Videx EC

didanosine

Dosage Form: capsule, delayed release
FULL PRESCRIBING INFORMATION

WARNING: PANCREATITIS, LACTIC ACIDOSIS and HEPATOMEGALY with STEATOSIS

Fatal and nonfatal pancreatitis has occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Videx EC should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis [see Warnings and Precautions (5.1)].

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk [see Warnings and Precautions (5.2)].

Indications and Usage for Videx EC

VIDEX® EC (didanosine, USP), also known as ddI, in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus (HIV)-1 infection [see Clinical Studies (14)].

Videx EC Dosage and Administration

Videx EC should be administered on an empty stomach. Videx EC Delayed-Release Capsules should be swallowed intact.

Recommended Dosage (Adult and Pediatric Patients)

The recommended total daily dose is based on body weight and is administered as one capsule given on a once-daily schedule as outlined in Table 1.

The recommended total daily dose to be administered once daily to pediatric patients weighing at least 20 kg who can swallow capsules is based on body weight (kg), consistent with the recommended adult dosing guidelines (see Table 1). Please consult the complete prescribing information for VIDEX (didanosine) Pediatric Powder for Oral Solution for dosage and administration of didanosine to pediatric patients weighing less than 20 kg or who can not swallow capsules.

Table 1: Recommended Dosage (Adult and Pediatric Patients)

Body Weight	Dose
20 kg to less than 25 kg	200 mg once daily
25 kg to less than 60 kg	250 mg once daily
at least 60 kg	400 mg once daily

Renal Impairment

Dosing recommendations for Videx EC and VIDEX Pediatric Powder for Oral Solution are different for patients with renal impairment. Please consult the complete prescribing information on administration of VIDEX (didanosine) Pediatric Powder for Oral Solution to patients with renal impairment.

Adult Patients

In adult patients with impaired renal function, the dose of Videx EC should be adjusted to compensate for the slower rate of elimination. The recommended doses and dosing intervals of Videx EC in adult patients with renal insufficiency are presented in Table 2.

Table 2: Recommended Dosage in Patients with Renal Impairment by Body Weighta

Creatinine Clearance (mL/min)	Dosage (mg)
	at least 60 kg	less than 60 kg
a Based on studies using a buffered formulation of didanosine.
b Not suitable for use in patients less than 60 kg with CLcr less than 10 mL/min. An alternate formulation of didanosine should be used.
at least 60	400 once daily	250 once daily
30-59	200 once daily	125 once daily
10-29	125 once daily	125 once daily
less than 10	125 once daily	b

Pediatric Patients

Urinary excretion is also a major route of elimination of didanosine in pediatric patients, therefore the clearance of didanosine may be altered in pediatric patients with renal impairment. Although there are insufficient data to recommend a specific dose adjustment of Videx EC in this patient population, a reduction in the dose should be considered (see Table 2).

Patients Requiring Continuous Ambulatory Peritoneal Dialysis (CAPD) or Hemodialysis

For patients requiring CAPD or hemodialysis, follow dosing recommendations for patients with creatinine clearance of less than 10 mL/min, shown in Table 2. It is not necessary to administer a supplemental dose of didanosine following hemodialysis.

Dose Adjustment

Concomitant Therapy with Tenofovir Disoproxil Fumarate

In patients who are also taking tenofovir disoproxil fumarate, a dose reduction of Videx EC to 250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min) or 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min) once daily taken together with tenofovir disoproxil fumarate and a light meal (400 kcalories or less, 20% fat or less) or in the fasted state is recommended. The appropriate dose of Videx EC coadministered with tenofovir disoproxil fumarate in patients with creatinine clearance of less than 60 mL/min has not been established [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

Dosage Forms and Strengths

VIDEX EC (didanosine, USP) Delayed-Release Capsules are white, opaque capsules as described below:

• 125 mg capsule imprinted with “BMS 125 mg 6671” in Tan


• 200 mg capsule imprinted with “BMS 200 mg 6672” in Green


• 250 mg capsule imprinted with “BMS 250 mg 6673” in Blue


• 400 mg capsule imprinted with “BMS 400 mg 6674” in Red

Contraindications

These recommendations are based on either drug interaction studies or observed clinical toxicities.

Allopurinol

Coadministration of didanosine and allopurinol is contraindicated because systemic exposures of didanosine are increased, which may increase didanosine-associated toxicity [see Clinical Pharmacology (12.3)].

Ribavirin

Coadministration of didanosine and ribavirin is contraindicated because exposures of the active metabolite of didanosine (dideoxyadenosine 5′-triphosphate) are increased. Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving both didanosine and ribavirin.

Warnings and Precautions

Pancreatitis

Fatal and nonfatal pancreatitis has occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Videx EC should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Patients treated with Videx EC in combination with stavudine may be at increased risk for pancreatitis.

When treatment with life-sustaining drugs known to cause pancreatic toxicity is required, suspension of Videx EC (didanosine) therapy is recommended. In patients with risk factors for pancreatitis, Videx EC should be used with extreme caution and only if clearly indicated. Patients with advanced HIV-1 infection, especially the elderly, are at increased risk of pancreatitis and should be followed closely. Patients with renal impairment may be at greater risk for pancreatitis if treated without dose adjustment. The frequency of pancreatitis is dose related. [See Adverse Reactions (6).]

Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk [see Use in Specific Populations (8.1)]. Particular caution should be exercised when administering Videx EC to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with VIDEX EC should be suspended in any patient who develops clinical signs or symptoms with or without laboratory findings consistent with symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Hepatic Toxicity

The safety and efficacy of Videx EC have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.

Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. This combination should be avoided. [See Adverse Reactions (6).]

Non-cirrhotic Portal Hypertension

Postmarketing cases of non-cirrhotic portal hypertension have been reported, including cases leading to liver transplantation or death. Cases of didanosine-associated non-cirrhotic portal hypertension were confirmed by liver biopsy in patients with no evidence of viral hepatitis. Onset of signs and symptoms ranged from months to years after start of didanosine therapy. Common presenting features included elevated liver enzymes, esophageal varices, hematemesis, ascites, and splenomegaly.

Patients receiving Videx EC should be monitored for early signs of portal hypertension (eg, thrombocytopenia and splenomegaly) during routine medical visits. Appropriate laboratory testing including liver enzymes, serum bilirubin, albumin, complete blood count, and international normalized ratio (INR) and ultrasonography should be considered. Videx EC should be discontinued in patients with evidence of non-cirrhotic portal hypertension.

Peripheral Neuropathy

Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients receiving didanosine therapy. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, in patients with a history of neuropathy, or in patients being treated with neurotoxic drug therapy, including stavudine. Discontinuation of Videx EC should be considered in patients who develop peripheral neuropathy. [See Adverse Reactions (6).]

Retinal Changes and Optic Neuritis

Retinal changes and optic neuritis have been reported in patients taking didanosine. Periodic retinal examinations should be considered for patients receiving Videx EC [see Adverse Reactions (6)].

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Videx EC. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

 Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections:

• Pancreatitis [see Boxed Warning, Warnings and Precautions (5.1)]


• Lactic acidosis/severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.2)]


• Hepatic toxicity [see Warnings and Precautions (5.3)]


• Non-cirrhotic portal hypertension [see Warnings and Precautions (5.4)]


• Peripheral neuropathy [see Warnings and Precautions (5.5)]


• Retinal changes and optic neuritis [see Warnings and Precautions (5.6)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

Study Al454-152 was a 48-week, randomized, open-label study comparing Videx EC (400  mg once daily) plus stavudine (40 mg twice daily) plus nelfinavir (750 mg three times daily) to zidovudine (300 mg) plus lamivudine (150 mg) combination tablets twice daily plus nelfinavir (750 mg three times daily) in 511 treatment-naive patients. Selected clinical adverse reactions that occurred in combination with other antiretroviral agents are provided in Table 3.

