Cinoxacin

Cinoxacin is an antibacterial agent belonging to the pharmacological class of Cinnolines derivative.

Cinoxacin has been approved to relieve symptoms and also for the treatment and maintenance of initial and recurrent urinary tract infections in adults. These infections should be caused by specific microorganisms that are susceptible to the medication. The susceptible microorganisms include Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.

Cinoxacin is readily absorbed following oral administration, with rapid absorption observed. While the presence of food during intake may result in a delay in the absorption process, it does not significantly impact the overall extent of drug absorption. The drug exhibits a moderate to high protein binding capacity, with approximately 60 to 80% of the drug binding to proteins in the bloodstream. Hepatic metabolism plays a role in the biotransformation of cinoxacin, with approximately 30-40% of the drug being metabolized into inactive metabolites.

The common side effects involved in using Cinoxacin are Nausea, Headache, Dizziness, Rash, Itching, Hives, Abdominal pain, Insomnia, Drowsiness, Tingling sensation, Sensitivity of eyes to light

Cinoxacin is available in the form of Tablets.

Cinoxacin is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Cinoxacin belongs to the pharmacological class of Cinnolines derivative.

Cinoxacin exhibits strong, yet reversible, binding to DNA, which interferes with the synthesis of RNA and subsequently affects protein synthesis. Additionally, it appears to possess inhibitory effects on DNA gyrase, an enzyme crucial for the accurate separation of replicated DNA. Through the inhibition of this enzyme, cinoxacin hinders DNA replication and the division of cells.

Cinoxacin has been approved to relieve symptoms and also for the treatment and maintenance of initial and recurrent urinary tract infections in adults. These infections should be caused by specific microorganisms that are susceptible to the medication. The susceptible microorganisms include Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.

Cinoxacin is found to be available in the form of Tablets.

Cinoxacin can be used in the following treatment:

• Initial and recurrent urinary tract infections in adults. These infections should be caused by specific microorganisms that are susceptible to the medication. The susceptible microorganisms include Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.

Cinoxacin can help to relieve symptoms and also for the treatment and maintenance of initial and recurrent urinary tract infections in adults. These infections should be caused by specific microorganisms that are susceptible to the medication. The susceptible microorganisms include Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.

Cinoxacin is approved for use in the following clinical indications:

• Initial and recurrent urinary tract infections in adults. These infections should be caused by specific microorganisms that are susceptible to the medication. The susceptible microorganisms include Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.

Cinoxacin is indicated for the treatment of both initial and recurrent urinary tract infections in adults. These infections should be caused by specific microorganisms that are susceptible to the medication. The susceptible microorganisms include Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species. Cinoxacin is specifically effective against these strains of bacteria when treating urinary tract infections in adults.

For the treatment of urinary tract infections in adults, the recommended dosage of cinoxacin is 1 g per day. This can be administered orally in either two divided doses of 500 mg each (b.i.d.) or four divided doses of 250 mg each (q.i.d.). The duration of treatment typically ranges from 7 to 14 days. It is important to note that doses should be taken at least 2 hours before or after consuming certain substances such as antacids containing magnesium or aluminum, sucralfate, metal cations like iron, and multivitamin preparations containing zinc. This also includes Videx (didanosine) chewable tablets or the pediatric powder for oral solution.

Cinoxacin Tablets (oral): 250 mg , 500 mg.

• Dosage Adjustments in Kidney Patients:

For patients with normal renal function (creatinine clearance >80 mL/min/1.73 m²), the recommended dosage is 500 mg twice daily (b.i.d.). In cases of mild impairment (creatinine clearance 80-50 mL/min/1.73 m²), the dosage should be reduced to 250 mg three times daily (t.i.d.). Patients with moderate impairment (creatinine clearance 50-20 mL/min/1.73 m²) should take 250 mg twice daily (b.i.d.). For patients with marked impairment (creatinine clearance <20 mL/min/1.73 m²), a dosage of 250 mg once daily (q.d.) is recommended. It is important to follow these dosage guidelines to ensure the medication is appropriately adjusted for individuals with renal impairment.

