Ceftriaxone & Sulbactam For Injection

Ceftriaxone & Sulbactam For Injection Uses, Dosage, Side Effects, Food Interaction and all others data.

Lidocaine is an amide type local anaesth. It stabilises the neuronal membrane and inhibits Na ion movements, which are necessary for conduction of impulses. In the heart, lidocaine reduces depolarisation of the ventricles during diastole and automaticity in the His-Purkinje system. Duration of action potential and effective refractory period are also reduced.

Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure . With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present . The net effect is normally a modest hypotension when the recommended dosages are not exceeded .

In particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction . Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse .

Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base . As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values . This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection . The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection .

Sulbactam is a β-lactamase inhibitor given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys antibiotic activity.

Ceftriaxone & Sulbactam For Injection
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Ceftriaxone & Sulbactam For Injection
Generic	Ceftriaxone Sodium + Sulbactam + Lidocaine
Weight	1000mg, 500mg, 1%
Type	Powder For Injection
Therapeutic Class
Manufacturer	Akums Drugs & Pharmaceuticals Ltd
Available Country	India, Nigeria
Last Updated:	September 19, 2023 at 7:00 am

Uses

Ceftriaxone is indicated for the treatment of the following major infections: Lower respiratory tract infections Acute Bacterial Otitis Media Skin and skin structure infections Urinary tract infections Gonorrhea Bacterial Septicemia Bone and joint infections Meningitis Prevention of postoperative infections Perioperative prophylaxis of infections associated with surgery

Lidocaine is a topical anesthetic used for the following purposes-

To help prevent pain associated with minor surgical procedures in the ear, nose and throat
To help prevent pain and or discomfort during dental procedures (e.g., prior to an injection)
During general anesthesia to prevent coughing
To help prevent pain during the final stages of childbirth, before the cutting or stitching of the perineum (skin between the vagina and anus)

Sulbactam is an beta-lactamase inhibitor antibiotic combined with other antibiotics to treat a variety of susceptible bacterial infections.

Sulbactam is currently available in combination products with ampicillin. Within this formulation it is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below. Skin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus, Escherichia coli, Klebsiella spp. (including K. pneumoniae), Proteus mirabilis, Bacteroides fragilis, Enterobacter spp., and Acinetobacter calcoaceticus. Intra-Abdominal Infections caused by beta-lactamase producing strains of Escherichia coli, Klebsiella spp. (including K. pneumoniae), Bacteroides spp. (including B. fragilis), and Enterobacter spp. Gynecological Infections caused by beta-lactamase producing strains of Escherichia coli, and Bacteroides spp. (including B. fragilis).

Ceftriaxone & Sulbactam For Injection is also used to associated treatment for these conditions: Acute Otitis Media, Anal Fissures, Anorectal discomfort, Arrhythmia, Back Pain Lower Back, Bacterial Vaginosis (BV), Burns, Cervical Syndrome, Earache, Hemorrhoids, Infection, Inflammatory Reaction caused by ear infection-not otherwise specified, Insect Bites, Joint Pain, Mixed Vaginal Infections, Multiple Myeloma (MM), Myringitis, Neuritis, Osteolysis caused by Bone Tumors, Osteoporosis, Otitis Externa, Pain caused by ear infection-not otherwise specified, Pain, Inflammatory, Post-Herpetic Neuralgia (PHN), Postherpetic Neuralgia, Primary Hyperparathyroidism, Rheumatic Diseases, Rheumatic Joint Disease, Sciatica, Skin Irritation, Soft Tissue Inflammation, Sore Throat, Sunburn, Susceptible infections, Trichomonas Vaginitis, Ulcers, Leg, Urethral Strictures, Vulvovaginal Candidiasis, Abrasions, Anal discomfort, Arrhythmia of ventricular origin, Cutaneous lesions, Gum pain, Minor burns, Superficial Wounds, Susceptible Bacterial Infections, Ulceration of the mouth, Viral infections of the external ear canal, Post Myocardial Infarction Treatment, Regional Anesthesia, Local anesthesia therapyAnimal bite, Bacterial Infections, Bacterial Infections caused by Beta lactamase producing bacteria, Bacterial Sinusitis, Bites, Human, Catheter Related Infections, Community Acquired Pneumonia (CAP), Gynaecological infection, Infective Endocarditis, Intra-Abdominal Infections, Nosocomial Pneumonia, Postoperative Infections, Postoperative Wound Infection, Skin and Subcutaneous Tissue Bacterial Infections, Complicated Bacterial Infections caused by Beta lactamase producing bacteria, Moderate Bacterial Infections, Severe Bacterial Infections

