At present time four drugs in the United States are approved by the FDA for the treatment and prevention of flu:

* Neuraminidase inhibitors: Oseltamivir (brand name: Tamiflu) and Zanamivir (brand name: Relenza)
* Adamantane derivatives: Amantadine (brand name: Symmetrel) and Rimantadine (brand name: Flumadine)

The U.S. Food and Drug Administration (FDA) approved two drugs to both treat and prevent influenza type A - Amantadine in 1976 and Rimantadine in 1993. In 1999, FDA approved two new antiviral medications to fight the flu: Zanamivir (Relenza), the first neuraminidase inhibitor, and Oseltamivir (Tamiflu), the first of a new class of antiviral drugs called neuraminidase inhibitors. The antiviral drugs approved for influenza in the United States all are prescription drugs.

Influenza antiviral medications are drugs that suppress the ability of influenza viruses to reproduce. When used correctly, they can reduce the duration of symptoms and some complications from influenza virus infection. When used for treatment within the first 2 days of illness, all 4 antiviral medications are similarly effective in reducing by 1 or 2 days the duration of illness caused by influenza A viruses, and make you less contagious to others. Only Oseltamivir and Zanamivir are effective against influenza B viruses, though they do not cure influenza outright.

Oseltamivir and Zanamivir are preferred for treatment in part because influenza viruses are more likely to develop resistance to Amantadine and Rimantadine. The 4 influenza antiviral drugs are effective only against influenza viruses. They will not help reduce symptoms associated with the common cold.

All of the antiviral drugs are different in terms of who can take them, approved uses, approved ages, how they are given, any dosing changes based on age or medical conditions, side effects and costs.

Mechanism of Action

The surfaces of influenza viruses are dotted with neuraminidase proteins. Neuraminidase inhibitors block the enzyme's activity and prevent new virus particles from being released, thereby limiting the spread of infection. Zanamivir is inhaled through a device called a Diskhaler. This inhaler device delivers the medicine to the lungs, where the influenza virus multiplies. Oseltamivir is taken as a pill. Zanamivir and Oseltamivir help prevent influenza A and influenza B viruses from multiplying in the body by interfering with the production and release of virus from cells that line the respiratory tract. This may slow the spread of the infection within the airways and lungs.

Amantadine and Rimantadine: inhibit entry and uncoating of influenza A virus. These drugs block penetration and uncoating of the virus by preventing acidification of the endosome and thus the pH-dependent activation of the fusion activity of the virus hemagglutinin by interfering with the function of the M2 protein of Influenza A virus. Both agents are active against some influenza A virus strains (H1N1, H2N2, H3N2), but are inactive against influenza B (influenza B does not possess a M2 protein).

Medical Uses

To treat flu: Symmetrel (Amantadine), Flumadine (Rimantadine), Tamiflu (Oseltamivir), Relenza (Zanamivir).

To prevent flu: Symmetrel (Amantadine), Flumadine (Rimantadine), Tamiflu (Oseltamivir). Zanamivir is not currently approved for preventive use.

Used against influenza type A: Symmetrel (Amantadine), Flumadine (Rimantadine), Tamiflu (Oseltamivir), Relenza (Zanamivir).

Used against influenza type B: Tamiflu (Oseltamivir), Relenza (Zanamivir).

Dosage forms

* Amantadine and Rimantadine are taken orally in pill form.
* Tamiflu, the first neuraminidase inhibitor in pill form. It is also available as liquid suspension for children.
* Zanamivir is administered by inhalation. Zanamivir can be inhaled using a device known as a Diskhaler.

Age

* Zanamivir is used for people age 7 and older.
* Oseltamivir is used to treat flu in people age 1 and older; to prevent flu in adults and children age 13 and older.
* Amantadine is used in adults and in children older than age 1.
* Rimantadine is used to prevent and treat type A influenza in adults and children age 1 and older.

Possible Side Effects

Side effects differ widely for each antiviral medication. The neuraminidase inhibitors generally cause fewer side effects than the older flu drugs.

Amantadine: The most common side effects associated with Amantadine relate to the nervous and gastrointestinal systems. Elderly people are especially sensitive to the effects of Amantadine. Amantadine may cause light-headedness, difficulty concentrating, dizziness, nervousness, insomnia, confusion, loss of balance, and seizures. Elderly patients often have reduced renal function and are better treated with Rimantadine, which is 75% metabolized by the liver.

Rimantadine: CNS effects like light-headedness, dizziness, headache, difficulty concentrating, nervousness, insomnia, loss of balance, and seizures. Side effects occur less often with Rimantadine than Amantadine.

Zanamivir: Some people who have asthma or chronic obstructive pulmonary disease (COPD) and use Zanamivir may experience reduced lung function and have difficulty breathing. Other side effects usually do not need medical attention, and may go away as your body adjusts to the medicine.

Oseltamivir: The most frequent side effects are nausea, vomiting, diarrhea. These symptoms are mostly mild to moderate and generally occurred within the first two days of administration of the drug.

None of these drugs is recommended for use during pregnancy or nursing. These drugs have not been evaluated in pregnant women.

Cost

Both drugs Amantadine and Rimantadine are available as generic. Oseltamivir and Zanamivir are new medications and are available only as brand name drugs. Therefore, of the four antiviral flu medications, Zanamivir and Oseltamivir are the most expensive.

Conclusions

Amantadine and Rimantadine are of limited use today due to side effects and the rapid appearance of resistant virus that can be spread to close contacts. Furthermore, Amantadine is associated with several drug interactions (with antihistamines or other medications that stimulate the central nervous system) that may increase the risk of side effects such as insomnia, anxiety, and seizures. Also they are only effective against influenza A, a less dangerous form of flu than influenza B.