Septra

Septra is part of the drug class:

• Intermediate acting sulfonamides

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• warfarin (Coumadin, Jantoven)
• phenytoin (Dilantin)
• methotrexate (Trexall, Rheumatrex)
• cyclosporine (Gengraf, Neoral, Sandimmune)
• digoxin (Lanoxin)
• pyrimethamine (Daraprim)
• indomethacin (Indocin)
• leucovorin (Wellcovorin)
• thiazide diuretics such as hydrochlorothiazide (Esidrix, HydroDiuril, Hydro-Par, Oretic) and chlororthalidone (Thalitone, Hygroton)
• medications that use the enzyme CYP2C8 such as pioglitazone (Actos), repaglinide (Prandin), and rosiglitazone (Avandia)
• medications that use the enzyme CYP2C9 such as glipizide (Glucotrol) and glyburide (Micronase, DiaBeta)
• metformin (Glucophage)

This is not a complete list of Septra drug interactions. Ask your doctor or pharmacist for more information.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Septra, there are no specific foods that you must exclude from your diet when receiving Septra.

Take Septra exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Septra dose your doctor recommends will be based on:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your kidney function
• your body size (body surface area)
• your age
• your weight

The recommended dose range for Septra in adults is 160 mg/80 mg to 2000 mg/400 mg.

The recommended dose range for Septra in children is 80 mg/40 mg to 2000 mg/400 mg.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of sulfamethoxazole and trimethoprim combination in children 2 months of age and older. Because of the toxicity of the combination of sulfamethoxazole and trimethoprim, use in infants younger than 2 months of age is not recommended.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of sulfamethoxazole and trimethoprim combination in the elderly. However, elderly patients are more likely to have a folate deficiency, age-related kidney or liver problems, and may be more likely to experience unwanted side effects (eg, severe skin rash, increased potassium in the body, or problems with blood clotting or the immune system). There may be an adjustment in the dose for elderly patients receiving sulfamethoxazole and trimethoprim combination.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Dofetilide
• Levomethadyl
• Methenamine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Acenocoumarol
• Ajmaline
• Amiloride
• Amiodarone
• Amitriptyline
• Amoxapine
• Aprindine
• Arsenic Trioxide
• Astemizole
• Azathioprine
• Azilsartan
• Azilsartan Medoxomil
• Azimilide
• Benazepril
• Bretylium
• Candesartan Cilexetil
• Captopril
• Ceritinib
• Chloral Hydrate
• Chloroquine
• Chlorpromazine
• Cholera Vaccine, Live
• Clarithromycin
• Desipramine
• Dibenzepin
• Digoxin
• Disopyramide
• Dolasetron
• Doxepin
• Droperidol
• Eltrombopag
• Enalapril
• Enalaprilat
• Enflurane
• Eplerenone
• Eprosartan
• Erythromycin
• Flecainide
• Fluconazole
• Fluoxetine
• Foscarnet
• Fosinopril
• Gemifloxacin
• Halofantrine
• Haloperidol
• Halothane
• Hydroquinidine
• Ibutilide
• Imipramine
• Irbesartan
• Isoflurane
• Isradipine
• Leucovorin
• Lidoflazine
• Lisinopril
• Lorcainide
• Losartan
• Mefloquine
• Mercaptopurine
• Methotrexate
• Moexipril
• Nortriptyline
• Octreotide
• Olmesartan Medoxomil
• Pentamidine
• Perindopril
• Pirmenol
• Prajmaline
• Probucol
• Procainamide
• Prochlorperazine
• Propafenone
• Pyrimethamine
• Quinapril
• Quinidine
• Ramipril
• Risperidone
• Sematilide
• Sertindole
• Sotalol
• Spiramycin
• Spironolactone
• Sultopride
• Tedisamil
• Telithromycin
• Telmisartan
• Trandolapril
• Triamterene
• Trifluoperazine
• Trimipramine
• Valsartan
• Vasopressin
• Warfarin
• Zofenopril
• Zotepine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetohexamide
• Amantadine
• Aminolevulinic Acid
• Anisindione
• Didanosine
• Fosphenytoin
• Phenytoin
• Repaglinide
• Rifabutin
• Rosiglitazone
• Tolbutamide

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, history of or
• Folate (vitamin B9) deficiency or
• HIV or AIDS or
• Kidney disease or
• Liver disease or
• Malabsorption syndrome (difficulty of absorbing food in the body) or
• Malnutrition state (nutrition disorder)—Use with caution. May have an increased chance of serious side effects.