Table 3: Selected Clinical Adverse Reactions, Study AI454-152a

Adverse Reactions	Percent of Patientsb,c
	VIDEX EC + stavudine + nelfinavir n=258	zidovudine/lamivudined + nelfinavir n=253
a Median duration of treatment was 62 weeks in the Videx EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group.
b Percentages based on treated patients.
c The incidences reported included all severity grades and all reactions regardless of causality.
d Zidovudine/lamivudine combination tablet.
* This event was not observed in this study arm.
Diarrhea	57	58
Peripheral Neurologic Symptoms/Neuropathy	25	11
Nausea	24	36
Headache	22	17
Rash	14	12
Vomiting	14	19
Pancreatitis (see below)	less than 1	*

In clinical trials using a buffered formulation of didanosine, pancreatitis resulting in death was observed in one patient who received didanosine plus stavudine plus nelfinavir, one patient who received didanosine plus stavudine plus indinavir, and 2 of 68 patients who received didanosine plus stavudine plus indinavir plus hydroxyurea. In an early access program, pancreatitis resulting in death was observed in one patient who received Videx EC plus stavudine plus hydroxyurea plus ritonavir plus indinavir plus efavirenz [see Warnings and Precautions (5)].

The frequency of pancreatitis is dose related. In phase 3 studies with buffered formulations of didanosine, incidence ranged from 1% to 10% with doses higher than are currently recommended and 1% to 7% with recommended dose.

Selected laboratory abnormalities that occurred in a study of Videx EC in combination with other antiretroviral agents are shown in Table 4.

Table 4: Selected Laboratory Abnormalities, Study AI454-152a

	Percent of Patientsb
	Videx EC + stavudine + nelfinavir n=258		zidovudine/lamivudinec + nelfinavir n=253
Parameter	Grades 3-4d	All Grades	Grades 3-4d	All Grades
a Median duration of treatment was 62 weeks in the Videx EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group.
b Percentages based on treated patients.
c Zidovudine/lamivudine combination tablet.
d Greater than 5 x ULN for SGOT and SGPT, at least 2.1 x ULN for lipase, and at least 2.6 x ULN for bilirubin (ULN = upper limit of normal).
SGOT (AST)	5	46	5	19
SGPT (ALT)	6	44	5	22
Lipase	5	23	2	13
Bilirubin	less than 1	9	less than 1	3

Pediatric Patients

In clinical trials, 743 pediatric patients between 2 weeks and 18 years of age have been treated with didanosine. Adverse reactions and laboratory abnormalities reported to occur in these patients were generally consistent with the safety profile of didanosine in adults.

In pediatric phase 1 studies, pancreatitis occurred in 2 of 60 (3%) patients treated at entry doses below 300 mg/m2/day and in 5 of 38 (13%) patients treated at higher doses. In study ACTG 152, pancreatitis occurred in none of the 281 pediatric patients who received didanosine 120 mg/m2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg/m2 every 12 hours in combination with zidovudine [see Clinical Studies (14)].

Retinal changes and optic neuritis have been reported in pediatric patients.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of didanosine. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to didanosine, or a combination of these factors.

 

Blood and Lymphatic System Disorders - anemia, leukopenia, and thrombocytopenia.

  

 

Body as a Whole - abdominal pain, alopecia, anaphylactoid reaction, asthenia, chills/fever, pain, and redistribution/accumulation of body fat [see Warnings and Precautions (5.8)].

  

 

Digestive Disorders - anorexia, dyspepsia, and flatulence.

  

 

Exocrine Gland Disorders - pancreatitis (including fatal cases) [see Warnings and Precautions (5.1)], sialoadenitis, parotid gland enlargement, dry mouth, and dry eyes.

  

 

Hepatobiliary Disorders - symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [see Warnings and Precautions (5.2)]; non-cirrhotic portal hypertension [see Warnings and Precautions (5.4)]; hepatitis and liver failure.

  

 

Metabolic Disorders - diabetes mellitus, elevated serum alkaline phosphatase level, elevated serum amylase level, elevated serum gamma-glutamyltransferase level, elevated serum uric acid level, hypoglycemia, and hyperglycemia.

  

 

Musculoskeletal Disorders - myalgia (with or without increases in creatine kinase), rhabdomyolysis including acute renal failure and hemodialysis, arthralgia, and myopathy.

  

 

Ophthalmologic Disorders - retinal depigmentation and optic neuritis [see Warnings and Precautions (5.6)].

Use with Stavudine- and Hydroxyurea-Based Regimens

When didanosine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when didanosine is used alone. Thus, patients treated with Videx EC in combination with stavudine, with or without hydroxyurea, may be at increased risk for pancreatitis and hepatotoxicity, which may be fatal, and severe peripheral neuropathy [see Warnings and Precautions (5)]. The combination of Videx EC and hydroxyurea, with or without stavudine, should be avoided.

Drug Interactions

Established Drug Interactions

Clinical recommendations based on the results of drug interaction studies are listed in Table 5. Pharmacokinetic results of drug interaction studies are shown in Tables 9-12 [see Contraindications (4.1 and 4.2), Clinical Pharmacology (12.3)].

Table 5: Established Drug Interactions Based on Studies with Videx EC or Studies with Buffered Formulations of Didanosine and Expected to Occur with Videx EC

Drug	Effect	Clinical Comment
↑ Indicates increase.
↓ Indicates decrease.
a Coadministration of didanosine with food decreases didanosine concentrations. Thus, although not studied, it is possible that coadministration with heavier meals could reduce didanosine concentrations further.
ganciclovir	↑ didanosine concentration	If there is no suitable alternative to ganciclovir, then use in combination with Videx EC with caution. Monitor for didanosine-associated toxicity.
methadone	↓ didanosine concentration	If coadministration of methadone and didanosine is necessary, the recommended formulation of didanosine is Videx EC. Patients should be closely monitored for adequate clinical response when Videx EC is coadministered with methadone, including monitoring for changes in HIV RNA viral load. Do not coadminister methadone with VIDEX pediatric powder due to significant decreases in didanosine concentrations.
nelfinavir	No interaction 1 hour after didanosine	Administer nelfinavir 1 hour after Videx EC.
tenofovir disoproxil fumarate	↑ didanosine concentration	A dose reduction of Videx EC to the following dosage once daily taken together with tenofovir disoproxil fumarate and a light meal (400 kcalories or less and 20% fat or less) or in the fasted state is recommended.a 250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min) 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min) Patients should be monitored for didanosine-associated toxicities and clinical response.

Exposure to didanosine is increased when coadministered with tenofovir disoproxil fumarate [Table 5 and see Clinical Pharmacokinetics (12.3, Tables 9 and 10)]. Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Coadministration of tenofovir disoproxil fumarate with Videx EC should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities and clinical response. Videx EC should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop [see Dosage and Administration (2.3), Warnings and Precautions (5)]. Suppression of CD4 cell counts has been observed in patients receiving tenofovir disoproxil fumarate with didanosine at a dose of 400 mg daily.

Predicted Drug Interactions

Predicted drug interactions with VIDEX EC are listed in Table 6.

Table 6: Predicted Drug Interactions with Videx EC

Drug or Drug Class	Effect	Clinical Comment
↑ Indicates increase.
a Only if other drugs are not available and if clearly indicated. If treatment with life-sustaining drugs that cause pancreatic toxicity is required, suspension of Videx EC is recommended [see Warnings and Precautions (5.1)].
b [See Warnings and Precautions (5.6).]
Drugs that may cause pancreatic toxicity	↑ risk of pancreatitis	Use only with extreme caution.a
Neurotoxic drugs	↑ risk of neuropathy	Use with caution.b

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category B

Reproduction studies have been performed in rats and rabbits at doses up to 12 and 14.2 times the estimated human exposure (based upon plasma levels), respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to didanosine. At approximately 12 times the estimated human exposure, didanosine was slightly toxic to female rats and their pups during mid and late lactation. These rats showed reduced food intake and body weight gains but the physical and functional development of the offspring was not impaired and there were no major changes in the F2 generation. A study in rats showed that didanosine and/or its metabolites are transferred to the fetus through the placenta. Animal reproduction studies are not always predictive of human response.

