a) Congestive heart failure, hypertension, tachycardia, dysrhythmias, myocardial infarction, vasculitis, and syncope have been reported during therapeutic use of NSAIDs or mefenamic acid (Prod Info PONSTEL(R) oral capsules, 2008).

a) Hypertension may occur following overdose, but is considered a rare effect (Prod Info PONSTEL(R) oral capsules, 2008).

a) Edema has been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).
b) Fluid retention has been reported in receiving mefenamic acid (Prod Info PONSTEL(R) oral capsules, 2008).

a) Respiratory depression and pneumonia have been reported during therapeutic use of mefenamic acid. Respiratory depression is considered a rare effect of overdose (Prod Info PONSTEL(R) oral capsules, 2008).

a) Respiratory depression is considered a rare effect of overdose (Prod Info PONSTEL(R) oral capsules, 2008).

a) Dizziness and headaches have been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).
b) Drowsiness, nervousness, and insomnia have also been reported in patients receiving mefenamic acid (Prod Info PONSTEL(R) oral capsules, 2008).

a) SUMMARY: Seizures are a predominant feature of overdose with mefenamic acid (S Sweetman , 2001).
b) CASE SERIES: In a series of 29 patients with significant ingestions (plasma concentration greater than 10 mcg/mL), seizures occurred in 11 (38%) (Balali-Mood et al, 1981). In another study seizures were reported in 6 of 12 patients ingesting greater than 10 grams and in 9 of 21 patients ingesting between 5 and 10 grams (Graf et al, 1994).
c) CASE SERIES: In 11 patients with seizures, a single generalized tonic-clonic seizure was reported; five had more than one seizure, and one patient had repeated seizures not controlled by diazepam (Balali-Mood et al, 1981). Status epilepticus was reported in two cases (Young, 1979; Balali-Mood et al, 1981).
d) CASE REPORT: Two hours after two injections of a 2.25 gram suspension of mefenamic acid and water, and after the oral ingestion of 5 grams mefenamic acid, a 22-year-old heroin addict experienced a tonic-clonic seizure (McKillop & Canning, 1987).
e) CASE REPORT: A 19-year-old woman had a generalized motor seizure followed by a 20 to 30 second period of rigidity and apnea after ingesting between 6.25 and 7.5 grams of mefenamic acid (Frank et al, 1983).

a) CASE REPORT: Redmond (1981) reported acute dyskinesia, possibly induced by an unknown quantity of mefenamic acid, alcohol, and diazepam. The 45-year-old male was treated with 1 mg of benztropine intravenously and the dyskinesia was abolished. Diazepam and alcohol have not been associated with acute dyskinesias, in spite of their frequency of overdose (Redmond, 1981).

a) CASE REPORT: Restlessness, agitation, and a depressed level of consciousness were reported in a 30-year-old man with peak mefenamic acid serum concentration of 46 mcg/mL (Turnbull et al, 1988).
b) CASE REPORT: Agitation and confusion occurred following an ingestion of 5 grams of mefenamic acid and injection of 2.25 grams of mefenamic acid suspended in water in a 22-year-old heroin addict (McKillop & Canning, 1987).

a) CASE SERIES/INCIDENCE: Coma was reported in 58% of adults ingesting greater than 10 grams of mefenamic acid, and occurred in 43% of patients ingesting between 5 and 10 grams (Graf et al, 1994). It is considered a rare effect of overdose (Prod Info Ponstel(R), mefenamic acid, 2000).
b) CASE REPORT: A 13-year-old girl developed a coma after ingestion of 5 to 10 g of mefenamic acid. Less than 2 hours after ingestion, she was comatose with no response to painful stimuli. Muscle twitching and a grand mal seizure followed, treated with diazepam. The patient improved during the next 12 hours. Other drugs were not identified by toxic drug screen (Gossinger et al, 1982).
c) CASE REPORT: Coma lasting 24 hours was described in an 81-year-old woman who reported ingesting 50 grams of mefenamic acid. Hyperreflexia and bilateral extensor plantar responses were present (Hendrickse, 1988).

a) Nausea, vomiting, abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, and GI ulcer have been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).
b) Gastrointestinal irritation and esophageal or gastroduodenal ulceration have occurred during therapeutic administration, but are rare effects of acute overdose (De Caestecker & Heading, 1988; Prod Info Ponstel(R), mefenamic acid, 2000).

a) Gastrointestinal irritation and esophageal or gastroduodenal ulceration have occurred during therapeutic administration, but are rare effects of acute overdose (De Caestecker & Heading, 1988; Prod Info Ponstel(R), mefenamic acid, 2000).

