SELVO BH ORAL SOLUTION (Each ml contains LEVOFLOXACIN HEMIHYDRATE USP+BROMOHEXINE HCL

Indications

• Bacterial infections
• Acute exacerbation of chronic obstructive pulmonary disease
• Community-acquired pneumonia
• Hospital-acquired pneumonia
• Urinary tract infections
• Complicated urinary tract infections
• Prostatitis
• Chronic pulmonary infections due to Pseudomonas aeruginosa
• Helicobacter pylori eradication (in combination with other drugs)

Dosage

Adults: 500 mg once daily for 5-14 days depending on the infection type and severity; for intravenous infusion, 500 mg to be given over at least 60 minutes.

Mechanism of action

Levofloxacin exerts its antimicrobial activity through the inhibition of two key bacterial enzymes: DNA gyrase and topoisomerase IV. DNA gyrase introduces negative supercoils into DNA during replication, while topoisomerase IV is essential for unlinking newly replicated chromosomes, allowing cell division. By inhibiting these enzymes, levofloxacin blocks DNA replication, resulting in cell death.

Pharmacodynamics

Levofloxacin is bactericidal and inhibits bacterial DNA replication. It has a longer duration of action than many other antibiotics, allowing for less frequent dosing. The drug may cause QTc-interval prolongation, necessitating caution in patients with risk factors for this condition. Levofloxacin shows in vitro activity against various bacterial pathogens, and while resistance can develop, it typically arises from mutations in target enzymes or drug efflux mechanisms.

Pharmacokinetics

Levofloxacin is well absorbed following oral administration, with peak plasma concentrations occurring within 1-2 hours. It has a volume of distribution of approximately 100 L and is approximately 30-40% protein bound. The drug is primarily excreted unchanged in the urine, with a half-life of about 6-8 hours, allowing for once or twice daily dosing.

Contra-indications

• Hypersensitivity to levofloxacin or other fluoroquinolones
• History of tendon disorders related to fluoroquinolone use
• Patients with a history of myasthenia gravis

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• QT interval prolongation
• Tendon rupture
• Clostridioides difficile-associated diarrhea
• Nephritis tubulointerstitial

Interactions

• Concurrent use with other drugs that prolong the QT interval
• Antacids, sucralfate, metal cations (e.g. magnesium, aluminum, calcium) can reduce absorption
• NSAIDs may increase the risk of CNS stimulation
• Warfarin may have increased anticoagulant effects

Precautions

• Use cautiously in patients with a history of seizures or CNS disorders
• Monitor for signs of tendon damage
• Consider risks in patients with electrolyte disturbances
• Use with caution in patients with renal impairment

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises caution; levofloxacin may be excreted in breast milk.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• 500 mg tablet for oral use
• Solution for intravenous infusion
• Nebuliser solution
• Eye drops

Indications

• Chronic bronchitis
• Asthma
• Bronchiectasis
• Pneumonia
• Respiratory tract infections with productive cough

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Additionally, bromhexine has been shown to inhibit the transmembrane serine protease 2 receptor (TMPRSS2), which plays a crucial role in viral respiratory diseases. This inhibition may help in preventing or treating various respiratory illnesses, including COVID-19, by blocking viral entry into cells.

Pharmacodynamics

Bromhexine thins airway secretions, thus improving breathing and alleviating discomfort associated with thick mucus in the airways. Its action is particularly beneficial in respiratory disorders where mucus obstruction is a significant issue.

Pharmacokinetics

Bromhexine is well absorbed after oral administration, with peak plasma concentrations typically reached within 1 to 2 hours. It is metabolized in the liver, primarily to ambroxol, which is its active metabolite. The elimination half-life of bromhexine is approximately 8 to 12 hours, and it is excreted mainly through urine. The pharmacokinetics can be influenced by factors such as liver function and concurrent medications.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Vomiting
• Diarrhea
• Allergic reactions

Precautions

• Use with caution in patients with peptic ulcer disease
• Monitor patients with asthma or bronchospastic conditions

Pregnancy

Bromhexine should be used during pregnancy only if clearly needed and after careful consideration of the potential benefits and risks.

Breast-feeding

Bromhexine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Syrup
• Solution for inhalation

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

The exact mechanism of action for Hemi is not explicitly detailed in the available resources, but compounds with similar structure may act by modulating neurotransmitter levels, inhibiting enzymes, or affecting cellular signaling pathways.