There are no adequate and well-controlled studies of didanosine in pregnant women. Didanosine should be used during pregnancy only if the potential benefit justifies the potential risk.

Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. It is unclear if pregnancy augments the risk of lactic acidosis/hepatic steatosis syndrome reported in nonpregnant individuals receiving nucleoside analogues [see Warnings and Precautions (5.2)]. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk. Healthcare providers caring for HIV-infected pregnant women receiving didanosine should be alert for early diagnosis of lactic acidosis/hepatic steatosis syndrome.

Antiretroviral Pregnancy Registry

To monitor maternal-fetal outcomes of pregnant women exposed to didanosine and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

Nursing Mothers

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. A study in rats showed that following oral administration, didanosine and/or its metabolites were excreted into the milk of lactating rats. It is not known if didanosine is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving didanosine.

Pediatric Use

Use of didanosine in pediatric patients from 2 weeks of age through adolescence is supported by evidence from adequate and well-controlled studies of didanosine in adult and pediatric patients [see Dosage and Administration (2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)]. Additional pharmacokinetic studies in pediatric patients support use of Videx EC in pediatric patients who weigh at least 20 kg.

Geriatric Use

In an Expanded Access Program using a buffered formulation of didanosine for the treatment of advanced HIV infection, patients aged 65 years and older had a higher frequency of pancreatitis (10%) than younger patients (5%) [see Warnings and Precautions (5.1)]. Clinical studies of didanosine, including those for Videx EC, did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently than younger subjects. Didanosine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. In addition, renal function should be monitored and dosage adjustments should be made accordingly [see Dosage and Administration (2.2)].

Renal Impairment

Patients with renal impairment (creatinine clearance of less than 60 mL/min) may be at greater risk of toxicity from didanosine due to decreased drug clearance [see Clinical Pharmacology (12.3)]. A dose reduction is recommended for these patients [see Dosage and Administration (2)].

Overdosage

There is no known antidote for didanosine overdosage. In phase 1 studies, in which buffered formulations of didanosine were initially administered at doses ten times the currently recommended dose, toxicities included: pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia, and hepatic dysfunction. Didanosine is not dialyzable by peritoneal dialysis, although there is some clearance by hemodialysis [see Clinical Pharmacology (12.3)].

Videx EC Description

VIDEX® EC is the brand name for an enteric-coated formulation of didanosine, USP, a synthetic purine nucleoside analogue active against HIV-1. Videx EC Delayed-Release Capsules, containing enteric-coated beadlets, are available for oral administration in strengths of 125, 200, 250, and 400 mg of didanosine. The inactive ingredients in the beadlets include carboxymethylcellulose sodium 12, diethyl phthalate, methacrylic acid copolymer, sodium hydroxide, sodium starch glycolate, and talc. The capsule shells contain gelatin and titanium dioxide. The capsules are imprinted with edible inks.

Didanosine is also available in a powder formulation. Please consult the prescribing information for VIDEX (didanosine) Pediatric Powder for Oral Solution for additional information.

The chemical name for didanosine is 2′,3′-dideoxyinosine. The structural formula is:

Didanosine is a white crystalline powder with the molecular formula C10H12N4O3 and a molecular weight of 236.2. The aqueous solubility of didanosine at 25° C and pH of approximately 6 is 27.3 mg/mL. Didanosine is unstable in acidic solutions. For example, at pH less than 3 and 37° C, 10% of didanosine decomposes to hypoxanthine in less than 2 minutes. In Videx EC, an enteric coating is used to protect didanosine from degradation by stomach acid.

Videx EC - Clinical Pharmacology

Mechanism of Action

Didanosine is an antiviral agent [see Clinical Pharmacology (12.4)].

Pharmacokinetics

The pharmacokinetic parameters of didanosine in HIV-infected adult and pediatric patients are summarized in Table 7, by weight ranges that correspond to recommended doses (Table 1). Didanosine is rapidly absorbed, with peak plasma concentrations generally observed from 0.25 to 1.50 hours following oral dosing with a buffered formulation. Increases in plasma didanosine concentrations were dose proportional over the range of 50 to 400 mg. In adults, the mean (± standard deviation) oral bioavailability following single oral dosing with a buffered formulation is 42 (±12)%. After oral administration, the urinary recovery of didanosine is approximately 18 (±8)% of the dose. The CSF-plasma ratio following IV administration is 21 (±0.03)%. Steady-state pharmacokinetic parameters did not differ significantly from values obtained after a single dose. Binding of didanosine to plasma proteins in vitro was low (less than 5%). Based on data from in vitro and animal studies, it is presumed that the metabolism of didanosine in man occurs by the same pathways responsible for the elimination of endogenous purines.

Table 7: Pharmacokinetic Parameters for Didanosine in HIV-infected Patients

a The pharmacokinetic parameters (mean ± standard deviation) of didanosine were determined by a population pharmacokinetic model based on combined clinical studies.
Parametera	Pediatrics			Adults
	20 kg to less than 25 kg n=10	25 kg to less than 60 kg n=17	At least 60 kg n=7	At least 60 kg n=44
Apparent clearance (L/h)	89.5 ± 21.6	116.2 ± 38.6	196.0 ± 55.8	174.5 ± 69.7
Apparent volume of distribution (L)	98.1 ± 30.2	154.7 ± 55.0	363 ± 137.7	308.3 ± 164.3
Elimination half-life (h)	0.75 ± 0.13	0.92 ± 0.09	1.26 ± 0.19	1.19 ± 0.21
Steady-state AUC (mg•h/L)	2.38 ± 0.66	2.36 ± 0.70	2.25 ± 0.89	2.65 ± 1.07

Comparison of Didanosine Formulations

In Videx EC, the active ingredient, didanosine, is protected against degradation by stomach acid by the use of an enteric coating on the beadlets in the capsule. The enteric coating dissolves when the beadlets empty into the small intestine, the site of drug absorption. With buffered formulations of didanosine, administration with antacid provides protection from degradation by stomach acid.

In healthy volunteers, as well as subjects infected with HIV-1, the AUC is equivalent for didanosine administered as the Videx EC formulation relative to a buffered tablet formulation. The peak plasma concentration (Cmax) of didanosine, administered as Videx EC, is reduced approximately 40% relative to didanosine buffered tablets. The time to the peak concentration (Tmax) increases from approximately 0.67 hours for didanosine buffered tablets to 2.0 hours for Videx EC.

Effect of Food

In the presence of food, the Cmax and AUC for Videx EC were reduced by approximately 46% and 19%, respectively, compared to the fasting state [see Dosage and Administration (2)]. Videx EC should be taken on an empty stomach.

Special Populations

Renal Insufficiency: Data from two studies using a buffered formulation of didanosine indicated that the apparent oral clearance of didanosine decreased and the terminal elimination half-life increased as creatinine clearance decreased (see Table 8). Following oral administration, didanosine was not detectable in peritoneal dialysate fluid (n=6); recovery in hemodialysate (n=5) ranged from 0.6% to 7.4% of the dose over a 3-4 hour dialysis period. The absolute bioavailability of didanosine was not affected in patients requiring dialysis. [See Dosage and Administration (2.2).]

Table 8: Mean ± SD Pharmacokinetic Parameters for Didanosine Following a Single Oral Dose of a Buffered Formulation

	Creatinine Clearance (mL/min)
Parameter	at least 90 n=12	60-90 n=6	30-59 n=6	10-29 n=3	Dialysis Patients n=11
ND = not determined due to anuria.
CLcr = creatinine clearance.
CL/F = apparent oral clearance.
CLR = renal clearance.
CLcr (mL/min)	112 ± 22	68 ± 8	46 ± 8	13 ± 5	ND

Boots Sore Throat Relief Lozenges Blackcurrant Flavour Sugar Free

1. Name Of The Medicinal Product

Boots Sore Throat Relief Lozenges Blackcurrant Flavour Sugar Free

2. Qualitative And Quantitative Composition

Active ingredient	mg/lozenge
Amylmetacresol BP	0.6

3. Pharmaceutical Form

Lozenge

4. Clinical Particulars

4.1 Therapeutic Indications

For the short-term symptomatic relief of sore throats.