• Anemia, megaloblastic (caused by low levels of folic acid in the body) or
• Drug-induced thrombocytopenia (low platelets in the blood) after using this medicine or
• Kidney disease, severe or
• Liver disease, severe—Should not be used in patients with these conditions.

• Asthma or
• Diabetes or
• Hyperkalemia (high potassium in the blood) or
• Hyponatremia (low sodium in the blood) or
• Porphyria (enzyme problem) or
• Severe allergies or
• Thyroid problems—Use with caution. May make these conditions worse.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency (an enzyme problem)—May cause hemolytic anemia (blood disorder) in patients with this condition.

• Streptococcal infection (group A β-hemolytic)—Sulfonamides should not be used in patients with this condition.

Septra (trimethoprim and sulfamethoxazole) is a synthetic antibacterial combination product. Each Septra Tablet contains 80 mg trimethoprim and 400 mg sulfamethoxazole and the inactive ingredients docusate sodium (0.4 mg per tablet), FD&C Red No. 40, magnesium stearate, povidone, and sodium starch glycolate.

Each Septra DS (double strength) Tablet contains 160 mg trimethoprim and 800 mg sulfamethoxazole and the inactive ingredients docusate sodium (0.8 mg per tablet), FD&C Red No. 40, magnesium stearate, povidone, and sodium starch glycolate.

Each teaspoonful (5 mL) of Septra Suspension contains 40 mg trimethoprim and 200 mg sulfamethoxazole and the inactive ingredients alcohol 0.26%, methylparaben 0.1% and sodium benzoate 0.1% (added as preservatives), carboxymethylcellulose sodium, citric acid, FD&C Red No. 40 and Yellow No. 6, flavor, glycerin, microcrystalline cellulose, polysorbate 80, saccharin sodium, and sorbitol. Each teaspoonful (5 mL) of Septra Grape Suspension contains 40 mg trimethoprim and 200 mg sulfamethoxazole and the inactive ingredients alcohol 0.26%, methylparaben 0.1%, and sodium benzoate 0.1% (added as preservatives), carboxymethylcellulose sodium, citric acid, FD&C Red No. 40 and Blue No. 1, flavor, glycerin, microcrystalline cellulose, polysorbate 80, saccharin sodium, and sorbitol. Both tablet and suspension forms are for oral administration.

Trimethoprim is 5-[(3,4,5-trimeth-oxyphenyl)methyl]-2,4- pyrimidinediamine. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.32, and the molecular formula C14H18N4O3. The structural formula is:

Sulfamethoxazole is 4-amino-N-(5-methyl-3-isoxazolyl)benzenesulfonamide. It is an almost white, odorless, tasteless compound with a molecular weight of 253.28, and the molecular formula C10H11N3O3S. The structural formula is:

Septra is rapidly absorbed following oral administration. Both sulfamethoxazole and trimethoprim exist in the blood as unbound, protein-bound, and metabolized forms; sulfamethoxazole also exists as the conjugated form. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation, although the glucuronide conjugate has been identified. The principal metabolites of trimethoprim are the 1- and 3-oxides and the 3'- and 4'-hydroxy derivatives. The free forms of sulfamethoxazole and trimethoprim are considered to be the therapeutically active forms. Approximately 44% of trimethoprim and 70% of sulfamethoxazole are bound to plasma proteins. The presence of 10 mg percent sulfamethoxazole in plasma decreases the protein binding of trimethoprim by an insignificant degree; trimethoprim does not influence the protein binding of sulfamethoxazole.