How Ceftriaxone & Sulbactam For Injection works

Lidocaine is a local anesthetic of the amide type . It is used to provide local anesthesia by nerve blockade at various sites in the body . It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action . In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes . At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions . The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization . As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential . This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place .

In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system . After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction .

Sulbactam is an irreversible inhibitor of β-lactamase; by binding and inhibiting β-lactamase produced by bacterial cells, sulbactam is thereby able to prevent it from reducing antibiotic activity. Although sulbactam alone possesses little useful antibacterial activity, except against the Neisseriaceae, whole organism studies have shown that sulbactam restores ampicillin activity against beta-lactamase producing strains. In particular, sulbactam has good inhibitory activity against the clinically important plasmid mediated beta-lactamases most frequently responsible for transferred drug resistance. The presence of sulbactam in formulations with ampicillin effectively extends the antibacterial spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibacterials. Thus, products with ampicillin + sulbactam possess the properties of a broad-spectrum antibacterial and a beta-lactamase inhibitor.

Dosage

Ceftriaxone & Sulbactam For Injection dosage

Adult: The usual dose is 1 to 2 gm by intravenous or intramuscular administration once a day (or in equally divided doses twice a day). Pneumonia, Bronchitis, Acute bacterial otitis media, Skin and skin structure infection, Urinary tract infections, Bacterial Septicemia, Bone and joint infections, Meningitis: 1 to 2 g IV or IM once a day (or in equally divided doses twice a day); Maximum dose: 4 gm/day Uncomplicated gonococcal infections: 250 mg IM as a single dose Surgical prophylaxis: 1 g IV as a single dose 30 to 120 minutes before surgery Infants and Children (01 month or older): The usual dose is 50 to 75 mg/kg intravenous or intramuscular administration once a day (or in equally divided doses twice a day). Pneumonia, Bronchitis, Skin and skin structure infection, Urinary tract infections, Bacterial Septicemia, Bone and joint infections: 50 to 75 mg/kg IV or IM once a day (or in equally divided doses twice a day); Maximum dose: 2 gm/day Acute bacterial otitis media: 50 mg/kg IM in single dose; Maximum dose: 1 gm/day Meningitis: 100 mg/kg IV or IM in single daily dose or (or in equally divided doses twice a day); Maximum dose: 4 gm/day Duration of therapy: Continue for more than 2 days after signs and symptoms of infection have disappeared. Usual duration is 4 to 14 days; in complicated infections, longer therapy may be required.

Intramuscular:Emergency treatment of ventricular arrhythmias: 300 mg injected into the deltoid muscle, repeat after 60-90 min if necessary.

Intraspinal:Spinal anaesthesia: As hyperbaric soln of 1.5% or 5% lidocaine in 7.5% glucose soln. Normal vaginal delivery: Up to 50 mg (as 5% soln) or 9-15 mg (as 1.5% soln). Caesarian operation: Up to 75 mg (as 5% soln). Other surgical procedures: 75-100 mg.Intravenous:Pulseless ventricular fibrillation or ventricular tachycardia : 1-1.5 mg/kg repeated as necessary. Max: 3 mg/kg. For ventricular arrhythmias in more stable patients: Usual loading dose: 50-100 mg as an IV inj at 25-50 mg/min, may repeat once or twice up to a max of 200-300 mg in 1 hr, followed by 1-4 mg/min via continuous IV infusion. May need to reduce dose if the infusion is longer than 24 hr.