4.2 Posology And Method Of Administration

For oral administration.

Adults, elderly and children over 12 years

One throat drop to be sucked when required up to a maximum of 8 throat drops in 24 hours.

Children 5-12 years

One throat drop to be sucked when required up to a maximum of 4 throat drops in 24 hours.

Children under 5 years

Not suitable.

4.3 Contraindications

Hypersensitivity to any of the ingredients.

4.4 Special Warnings And Precautions For Use

Keep all medicines out of the reach of children.

Do not exceed the stated dose.

If symptoms persist or worsen see your doctor.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically significant interactions are known.

4.6 Pregnancy And Lactation

The safety of this product has not been established during pregnancy and lactation, but is not expected to constitute a hazard. As with all drugs try to avoid taking the product during pregnancy or lactation.

4.7 Effects On Ability To Drive And Use Machines

No adverse effects are known.

4.8 Undesirable Effects

Occasionally hypersensitivity reactions and soreness of the tongue are a possibility.

4.9 Overdose

Slight overdosage should not present a problem other than gastrointestinal discomfort. Treatment should be symptomatic. In cases of severe overdosage, empty the stomach by gastric lavage. Administer a saline laxative and activated charcoal by mouth.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Amylmetacresol has antiseptic properties.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Isomalt

Levomenthol

Anthocyanin (E163)

Blackcurrant Flavour

Malic acid

Aspartame

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

PVC/PVdC strip: 24 months

Bag: 36 months

6.4 Special Precautions For Storage

PVC/PVdC strip: Do not store above 25°C

Store in the original package

Bag: None

6.5 Nature And Contents Of Container

a) PVC/PVdC blister heat sealed to hard tempered aluminium foil:

Blister packed in cardboard carton.

b) Individually wrapped in laminate: Lozenges sealed in a cellophane bag and packed into a carton.

Pack sizes: 6, 8, 10, 12, 16, 18, 20, 24, 30, 32, 36

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

The Boots Company PLC

1 Thane Road West

Nottingham NG2 3AA

8. Marketing Authorisation Number(S)

PL 00014/0603

9. Date Of First Authorisation/Renewal Of The Authorisation

26 February 1998

10. Date Of Revision Of The Text

September 2010

ampicillin

Generic Name: ampicillin (am pi SIL in)

Brand names: Principen, Totacillin, Omnipen, Omnipen-N, Totacillin-N

What is ampicillin?

Ampicillin is an antibiotic in the penicillin group of drugs. It fights bacteria in your body.

Ampicillin is used to treat many different types of infections caused by bacteria, such as ear infections, bladder infections, pneumonia, gonorrhea, and E. coli or salmonella infection.

Ampicillin may also be used for purposes not listed in this medication guide.

What is the most important information I should know about ampicillin?

Do not use this medication if you are allergic to ampicillin or to any other penicillin antibiotic, such as amoxicillin (Amoxil), carbenicillin (Geocillin), dicloxacillin (Dycill, Dynapen), oxacillin (Bactocill), penicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids), and others.

Before using ampicillin, tell your doctor if you are allergic to cephalosporins such as Ceclor, Ceftin, Duricef, Keflex, and others, or if you have asthma, kidney disease, a bleeding or blood clotting disorder, mononucleosis (also called "mono"), or a history of any type of allergy.

Ampicillin can make birth control pills less effective, which may result in pregnancy. Before taking ampicillin, tell your doctor if you use birth control pills. Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Ampicillin will not treat a viral infection such as the common cold or flu. Do not share this medication with another person, even if they have the same symptoms you have.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking ampicillin and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

What should I discuss with my healthcare provider before taking ampicillin?

Do not use this medication if you are allergic to ampicillin or to any other penicillin antibiotic, such as:

• 
  

  amoxicillin (Amoxil, Amoxicot, Biomox, Dispermox, Trimox);

  
  


• 
  

  carbenicillin (Geocillin);

  
  


• 
  

  dicloxacillin (Dycill, Dynapen);

  
  


• 
  

  oxacillin (Bactocill); or

  
  


• 
  

  penicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids, and others).

  
  

To make sure you can safely take ampicillin, tell your doctor if you are allergic to any drugs (especially cephalosporins such as Omnicef, Cefzil, Ceftin, Keflex, and others), or if you have:

• 
  

  asthma;

  
  


• 
  

  kidney disease;

  
  


• 
  

  a bleeding or blood clotting disorder;

  
  


• 
  

  mononucleosis (also called "mono");

  
  


• 
  

  a history of diarrhea caused by taking antibiotics; or

  
  


• 
  

  a history of any type of allergy.

  
  

FDA pregnancy category B. Ampicillin is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Ampicillin can make birth control pills less effective, which may result in pregnancy. Before taking ampicillin, tell your doctor if you use birth control pills. Ampicillin can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are taking ampicillin.

How should I take ampicillin?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take the medicine with a full glass of water. Ampicillin should be taken on an empty stomach, at least 1 hour before or 2 hours after eating a meal.

To be sure this medicine is helping your condition, your blood will need to be tested often. Your liver and kidney function may also need to be tested. Visit your doctor regularly.

If you are being treated for gonorrhea, your doctor may also have you tested for syphilis, another sexually transmitted disease.

Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Ampicillin will not treat a viral infection such as the common cold or flu. Do not share this medication with another person, even if they have the same symptoms you have.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using ampicillin.

Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include confusion, behavior changes, a severe skin rash, urinating less than usual, or seizure (black-out or convulsions).

What should I avoid while taking ampicillin?

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking ampicillin and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Ampicillin side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;

  
  


• 
  

  diarrhea that is watery or bloody;

  
  


• 
  

  fever, chills, body aches, flu symptoms;

  
  


• 
  

  easy bruising or bleeding, unusual weakness;

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  agitation, confusion, unusual thoughts or behavior; or

  
  


• 
  

  seizure (black-out or convulsions).

  
  

Less serious side effects may include

• 
  

  nausea, vomiting, stomach pain;

  
  


• 
  

  vaginal itching or discharge;

  
  


• 
  

  headache;

  
  


• 
  

  swollen, black, or "hairy" tongue; or

  
  


• 
  

  thrush (white patches or inside your mouth or throat).

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ampicillin Dosing Information

Usual Adult Dose for Bacterial Endocarditis Prophylaxis:

Low to moderate risk: 2 g IV or IM 30 minutes before procedure.

High risk: Ampicillin 2 g plus gentamicin 1.5 mg/kg IV or IM 30 minutes before procedure. Follow with ampicillin 1 g IV or IM, or amoxicillin 1 g orally, 6 hours after initial dose.

Usual Adult Dose for Bronchitis:

Bacterial exacerbations of chronic bronchitis:
250 to 500 mg orally every 6 hours for 5 to 10 days, depending on the nature and severity of the infection.

Usual Adult Dose for Endocarditis:

Enterococcal:
Ampicillin 2 g IV every 4 hours plus gentamicin 1 mg/kg IV every 8 hours for 4 to 6 weeks.

Usual Adult Dose for Gastroenteritis:

250 to 500 mg orally every 6 hours.

Usual Adult Dose for Intraabdominal Infection:

1 to 2 g IV every 4 to 6 hours in combination with other antibiotics, depending on the nature and severity of the infection.

Duration: 10-14 days.

Usual Adult Dose for Leptospirosis:

Moderate to severe: 0.5 to 1 g intravenously every 6 hours.
Mild: 500 to 750 mg orally every 6 hours.

Usual Adult Dose for Meningitis:

IV:
200 mg/kg/day (up to 12 g/day) IV in equally divided doses every 4 hours, in combination with other parenteral antibiotics.

Intrathecal or intraventricular:
10 to 50 mg/day in addition to IV antibiotics.

Usual Adult Dose for Peritonitis:

CAPD-associated peritonitis: 250 to 500 mg orally twice daily and/or 100 to 125 mg/L exchange intraperitoneally, with or without other antibiotics depending on the nature and severity of the infection.

