Rimantadine

Flumadine

No information provided.

As with any overdose, supportive therapy should be administered as indicated. Overdoses of a related drug, amantadine, have been reported with adverse reactions consisting of agitation, hallucinations, cardiac arrhythmia and death. The administration of intravenous physostigmine (a cholinergic agent) at doses of 1 to 2 mg in adults (Ref. 7) and 0.5 mg in children (Ref. 8) repeated as needed as long as the dose did not exceed 2 mg/hour has been reported anecdotally to be beneficial in patients with central nervous system effects from overdoses of amantadine.

Do not use this medicine if you are allergic to rimantadine or a similar medicine called amantadine (Symmetrel).

Before taking rimantadine, tell your doctor if you are allergic to any drugs, or if you have a seizure disorder, kidney disease, or liver disease.

Take this medication for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated.

Do not use FluMist nasal influenza "live vaccine" while you are being treated with rimantadine and for at least 48 hours after you stop taking rimantadine. The nasal vaccine may not be as effective if you receive it while you are taking rimantadine. Before taking rimantadine, tell your doctor if you have received a nasal flu vaccine within the past 14 days.

Avoid coming into close contact with someone who has a weak immune system, such as a person who is taking steroids, being treated for cancer, or has a bone marrow disorder or an illness such as HIV or AIDS. If you have a type of influenza that is resistant to rimantadine, your body may actually shed that virus and a person with a weak immune system could easily become ill from being near you.

It is important that your doctor check the progress of you or your child at regular visits to allow changes in your dose and to check for any unwanted effects.

rimantadine may cause some people to become dizzy or confused, or to have trouble concentrating. Make sure you know how you react to rimantadine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or confused. If these reactions are especially bothersome, check with your doctor.

If your or your child's symptoms do not improve within a few days, or if they become worse, check with your doctor.

While you are being treated with rimantadine, do not have any immunizations (vaccinations) without your doctor's approval. Live virus vaccinations should not be given for 2 days after stopping rimantadine, and rimantadine should be not be given 2 weeks after receiving live vaccines.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• It is used to treat or prevent influenza A.

• If you have an allergy to rimantadine or any other part of rimantadine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding. Do not breast-feed while you take this medicine.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take rimantadine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Rimantadine hydrochloride is a synthetic antiviral drug available as a 100 mg film-coated tablet. Each film-coated tablet contains 100 mg of Rimantadine hydrochloride. In addition, each tablet contains the following inactive ingredients: hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, purified water, sodium starch glycolate and FD&C Yellow No. 6 Lake. Film coating material, Opadry (YS-1-19025-A), contains hypromellose and macrogol.

Rimantadine hydrochloride is a white to off-white crystalline powder which is freely soluble in water (50 mg/mL at 20°C). Chemically, Rimantadine hydrochloride is alpha-methyltricyclo-[3.3.1.1/3.7]decane-1-methanamine hydrochloride, with an empirical formula of C12H21N•HCl, a molecular weight of 215.77 and the following structural formula:

As with any overdose, supportive therapy should be administered as indicated. Overdoses of a related drug, amantadine, have been reported with adverse reactions consisting of agitation, hallucinations, cardiac arrhythmia and death. The administration of intravenous physostigmine (a cholinergic agent) at doses of 1 to 2 mg in adults (Ref. 7) and 0.5 mg in children (Ref. 8) repeated as needed as long as the dose did not exceed 2 mg/hour has been reported anecdotally to be beneficial in patients with central nervous system effects from overdoses of amantadine.

FOR PROPHYLAXIS IN ADULTS AND CHILDREN

The recommended adult dose of Rimantadine hydrochloride is 100 mg twice a day. Study durations ranged from 11 days to 6 weeks in adult and elderly patients. In patients with severe hepatic dysfunction, severe renal impairment (CrCl 5 to 29 mL/min) or renal failure (CrCl ≤ 10 mL/min) and in elderly nursing home patients, a dose reduction to 100 mg daily is recommended. Because of the potential for accumulation of Rimantadine metabolites during multiple dosing, patients with hepatic or renal impairment should be monitored for adverse effects.

• Study duration ranged from 5 weeks to 6 weeks in pediatric subjects.
• In children 1 year to 9 years of age, Rimantadine hydrochloride should be administered once a day, at a dose of 5 mg/kg but not exceeding 150 mg.
• For children 10 years of age or older, use the adult dose.

