OSELTAMIVIR-PHOSPAHTE~75 75MG CAPSULES

Indications

• Prevention of influenza
• Treatment of influenza

Dosage

Children: Child 1–11 months: 3 mg/kg once daily for 10 days for post-exposure prophylaxis; Child 1–12 years (body-weight up to 15 kg): 30 mg once daily for 10 days

Adults: 75 mg once daily for 10 days for post-exposure prophylaxis; for up to 6 weeks (or up to 12 weeks if immunocompromised) during an epidemic.

Mechanism of action

Oseltamivir phosphate is a pro-drug converted to its active form, oseltamivir carboxylate, which selectively inhibits the neuraminidase enzymes of influenza viruses. This inhibition prevents the release of new viral particles from infected cells and reduces viral shedding, thereby decreasing infectivity and limiting the spread of the virus. The drug is effective against both influenza A (including pandemic H1N1) and influenza B.

Pharmacodynamics

Postmarketing reports suggest that oseltamivir may be associated with neuropsychiatric events such as delirium and abnormal behavior, particularly in pediatric patients. These events can lead to self-injury or other serious outcomes. While the exact contribution of oseltamivir to these events is unclear, influenza itself can cause neurologic symptoms, and such incidents have been noted to occur rapidly but resolve quickly.

Pharmacokinetics

Following oral administration, oseltamivir is rapidly absorbed and converted to its active form, oseltamivir carboxylate, primarily in the liver. Peak plasma concentrations of the active metabolite are achieved within 2-3 hours. Oseltamivir has a half-life of approximately 6-10 hours, allowing for once or twice-daily dosing depending on the indication. The drug is eliminated through renal pathways, necessitating dose adjustments in patients with renal impairment.

Adverse effects

• Dizziness
• Gastrointestinal discomfort
• Nausea
• Sleep disorders
• Vertigo
• Vomiting
• Arrhythmia
• Impaired consciousness
• Seizure
• Skin reactions
• Angioedema
• Anxiety
• Abnormal behavior
• Confusion
• Delirium
• Delusions
• Hemorrhage
• Hallucination
• Hepatic disorders
• Self-injurious behavior
• Severe cutaneous adverse reactions (SCARs)
• Thrombocytopenia
• Visual impairment

Interactions

• Leflunomide: Unknown (increases exposure)
• Nitisinone: Unknown (increases exposure)
• Teriflunomide: Unknown (increases exposure)

Precautions

• Monitor for neuropsychiatric events, especially in pediatric patients
• Use with caution in patients with renal impairment
• Evaluate potential risks versus benefits in pregnant or breastfeeding women

Pregnancy

Although safety data are limited, oseltamivir can be used in pregnant women when the potential benefit outweighs the risk, especially during a pandemic.

Breast-feeding

Although safety data are limited, oseltamivir is the preferred drug for breastfeeding women when the potential benefit outweighs the risk, especially during an epidemic.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Capsules
• Oral suspension

Indications

• Hypophosphatemia
• Osteoporosis
• Rickets
• Renal osteodystrophy

Dosage

Children: Refer to specific clinical guidelines or pharmacological references for appropriate dosing.

Adults: Refer to specific clinical guidelines or pharmacological references for appropriate dosing.

Mechanism of action

Phosphate acts primarily by facilitating various biochemical reactions involving energy transfer and storage. It contributes to the formation of adenosine triphosphate (ATP), which is the primary energy currency of the cell. Phosphate ions influence enzymatic activities and are involved in signal transduction pathways, regulating cellular processes such as metabolism and cell growth.

Pharmacodynamics

Phosphate is essential for numerous physiological functions, including energy metabolism, bone formation, and acid-base balance. The concentration of phosphate in the blood is tightly regulated by hormones such as parathyroid hormone (PTH) and calcitriol, which influence its absorption in the intestines and excretion by the kidneys. An imbalance in phosphate levels can lead to conditions like hypophosphatemia or hyperphosphatemia, affecting muscle function, bone health, and overall metabolic processes.

Pharmacokinetics

Phosphate is absorbed primarily in the gastrointestinal tract, with the efficiency of absorption varying depending on dietary factors and the presence of other substances. Once absorbed, phosphate is distributed throughout the body, with significant amounts stored in bones and teeth. The kidneys play a crucial role in regulating phosphate levels through filtration and reabsorption processes. Phosphate homeostasis is influenced by dietary intake, renal function, and hormonal regulation.

Adverse effects

• Hyperphosphatemia
• Diarrhea
• Nausea
• Abdominal pain
• Bone pain

Precautions

• Use with caution in patients with renal impairment
• Monitor serum phosphate levels during therapy
• May interact with other minerals such as calcium

Pregnancy

Phosphate is generally considered safe during pregnancy when used as directed, but excessive phosphate levels should be avoided.

Breast-feeding

Phosphate is excreted in breast milk; however, it is typically considered safe during breastfeeding.

Storage

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

Formulations

• Oral tablets
• Oral solutions
• Intravenous injections

Mechanism of action

Oseltamivir phosphate is a pro-drug of the active metabolite (oseltamivir carboxylate) which is a potent and selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface. Viral neuraminidase enzyme activity is important for viral entry into uninfected cells, for the release of recently formed virus particles from infected cells, and for the further spread of the infectious virus in the body. Oseltamivir activity reduces viral shedding and infectivity. Oseltamivir is effective agaisnt viral neuraminidases of influenza A (including pandemic H1N1) and influenza B. Oseltamivir is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. The proposed mechanism of action of oseltamivir is inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release.

Pharmacodynamics

There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir to these events has not been established. Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.