Secondary: 1 to 2 g IV every 4 to 6 hours in combination with other antibiotics, depending on the nature and severity of the infection.

Duration: 10 to 14 days.

Usual Adult Dose for Pneumonia:

Beta-lactamase negative, penicillin-susceptible: 1 to 2 g IV every 4 to 6 hours, in combination with other antibiotic(s) depending on the nature and severity of the infection.

Usual Adult Dose for Prevention of Perinatal Group B Streptococcal Disease:

As an alternative to penicillin G: 2 g IV as a loading dose, followed by 1 g every 4 hours until delivery.

Usual Adult Dose for Pyelonephritis:

500 mg to 2 g IV or IM every 4 to 6 hours with or without other antibiotics, depending on the nature and severity of the infection.
Duration: 2 to 3 weeks.

Usual Adult Dose for Septicemia:

1 to 2 g IV every 3 to 4 hours, in combination with other antibiotics.

Usual Adult Dose for Shigellosis:

500 mg orally every 6 hours for 5 days

Usual Adult Dose for Skin or Soft Tissue Infection:

250 to 500 mg orally every 6 hours or 1 to 2 g IV every 4 to 6 hours, depending on the nature and severity of the infection.

Usual Adult Dose for Surgical Prophylaxis:

Liver transplant: Ampicillin 1 g plus cefotaxime 1 g IV at induction, then every 6 hours for 48 hours after closure.

Usual Adult Dose for Typhoid Fever:

Severe, fully susceptible: 25 mg/kg IV or IM every 6 hours for 10 to 14 days.
Carrier state: 1.5 g orally or IV with probenecid 500 mg every 6 hours for 6 weeks.
Fluoroquinolones or amoxicillin are considered the drugs of choice.

Usual Adult Dose for Otitis Media:

500 mg orally or 1 to 2 g IV or IM every 6 hours, depending on the nature and severity of the infection.

Usual Adult Dose for Pharyngitis:

500 mg orally or 1 to 2 g IV or IM every 6 hours, depending on the nature and severity of the infection.

Usual Adult Dose for Sinusitis:

500 mg orally or 1 to 2 g IV or IM every 6 hours, depending on the nature and severity of the infection.

Usual Adult Dose for Upper Respiratory Tract Infection:

500 mg orally or 1 to 2 g IV or IM every 6 hours, depending on the nature and severity of the infection.

Usual Adult Dose for Urinary Tract Infection:

Mild, uncomplicated: 250 to 500 mg orally every 6 hours
Severe, complicated: 500 mg to 2 g IV every 4 to 6 hours with or without other antibiotics, depending on the nature and severity of the infection.

Usual Pediatric Dose for Bacterial Endocarditis Prophylaxis:

Low to moderate risk: 50 mg/kg IV or IM 30 minutes before procedure.

High risk: 50 mg/kg plus gentamicin 1.5 mg/kg, both intramuscularly or IV 30 minutes before procedure. Follow with ampicillin 25 mg/kg IV or IM, or amoxicillin 25 mg/kg orally, 6 hours after initial dose.

Usual Pediatric Dose for Meningitis:

Neonates:
2000 g: 50 mg/kg IV every 8 hours.
> 7 days, birthweight > 7 days, birthweight 1200 to 2000 g: 50 mg/kg IV every 8 hours.
> 7 days, birthweight > 2000 g: 50 mg/kg IV every 6 hours.

Infants and children:
50 to 100 mg/kg IV every 6 hours. Maximum dose 12 g/day.

Ampicillin should be given in combination with another antibiotic, depending on the nature of the infection.

Usual Pediatric Dose for Skin or Soft Tissue Infection:

IV: 6.25 to 12.5 mg/kg every 6 hours (maximum 12 g/day).

Oral: 6.25 to 12.5 mg/kg every 6 hours (maximum 2 to 3 g/day).

Usual Pediatric Dose for Upper Respiratory Tract Infection:

IV: 6.25 to 12.5 mg/kg every 6 hours (maximum 12 g/day).

Oral: 6.25 to 12.5 mg/kg every 6 hours (maximum 2 to 3 g/day).

Usual Pediatric Dose for Surgical Prophylaxis:

Liver transplant: Ampicillin 50 mg/kg plus cefotaxime 50 mg/kg at induction and every 6 hours for 48 hours after closure.

What other drugs will affect ampicillin?

Tell your doctor about all other medicines you use, especially:

• 
  

  allopurinol (Zyloprim);

  
  


• 
  

  methotrexate (Rheumatrex, Trexall);

  
  


• 
  

  probenecid (Benemid);

  
  


• 
  

  a sulfa drug (such as Bactrim or Septra); or

  
  


• 
  

  a tetracycline antibiotic such as demeclocycline (Declomycin), doxycycline (Adoxa, Doryx, Oracea, Vibramycin), minocycline (Dynacin, Minocin, Solodyn, Vectrin), or tetracycline (Brodspec, Panmycin, Sumycin, Tetracap).

  
  

This list is not complete and there may be other drugs that can interact with ampicillin. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More ampicillin resources

• Ampicillin Side Effects (in more detail)
• Ampicillin Use in Pregnancy & Breastfeeding
• Drug Images
• Ampicillin Drug Interactions
• Ampicillin Support Group
• 3 Reviews for Ampicillin - Add your own review/rating

• Ampicillin Prescribing Information (FDA)


• Ampicillin Professional Patient Advice (Wolters Kluwer)


• Ampicillin Monograph (AHFS DI)


• Ampicillin MedFacts Consumer Leaflet (Wolters Kluwer)


• Ampicillin Sodium and Sulbactam Sodium Monograph (AHFS DI)


• Principen Advanced Consumer (Micromedex) - Includes Dosage Information

Compare ampicillin with other medications

• Bacterial Endocarditis Prevention
• Bronchitis
• Endocarditis
• Gastroenteritis
• Intraabdominal Infection
• Kidney Infections
• Leptospirosis
• Meningitis
• Otitis Media
• Peritonitis
• Pharyngitis
• Pneumonia
• Prevention of Perinatal Group B Streptococcal Disease
• Septicemia
• Shigellosis
• Sinusitis
• Skin Infection
• Surgical Prophylaxis
• Typhoid Fever
• Upper Respiratory Tract Infection
• Urinary Tract Infection

Where can I get more information?

• Your pharmacist can provide more information about ampicillin.

See also: ampicillin side effects (in more detail)

Mycophenolate Mofetil

Pronunciation: MYE-koe-FEN-oh-late MOE-fe-til
Generic Name: Mycophenolate Mofetil
Brand Name: CellCept

Mycophenolate Mofetil weakens your immune system, which may decrease your ability to fight illness or infection. It may also increase the risk of certain types of cancer (eg, lymphoma). Use Mycophenolate Mofetil only under close medical supervision.

Mycophenolate Mofetil may cause birth defects or fetal death if taken during pregnancy. Women who may become pregnant must use an effective form of birth control while they are taking Mycophenolate Mofetil.

Mycophenolate Mofetil is used for:

Preventing organ rejection following kidney, liver, or heart transplants. Mycophenolate Mofetil is used in combination with other medicines. It may also be used for other conditions as determined by your doctor.

Mycophenolate Mofetil is an immunosuppressant. It works by decreasing the activity of certain cells that make up part of the immune system to help reduce the risk of organ transplant rejection.

Do NOT use Mycophenolate Mofetil if:

• you are allergic to any ingredient in Mycophenolate Mofetil or to mycophenolic acid


• you are taking azathioprine, cholestyramine, colestipol, or another medicine that contains mycophenolate or mycophenolic acid


• you are taking norfloxacin and metronidazole together


• you have a rare hereditary deficiency of hypoxanthine guanine phosphoribosyl-transferase (HGPRT), such as Lesch-Nyhan syndrome or Kelley-Seegmiller syndrome

Contact your doctor or health care provider right away if any of these apply to you.