a) CASE REPORT: Hematemesis, vomiting, and diarrhea were reported in a 22-year-old heroin addict following an oral ingestion of 5 grams (20 tablets) and 2 hours after the intravenous injection of 2.25 grams of mefenamic acid mixed with water (McKillop & Canning, 1987).
b) CASE REPORT: Abdominal pain, vomiting, and diarrhea lasting 18 hours were reported after ingesting 12.5 grams of mefenamic acid by a 30-year-old male patient (Turnbull et al, 1988).

a) Gross bleeding or perforation, hematemesis, melena and rectal bleeding have all been reported with therapeutic use of mefenamic acid (Prod Info PONSTEL(R) oral capsules, 2008).

a) Gastrointestinal bleeding can occur following overdose (Prod Info PONSTEL(R) oral capsules, 2008).
b) CASE REPORT: A 71-year-old female with symptoms of intermittent black stools, "coffee-ground" emesis, and epigastric pain was diagnosed with several ulcers and esophagitis after taking 12 Chinese herbal pills daily (brand name unknown) for several months (Gertner et al, 1995). The pills were analyzed and contained varying doses of mefenamic acid and diazepam. Initial hemoglobin was 5.8 gm/dL with a normal bleeding time; treatment included 4 units of packed red blood cells.

a) Diarrhea and steatorrhea have been reported with chronic therapeutic use (Isaacs et al, 1987).
b) Diarrhea due to proctitis or ileocolitis was described in 4 patients taking mefenamic acid for arthritis in doses of 500 mg two to three times daily for 6 weeks or longer (Phillips et al, 1983; Rampton & Tapping, 1983).

a) Diarrhea lasting up to 18 hours has been reported after mefenamic acid overdose (Turnbull et al, 1988).

a) SUMMARY: Pancreatitis has developed following therapeutic use of mefenamic acid (Prod Info PONSTEL(R) oral capsules, 2008).
b) CASE REPORT: Pancreatitis was reported in a 32-year-old patient following termination of a second cycle of mefenamic acid, 250 mg 4 times per day (Van Walraven et al, 1982).

a) Elevated liver enzymes has been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).

a) Rare cases of fatal fulminant hepatitis have been reported during treatment with nonsteroidal anti-inflammatory agents (Prod Info PONSTEL(R) oral capsules, 2008).

a) Rare cases of hepatic failure, some with fatal outcomes, have been reported during treatment with nonsteroidal anti-inflammatory agents (Prod Info PONSTEL(R) oral capsules, 2008).

a) Abnormal renal function has been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).
b) Cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, and proteinuria have rarely been reported in patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).

a) Non-oliguric reversible renal failure has been reported with therapeutic mefenamic acid administration of 12 to 15 grams over 4 to 5 days (Court & Volans, 1984). This effect has been frequently observed in the elderly (Grant & MacConnachie, 1995).
b) Irreversible renal interstitial nephritis has occurred with chronic use (Boletis et al, 1989).

a) While renal failure has not been a prominent acute overdose effect (Prod Info PONSTEL(R) oral capsules, 2008; Venning et al, 1980; Malik et al, 1980; Robertson et al, 1980), it has been reported in one case after a single acute overdose (Turnbull et al, 1988).
b) ADULTERANT: A Chinese herbal medicine (Tung Shueh) containing mefenamic acid (not quantitated) and diazepam (0.43 mg per pill) was consumed for 4 weeks (8 herbal pills daily), and resulted in acute interstitial nephritis in a 51-year-old woman (Abt et al, 1995). Renal function returned following limited hemodialysis.

a) CASE REPORT: Renal papillary necrosis was described in a 47-year-old man ingesting mefenamic acid therapeutically for 10 years and in a 58-year-old woman ingesting 10 capsules per week for 2 years (Segasothy et al, 1987).

a) CASE REPORT: A 13-year-old boy with a history of focal segmental glomerulosclerosis developed renal impairment 8 months after initiation of mefenamic acid 750 mg/day, which progressed after discontinuation of the drug. Fibrosis was suspected, but not confirmed by biopsy (Itami et al, 1990).

a) Metabolic acidosis was reported in 4 of 12 adults (30%) ingesting greater than 10 grams mefenamic acid and in 5 of 21 adults (25%) ingesting between 5 to 10 grams (Graf et al, 1994).
b) CASE REPORT: Severe metabolic acidosis (pH 6.92, bicarbonate 6 mEq/L) has been reported after mefenamic acid induced seizures (Frank et al, 1983).