(see Directions for Compounding of an Oral Suspension from Rimantadine Hydrochloride Tablets to prepare an oral suspension for administration to children and patients with difficulty swallowing tablets).

The safety and efficacy of Rimantadine hydrochloride for prophylaxis of influenza in pediatric patients younger than 1 year of age have not been established.

FOR TREATMENT IN ADULTS

The recommended adult dose of Rimantadine hydrochloride is 100 mg twice a day for 7 days. In patients with severe hepatic dysfunction, severe renal impairment (CrCl 5 to 29 mL/min) or renal failure (CrCl ≤ 10 mL/min) and elderly nursing home patients, a dose reduction to 100 mg daily is recommended. Because of the potential for accumulation of Rimantadine metabolites during multiple dosing, patients with hepatic or renal impairment should be monitored for adverse effects. Rimantadine hydrochloride therapy should be initiated as soon as possible, preferably within 48 hours after onset of signs and symptoms of influenza A infection. Therapy should be continued for approximately seven days from the initial onset of symptoms.

Rimantadine hydrochloride is not indicated for treatment of influenza in pediatric patients 16 years or younger.

Directions for the Compounding of an Oral Suspension from Rimantadine Hydrochloride Tablets (Final Concentration = 10 mg/mL)1

These directions are provided for use only during emergency situations, for patients who have difficulty swallowing tablets or where lower doses are needed. The pharmacist may compound a suspension (10 mg/mL) from Rimantadine hydrochloride tablets, 100 mg using Ora-Sweet®.1 Other vehicles have not been studied.

To make an oral suspension (10 mg/mL) from 100 mg Rimantadine hydrochloride tablets, you will need the following:

• 100 mg tablets of Rimantadine hydrochloride
• Ora-Sweet® (a vehicle manufactured by Paddock Laboratories)
• a graduated cylinder
• a mortar and pestle
• an Amber Glass or Polyethylene terephthalate plastic (PET) bottle
• a funnel (optional)

A 100 mg tablet of Rimantadine hydrochloride is required for each 10 mL of compounded oral suspension to make a concentration of 10 mg/mL.

A compounded oral suspension is stable for 14 days. Therefore, the maximum amount of oral suspension that can be dispensed to a patient should not exceed a 14 day supply.

Step A: Guidance for how to determine the Number of Tablets and Total Volume needed to compound a 10 mg/mL oral suspension for each patient

• Verify the prescribed dose is correct.
• Calculate the mg amount of Rimantadine hydrochloride needed for the duration of therapy.
  (Daily Dose) × (Number of days) = (mg of Rimantadine hydrochloride)
  For example, 75 mg/day × 10 days = 750 mg
• Round up the mg of Rimantadine hydrochloride amount to the next 100 mg designation.
  For example, Round up 750 mg to 800 mg
• Calculate the Number of 100 mg tablets that are required for the compounded oral suspension.
  (Rounded mg of Rimantadine hydrochloride) ÷ (100 mg/tablet) = (Number of tablets)
  For example, 800 mg ÷100 mg/tablet = 8 tablets
• Calculate the Total Volume of compounded oral suspension (10 mg/mL) (Rounded mg of Rimantadine hydrochloride) ÷ (10 mg/mL) = (Total Volume)
  For example, 800 mg ÷ 10 mg/mL = 80 mL

Step B: Once the total Number of Tablets and Volume are determined then follow the procedures below for compounding the oral suspension (10 mg/mL) from Rimantadine hydrochloride tablets 100 mg

Verify your calculations before you begin to compound an oral suspension.

A 100 mg tablet of Rimantadine hydrochloride is required for each 10 mL of compounded oral suspension to make a concentration of 10 mg/mL.