Intravenous:Intravenous regional anaesthesia: As 0.5% soln w/o epinephrine: 50-300 mg. Max: 4 mg/kg.

Parenteral:Percutaneous infiltration anaesthesia: As 0.5% or 1% soln: 5-300 mg.Sympathetic nerve block: As 1% soln: 50 mg for cervical block or 50-100 mg for lumbar block.Peripheral nerve block:

As 1.5% soln: For brachial plexus block: 225-300 mg.
As 2% soln: For dental nerve block: 20-100 mg.
As 1% soln: For intercostal nerve block: 30 mg;
For paracervical block: 100 mg on each side, repeated not more frequently than every 90 min;
For paravertebral block: 30-50 mg;
For pudendal block: 100 mg on each side.
As 4% soln: For retrobulbar block: 120-200 mg.

Spray:

The maximum dose is 200 mg (Approximately 20 spray).
In dentistry, the normal dose is 1-5 sprays. Two sprays per quarter of the mouth is recommended, with a maximum of 3 sprays per quarter of the mouth over 30 minutes.
In sinus procedures 3 sprays are used.
In procedures of the throat and windpipe, up to 20 sprays may be necessary.
Up to 20 sprays may be necessary in childbirth (cesarian procedure).
Lower doses are used for children aged 3-12 years. Lidocaine 10% Spray is not recommended for children under 3 years.

Topical: Anaesthesia before e.g. venepuncture (not for infants), apply a thick layer under an occlusive dressing 1-5 hours before procedure; split skin grafting, apply a thick layer under an occlusive dressing 2-5 hours before procedure; genital warts (not for children), apply up to 10 gm 5-10 minutes before removal.

Preparation of Solutions for Intramuscular / Intravenous Injections: For Intramuscular Injection: 250 mg or 500 mg Ceftriaxone should be dissolved in 2 ml Lidocaine HCI 1% injection or 1 g Ceftriaxone in 3.5 ml of Lidocaine HCI 1% injection. For Intravenous Injection: 250 mg or 500 mg Ceftriaxone should be dissolved in 5 ml of Water for injection or 1 g Ceftriaxone in 10 ml of Water for injection USP or 2 g Ceftriaxone in 20 ml of Water for injection. The injection should be administered over 2-4 minutes, by Intramuscular or Intravenous injection or by tubing infusion over a period of 30 minutes at concentration between 10 mg/mL and 40 mg/mL. Before starting treatment through Ceftriaxone injection, patient tolerance test should be checked by administration of a test dose. (The use of freshly reconstituted solution is recommended. However, it maintains potency for at least 6 hours at room temperature or 24 hours at 5°C).

Side Effects

Ceftriaxone is generally well tolerated. A few side effects such as gastro-intestinal effects including diarrhea, nausea and vomiting, stomatitis and glossitis; cutaneous reactions including rash, pruritus, urticaria, edema and erythema multiforme; hematologic reactions including eosinophilia, thrombocytopenia, leucopenia, anemia and neutropenia; hepatic reactions including elevations of SGOT or SGPT, bilirubinemia; CNS reactions including nervousness, confusion, sleep disturbances, headache, hyperactivity, convulsion, hypertonia and dizziness were reported. Local phlebitis occurs rarely following intravenous administration but can be minimized by slow injections over 2-4 minutes.

Arrhythmia, bradycardia, arterial spasms, CV collapse, oedema, flushing, hert block, hypotension, sinus node suppression, agitation, anxiety, coma, confusion, drowsiness, hallucinations, euphoria, headache, hyperaesthesia, hypoaesthesia, lightheadedness, lethargy, nervousness, psychosis, seizure, slurred speech, unconsciousness, somnolence, nausea, vomiting, metallic taste, tinnitus, disorientation, dizziness, paraesthesia, resp depression and convulsions. Patch: Bruising, depigmentation, petechiae, irritation. Ophth: Conjunctival hyperaemia, corneal epithelial changes, diplopia,visual changes.

