Brand Name
Motofen
Generic Name
Difenoxin
View Brand Information FDA approval date: April 11, 2017
Classification: Cholinergic Muscarinic Antagonist
Form: Tablet
What is Motofen (Difenoxin)?
MOTOFEN ® is indicated as adjunctive therapy in the management of acute nonspecific diarrhea and acute exacerbations of chronic functional diarrhea.
Approved To Treat
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Brand Information
Motofen (difenoxin and atropine sulfate)
1DESCRIPTION
Each five-sided dye free MOTOFEN
The structural formula is:
Atropine sulfate is present to discourage deliberate overdose.
Atropine sulfate, an anticholinergic, is benzeneacetic acid, α-(hydroxymethyl)-, 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, endo-(±)-, (2:1) (salt), monohydrate and has the following structural formula:
Inactive Ingredients: calcium stearate, cellulose, lactose, corn starch.
2CLINICAL PHARMACOLOGY
Animal studies have shown that difenoxin hydrochloride manifests its antidiarrheal effect by slowing intestinal motility. The mechanism of action is by a local effect on the gastrointestinal wall.
Difenoxin is the principal active metabolite of diphenoxylate.
Following oral administration of MOTOFEN
3INDICATIONS AND USAGE
MOTOFEN
4CONTRAINDICATIONS
MOTOFEN
MOTOFEN
MOTOFEN
5WARNINGS
MOTOFEN
FLUID AND ELECTROLYTE BALANCE– THE USE OF MOTOFEN® DOES NOT PRECLUDE THE ADMINISTRATION OF APPROPRIATE FLUID AND ELECTROLYTE THERAPY. DEHYDRATION, PARTICULARLY IN CHILDREN, MAY FURTHER INFLUENCE THE VARIABILITY OF RESPONSE TO MOTOFEN ®AND MAY PREDISPOSE TO DELAYED DIFENOXIN INTOXICATION. DRUG-INDUCED INHIBITION OF PERISTALSIS MAY RESULT IN FLUID RETENTION IN THE COLON, AND THIS MAY FURTHER AGGRAVATE DEHYDRATION AND ELECTROLYTE IMBALANCE.
IF SEVERE DEHYDRATION OR ELECTROLYTE IMBALANCE IS MANIFESTED, MOTOFEN
Ulcerative Colitis– In some patients with acute ulcerative colitis, agents which inhibit intestinal motility or delay intestinal transit time have been reported to induce toxic megacolon. Consequently, patients with acute ulcerative colitis should be carefully observed and MOTOFEN ®therapy should be discontinued promptly if abdominal distention occurs or if other untoward symptoms develop.
Liver and Kidney Disease– MOTOFEN ®should be used with extreme caution in patients with advanced hepatorenal disease and in all patients with abnormal liver function tests since hepatic coma may be precipitated.
Atropine– A subtherapeutic dose of atropine has been added to difenoxin hydrochloride to discourage deliberate overdosage. Usage of MOTOFEN ®in recommended doses is not likely to cause prominent anticholinergic side effects, but MOTOFEN ®should be avoided in patients in whom anticholinergic drugs are contraindicated. The warnings and precautions for use of anticholinergic agents should be observed. In children, signs of atropinism may occur even with recommended doses of MOTOFEN ®, particularly in patients with Down’s Syndrome.
6PRECAUTIONS
Information for Patients
CAUTION PATIENTS TO ADHERE STRICTLY TO RECOMMENDED DOSAGE SCHEDULES. THE MEDICATION SHOULD BE KEPT OUT OF REACH OF CHILDREN SINCE ACCIDENTAL OVERDOSAGE MAY RESULT IN SEVERE, EVEN FATAL, RESPIRATORY DEPRESSION.
MOTOFEN
6.1Drug Interactions
Since the chemical structure of difenoxin hydrochloride is similar to meperidine hydrochloride, the concurrent use of MOTOFEN
MOTOFEN
Diphenoxylate hydrochloride, from which the principal active metabolite difenoxin is derived, was found to inhibit the hepatic microsomal enzyme system at a dose of 2 mg/kg/day in studies conducted with male rats. Therefore, difenoxin has the potential to prolong the biological half-lives of drugs for which the rate of elimination is dependent on the microsomal drug metabolizing enzyme system.
6.2Carcinogenesis, Mutagenesis, Impairment of Fertility
No evidence of carcinogenesis was found in a long-term study of difenoxin hydrochloride/atropine in the rat. In this 104 week study, rats received dietary doses of 0, 1.25, 2.5, or 5 mg/kg/day difenoxin/atropine (20:1 ratio).