Before using Mycophenolate Mofetil:

Some medical conditions may interact with Mycophenolate Mofetil. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have immune system problems or have been taking another medicine that may suppress your immune system


• if you have stomach or intestinal problems (eg, ulcers), or kidney problems


• if you have a personal or family history of skin cancer, blood cancer (eg, lymphoma), or other blood problems


• if you are scheduled for a vaccination


• if you will be in close contact with a person who has shingles, another type of herpes infection, or cytomegalovirus (CMV) infection

Some MEDICINES MAY INTERACT with Mycophenolate Mofetil. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Acyclovir, azathioprine, ganciclovir, mycophenolic acid, or probenecid because they may increase the risk of Mycophenolate Mofetil's side effects


• Cholestyramine, colestipol, cyclosporine, norfloxacin along with metronidazole, or rifampin because they may decrease Mycophenolate Mofetil's effectiveness


• Live vaccines or oral contraceptives because their effectiveness may be decreased by Mycophenolate Mofetil

This may not be a complete list of all interactions that may occur. Ask your health care provider if Mycophenolate Mofetil may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Mycophenolate Mofetil:

Use Mycophenolate Mofetil as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Mycophenolate Mofetil comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Mycophenolate Mofetil refilled.


• Take Mycophenolate Mofetil by mouth on an empty stomach at least 1 hour before or 2 hours after eating unless your doctor tells you otherwise.


• Swallow Mycophenolate Mofetil whole. Do not break, crush, or chew before swallowing.


• Do not take an antacid that has aluminum or magnesium in it within 3 hours of taking Mycophenolate Mofetil.


• If you take a calcium-free phosphate binder (eg, sevelamer), take it 2 hours after taking Mycophenolate Mofetil.


• If you miss a dose of Mycophenolate Mofetil, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Mycophenolate Mofetil.

Important safety information:

• Mycophenolate Mofetil may cause blurred vision, drowsiness, or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Mycophenolate Mofetil with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Women who may become pregnant must have a negative pregnancy test within 1 week before starting Mycophenolate Mofetil.


• Women who may become pregnant must use 2 effective forms of birth control for 4 weeks before they start Mycophenolate Mofetil, during treatment, and for 6 weeks after they stop Mycophenolate Mofetil. Check with your doctor if you have any questions about effective birth control.


• Hormonal birth control (eg, birth control pills) may not work as well while you are taking Mycophenolate Mofetil. Discuss any questions or concerns with your doctor.


• Mycophenolate Mofetil may increase your risk of developing certain types of cancer (eg, lymphoma, skin cancer). Avoid the sun, sunlamps, or tanning booths while you take Mycophenolate Mofetil. Use a sunscreen and wear protective clothing if you must be outside for more than a short time. Tell your doctor right away if you notice a change in the size or color of a mole or if you develop any new or unusual skin growths.


• Mycophenolate Mofetil may lower the ability of your body to fight infection and may increase the risk of severe or fatal infections. Avoid contact with people who have colds, shingles, other herpes infections, cytomegalovirus (CMV), or other infections. Tell your doctor right away if you notice signs of infection like fever, sore throat, rash, or chills.


• Some patients treated with Mycophenolate Mofetil have developed severe and sometimes fatal infections, such as progressive multifocal leukoencephalopathy (PML) or severe kidney problems associated with BK virus infection. Discuss any questions or concerns with your doctor.


• Tell your doctor right away if you notice symptoms of PML (eg, confusion or disorientation; depression; changes in thinking, strength, or vision; one-sided weakness; trouble walking or talking; loss of balance or coordination).


• Tell your doctor right away if you notice symptoms of kidney problems (eg, change in the amount of urine produced, difficult or painful urination, blood in the urine). In kidney transplant patients, BK virus infection may cause loss of the transplanted kidney. Discuss any questions or concerns with your doctor.


• Some patients treated with Mycophenolate Mofetil have developed a type of anemia called pure red cell aplasia (PRCA). Contact your doctor right away if you experience severe or persistent tiredness or weakness, sluggishness, or unusually pale skin.


• Mycophenolate Mofetil may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.


• Diarrhea may occur with Mycophenolate Mofetil. If you develop diarrhea, check with your doctor or pharmacist about ways to lessen this effect. Do not stop Mycophenolate Mofetil without talking with your doctor.


• Do not change brands or doseforms (eg, tablets, suspension, injection) of Mycophenolate Mofetil without talking with your doctor.


• Do not receive a live vaccine (eg, measles, mumps) while you are using Mycophenolate Mofetil. Talk with your doctor before you receive any vaccine.


• Lab tests, including complete blood cell counts and kidney function, may be performed while you use Mycophenolate Mofetil. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Mycophenolate Mofetil with caution in the ELDERLY; they may be more sensitive to its effects, especially infection, stomach or intestinal bleeding, and trouble breathing.


• Caution is advised when using Mycophenolate Mofetil in CHILDREN; they may be more sensitive to its effects.


• PREGNANCY and BREAST-FEEDING: Mycophenolate Mofetil may cause birth defects or fetal death if you take it while you are pregnant. Do not become pregnant while you are taking Mycophenolate Mofetil. If you think you may be pregnant, contact your doctor right away. It is not known if Mycophenolate Mofetil is found in breast milk. Do not breast-feed while taking Mycophenolate Mofetil.

Possible side effects of Mycophenolate Mofetil:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Anxiety; back pain; constipation; cough; diarrhea; dizziness; headache; loss of appetite; mild stomach pain; mild tiredness or weakness; nausea; tremor; trouble sleeping; upset stomach; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; bloody or black stools; change in the amount of urine produced; chest pain or pounding in the chest; fainting; irregular heartbeat; mental or mood changes (eg, abnormal thinking); night sweats; numbness, tingling, or swelling of the arms, legs, hands, ankles, or feet; severe headache, dizziness, or blurred vision; severe vomiting or stomach pain; shortness of breath; sluggishness; swollen glands; symptoms of infection (eg, fever, chills, cough, sore throat); symptoms of urinary tract infection (eg, blood in the urine; difficult, frequent, or painful urination; lower stomach or back pain); unusual bruising or bleeding; unusual or persistent tiredness or weakness; unusual skin lumps or growths; unusual weight loss; unusually pale skin; vomiting blood that looks like coffee grounds; white patches in the mouth or throat; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Mycophenolate Mofetil side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include diarrhea; nausea; vomiting.

Proper storage of Mycophenolate Mofetil:

Store Mycophenolate Mofetil at 77 degrees F (25 degrees C) in a tightly closed container. Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Mycophenolate Mofetil out of the reach of children and away from pets.

General information:

• If you have any questions about Mycophenolate Mofetil, please talk with your doctor, pharmacist, or other health care provider.


• Mycophenolate Mofetil is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Mycophenolate Mofetil. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Mycophenolate Mofetil resources

• Mycophenolate Mofetil Side Effects (in more detail)
• Mycophenolate Mofetil Dosage
• Mycophenolate Mofetil Use in Pregnancy & Breastfeeding
• Drug Images
• Mycophenolate Mofetil Drug Interactions
• Mycophenolate Mofetil Support Group
• 27 Reviews for Mycophenolate Mofetil - Add your own review/rating

• Mycophenolate Mofetil Prescribing Information (FDA)


• mycophenolate mofetil Advanced Consumer (Micromedex) - Includes Dosage Information


• CellCept Prescribing Information (FDA)


• Cellcept Advanced Consumer (Micromedex) - Includes Dosage Information


• Cellcept Consumer Overview

Compare Mycophenolate Mofetil with other medications

• Autoimmune Hepatitis
• Bullous Pemphigoid
• Cogan's Syndrome
• Crohn's Disease
• Dermatomyositis
• Evan's Syndrome
• Graft-versus-host disease
• High Cholesterol
• Inflammatory Bowel Disease
• Multiple Sclerosis
• Myasthenia Gravis
• Nephrotic Syndrome
• Organ Transplant, Rejection Prophylaxis
• Pemphigoid
• Pemphigus
• Psoriatic Arthritis
• Pulmonary Fibrosis
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus
• Ulcerative Colitis
• Uveitis

Mefenamic Acid

Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: N-(2,3-xylyl)anthranilic acid
Molecular Formula: C₁₅H₁₅NO₂
CAS Number: 61-68-7
Brands: Ponstel

• Cardiovascular Risk


• 
  

  Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).^{125 b} Risk may increase with duration of use.^{125 b} Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.^{125 b} (See Cardiovascular Effects under Cautions.)