Pharmacodynamics

Hemi may exhibit pharmacodynamic properties that include modulation of neural activity or inhibition of specific biochemical pathways. Its effects could be dose-dependent and vary based on the therapeutic context.

Pharmacokinetics

The pharmacokinetic profile of Hemi, including absorption, distribution, metabolism, and excretion, is not well-documented in the provided resources. Generally, compounds in this class may undergo first-pass metabolism and have a variable half-life.

Dosage

Children: Refer to the specific formulation or active ingredient for dosing information.

Adults: Refer to the specific formulation or active ingredient for dosing information.

Mechanism of action

The mechanism of action of hemihydrate forms of drugs can vary widely depending on the specific compound. In many cases, the hemihydrate form enhances the solubility of the active ingredient, which facilitates its dissolution and absorption in the gastrointestinal tract.

Pharmacodynamics

Pharmacodynamics of hemihydrate compounds generally relates to the pharmacological effects that arise from the active drug once it is absorbed. The effects may vary based on the specific drug and its therapeutic target, but overall, the hemihydrate form aims to improve efficacy by ensuring adequate plasma concentrations are achieved more effectively than non-hydrated forms.

Pharmacokinetics

The pharmacokinetics of hemihydrate drugs typically demonstrate improved dissolution rates due to the presence of water, which can lead to increased absorption. This may result in quicker onset of action and modified half-lives. The specifics of absorption, distribution, metabolism, and excretion will depend on the active ingredient and its properties.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from moisture and heat. Keep container tightly closed.

Mechanism of action

Levofloxacin, like other fluoroquinolone antibiotics, exerts its antimicrobial activity via the inhibition of two key bacterial enzymes: DNA gyrase and topoisomerase IV. Both targets are type II topoisomerases, but have unique functions within the bacterial cell. DNA gyrase is an enzyme found only in bacteria that introduces negative supercoils into DNA during replication - this helps to relieve torsional strain caused by the introduction of positive supercoils during replication, and these negative supercoils are essential for chromosome condensation and the promotion of transcription initiation. It is comprised of four subunits (two A subunits and two B subunits) of which the A subunits appear to be the target of fluoroquinolone antibiotics. Bacterial topoisomerase IV, in addition to contributing to the relaxation of positive supercoils, is essential at the terminal stages of DNA replication and functions to “unlink” newly replicated chromosomes to allow for the completion of cell division. Inhibition of these enzymes by levofloxacin likely occurs via complexation with the topoisomerase enzymes. The end result is a blockade of DNA replication, thus inhibiting cell division and resulting in cell death. Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP).

Pharmacodynamics

Levofloxacin is bactericidal and exerts its antimicrobial effects via inhibition of bacterial DNA replication. It has a relatively long duration of action in comparison with other antibiotics that allows for once or twice daily dosing. Levofloxacin is associated with QTc-interval prolongation and should be used with caution in patients with other risk factors for prolongation (e.g. hypokalemia, concomitant medications). Levofloxacin has demonstrated _in vitro_ activity against a number of aerobic gram-positive and gram-negative bacteria and may carry some activity against certain species of anaerobic bacteria and other pathogens such as _Chlamydia_ and _Legionella_. Resistance to levofloxacin may develop, and is generally due to mutations in DNA gyrase or topoisomerase IV, or via alterations to drug efflux. Cross-resistance may occur between levofloxacin and other fluoroquinolones, but is unlikely to develop between levofloxacin and other antibiotic classes (e.g. macrolides) due to significant differences in chemical structure and mechanism of action. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

Mechanism of action

Inflammation of the airways, increased mucus secretion, and altered mucociliary clearance are the hallmarks of various diseases of the respiratory tract. Mucus clearance is necessary for lung health; bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Recent have studies have demonstrated that bromhexine inhibits the transmembrane serine protease 2 receptor (TMPRSS2) in humans. Activation of TMPRSS2 plays an important role in viral respiratory diseases such as influenza A and Middle East Respiratory Syndrome (MERS). Inhibition of receptor activation and viral entry by bromhexine may be effective in preventing or treating various respiratory illnesses, including COVID-19. In vitro studies have suggested the action of ambroxol (a metabolite of bromhexine) on the angiogensin-converting enzyme receptor 2 (ACE2), prevents entry of the viral envelope-anchored spike glycoprotein of SARS-Cov-2 into alveolar cells or increases the secretion of surfactant, preventing viral entry.

Pharmacodynamics

Bromhexine thins airway secretions, improving breathing and discomfort associated with thick mucus in airways associated with a variety of respiratory conditions.