Toxicity

Symptoms of overdose and/or acute systemic toxicity involves central nervous system toxicity that presents with symptoms of increasing severity . Patients may present initially with circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis, and tinnitus . Visual disturbance and muscular tremors or muscle twitching are more serious and precede the onset of generalized convulsions . These signs must not be mistaken for neurotic behavior . Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes . Hypoxia and hypercapnia occur rapidly following convulsions due to increased muscular activity, together with the interference with normal respiration and loss of the airway . In severe cases, apnoea may occur. Acidosis increases the toxic effects of local anesthetics . Effects on the cardiovascular system may be seen in severe cases . Hypotension, bradycardia, arrhythmia and cardiac arrest may occur as a result of high systemic concentrations, with potentially fatal outcome .

Pregnancy Category B has been established for the use of lidocaine in pregnancy, although there are no formal, adequate, and well-controlled studies in pregnant women . General consideration should be given to this fact before administering lidocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place . Ultimately, although animal studies have revealed no evidence of harm to the fetus, lidocaine should not be administered during early pregnancy unless the benefits are considered to outweigh the risks . Lidocaine readily crosses the placental barrier after epidural or intravenous administration to the mother . The ratio of umbilical to maternal venous concentration is 0.5 to 0.6 . The fetus appears to be capable of metabolizing lidocaine at term . The elimination half-life in the newborn of the drug received in utero is about three hours, compared with 100 minutes in the adult . Elevated lidocaine levels may persist in the newborn for at least 48 hours after delivery . Fetal bradycardia or tachycardia, neonatal bradycardia, hypotonia or respiratory depression may occur .

Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity . The potential for toxicity depends upon the procedure performed, the type and amount of drug used, and the technique of drug administration . Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function .

Maternal hypotension has resulted from regional anesthesia . Local anesthetics produce vasodilation by blocking sympathetic nerves . Elevating the patient’s legs and positioning her on her left side will help prevent decreases in blood pressure . The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable .

Epidural, spinal, paracervical, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts . In one study, paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation . However, spinal and epidural anesthesia have also been reported to prolong the second stage of labor by removing the parturient’s reflex urge to bear down or by interfering with motor function . The use of obstetrical anesthesia may increase the need for forceps assistance .

The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life . The long-term significance of these observations is unknown . Fetal bradycardia may occur in 20 to 30 percent of patients receiving paracervical nerve block anesthesia with the amide-type local anesthetics and may be associated with fetal acidosis . Fetal heart rate should always be monitored during paracervical anesthesia . The physician should weigh the possible advantages against risks when considering a paracervical block in prematurity, toxemia of pregnancy, and fetal distress . Careful adherence to the recommended dosage is of the utmost importance in obstetrical paracervical block . Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection . Cases compatible with unintended fetal intracranial injection of local anesthetic solution have been reported following intended paracervical or pudendal block or both. Babies so affected present with unexplained neonatal depression at birth, which correlates with high local anesthetic serum levels, and often manifest seizures within six hours . Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication .

It is not known whether this drug is excreted in human milk . Because many drugs are excreted in human milk, caution should be exercised when lidocaine is administered to a nursing woman .

Dosages in children should be reduced, commensurate with age, body weight and physical condition .

The oral LD 50 of lidocaine HCl in non-fasted female rats is 459 (346-773) mg/kg (as the salt) and 214 (159-324) mg/kg (as the salt) in fasted female rats .

Precaution

As with other cephalosporins, anaphylactic shock cannot be ruled out even if a thorough patient history is taken. Anaphylactic shock requires immediate countermeasures such as intravenous epinephrine followed by a glucocorticoid. In rare cases, shadows suggesting sludge have been detected by sonograms of the gallbladder. This condition was reversible on discontinuation or completion of Ceftriaxone therapy. Even if such findings are associated with pain, conservative, nonsurgical management is recommended. During prolonged treatment the blood picture should be checked at regular intervals.

Patient with pseudocholinesterase deficiency, resp depression. Hepatic and renal impairment. Elderly or debilitated patients. Pregnancy and lactation.

Interaction

No drug interactions have been reported.

