Rimantadine

Hydrochloride salt freely soluble (50 mg/ml at 20 °C)

9.15e-03 g/L

>300 °C

> 300 °C

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl rimantadine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Concurrent use of a single dose of rimantadine with cimetidine reduces rimantadine clearance by 18% in healthy adults; the clinical significance si thought to be minimal at this time.

Because influenza antiviral agents reduce replication of influenza viruses, do not administer influenza virus vaccine live intranasal until at least 48 hours after rimantadine is discontinued and do not administer rimantadine until at least 2 weeks after administration of influenza virus vaccine live intranasal. Cimetidine

Concurrent use of acetaminophen or aspirin with rimantadine reduces the peak serum concentration of rimantadine by approximately 11%; the clinical significance is thought to be minimal at this time.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

rimantadine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ A study in male and female rats given doses of up to 60 mg/kg of body weight per day showed no impairment of fertility.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ It has been shown to be embryotoxic in rats when given at a dose of 200 mg/kg/day, and has caused fetal resorption. Maternal toxicity included ataxia, tremors, seizures, and significantly reduced weight gain.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Rimantadine was not embryotoxic when given to rabbits in doses of up to 50 mg/kg/day. However, there was evidence of a change in the ratio of fetuses with 12 ribs to fetuses with 13 ribs; normally the ratio is 50:50 in a litter, but the ratio was 80:20 after rimantadine treatment.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Rimantadine hydrochloride has been reported to be embryotoxic (ie, increased fetal resorption) in rats when administered in a dosage of 200 mg/kg daily; this dose also was associated with several maternal effects including ataxia, tremor, seizures, and substantially reduced weight gain. While developmental abnormality (i.e., change in the ratio of 12 or 13 ribs) was observed in rabbits given rimantadine hydrochloride dosages of 50 mg/kg daily, embryotoxicity was not observed.

For more Non-Human Toxicity Excerpts (Complete) data for RIMANTADINE (6 total), please visit the HSDB record page.

While the effect of rimantadine therapy on the incidence of seizures in patients with seizure disorders has not been fully evaluated, patients with active seizure disorders appear to be at risk of increased frequency of seizures during amantadine therapy. Therefore, rimantadine-treated patients with a history of epilepsy or other seizures should be observed closely for possible seizure activity.

While data specific to rimantadine were not located(SRC, 2006), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).

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) ... repeated as needed ... has been reported anecdotally to be beneficial in patients with central nervous system effects from overdoses of amantadine.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl rimantadine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Rimantadine, a cyclic amine, is a synthetic antiviral drug and a derivate of adamantane, like a similar drug amantadine. Rimantadine is inhibitory to the in vitro replication of influenza A virus isolates from each of the three antigenic subtypes (H1N1, H2H2 and H3N2) that have been isolated from man. Rimantadine has little or no activity against influenza B virus. Rimantadine does not appear to interfere with the immunogenicity of inactivated influenza A vaccine.

The mechanism of action of rimantadine is not fully understood. Rimantadine appears to exert its inhibitory effect early in the viral replicative cycle, possibly inhibiting the uncoating of the virus. The protein coded by the M2 gene of influenza A may play an important role in rimantadine susceptibility.

Rimantadine is thought to exert its inhibitory effect early in the viral replicative cycle, possibly by blocking or greatly reducing the uncoating of viral RNA within host cells. Genetic studies suggest that a single amino acid change on the transmembrane portion of the M2 protein can completely eliminate influenza A virus susceptibility to rimantadine.

Rimantadine, like amantadine, inhibits viral replication by interfering with the influenza A virus M2 protein, an integral membrane protein. The M2 protein of influenza A functions as an ion channel and is important in at least 2 aspects of virus replication, disassembly of the infecting virus particle and regulation of the ionic environment of the transport pathway. By interfering with the ion channel function of the M2 protein, rimantadine inhibits 2 stages in the replicative cycle of influenza A. Early in the virus reproductive cycle, rimantadine inhibits uncoating of the virus particle, presumably by inhibiting the acid-mediated dissociation of the virion nucleic acid and proteins, which prevents nuclear transport of viral genome material. Rimantadine also prevents viral maturation in some strains of influenza A (e.g., H7 strains) by promoting pH-induced conformational changes in influenza A hemagglutinin during its intracellular transport late in the replicative cycle. Adsorption of the virus to and penetration into cells do not appear to be affected by rimantadine. In addition, rimantadine does not interfere with the synthesis of viral components (e.g., RNA-directed RNA polymerase activity).

25 to 30 hours in young adults (22 to 44 years old). Approximately 32 hours in elderly (71 to 79 years old) and in patients with chronic liver disease. Approximately 13 to 38 hours in children (4 to 8 years old).

Young adults (22 to 44 years old): 25 to 30 hours. Older adults (71 to 79 years old) and patients with chronic liver disease: Approximately 32 hours. Children (4 to 8 years old): 13 to 38 hours.

Following oral administration, rimantadine is extensively metabolized in the liver with less than 25% of the dose excreted in the urine as unchanged drug. Glucuronidation and hydroxylation are the major metabolic pathways.

Rimantadine hydrochloride is metabolized extensively in the liver to at least 3 hydroxylated metabolites. These have been designated as conjugated and unconjugated 3-, 4a-, and 4beta-hydroxylated metabolites. A glucuronide conjugate of rimantadine also has been identified.

Extensively metabolized in the liver; glucuronidation and hydroxylation are the major metabolic pathways.

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RIMANTADINE

Established Pharmacologic Class [EPC] - Influenza A M2 Protein Inhibitor

Mechanisms of Action [MoA] - M2 Protein Inhibitors

Rimantadine is an Influenza A M2 Protein Inhibitor. The mechanism of action of rimantadine is as a M2 Protein Inhibitor.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.

Compounds that inhibit cell production of DNA or RNA.

Well absorbed, with the tablet and syrup formulations being equally absorbed after oral administration.

Following oral administration, rimantadine is extensively metabolized in the liver with less than 25% of the dose excreted in the urine as unchanged drug.

Protein binding: Moderate (approximately 40%).

Distribution: VolD - Adults: 17 to 25 L/kg. Children: MEan of 289 L. Concentrations in the nasal mucus average 50% higher than those in plasma.

Well absorbed; tablets and syrup are absorbed equally well after oral administration.

Time to peak concentration: 1 to 4 hours.

Antiviral

Antiviral; Nucleic Acid Synthesis Inhibitors

Oral: Solution: 50 mg/5 mL Flumadine Syrup ( with parabens) (Forest) Tablets, film-coated: 100 mg Flumadine ( with polyethylene glycol) (Forest).

Formulated as the hydrochloride salt

Administered PO, intranasal, SC, IP, or aerosol routes