin power mixture for intramuscular injection
• 750mg imipenem and 750mg cilastatin power mixture for intramuscular injection

Intravenous

• 250mg imipenem, 250mg cilastatin, and 10mg sodium bicarbonate power mixture for intravenous injection
• 500mg imipenem, 500mg cilastatin, and 20mg sodium bicarbonate power mixture for intravenous injection

Mild infections

• (fully susceptible) 250 mg IV every 6 hr; (moderately susceptible including P. aeruginosa) 500 mg IV every 6 hr

Moderate infections

• (fully susceptible) 500 mg IV every 6-8 hr; (moderately susceptible including P. aeruginosa) 500 mg IV every 6 hr or 1 g IV every 8 hr

Severe, life-threatening infections

• (fully susceptible) 500 mg IV every 6 hr; (moderately susceptible including P. aeruginosa) 1 g IV every 8 hr or 1 g IV every 6 hr; maximum 50 mg/kg/day or 4 g/day, whichever is lower

Cystic fibrosis

• (12 years and older) up to 90 mg/kg/day IV divided every 6 hr; maximum 4 g/day

Urinary tract infections, uncomplicated

• 250 mg IV every 6 hr

Urinary tract infections, complicated

• 500 mg IV every 6 hr

Gynecologic infections

• 500-750 mg IM every 12 hr

Intra-abdominal infections

• 750 mg IM every 12 hr

Lower respiratory tract infections

• 500-750 mg IM every 12 hr

Skin/skin structure infections

• 500-750 mg IM every 12 hr

Side Effects of Imipenem

Most Common

• pain, swelling, redness, bruising, or hardening where the medicine was injected;
• nausea
• vomiting
• diarrhea
• confusion
• drooping eyelids
• seizures
  
• headache
• redness, pain, or swelling at the injection site

Common 

• severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
• hives
• itching
• rash
• difficulty breathing or swallowing
• blisters on the skin, mouth, nose, and eyes
• sloughing (shedding) of skin
• confusion
• seizures

Rare

• severe stomach pain, diarrhea that is watery or bloody;
• upper stomach pain, loss of appetite;
• jaundice (yellowing of the skin or eyes);
• a seizure (convulsions);
• fever; or
• a light-headed feeling, like you might pass out.
• dizziness, drowsiness;
• nausea, vomiting, diarrhea; or
• itching, rash.

Imipenem and cilastatin injection may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Drug Interactions of Imipenem

• amifampridine
• aminophylline
• anisindione
• bcg
• bupropion
• cholera vaccine, live
• cyclosporine
• dicumarol
• divalproex sodium
• dyphylline
• entecavir
• estradiol
• ethinyl estradiol
• evening primrose
• fluphenazine
• ganciclovir
• ginkgo
• indium oxyquinoline in-111
• iohexol
• iopamidol
• lindane topical
• metrizamide
• mycophenolate mofetil
• mycophenolic acid
• oxtriphylline
• pemetrexed
• polyethylene glycol 3350 with electrolytes
• probenecid
• theophylline
• tramadol
• typhoid vaccine, live
• valganciclovir
• valproic acid
• warfarin

Pregnancy

Category C: Risk unknown. Human studies are inadequate.

Before using imipenem and cilastatin injection,

• tell your doctor and pharmacist if you are allergic to imipenem or cilastatin; other carbapenem antibiotics such as doripenem (Doribax), ertapenem (Invanz), or meropenem (Merrem); local anesthetics such as bupivacaine (Exparel, Marcaine, Sensorcaine), etidocaine (Duranest), lidocaine, mepivacaine (Carbocaine, Prolocaine), or prilocaine (Citanest); cephalosporins such as cefaclor (Ceclor), cefadroxil (Duricef), or cephalexin (Keflex); other beta-lactam antibiotics such as penicillin or amoxicillin (Amoxil, Trimox, Wymox); any other medications; or any of the ingredients in imipenem and cilastatin injection. Ask your pharmacist or check the manufacturer’s patient information for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: ganciclovir, probenecid (Probalan), or valproic acid (Depakene, Depakote). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever brain lesions, seizures, or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using imipenem and cilastatin injection, call your doctor.