Peak blood levels for the individual components occur 1 to 4 hours after oral administration. The mean serum half-lives of sulfamethoxazole and trimethoprim are 10 and 8 to 10 hours, respectively. However, patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage regimen adjustment (see DOSAGE AND ADMINISTRATION). Detectable amounts of trimethoprim and sulfamethoxazole are present in the blood 24 hours after drug administration. During administration of 160 mg trimethoprim and 800 mg sulfamethoxazole b.i.d., the mean steady-state plasma concentration of trimethoprim was 1.72 mcg/mL. The steady-state minimal plasma levels of free and total sulfamethoxazole were 57.4 mcg/mL and 68.0 mcg/mL, respectively. These steady-state levels were achieved after 3 days of drug administration.1

Excretion of sulfamethoxazole and trimethoprim is primarily by the kidneys through both glomerular filtration and tubular secretion. Urine concentrations of both sulfamethoxazole and trimethoprim are considerably higher than are the concentrations in the blood. The average percentage of the dose recovered in urine from 0 to 72 hours after a single oral dose is 84.5% for total sulfonamide and 66.8% for free trimethoprim. Thirty percent of the total sulfonamide is excreted as free sulfamethoxazole, with the remaining as N4-acetylated metabolite.2 When administered together as Septra, neither sulfamethoxazole nor trimethoprim affects the urinary excretion pattern of the other.

Both trimethoprim and sulfamethoxazole distribute to sputum, vaginal fluid, and middle ear fluid; trimethoprim also distributes to bronchial secretions, and both pass the placental barrier and are excreted in human milk.

Geriatric Pharmacokinetics:

The pharmacokinetics of sulfamethoxazole 800 mg and trimethoprim 160 mg were studied in 6 geriatric subjects (mean age: 78.6 years) and 6 young healthy subjects (mean age: 29.3 years) using a non-US approved formulation. Pharmacokinetic values for sulfamethoxazole in geriatric subjects were similar to those observed in young adult subjects. The mean renal clearance of trimethoprim was significantly lower in geriatric subjects compared with young adult subjects (19 mL/h/kg vs. 55 mL/h/kg). However, after normalizing by body weight, the apparent total body clearance of trimethoprim was an average 19% lower in geriatric subjects compared with young adult subjects.3

Microbiology:

Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus, Septra blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria.

In vitro studies have shown that bacterial resistance develops more slowly with Septra than with either trimethoprim or sulfamethoxazole alone.

In vitro serial dilution tests have shown that the spectrum of antibacterial activity of Septra includes the common urinary tract pathogens with the exception of Pseudomonas aeruginosa. The following organisms are usually susceptible: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and indole-positive Proteus species including Proteus vulgaris.

The usual spectrum of antimicrobial activity of Septra includes bacterial pathogens isolated from middle ear exudate and from bronchial secretions (Haemophilus influenzae, including ampicillin-resistant strains, and Streptococcus pneumoniae), and enterotoxigenic strains of Escherichia coli (ETEC) causing bacterial gastroenteritis. Shigella flexneri and Shigella sonnei are also usually susceptible.

TMP=trimethoprim

SMX=sulfamethoxazole

*Rudoy RC, Nelson JD, Haltalin KC. Antimicrobial Agents and Chemotherapy. 1974;5:439-443.

Susceptibility Testing:

The recommended quantitative disc susceptibility method may be used for estimating the susceptibility of bacteria to Septra.4,5 With this procedure, a report from the laboratory of "Susceptible to trimethoprim and sulfamethoxazole" indicates that the infection is likely to respond to therapy with Septra. If the infection is confined to the urine, a report of "Intermediate susceptibility to trimethoprim and sulfamethoxazole" also indicates that the infection is likely to respond. A report of "Resistant to trimethoprim and sulfamethoxazole" indicates that the infection is unlikely to respond to therapy with Septra.

Septra contains a combination of sulfamethoxazole and trimethoprim. Sulfamethoxazole and trimethoprim are are both antibiotics that treat different types of infection caused by bacteria.

Septra is used to treat ear infections, urinary tract infections, bronchitis, traveler's diarrhea, shigellosis, and Pneumocystis jiroveci pneumonia.

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

You should not use Septra if you have severe liver or kidney disease, anemia caused by folic acid deficiency, or a history of low blood platelets caused by taking trimethoprim or any sulfa drug.

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 this medication and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Avoid exposure to sunlight or tanning beds. This medication can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.