No experiments have been conducted to determine the mutagenic potential of MOTOFEN
6.3Pregnancy/Teratogenic Effects
Pregnancy Category C. Reproduction studies in rats and rabbits with doses at 31 and 61 times the human therapeutic dose respectively, on a mg/kg basis, demonstrated no evidence of teratogenesis due to MOTOFEN
Pregnant rats receiving oral doses of difenoxin hydrochloride/atropine 20 times the maximum human dose had an increase in delivery time as well as a significant increase in the percent of stillbirths.
Neonatal survival in rats was also reduced with most deaths occurring within four days of delivery.
There are no well controlled studies in pregnant women. MOTOFEN
6.4Nursing Mothers
Because of the potential for serious adverse reactions in nursing infants from MOTOFEN
6.5Pediatric Use
SAFETY AND EFFECTIVENESS IN CHILDREN BELOW THE AGE OF 12 HAVE NOT BEEN ESTABLISHED. MOTOFEN
7ADVERSE REACTIONS
In view of the small amount of atropine present (0.025 mg/tablet), such effects such as dryness of the skin and mucous membranes, flushing, hyperthermia, tachycardia and urinary retention are very unlikely to occur, except perhaps in children.
Many of the adverse effects reported during clinical investigation of MOTOFEN
Gastrointestinal:Nausea, 1 in 15 patients; vomiting, 1 in 30 patients; dry mouth, 1 in 30 patients; epigastric distress, 1 in 100 patients; and constipation, 1 in 300 patients.
Central Nervous System:Dizziness and light-headedness, 1 in 20 patients; drowsiness, 1 in 25 patients; and headache, 1 in 40 patients; tiredness, nervousness, insomnia and confusion ranged from 1 in 200 to 1 in 600 patients.
Other less frequent reactions:Burning eyes and blurred vision occurred in a few cases.
The following adverse reactions have been reported in patients receiving chemically-related drugs: numbness of extremities, euphoria, depression, sedation, anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus, toxic megacolon, paralytic ileus, pancreatitis, and anorexia.
THIS MEDICATION SHOULD BE KEPT IN A CHILD-RESISTANT CONTAINER AND OUT OF THE REACH OF CHILDREN SINCE AN OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH.
8DRUG ABUSE AND DEPENDENCE
MOTOFEN
Addiction to (dependence on) difenoxin hydrochloride is theoretically possible at high dosage. Therefore, the recommended dosage should not be exceeded. Because of the structural and pharmacological similarities of difenoxin hydrochloride to drugs with a definite addiction potential, MOTOFEN
9OVERDOSAGE
Diagnosis and Treatment
In the event of overdosage (initial signs may include dryness of the skin and mucous membranes, flushing, hyperthermia and tachycardia followed by lethargy or coma, hypotonic reflexes, nystagmus, pinpoint pupils and respiratory depression) gastric lavage, establishment of a patent airway and possibly mechanically assisted respiration are advised.
The narcotic antagonist naloxone may be used in the treatment of respiratory depression caused by narcotic analgesics of pharmacologically related compounds such as MOTOFEN
To counteract respiratory depression caused by MOTOFEN
Adult Dosage:The usual initial adult dose of naloxone is 0.4 mg (one mL) administered intravenously. If respiratory function does not adequately improve after the initial dose, the same IV dose may be repeated at two-to-three minute intervals.
Children:The usual adult dose of naloxone for children is 0.01 mg/kg of body weight administered intravenously and
repeated at two-to-three minute intervals if necessary.
repeated at two-to-three minute intervals if necessary.
Since the duration of action of difenoxin hydrochloride is longer than that of naloxone, improvement of respiration following administration may be followed by recurrent respiratory depression. Consequently, continuous observation is necessary until the effect of difenoxin hydrochloride on respiration (which effect may persist for many hours) has passed. Supplemental intramuscular doses of naloxone may be utilized to produce a longer lasting effect. TREAT ALL POSSIBLE MOTOFEN
Although signs of overdosage and respiratory depression may not be evident soon after ingestion of difenoxin hydrochloride, respiratory depression may occur from 12 to 30 hours later.
10DOSAGE AND ADMINISTRATION
The recommended starting dose of MOTOFEN
Studies in children below the age of 12 have been inadequate to evaluate the safety and effectiveness of MOTOFEN
11HOW SUPPLIED
MOTOFEN