References

Side Effects of Ertapenem

The Most Common 

• severe stomach pain, diarrhea that is watery or bloody;
• tremors, twitching, or rigid (very stiff) muscles
• a seizure (convulsions);
• unusual changes in your mood or behavior.
• Nausea – vomiting
• diarrhea
• constipation
• headache
• dizziness
• stomach pain
• fever
• cough
• confusion
• difficulty falling asleep or staying asleep
• redness or irritation at the injection site
• swelling, redness, burning, itching, or irritation of the vagina
• swelling of the hands, feet, ankles, or lower legs

Common

• pain, redness, or mild swelling where the injection was given.
• severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
• hives
• rash
• itching
• difficulty breathing or swallowing
• seizures
• unusual tiredness or weakness
• pale skin
• fast or irregular heartbeat
• shortness of breath
• chest pain

Drugs Interactions Of Ertapenem 

• amifampridine
• BCG
• bupropion
• cholera vaccine, live
• divalproex sodium
• entecavir
• estradiol
• ethinyl estradiol
• evening primrose
• fluphenazine
• ginkgo
• indium oxyquinoline in-111
• iohexol
• iopamidol
• lindane topical
• metrizamide
• mycophenolate mofetil
• mycophenolic acid
• pemetrexed
• polyethylene glycol 3350 with electrolytes
• probenecid
• tramadol
• typhoid vaccine, live
• valproic acid
• How should this medicine be used?

Pregnancy Category

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.

• AU TGA pregnancy category – B3
• US FDA pregnancy category – Not assigned.

Animal studies have revealed evidence of slightly decreased fetal weight and effects on vertebral ossification. While no maternal or embryofetal effects were observed in pregnant rats administered IV doses up to 700 mg/kg/day (about 1.2 times the maximum recommended human dose based on AUC) during organogenesis, slight decreases in average fetal weight and an associated decrease in the average number of ossified sacrocaudal vertebrae were observed in pregnant mice administered IV doses up to 700 mg/kg/day (about 3 times the MRHD based on body surface area comparison) during organogenesis. This drug crossed the placental barrier in rats. There are no controlled data in human pregnancy.

AU TGA pregnancy category B3

Drugs have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned

The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Dosage of Doripenem

• Strengths: 500 mg; 250 mg

 Intraabdominal Infection

• 500 mg via IV infusion every 8 hours
• Duration of therapy: 5 to 14 days

Pyelonephritis

• 500 mg via IV infusion every 8 hours
• Duration of therapy: 10 days

Urinary Tract Infection

• 500 mg via IV infusion every 8 hours
• Duration of therapy: 10 days

Doripenem injection comes as a liquid to be injected intravenously (into a vein). It is usually given every 8 hours. The length of your treatment depends on the type of infection being treated.

Side Effects of Doripenem

Most Common

• blisters on the skin, mouth, nose, and eyes
• sloughing (shedding) of skin
• fever
• difficulty breathing or swallowing
• seizures
• watery or bloody stools (up to 2 months after your treatment)
• Bluish color
• diarrhea
• pain, tenderness, or swelling of the foot or leg
• pale skin
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

Common

• Abdominal or stomach cramps, pain, or tenderness
• bloody urine
• diarrhea
• redness, pain, or swelling at the injection site
• decreased frequency or amount of urine
• fever
• increased blood pressure
• increased thirst
• itching or pain of the vagina or genital area
• loss of appetite
• lower back or side pain
• nausea or vomiting
• sore mouth or tongue
• swelling of the face, fingers, or lower legs
• thick, white vaginal discharge with mild or no odor
• troubled breathing
• watery and severe diarrhea, which may also be bloody
• weight gain
• white patches in the mouth or on the tongue

Rare

• Blistering, peeling, or loosening of the skin
• chills
• cough
• difficulty with swallowing or sore throat
• dizziness
• fast heartbeat
• itching
• joint or muscle pain
• loss of bladder control
• muscle spasm or jerking of extremities
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• skin rash or hives
• sores, ulcers, or white spots in the mouth or on the lips
• sudden loss of consciousness
• tightness in the chest

Drugs Interactions of Doripenem

• BCG
• cholera vaccine, live
• divalproex sodium
• entecavir
• estradiol
• ethinyl estradiol
• indium oxyquinoline in-111
• mycophenolate mofetil
• mycophenolic acid
• pemetrexed
• probenecid
• typhoid vaccine, live
• valproic acid

Pregnancy Category of Doripenem

FDA Pregnancy Category – B

No information is available on the clinical use of doripenem during breastfeeding. Its excretion into breastmilk is likely similar to that of imipenem and meropenem, which produce low levels of milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant’s gastrointestinal flora, resulting in diarrhea or thrush has been reported with beta-lactams, but these effects have not been adequately evaluated. Doripenem is acceptable in nursing mothers.