a) Hematologic effects reported with mefenamic acid include agranulocytosis, pancytopenia, lymphadenopathy, and thrombocytopenia (Prod Info PONSTEL(R) oral capsules, 2008).
b) Increased bleeding time has been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).

a) Anemia has been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).
b) Various anemias (hemolytic and aplastic) have been seen rarely in therapeutic use, but have NOT been reported after acute overdose (Prod Info PONSTEL(R) oral capsules, 2008).

a) Rash and pruritus has been reported in up to 10% of patients taking mefenamic acid or other NSAIDs (Prod Info PONSTEL(R) oral capsules, 2008).
b) Various dermatological effects (e.g., erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria, angioedema, fixed drug eruption, pseudoporphyria, and toxic epidermal necrolysis) have been reported rarely following therapeutic use of mefenamic acid; they are not characteristic of acute overdose (Prod Info PONSTEL(R) oral capsules, 2008; O'Hagan et al, 1998; Watson & Watt, 1986; Mohamed, 1991; Sowden & Smith, 1990).

a) Anaphylaxis has been reported with therapeutic use of NSAIDs; symptoms may occur in overdose (Prod Info PONSTEL(R) oral capsules, 2008).

a) CASE REPORT: A 60-year-old male developed significant hyponatremia (124 mmol/L) and hyperkalemia (6.8 mmol/L) following 1 gram of mefenamic acid daily (total dose) for 3 days secondary to mefenamic acid-induced hyporeninemic hypoaldosteronism. Treatment was symptomatic (Chan et al, 1995). The authors suggested a temporal relationship between the alteration in hormone levels and mefenamic acid use.

a) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

a) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
b) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) Patients with muscle twitching and seizures generally had serum levels above a line joining 100 micrograms/milliliter at 2 hours postingestion, and 5 micrograms/milliliter at 15 hours postingestion. However, seizures have occurred when mefenamic acid concentrations were well below this line (Balali-Mood et al, 1981).

a) Three hours postingestion blood concentrations were 72 micrograms/milliliter in a 14-year-old girl who had a grand mal seizure (Robson et al, 1979).
b) Concentrations on admission were 46 micrograms/milliliter in a 30-year-old male sustaining a grand mal seizure (Turnbull et al, 1988).
c) Ingestion of 5 to 10 grams mefenamic acid in a 13-year-old resulted in a serum level of 22 micrograms/ml 6 hours after ingestion. Authors cite peak plasma concentrations of 73 +/- 46 micrograms/ml as an average in another series of patients presenting with convulsions (Gossinger et al, 1982a).

a) 400 mg/kg (RTECS , 2001)

a) 120 mg/kg (RTECS , 2001)

a) 525 mg/kg (RTECS , 2001)

a) 327 mg/kg (RTECS , 2001)

a) 740 mg/kg (RTECS , 2001)

a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

a) EMESIS AND LAVAGE - Due to potential for seizures, emesis is not recommended. Gastric lavage may be facilitated by light sedation.
b) ACTIVATED CHARCOAL - Administer activated charcoal, 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
c) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

a) DIAZEPAM - Dose of diazepam for DOGS & CATS is 0.5 milligram/kilogram intravenous bolus; may repeat dose every ten minutes for four total doses. Give slowly over 1 to 2 minutes.
b) PHENOBARBITAL may be used as adjunct treatment at 5 to 30 milligrams/kilogram over 5 to 10 minutes intravenously.
c) REFRACTORY SEIZURES - Consider anaesthesia or heavy sedation. Administer pentobarbital to DOGS & CATS at a dose of 3 to 15 milligrams/kilogram intravenously slowly to effect. The dose may need to be repeated in 4 to 8 hours. Be sure to protect the airway.

a) TRANSFUSION - Transfuse with whole blood or plasma, 25 milliliters/kilogram.
b) FLUID THERAPY - If necessary, begin fluid therapy at maintenance doses (66 milliliters solution/kilogram body weight/day intravenously) or, in hypotensive patients, at high doses (up to shock dose 60 milliliters/kilogram/hour). Monitor for urine production and pulmonary edema.

1) Begin treatment immediately.
2) Keep animal warm and do not handle unnecessarily.
3) Sample vomitus, blood, urine, and feces for analysis.
4) Remove the patient and other animals from the source of contamination.
5) Treatment should always be done on the advice and with the consultation of a veterinarian. Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.
6) ANIMAL POISON CONTROL CENTERS

1) GENERAL TREATMENT