• Dosage Adjustments in Hepatic Impairment Patients:

No dosage adjustments are necessary.

• Dosage Adjustments in Pediatric Patients:

No relevant data had been found.

Tablets.

While there are no specific dietary restrictions associated with the use of Cinoxacin.

Cinoxacin may be contraindicated under the following conditions:

• Cinoxacin is contraindicated in patients who have demonstrated hypersensitivity to the drug.

• If a person has had previous hypersensitivity reactions to cinoxacin, it is advised to discontinue the medication if an allergic reaction occurs. Serious acute hypersensitivity reactions may require various resuscitative measures, including epinephrine, oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management as deemed necessary by your healthcare professional.
• There have been rare reports of convulsions and abnormal electroencephalograms in a few patients taking  class antimicrobials. However, no definitive causal relationship has been established. Convulsions increased intracranial pressure, and toxic psychoses have also been reported with other drugs in this class.
• Quinolones may cause central nervous system (CNS) stimulation, leading to symptoms such as tremors, restlessness, light-headedness, confusion, or hallucinations. If you experience any of these reactions while taking cinoxacin, discontinue the medication and seek appropriate medical attention. It's important to note that cinoxacin, like all quinolones, should be used cautiously in patients with known or suspected CNS disorders, including severe cerebral arteriosclerosis, epilepsy, and other conditions that may increase the risk of seizures .
• Achilles tendon ruptures, and other tendon injuries requiring surgical repair or resulting in prolonged disability have been reported with the use of quinolones. If you experience pain, inflammation, or tendon rupture while taking cinoxacin, discontinue the medication and seek medical attention promptly.

It is generally recommended to avoid consuming alcohol while taking Cinoxacin. Alcohol can interact with Cinoxacin and increase the risk of certain side effects. Here are some alcohol-related warnings associated with the use of Cinoxacin:

Increased risk of liver damage: Both Cinoxacin and alcohol can individually affect liver function. When used together, they can increase the risk of liver damage or impair liver function. This can lead to symptoms such as abdominal pain, yellowing of the skin or eyes (jaundice), dark urine, and fatigue. It is important to avoid alcohol consumption to protect your liver while taking Cinoxacin.

Enhanced drowsiness and dizziness: Cinoxacin and alcohol can both cause drowsiness and dizziness. When used together, these effects can be intensified, impairing your coordination and judgment. It is crucial to avoid alcohol to prevent an increased risk of accidents or injuries.

Worsening gastrointestinal side effects: Both Cinoxacin and alcohol can cause gastrointestinal side effects such as nausea, vomiting, and stomach upset. Consuming alcohol can exacerbate these symptoms and make them more severe. It is advisable to avoid alcohol to minimize gastrointestinal discomfort while taking Cinoxacin.

The excretion of cinoxacin in human milk is not well understood. Since other drugs within the same class are excreted in human milk and due to the potential for serious adverse reactions in nursing infants, a decision must be made whether to discontinue breastfeeding or discontinue the use of cinoxacin. This decision should consider the significance of the drug to the mother's treatment.

Pregnancy:

Teratogenic Effects - Category C

Reproduction studies conducted on rats and rabbits, using doses up to 10 times the daily human dose, have not shown any signs of impaired fertility or fetal harm caused by cinoxacin. Nevertheless, there is a lack of sufficient and well-controlled studies in pregnant women. Therefore, cinoxacin should only be used during pregnancy if the potential benefits outweigh the potential risks to the fetus.

There are no specific food warnings related to the use of cinoxacin. However, it is generally recommended to take cinoxacin on an empty stomach, as food may interfere with its absorption. Therefore, it is advisable to take cinoxacin at least 1 hour before or 2 hours after meals.