Before Taking This medication

Dosage adjustment is necessary in patients with moderate and severe renal impairment. Doripenem’s FDA label includes a warning against use in ventilator-associated bacterial pneumonia, as a clinical trial for that indication, resulted in increased mortality with doripenem (23% vs. 16.7% receiving imipenem) as well as lower clinical response rates. Seizures have been reported with doripenem treatment; patients at greater risk of developing seizures we found to have pre-existing central nervous system (CNS) conditions, compromised renal function, or patients receiving higher doses than 500 mg every 8 hours. Doripenem also reduces plasma levels of valproic acid when administered concomitantly; therefore patients with pre-existing seizure disorders on valproic acid are at even higher risk of breakthrough seizures if receiving both drugs at the same time. Doripenem is considered pregnancy category B as it was not found to be teratogenic or produce effects on ossification, developmental delays, or fetal weight in rat and rabbit studies. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. It is not known whether doripenem is excreted into breast milk, therefore caution should be exercised with doripenem administration to nursing women.

Before using doripenem injection

• tell your doctor and pharmacist if you are allergic to doripenem injection; other carbapenem antibiotics such as imipenem/cilastatin (Primaxin) or meropenem (Merrem); penicillins; cephalosporin antibiotics such as cefaclor, cefadroxil, cefuroxime (Ceftin, Zinacef), or cephalexin (Keflex); aztreonam (Azactam); or any other medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the following: probenecid (Probalan, in Col-Probenecid) and valproic acid (Depakene). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have any allergies and if you have or have ever had a stroke, seizures or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using doripenem injection, call your doctor.

References

Mechanism Of Action 

Biapenem is a 1-beta-methylcarbapenem antibiotic with a wide range of antibacterial activity. Biapenem has similar antibacterial activity to that of imipenem but is more stable against human renal dehydropeptidase-I and with less neurotoxicity.

Biapenem is a new parenteral carbapenem antibacterial agent with a broad spectrum of in vitro antibacterial activity encompassing many Gram-negative and Gram-positive aerobic and anaerobic bacteria, including species producing beta-lactamases. Biapenem is more stable than imipenem, meropenem, and panipenem to hydrolysis by human renal dihydro peptidase-I (DHP-I), and therefore does not require the coadministration of a DHP-I inhibitor. After intravenous administration, biapenem is widely distributed and penetrates well into various tissues (e.g. lung tissue) and body fluids (e.g. sputum, pleural effusion, abdominal cavity fluid). In randomized, nonblind, or double-blind clinical trials, biapenem showed good clinical and bacteriological efficacy (similar to that of imipenem/ cilastatin) in the treatment of adult patients with intra-abdominal infections, lower respiratory infections or complicated urinary tract infections. Biapenem is generally well tolerated. The most common adverse events in clinical trials were skin eruptions/rashes, nausea, and diarrhea.

Biapenem is a bacterial cell wall synthesis inhibitor with a broad spectrum of antibiotic activity in vitro. It is stable to hydrolysis by human renal dihydro peptidase I and showed good clinical and microbiological efficacy in the treatment of patients with intra-abdominal, lower respiratory tract, and complicated urinary tract infections. After intravenous administration, it is widely distributed, has linear pharmacokinetics, and is mainly eliminated in the urine with a half-life of approximately 1 h. Biapenem is well tolerated with the most common adverse side effects being skin eruptions/rashes, nausea, and diarrhea.

Indications of Biapenem

• Anti-Infective Agents
• Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.

Dosage of Biapenem

Due to their expanded spectra, the desire to avoid the generation of resistance, and the fact that, in general, they have poor oral bioavailability, they are administered intravenously in hospital settings for more serious infections.