  
  


• 
  

  Contraindicated for the treatment of pain in the setting of CABG surgery.^{125 b}

  
  

• GI Risk


• 
  

  Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).^{100 104 125 b} Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.^{100 101 104 125 b} Geriatric individuals are at greater risk for serious GI events.^{125 b} (See GI Effects under Cautions.)

  
  

Introduction

Prototypical NSAIA; anthranilic acid derivative (fenamate); structurally and pharmacologically related to meclofenamate sodium.^{125 a}

Uses for Mefenamic Acid

Consider potential benefits and risks of mefenamic acid therapy as well as alternative therapies before initiating therapy with the drug.^{125 b} Use lowest possible effective dosage and shortest duration of therapy consistent with patient’s treatment goals.^{125 b}

Pain

Relief of mild to moderate pain in patients ≥14 years of age when the duration of therapy ≤1 week.^{125 b}

Dysmenorrhea

Treatment of primary dysmenorrhea.^{125 b}

Fever

Has been used for reduction of fever† associated with infection in children; routine use as an antipyretic not recommended because of potential adverse effects.^a

Mefenamic Acid Dosage and Administration

General

• 
  

  Consider potential benefits and risks of mefenamic acid therapy as well as alternative therapies before initiating therapy with the drug.^{125 b}

  
  

Administration

Oral Administration

Administer orally.¹²⁵ May be administered in divided doses up to 4 times daily.¹²⁵

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.^{125 b} Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.^{125 b}

Pediatric Patients

Pain

Oral

Adolescents ≥14 years of age should receive dosage recommended for adults.¹²⁵ (See Adult Dosage.)

Adults

Pain

Oral

For mild to moderate pain in adults, 500 mg initially followed by 250 mg every 6 hours as necessary.¹²⁵

Dysmenorrhea

Oral

For relief of primary dysmenorrhea in adults, 500 mg initially followed by 250 mg every 6 hours as necessary.¹²⁵ Initiate at onset of bleeding and associated symptoms; treatment should not be necessary for >2–3 days.¹²⁵

Prescribing Limits

Pediatric Patients

Pain

Oral

Duration of therapy usually should not exceed 1 week.¹²⁵

Adults

Pain

Oral

Duration of therapy usually should not exceed 1 week.¹²⁵

Dysmenorrhea

Oral

Therapy should not be necessary for more than 2–3 days.¹²⁵

Special Populations

Hepatic Impairment

Dosage reduction may be required.¹²⁵

Renal Impairment

Dosage reduction may be required if used in patients with renal impairment.¹²⁵

Use not recommended in patients with preexisting renal disease or substantial renal impairment.¹²⁵

Geriatric Patients

Select dosage carefully since may be more likely to have decreased renal function.^{125 b}

Cautions for Mefenamic Acid

Contraindications

• 
  

  Known hypersensitivity to mefenamic acid or any ingredient in the formulation.^{125 b}

  
  


• 
  

  History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.^{125 b}

  
  


• 
  

  Treatment of perioperative pain in the setting of CABG surgery.^{125 b}

  
  


• 
  

  Active ulceration or chronic inflammation of upper or lower GI tract.¹²⁵

  
  


• 
  

  Preexisting renal disease.¹²⁵

  
  

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.^{125 129} Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.^{125 133 134 135} Information not available on risk associated with mefenamic acid at this time.^{133 134 135 136}

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events) and at the lowest effective dosage for the shortest duration necessary.^{125 b}

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).^{125 b}

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.^{125 b} (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.^{125 b} Use with caution in patients with hypertension; monitor BP.^{125 b} Impaired response to certain diuretics may occur.^{125 b} (See Specific Drugs under Interactions.)

Fluid retention and edema reported.^{125 b} Caution in patients with fluid retention or heart failure.^{125 b}

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.^{100 104 124 125 126 b}

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;^{124 127 h i} alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)^{124 h i} or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).^{125 h}

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.^{125 b}

Potential for overt renal decompensation.^{125 b} Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.^{125 128 b} (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.^{125 b}

Immediate medical intervention and discontinuance for anaphylaxis.^{125 b}

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.^{125 b}

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.^{125 b} Discontinue at first appearance of rash or any other signs of hypersensitivity (e.g., blisters, fever, pruritus).^{125 b}

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.^{125 b}

Elevations of serum ALT or AST reported.^{125 b}

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.^{125 b} Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur.^{125 b}

Hematologic Effects

Anemia reported rarely.^{125 b} Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.^{125 b}

May inhibit platelet aggregation and prolong bleeding time.^{125 b}

Ocular Effects

Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.^{125 a}

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.^{125 b}

May mask certain signs of infection.^{125 b}

Obtain CBC and chemistry profile periodically during long-term use.^{125 b}

Specific Populations

Pregnancy

Category C.^{125 b} Avoid use in third trimester because of possible premature closure of the ductus arteriosus.^{125 b}

Lactation

Distributed into milk.^{125 c} Discontinue nursing or the drug.¹²⁵

Pediatric Use

Safety and efficacy not established in children <14 years of age.¹²⁵

Geriatric Use

Use with caution in patients ≥65 years of age.^{125 b} Geriatric adults appear to tolerate therapy less well (e.g., possible higher incidence of adverse GI effects, greater risk of developing renal decompensation) than younger individuals.^{125 b} Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.^{125 b}

Substantially eliminated by kidneys; periodic monitoring of renal function may be useful since geriatric patients are more likely to have decreased renal function.¹²⁵ (See Geriatric Patients under Dosage and Administration and Renal Impairment under Cautions.)

Renal Impairment

Use not recommended in patients with preexisting renal disease or substantial renal impairment.¹²⁵

Common Adverse Effects

Abdominal pain,¹²⁵ constipation,¹²⁵ diarrhea,¹²⁵ dyspepsia,¹²⁵ flatulence,¹²⁵ gross bleeding/perforation,¹²⁵ heartburn,¹²⁵ nausea,¹²⁵ GI ulcers (gastric/duodenal),¹²⁵ vomiting,¹²⁵ abnormal renal function,¹²⁵ anemia,¹²⁵ dizziness,¹²⁵ edema,¹²⁵ elevated liver enzymes,¹²⁵ headaches,¹²⁵ increased bleeding time,¹²⁵ pruritus,¹²⁵ rashes,¹²⁵ tinnitus.¹²⁵

Interactions for Mefenamic Acid

Protein-bound Drugs

Possible pharmacokinetic interaction; potential for mefenamic acid to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs (e.g., oral anticoagulants, hydantoins, salicylates, sulfonamides, and sulfonylureas).^{125 a f} Observe for adverse effects if used with other protein-bound drugs.^a

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2C9: possible altered safety and efficacy of mefenamic acid.¹²⁵

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Reduced BP response to ACE inhibitor possible 125 128 b Possible deterioration of renal function in individuals with renal impairment128	Monitor BP128
Angiotensin II receptor antagonists	Reduced BP response to angiotensin II receptor antagonist possible128 Possible deterioration of renal function in individuals with renal impairment128	Monitor BP128
Antacids (magnesium-containing)	Increased peak plasma concentrations and AUC of mefenamic acid125 d
Anticoagulants (e.g., warfarin)	Possible bleeding complications125 128 a b e	Use with caution; frequent monitoring of PT advised125 128 a e
Aspirin	Increased risk of GI ulceration or other complications 125 128 b No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs125 b	Concomitant use generally not recommended125 b
Diuretics (furosemide, thiazides)	Reduced natriuretic effects possible125 b	Monitor for diuretic efficacy and renal failure125 b
Lithium	Increased plasma lithium concentrations105 125 b	Monitor for lithium toxicity105 125 b
Methotrexate	Possible toxicity associated with increased plasma methotrexate concentrations during concomitant NSAIA use125 b	Caution advised125 b