The adverse reactions related to Cinoxacin can be categorized as follows:

Common:

• Nausea
• Headache
• Dizziness
• Abdominal pain
• Diarrhea
• Vomiting
• Rash
• Itching

Less common:

• Insomnia
• Photophobia (sensitivity to light)
• Tingling sensation
• Tinnitus (ringing in the ears)
• Epigastric distress
• Fatigue
• Dry mouth
• Joint or muscle pain

Rare:

• Hives
• Severe allergic reactions
• Confusion or hallucinations
• Mood changes
• Difficulty breathing
• Swelling of the face, lips, or tongue (angioedema)
• Jaundice (yellowing of the skin or eyes)
• Unusual bleeding or bruising
• Signs of a serious skin reaction (e.g., blistering, peeling, severe rash)
• Seizures (in rare cases)

Interaction with Theophylline:

• Some quinolones have been reported to elevate plasma levels of theophylline when used concomitantly.
• Patients receiving theophylline-quinolone therapy may experience theophylline-related side effects.
• Consider monitoring theophylline plasma levels and adjusting theophylline dosage accordingly.

• Interaction with Caffeine:
• Quinolones have been shown to interfere with caffeine metabolism, potentially leading to reduced caffeine clearance and prolonged plasma half-life.
• Although this interaction has not been reported with cinoxacin, caution is advised when administering cinoxacin with caffeine-containing products.
• Interaction with Antacids, Sucralfate, Iron, Multivitamins, or Videx:
• Antacids or sucralfate can significantly hinder the absorption of certain quinolones, resulting in low urine levels.
• Concurrent use of quinolones with products containing iron, zinc-containing multivitamins, or Videx (didanosine) chewable/buffered tablets may also lead to low urine levels.

• Interaction with Oral Anticoagulants:
• Quinolones, including cinoxacin, may potentiate the effects of oral anticoagulants like warfarin or its derivatives.
• Close monitoring of prothrombin time or other appropriate coagulation tests is recommended when these products are administered together.

• Potential Seizure Risk:
• Seizures have been reported in patients taking another class of quinolone antimicrobial along with the nonsteroidal anti-inflammatory drug fenbufen.
• Animal studies suggest an increased potential for seizures when these two drugs are used concurrently.

• Interaction with Cyclosporine:
• Concomitant use of quinolones and cyclosporine has been reported to elevate cyclosporine serum levels.

The following are the side effects involving Cinoxacin:

• Nausea
• Headache
• Dizziness
• Rash
• Itching
• Hives
• Abdominal pain
• Insomnia
• Drowsiness
• Tingling sensation
• Sensitivity of eyes to light
• Burning sensation in the groin area
• Ringing in the ears

Pregnancy:

Teratogenic Effects - Category C

Reproduction studies conducted on rats and rabbits, using doses up to 10 times the daily human dose, have not shown any signs of impaired fertility or fetal harm caused by cinoxacin. Nevertheless, there is a lack of sufficient and well-controlled studies in pregnant women. Therefore, cinoxacin should only be used during pregnancy if the potential benefits outweigh the potential risks to the fetus.

Lactation:

The excretion of cinoxacin in human milk is not well understood. Since other drugs within the same class are excreted in human milk and due to the potential for serious adverse reactions in nursing infants, a decision must be made whether to discontinue breastfeeding or discontinue the use of cinoxacin. This decision should consider the significance of the drug to the mother's treatment.

Pediatric:

The safety and efficacy of cinoxacin have not been established in pediatric patients and adolescents under 18 years of age. Studies conducted on juvenile animals have shown that cinoxacin can cause arthropathy.

Geriatric Use:

Pharmacokinetics in Geriatric Patients:

● Following a single 500 mg dose of cinoxacin, geriatric patients exhibited peak serum concentrations similar to those observed in all adult patients.

● Among twenty patients aged 70-89, repeated administration of cinoxacin did not result in drug accumulation (refer to Geriatric section in Clinical Pharmacology).

● Based on age alone, no dosage adjustment is necessary. However, in geriatric patients with impaired renal function, dosage reduction is recommended (refer to Impaired Renal Function in Dosage and Administration).