• Information not available

References

Mechanism Of Action 

Information not available

Indications of Carbapenem

• Aspiration Pneumonia
• Bacteremia
• Bacterial Infection
• Bone infection
• Bronchitis
• Deep Neck Infection
• Endocarditis
• Endometritis
• Febrile Neutropenia
• Infection Prophylaxis
• Intraabdominal Infection
• Joint Infection
• Kidney Infections
• Lemierre’s Syndrome
• Meningitis
• Nosocomial Pneumonia
• Pelvic Infections
• Peritonitis
• Pneumonia
• Pneumonia with Cystic Fibrosis
• Septicemia
• Skin and Structure Infection
• Skin or Soft Tissue Infection
• Urinary Tract Infection

Intra-abdominal infections

The carbapenem ertapenem is one of several first-line agents recommended by the Infectious Disease Society of America for the empiric treatment of community-acquired intra-abdominal infections of mild-to-moderate severity. Agents with anti-pseudomonal activity, including doripenem, imipenem, and meropenem are not recommended in this population. Doripenem, imipenem, and meropenem are recommended for high-risk community-acquired abdominal infections and for abdominal infections that are hospital-acquired.^[rx]

Complicated urinary tract infections

A 2015 systematic review found little evidence that would support the identification of the best antimicrobial regimen for complicated urinary tract infections but identified three high-quality trials supporting high cure rates with doripenem, including in patients with levofloxacin-resistant E. coli infections.^[rx]

Pneumonia

The carbapenems imipenem and meropenem are recommended by the American Thoracic Society and the Infectious Disease Society of America as one of several first-line therapy options for people with late-onset hospital-acquired or ventilator-associated pneumonia, especially when Pseudomonas, Acinetobacter, or extended-spectrum beta-lactamase-producing Enterobacteriaceae are suspected pathogens. Combination therapy, typically with an aminoglycoside, is recommended for Pseudomonas infections to avoid resistance development during treatment.

Carbapenems are less commonly used in the treatment of community-acquired pneumonia, as community-acquired strains of the most common responsible pathogens (Streptococcus pneumoniae, Haemophilus influenza, atypical bacteria, and Enterobacteriaceae) are typically susceptible to narrower spectrum and/or orally administered agents such as fluoroquinolones, amoxicillin, or azithromycin. Imipenem and meropenem are useful in cases in which P. aeruginosa is a suspected pathogen.^[rx]

Bloodstream Infections

A 2015 meta-analysis concluded that the anti-pseudomonal penicillin-beta lactamase inhibitor combination piperacillin-tazobactam gives results equivalent to treatment with a carbapenem in patients with sepsis.^[rx] In 2015, the National Institute for Health and Care Excellence recommended piperacillin-tazobactam as first-line therapy for the treatment of bloodstream infections in neutropenic cancer patients.^[rx]

For bloodstream infections known to be due to extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenems are superior to alternative treatments.^[rx]

Spectrum of activity

Carbapenems exhibit broad-spectrum activity against gram-negative bacteria and somewhat narrower activity against gram-positive bacteria. For empiric therapy (treatment of infections prior to identification of the responsible pathogen) they are often combined with a second drug having broader spectrum gram-positive activity.

Contraindications of Carbapenem

Carbapenems are contraindicated in patients with prior allergic reactions to beta-lactam antibiotics. In addition, as the intramuscular formulations of ertapenem and imipenem are formulated with lidocaine, the intramuscular formulation of these two drugs are contraindicated in patients with prior adverse reactions to lidocaine.^[rx][rx] Furthermore, carbapenems are also contraindicated in patients who are taking valproic acid for seizures, as it has been shown to decrease valproic acid concentrations by as much as 90%.^[rx]

Dosage of Carbapenem

Due to their expanded spectra, the desire to avoid the generation of resistance, and the fact that, in general, they have poor oral bioavailability, they are administered intravenously in hospital settings for more serious infections. However, research is underway to develop an effective oral carbapenem.^[rx]

Side Effects Of Carbapenem

The Most Common

• headache
• diarrhea
• constipation
• nausea
• vomiting
• pain
• redness, pain, or swelling at the injection site
• tingling or pricking sensation
• difficulty falling asleep or staying asleep
• sores in the mouth or throat

Common

• seizures
• severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
• hives
• itching
• rash
• flushing
• swelling of the face, throat, tongue, lips, and eyes
• difficulty swallowing or breathing
• unusual tiredness or weakness
• pale skin
• fast or irregular heartbeat
• shortness of breath
• a return of fever or other signs of infection

Rare

• Agitation
• black, bloody, or tarry stools
• black, bloody vomit
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• burning sensation while urinating
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• cough
• dark urine
• decreased awareness or responsiveness
• decreased urine output
• depression
• diarrhea (watery and severe), which may also be bloody
• difficult or painful urination
• difficulty with breathing
• dilated neck veins
• extreme tiredness or weakness
• fever with or without chills
• headache
• hives or welts
• hostility
• irregular breathing
• irritability
• light-colored stools
• loss of consciousness

Drug Interactions of Carbapenem

• Information not available

References