Mefenamic Acid Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration.^{125 a} Peak plasma concentrations usually attained within 2–4 hours.^{125 a}

Food

Effect of food on rate and extent of absorption not known.¹²⁵

Distribution

Extent

Appears to cross the placenta.^g

Distributed into milk in small amounts.^{125 c}

Plasma Protein Binding

>90%.¹²⁵

Elimination

Metabolism

Metabolized by CYP2C9 to 3′-hydroxymethyl mefenamic acid; further oxidation to 3′-carboxymefenamic acid may occur. ¹²⁵ Mefenamic acid and its metabolites also are glucuronidated.¹²⁵

Elimination Route

Excreted in urine (52%) primarily as glucuronic acid conjugates of the drug and its metabolites and in feces (<20%).¹²⁵

Half-life

Mefenamic acid: approximately 2 hours.¹²⁵ Half-lives of 3′-hydroxymethyl mefenamic acid and 3′-carboxymefenamic acid may be longer than parent compound.¹²⁵

Special Populations

Half-life 5 times longer in preterm infants compared with adults.¹²⁵

In patients with renal or hepatic impairment, clearance of metabolites may be decreased.¹²⁵

Not substantially removed by hemodialysis.^{125 a}

Stability

Storage

Oral

Capsules

20–25°C (may be exposed to 15–30°C).^{125 a}

ActionsActions

• 
  

  Inhibits cyclooxygenase-1 (COX-1) and COX-2.^{117 118 119 120 121 122}

  
  


• 
  

  Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.^{125 a}

  
  

Advice to Patients

• 
  

  Importance of reading the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.^{125 b}

  
  


• 
  

  Risk of serious cardiovascular events with long-term use.^{125 133 134 135 136 b} Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.^{125 b}

  
  


• 
  

  Risk of GI bleeding and ulceration.^{100 104 125 b} Importance of notifying a clinician if signs and symptoms of serious adverse GI effects occur.^{125 b}

  
  


• 
  

  Importance of discontinuing mefenamic acid and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.^{125 b} Importance of seeking immediate medical attention if an anaphylactic reaction occurs.^{125 b}

  
  


• 
  

  Risk of hepatotoxicity.^{125 b} Importance of discontinuing therapy and contacting a clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.^{125 b}

  
  


• 
  

  Importance of notifying clinician if signs and symptoms of unexplained weight gain or edema develop.^{125 b}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹²⁵ Importance of avoiding mefenamic acid in late pregnancy (third trimester).¹²⁵

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹²⁵

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹²⁵ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mefenamic Acid

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	250 mg*	Ponstel	First Horizon

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ponstel 250MG Capsules (SHIONOGI PHARMA): 100/$1345.97 or 300/$3989.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Palmer JF. Letter sent to Lents CE, of Parke Davis, Division of Warner-Lambert Company regarding labeling revisions about gastrointestinal adverse reactions to Ponstel (mefenamic acid). Rockville, MD: Food and Drug Administration, Division of Oncology and Radiopharmaceutical Drug Products. 1988 Sep.

101. Food and Drug Administration. Labeling revisions for NSAIDs. FDA Drug Bull. 1989; 19:3-4.

102. Searle. Cytotec (misoprostol) prescribing information. Skokie, IL; 1989 Jan.

104. Soll AH, Weinstein WM, Kurata J et al. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991; 114:307-19. [IDIS 277370] [PubMed 1987878]

105. Nonsteroidal anti-inflammatory drug interactions: Lithium. In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:608-9.

106. Miller LG, Bowman RC, Bakht F. Sparing effect of sulindac on lithium levels. J Fam Prac. 1989; 28:592-3.

107. Corticosteroid interactions: nonsteroidal anti-inflammatory drugs (NSAIDs). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:562.

108. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994; 343:769-72. [IDIS 328176] [PubMed 7907735]

109. Hollander D. Gastrointestinal complications of nonsteroidal anti-inflammatory drugs: prophylactic and therapeutic strategies. Am J Med. 1994; 96:274-81. [IDIS 328041] [PubMed 8154516]

110. Schubert TT, Bologna SD, Yawer N et al. Ulcer risk factors: interaction between Helicobacter pylori infection, nonsteroidal use, and age. Am J Med. 1993; 94:413-7. [IDIS 314155] [PubMed 8475935]

111. Bateman DN, Kennedy JG. Non-steroidal anti-inflammatory drugs and elderly patients: the medicine may be worse than the disease. BMJ. 1995; 310:817-8. [IDIS 345154] [PubMed 7711609]

112. Piper JM, Ray WA, Daugherty JR et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991; 114:735-40. [IDIS 280191] [PubMed 2012355]

113. Lithium interactions: diclofenac. In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:607.

114. Ciba Geigy, Ardsley, NY: Personal communication on diclofenac 28:08.04.

115. Reviewers’ comments (personal observations) on diclofenac 28:08.04.

116. Searle. Cytotec (misoprostol) prescribing information. 1989 Jan.

117. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14. [IDIS 418284] [PubMed 9929039]

118. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8. [PubMed 8967954]

119. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmaco. 1997; 75:1088-95.

120. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.

121. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase—a review. Prostaglandins Other Lipid Mediators. 1998; 56:341-61. [PubMed 9990677]

122. Simon LS, Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(Suppl 5B):37-42S.

123. Morrison BW, Daniels SE, Kotey P et al. Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea: a randomized controlled study. Obstet Gynecol. 1999; 94:504-8. [IDIS 437014] [PubMed 10511349]

124. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999; 340:1888-99. [IDIS 426864] [PubMed 10369853]

125. First Horizon Pharmaceutical Corporation. Ponstel (mefenamic acid) capsules prescribing information. Alpharetta, GA; 2006 Jan.

126. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999; 26(suppl 56):18-24.

127. Lanza FL, and the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol. 1998; 93:2037-46. [IDIS 417402] [PubMed 9820370]

128. Merck & Co., Inc. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2007 Feb.

129. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.

130. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology website (). Accessed 2005 Oct 12.

131. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.

132. Pharmacia. Daypro (oxaprozin) caplets prescribing information. Chicago, IL; 2002 May.

133. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44. [PubMed 16968831]

134. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5. [PubMed 16740558]

135. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6. [PubMed 16968830]

136. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at: .

a. AHFS drug information 2007. McEvoy GK, ed. Mefenamic acid. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2096-9.

b. US Food and Drug Administration. Proposed NSAID Package Insert Labeling Template 1. From the FDA website (). Accessed 10 Oct 2005.

c. Buchanan RA, Eaton CJ, Koeff ST et al. The breast milk excretion of mefenamic acid. Curr Ther Res Clin Exp. 1968; 10: 592-7. [PubMed 4973976]

d. Neuvonen PJ, Kivistö KT. Enhancement of drug absorption by antacids: an unrecognized drug interaction. Clin Pharmacokinet. 1994; 27:120-8. [PubMed 7955775]

e. Chan TY. Adverse interactions between warfarin and nonsteroidal antinflammatory drugs: mechanisms, clinical significance, and avoidance. Ann Pharmacother. 1995; 29:1274-83. [PubMed 8672833]

f. Diana FJ, Veronich K, Kapoor AL. Binding of nonsteroidal anti-inflammatory agents and their effect on binding of racemic warfarin and its enantiomers to human serum albumin. J Pharm Sci. 1989; 78: 195-9. [PubMed 2724076]

g. MacKenzie IZ, Graf AK, Mitchell MD. Prostaglandins in the fetal circulation following maternal ingestion of a prostaglandin synthetase inhibitor during mid-pregnancy. Int J Gynaecol Obstet. 1985; 23: 455-8. [PubMed 2868938]

h. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis; 2002 update. Arthritis Rheum. 2002; 46:328-46. [IDIS 476480] [PubMed 11840435]

i. Anon. Drugs for rheumatoid arthritis. Med Lett Drugs Ther. 2000; 42:57-64. [PubMed 10887424]

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