Limited Data in Elderly Patients:

● Clinical studies of cinoxacin did not include a sufficient number of subjects aged 65 and over to establish whether they respond differently compared to younger subjects.

● Available clinical experience does not indicate differences in response between elderly and younger patients.

● When prescribing for an elderly patient, exercise caution in dose selection, typically starting at the lower end of the dosage range. This approach takes into consideration the higher likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of overdosage of Cinoxacin.

Signs and Symptoms:

• An overdose of cinoxacin may lead to various symptoms, including anorexia, nausea, vomiting, epigastric distress, and diarrhea.
• The severity of epigastric distress and diarrhea is directly related to the dose.
• Some patients have reported experiencing headaches, dizziness, insomnia, photophobia, tinnitus, and a tingling sensation.
• Other symptoms, if present, are likely associated with an underlying medical condition, an allergic reaction, or the ingestion of another potentially toxic medication.

Treatment:

• If an overdose is suspected, it is advisable to contact your regional Poison Control Center for the most up-to-date information on overdose treatment. This is because the recommended approaches for managing overdosage can change more rapidly than package inserts.
• When dealing with an overdose, consider the possibility of multiple drug overdoses, drug interactions, and unusual drug kinetics in the patient.
• Patients who have ingested an excessive amount of cinoxacin should be adequately hydrated to prevent crystalluria.
• Ensure the patient's airway is protected and provide ventilation and proper perfusion. Monitor and maintain the patient's vital signs, blood gases, serum electrolytes, and other parameters within acceptable ranges.
• Administration of activated charcoal may reduce drug absorption from the gastrointestinal tract and is often more effective than inducing vomiting or performing gastric lavage. Charcoal can be considered as an alternative to or in conjunction with gastric emptying. Multiple doses of charcoal may enhance the elimination of certain absorbed drugs over time. Airway protection is crucial when using gastric emptying or charcoal.
• Forced diuresis, peritoneal dialysis, hemodialysis, and charcoal hemoperfusion have not been proven to be beneficial in cases of cinoxacin overdose.

Pharmacodynamics

Cinoxacin is a synthetic antibacterial compound that exhibits in vitro effectiveness against numerous gram-negative aerobic bacteria, specifically targeting strains from the Enterobacteriaceae family. It exerts its bactericidal action by inhibiting the synthesis of bacterial deoxyribonucleic acid (DNA). Cinoxacin's activity remains potent across the complete range of urinary pH. Notably, there is cross-resistance between cinoxacin and nalidixic acid, as demonstrated in studies.

Pharmacokinetics

Absorption and Serum Concentrations

● Cinoxacin is rapidly absorbed following oral administration.

● A 500-mg dose of cinoxacin produced a peak serum concentration of 15 μg/mL in a fluorometric assay.

● After 6 hours, the serum concentration declined to approximately 1 to 2 μg/mL.

Urine Concentrations and Bacterial Activity

● A 500 mg dose of cinoxacin resulted in an average urine concentration of approximately 300 μg/mL during the first 4 hours.

● During the second 4-hour period, the urine concentration was approximately 100 μg/mL.

● These urine concentrations of cinoxacin exceeded the minimal inhibitory concentration (MIC) required to combat most gram-negative organisms commonly found in urinary tract infections.

Urinary Excretion and Metabolism

● Within 24 hours, 97% of a 500-mg oral dose of radiolabeled cinoxacin was recovered in the urine.

● Of the total amount excreted, 60% was in the form of unchanged cinoxacin, while the remainder consisted of inactive metabolic products.

Effect of Food and Serum Half-life

● The presence of food did not affect the overall absorption of cinoxacin.

● However, peak serum concentrations were reduced by 30% when taken with food.

● Despite the reduction in peak serum concentrations, the 24-hour urinary recovery of antibacterial activity remained unchanged.

● The average serum half-life of cinoxacin is 1.5 hours.

1. https://go.drugbank.com/drugs/DB00827
2. https://www.rxlist.com/cinobac-drug.htm
3. https://www.drugs.com/cons/cinoxacin.html
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