• Place the required number of Rimantadine hydrochloride 100 mg tablets into a clean mortar of sufficient size to contain the tablets and volume of vehicle, Ora-Sweet® used in Step 3.
• Grind the tablets and triturate to a fine powder using a pestle. Powder on the sides of the mortar or pestle should be removed using a spatula and incorporated into the trituration throughout the process.
• Slowly add approximately one-third (1/3) of the total volume of vehicle to the mortar while triturating until a uniform suspension is achieved.
• Transfer the suspension to an amber glass or a PET plastic bottle. Other types of bottles, such as non-PET plastic or uncolored bottles, have not been evaluated and should not be used. A funnel may be used to eliminate any spillage.
• Slowly add the second one-third (1/3) of the total volume of vehicle to the mortar, rinse the pestle and mortar by a triturating motion and transfer the contents into the bottle.
• Repeat the rinsing (Step 5) with the remaining one-third (1/3) of the vehicle, transferring the remaining contents to the fullest extent possible. Verify that the suspension is at the desired total volume or add additional vehicle if needed.
• Close the bottle using a child-resistant cap.
• Shake well to ensure homogeneous suspension. (Note: The active drug, Rimantadine HCl readily dissolves in the specified vehicle. The suspension is caused by some of the inert ingredients of Rimantadine hydrochloride tablets 100 mg which are insoluble in this vehicle.)

• Include an ancillary label on the bottle indicating "Shake Gently Before Use." This compounded suspension should be gently shaken prior to administration to minimize the tendency for air entrapment with the Ora-Sweet® preparation. The need to shake the compounded oral suspension gently prior to administration should be reviewed with the parent or guardian when the suspension is dispensed.
• Provide an oral dosing device (a graduated oral syringe or spoon) that will measure the prescribed dose (in mL). If possible, mark or highlight the graduation corresponding to the appropriate dose on the oral syringe or spoon for each patient.
• Include an Expiration Date label according to storage condition (see below) and a "Discard any Unused Portion" label to the bottle. Instruct the parent or guardian that any remaining material following completion of therapy or after the expiration date on the label must be discarded.

Room Temperature: Stable for 14 days when stored in ambient room temperature conditions. Other storage conditions have not been studied.

Note: The storage conditions are based on stability studies of compounded oral suspensions, using the above mentioned vehicle, which was placed in amber glass and PET plastic bottles at 25°C (77°F). Stability studies have not been conducted with other vehicles or bottle types.

• Flumadine

Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A (CDC/ACIP 2011). Please refer to the current Advisory Committee on Immunization Practices (ACIP) recommendations.

Influenza A virus, prophylaxis: Oral: 100 mg twice daily for 7 days after last known exposure. In institutional outbreaks, continue prophylaxis for at least 2 weeks and up to 7 days after the last known case identification. For prophylaxis after inactivated influenza vaccination, continue until immunity after vaccination develops (~2 weeks) (CDC/ACIP 2011; CDC 2016)

Influenza A virus, treatment: Oral: 100 mg twice daily for 5 to 7 days. Note: Initiate within 48 hours of symptom onset (CDC/ACIP 2011)

Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A (CDC/ACIP 2011). Please refer to the current Advisory Committee on Immunization Practices (ACIP) recommendations.

Influenza A virus, prophylaxis: Oral: Note: Duration of prophylaxis is 7 days after last known exposure. In institutional outbreaks, continue prophylaxis for at least 2 weeks and up to 7 days after the last known case identification. For prophylaxis after inactivated influenza vaccination, continue until immunity after vaccination develops (≥2 weeks) (CDC/ACIP 2011; CDC 2016)

Children and Adolescents:

1 to 9 years: 5 mg/kg/day in 1 to 2 divided doses; maximum: 150 mg/day (CDC/ACIP 2011)

≥10 years and <40 kg: 5 mg/kg/day in 2 divided doses (maximum dose: 200 mg/day) (CDC/ACIP 2011)

≥10 years and ≥40 kg: Refer to adult dosing.

Influenza A virus, treatment: Oral: Adolescents ≥17 years: Refer to adult dosing.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established (CDC 2011). Rimantadine is not effective in the prevention or treatment of influenza B virus infections.

• Renal impairment: Use with caution in patients with renal impairment.

• Seizures: Use with caution in patients with a history of seizure disorder; an increase in seizure incidence may occur. Discontinue if seizures occur.

Special populations:

• Elderly: The elderly are at higher risk for CNS (eg, dizziness, headache, weakness) and gastrointestinal (eg, nausea/vomiting, abdominal pain) adverse events; dosage adjustment is recommended in patients >65 years of age.

Other warnings/precautions:

• Resistance: May develop during treatment; viruses exhibit cross-resistance between amantadine and rimantadine.

Consult WARNINGS section for dosing related precautions.