Oseltamivir Phosphate

Usage

• Oseltamivir phosphate is prescribed for the treatment and prevention of influenza A and B infections. It is particularly effective when initiated within 48 hours of symptom onset for treatment and within 48 hours of exposure for prophylaxis. It can be used for prophylaxis in community outbreaks for up to six weeks.
• Pharmacological Classification: Antiviral, neuraminidase inhibitor.
• Mechanism of Action: Oseltamivir phosphate is a prodrug that is metabolized to oseltamivir carboxylate. Oseltamivir carboxylate inhibits the neuraminidase enzyme, which is essential for the release of newly formed influenza virus particles from infected cells. This action reduces viral replication and spread within the respiratory tract, alleviating symptoms and shortening the duration of illness.

Alternate Names

• International Nonproprietary Name (INN): Oseltamivir
• Brand Names: Tamiflu

How It Works

• Pharmacodynamics: Oseltamivir primarily affects the respiratory tract by inhibiting viral replication and release. It does not directly kill the virus, but hinders its ability to infect new cells.
• Pharmacokinetics: Oseltamivir phosphate is orally administered and well-absorbed. It’s rapidly converted by hepatic esterases to the active metabolite, oseltamivir carboxylate. Oseltamivir carboxylate has a bioavailability of approximately 80% when administered as oseltamivir phosphate. It is primarily eliminated renally as the active metabolite with a half-life of about 1-3 hours. No dose adjustment is needed for mild to moderate hepatic impairment, but it’s not recommended for severe liver disease.
• Mode of Action: Oseltamivir carboxylate selectively inhibits influenza neuraminidase, a viral surface glycoprotein. Neuraminidase is crucial for cleaving sialic acid residues on host cells, enabling the release of newly formed viral particles and facilitating viral spread. By inhibiting this enzyme, oseltamivir prevents viral egress and reduces the infection of new cells.
• Elimination Pathways: Primarily renal excretion as the active metabolite, oseltamivir carboxylate.

Dosage

Standard Dosage

Adults:

• Treatment: 75 mg orally twice daily for 5 days. Initiate within 48 hours of symptom onset.
• Prophylaxis: 75 mg orally once daily for at least 10 days. Initiate within 48 hours of exposure. In community outbreaks, administer for up to 6 weeks.

Children:

• Treatment (1 year and older): Dosage is weight-based, see detailed guidelines below. Initiate within 48 hours of symptom onset. Not recommended for treatment of children younger than 2 weeks of age unless prescribed for critical situations by doctor.
• Prophylaxis (1 year and older): Dosage is weight-based, see detailed guidelines below. Initiate within 48 hours of exposure. Not approved for prevention in children younger than 1 year.

Special Cases:

• Elderly Patients: Generally, no dose adjustments are needed unless renal impairment is present.
• Patients with Renal Impairment: Dose modifications are essential. See below for renal dose adjustments, for both treatment and prophylaxis.
• Patients with Hepatic Dysfunction: No dose adjustment is required for mild to moderate impairment. Not recommended for severe hepatic impairment.
• Patients with Comorbid Conditions: Consider individual patient factors like diabetes and cardiovascular disease for adjusting treatment duration.

Clinical Use Cases

Dosages for Clinical Use Cases are the same as treatment recommendations for adults and children and should be initiated within 48 hours. For severe illness, consult infectious disease specialist for personalized therapy:

• Intubation:
• Surgical Procedures:
• Mechanical Ventilation:
• Intensive Care Unit (ICU) Use: May require longer treatment duration (e.g., 10 days) and should be determined by clinical judgment. Infectious disease specialist should be consulted.
• Emergency Situations:

Dosage Adjustments

• Renal Impairment (Treatment):

  • CrCl > 60 mL/min: No adjustment required (75 mg BID)
  • CrCl 30-60 mL/min: 30 mg BID
  • CrCl 10-30 mL/min: 30 mg daily
  • ESRD (not on dialysis): Not recommended
  • ESRD (hemodialysis): 30 mg post-dialysis; not to exceed 5 days
  • ESRD (CAPD): Single 30 mg dose

• Renal Impairment (Prophylaxis):

  • CrCl > 60 mL/min: No adjustment required (75 mg daily)
  • CrCl 30-60 mL/min: 30 mg daily
  • CrCl 10-30 mL/min: 30 mg every other day
  • ESRD (not on dialysis): Not recommended
  • ESRD (hemodialysis): 30 mg post-dialysis; alternate days
  • ESRD (CAPD): 30 mg initially then once weekly