May increase serum levels with cimetidine and propranolol. Increased risk of cardiac depression with β-blockers and other antiarrhythmics. Additive cardiac effects with IV phenytoin. Hypokalaemia caused by acetazolamide, loop diuretics and thiazides may antagonise effect of lidocaine. Dose requirements may be increased with long-term use of phenytoin and other enzyme-inducers.

Volume of Distribution

The volume of distribution determined for lidocaine is 0.7 to 1.5 L/kg .

In particular, lidocaine is distributed throughout the total body water . Its rate of disappearance from the blood can be described by a two or possibly even three-compartment model . There is a rapid disappearance (alpha phase) which is believed to be related to uptake by rapidly equilibrating tissues (tissues with high vascular perfusion, for example) . The slower phase is related to distribution to slowly equilibrating tissues (beta phase) and to its metabolism and excretion (gamma phase) .

Lidocaine's distribution is ultimately throughout all body tissues . In general, the more highly perfused organs will show higher concentrations of the agent . The highest percentage of this drug will be found in skeletal muscle, mainly due to the mass of muscle rather than an affinity .

Penetration of both ampicillin and sulbactam into cerebrospinal fluid in the presence of inflamed meninges has been demonstrated after IV administration.

Elimination Route

In general, lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin . The agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream . And although lidocaine is also well absorbed across the gastrointestinal tract the oral bioavailability is only about 35% as a result of a high degree of first-pass metabolism . After injection into tissues, lidocaine is also rapidly absorbed and the absorption rate is affected by both vascularity and the presence of tissue and fat capable of binding lidocaine in the particular tissues .

The concentration of lidocaine in the blood is subsequently affected by a variety of aspects, including its rate of absorption from the site of injection, the rate of tissue distribution, and the rate of metabolism and excretion . Subsequently, the systemic absorption of lidocaine is determined by the site of injection, the dosage given, and its pharmacological profile . The maximum blood concentration occurs following intercostal nerve blockade followed in order of decreasing concentration, the lumbar epidural space, brachial plexus site, and subcutaneous tissue . The total dose injected regardless of the site is the primary determinant of the absorption rate and blood levels achieved . There is a linear relationship between the amount of lidocaine injected and the resultant peak anesthetic blood levels .

Nevertheless, it has been observed that lidocaine hydrochloride is completely absorbed following parenteral administration, its rate of absorption depending also on lipid solubility and the presence or absence of a vasoconstrictor agent . Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration .

Additionally, lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion .

Peak serum concentrations are reached almost immediately following a 15-minute intravenous infusion of sulbactam + ampicillin. Mean peak serum levels for sulbactam range from 48 to 88 mcg/mL following intravenous administration of 2000 mg of ampicillin plus 1000 mg sulbactam. After an intramuscular injection of 1000 mg ampicillin plus 500 mg sulbactam, peak sulbactam serum levels ranging from 6 to 24 mcg/mL are attained.

Half Life

The elimination half-life of lidocaine hydrochloride following an intravenous bolus injection is typically 1.5 to 2.0 hours . Because of the rapid rate at which lidocaine hydrochloride is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics . The half-life may be prolonged two-fold or more in patients with liver dysfunction .

~1 hr

Clearance

The mean systemic clearance observed for intravenously administered lidocaine in a study of 15 adults was approximately 0.64 +/- 0.18 L/min .

Elimination Route

The excretion of unchanged lidocaine and its metabolites occurs predominantly via the kidney with less than 5% in the unchanged form appearing in the urine . The renal clearance is inversely related to its protein binding affinity and the pH of the urine . This suggests by the latter that excretion of lidocaine occurs by non-ionic diffusion .

Approximately 75 to 85% of both ampicillin and sulbactam are excreted unchanged in the urine during the first 8 hours after administration.

Pregnancy & Breastfeeding use

Its safety in human pregnancy has not been established. Therefore, it should not be used in pregnancy unless absolutely indicated. Low concentrations of Ceftriaxone are excreted in human milk. Caution should be exercised when Ceftriaxone is administered to a lactating mother.

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).