Generic lamivudine tentatively approved
The FDA announced on Nov. 4, 2005, the tentative approval of Lamivudine Oral Solution, 10 mg/mL manufactured by Aurobindo Pharma LTD. of Hyderabad, India. Lamivudine Oral Solution is the first generic version of the already approved Epivir Oral Solution, 10 mg/mL, manufactured by GlaxoSmithKline. This child-friendly-product is indicated for use in pediatric patients with HIV from three months to 16 years.
Lamivudine is in the class of drugs called nucleoside reverse transcriptase inhibitors (NRTIs), which help keep the AIDS virus from reproducing. This antiretroviral drug is intended to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
FDA’s tentative approval of this product means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meet all of FDA’s safety, efficacy, and manufacturing quality standards required for marketing in the U.S., and it will now be available for consideration for purchase under the President’s Emergency Plan for AIDS Relief (PEPFAR).
FDA approves new Kaletra formulation
On Oct. 28, 2005, the Food and Drug Administration approved a new formulation of lopinavir/ritonavir (Kaletra). Lopinavir/ritonavir is now available as a film coated tablet (200mg/50mg) that provides advantages over the currently marketed capsule formulation for HIV-1 infected patients. Specifically, the tablet formulation:
- does not require refrigeration;
- can be administered without regard to meals;
- does not require dose adjustments for concomitant use with certain NNRTIs and PIs in treatment-naïve patients;
- has a decreased pill burden compared to the capsule formulation (2 tablets twice daily or 4 tablets once daily in treatment-naïve patients only vs 3 capsules twice daily or 6 capsules once daily in treatment-naïve patients only);
- The following additions and revisions were made to the package insert.
1. The clinical pharmacology section contains the following additions:
Pharmacokinetics
Plasma concentrations of lopinavir and ritonavir after administration of two 200/50 mg lopinavir/ritonavir tablets are similar to three 133.3/33.3 mg lopinavir/ritonavir capsules under fed conditions with less pharmacokinetic variability.
The capsule formulation will be phased out over time by the company. Kaletra is a product of Abbott Laboratories. The original formulation was approved on September 15, 2000.
Ritonavir and lopinavir/ritonavir package inserts are updated
The ritonavir (Norvir) and lopinavir/ritonavir (Kaletra) package inserts (product labeling) were recently updated to include information regarding interactions with fluticasone (a synthetic corticosteroid, the active component of Flonase nasal Spray) and trazodone (Desyrel, a non-tricyclic antidepressant). In addition, alfuzosin (an alpha-blocker used to increase the flow of urine in people with benign prostatic hypertrophy (BPH)) was added to the Contraindications section of the ritonavir package insert.
Listed below are labeling revisions for the ritonavir and lopinavir/ritonavir package inserts.
Summary of Label Changes
Ritonavir
Clinical Pharmacology:
Results of the drug interaction studies with ritonavir and fluticasone propionate aqueous nasal spray and trazodone were included:
Ritonavir increased fluticasone AUC and Cmax by approximately 350-fold and 25-fold respectively. This significant increase in plasma fluticasone propionate exposure resulted in a significant decrease (86%) in plasma cortisol AUC.
Ritonavir increased trazodone AUC and Cmax by 2.4 fold and 34%, respectively.
CONTRAINDICATIONS:
The Alpha1-adrenoreceptor antagonist drug, alfuzosin HCL, was added to the contraindicated list.
WARNINGS:
The following warning regarding fluticasone was included:
A drug interaction study in healthy subjects has shown that ritonavir significantly increases plasma fluticasone propionate exposures, resulting in significantly decreased serum cortisol concentrations. Systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. (see Precautions: Drug Interactions).
PRECAUTIONS:
In the Precautions section, the following clinical comment was included regarding the fluticasone interaction:
Concomitant use of fluticasone propionate and ritonavir increases plasma concentrations of fluticasone propionate, resulting in significantly reduced serum cortisol concentrations. Coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects (see Warnings).
The following clinical comments were included regarding the trazodone interaction:
Concomitant use of trazodone and ritonavir increases plasma concentrations of trazodone. Adverse events of nausea, dizziness, hypotension and syncope have been observed following coadministration of trazodone and ritonavir. If trazodone is used with a CYP3A4 inhibitor such as ritonavir, the combination should be used with caution and a lower dose of trazodone should be considered.
The FDA announced on Nov. 4, 2005, the tentative approval of Lamivudine Oral Solution, 10 mg/mL manufactured by Aurobindo Pharma LTD. of Hyderabad, India. Lamivudine Oral Solution is the first generic version of the already approved Epivir Oral Solution, 10 mg/mL, manufactured by GlaxoSmithKline. This child-friendly-product is indicated for use in pediatric patients with HIV from three months to 16 years.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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