• Pediatric Dosage (Treatment):

  • <15 kg: 30 mg BID
  • 15-23 kg: 45 mg BID
  • 23-40 kg: 60 mg BID

  • 40 kg: 75 mg BID

• Pediatric Dosage (Prophylaxis):

  • <15 kg: 30 mg daily
  • 15-23 kg: 45 mg daily
  • 23-40 kg: 60 mg daily

  • 40 kg: 75 mg daily

Side Effects

Common Side Effects

• Nausea
• Vomiting
• Diarrhea
• Headache

Rare but Serious Side Effects

• Severe allergic reactions (anaphylaxis, angioedema)
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Neuropsychiatric events (hallucinations, delirium, abnormal behavior), especially in children

Long-Term Effects

• No specific long-term effects have been identified.

Adverse Drug Reactions (ADR)

• Anaphylaxis
• Stevens-Johnson Syndrome
• Toxic Epidermal Necrolysis

Contraindications

• Hypersensitivity to oseltamivir or any component of the formulation.
• Hereditary fructose intolerance (for the oral suspension containing sorbitol).

Drug Interactions

• Probenecid: Reduces clearance of oseltamivir carboxylate.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA)
• Fetal Risks: Limited data suggest low risk; however, the benefits of treatment may outweigh risks in pregnant women with influenza. Consider the maternal and fetal risk due to the mother’s underlying condition, available safety data, and pathogenicity of the circulating influenza virus strain.
• Breastfeeding: Oseltamivir and its metabolite are excreted in breast milk at low concentrations. Consider breastfeeding before taking dose to minimize infant exposure. Monitor infant for potential adverse effects.

Drug Profile Summary

• Mechanism of Action: Neuraminidase inhibitor, preventing viral release.
• Side Effects: Nausea, vomiting, diarrhea, headache; rarely, severe allergic reactions, skin reactions, neuropsychiatric events.
• Contraindications: Hypersensitivity, hereditary fructose intolerance (oral suspension).
• Drug Interactions: Probenecid.
• Pregnancy & Breastfeeding: Category C; low levels excreted in breast milk.
• Dosage: Adults: 75 mg BID for treatment, 75 mg daily for prophylaxis. Pediatric and renal adjustments needed.
• Monitoring Parameters: Monitor for adverse reactions, particularly skin reactions and neuropsychiatric events. Renal function tests may be needed in patients with renal impairment.

Popular Combinations

Not generally used in combination with other antiviral drugs for influenza. Treatment with another antiviral may be given in severe/complicated influenza cases (with infectious disease expert consultation).

Precautions

• General Precautions: Assess for hypersensitivity and renal function prior to administration.
• Specific Populations: Close monitoring recommended for children for neuropsychiatric events. Pregnant and breastfeeding women: weigh benefits against risks.
• Lifestyle Considerations: No specific restrictions on alcohol, smoking, or diet.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Oseltamivir Phosphate?

A: Adults: 75 mg BID (twice daily) for treatment, 75 mg once daily for prophylaxis. Pediatric dosages are weight-based, see detailed guidelines above.

Q2: When should Oseltamivir be initiated for optimal efficacy?

A: Within 48 hours of symptom onset for treatment and within 48 hours of exposure for prophylaxis.

Q3: What are the common side effects?

A: Nausea, vomiting, diarrhea, and headache.

Q4: Are there any serious side effects I should be aware of?

A: Yes, although rare, severe allergic reactions, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), and neuropsychiatric events, especially in children, can occur.

Q5: Can Oseltamivir be used in patients with renal impairment?

A: Yes, but dosage adjustments are essential. Consult dosing guidelines based on creatinine clearance levels.

Q6: Is Oseltamivir safe during pregnancy and breastfeeding?

A: Oseltamivir is classified as Pregnancy Category C. Limited data suggest low risk. In breastfeeding, the drug is excreted in breast milk at low levels. Use cautiously and weigh benefits against risks, consulting with an infectious disease specialist if necessary.

Q7: What is the mechanism of action of Oseltamivir?

A: It inhibits the neuraminidase enzyme, preventing the release of new viral particles from infected cells.

Q8: How long does the protection from Oseltamivir last for prophylaxis?

A: Protection lasts as long as the medication is taken.

Q9: Can Oseltamivir treat other viral infections besides influenza?

A: No, it is only effective against influenza A and B viruses.

Q10: How should the oral suspension be stored?

A: Refrigerate the reconstituted oral suspension for up to 17 days. Unopened powder for oral suspension can be stored at room temperature. Consult the package insert for exact instructions.