1.SPORANOX HISTORY
(How was Sporanox discovered?)

Sporanox is a product of Janssen Pharmaceuticals.

Sporanox was approved by the US FDA in March 1997.

Janssen Pharmaceuticals is a member of the Johnson & Johnson family of companies, the world's most comprehensive and broadly based manufacturer of healthcare products, as well as a provider of related services, for the consumer, pharmaceutical, and medical devices and diagnostics markets.

Janssen produces and markets prescription medications in four therapeutic areas:

• central nervous system disorders,
• gastrointestinal health,
• pain management and
• the treatment of fungal infections

Note: World-drugs.net sells generic version of Sporanox

2.SPORANOX FACTS

Sporanox belongs to a class of drugs known as the triazoles. Sporanox is used in the treatment of fungal infections and works by interfering with their growth and repair mechanisms.

Sporanox inhibits the production of a molecule called ergosterol, which is a component of the fungal cell membrane. Damage to this membrane cannot be repaired and this interferes with the cells ability to reproduce. 

3.ABOUT SPORANOX MEDICATION

What are fungi?
Fungi are a major group of living things, originally considered plants but now treated as the separate kingdom Fungi. They occur in all environments on the planet and include important decomposers and parasites. Parasitic fungi infect animals, including humans, other mammals, birds, and insects, with consequences varying from mild itching to death. Other parasitic fungi infect plants.

Mold and yeast are two groups of plants in the fungus family. Both groups can cause allergic reactions. Fungal spores can circulate in the air and may cause allergic rhinitis when inhaled .

What are Fungal Infections?
Fungal infections are caused by microscopic plants (fungi) that can live on the skin. They can live on the dead tissues of the hair, nails, and outer skin layers.

Here are some common types of fungal infections:

Tinea is a type of fungal infection of the hair, skin, or nails. When it's on the skin, tinea usually begins as a small red area the size of a pea. As it grows, it spreads out in a circle or ring. Tinea is often called ringworm because it may look like tiny worms are under the skin (but of course, they're not!). Because the fungi that cause tinea (ringworm) live on different parts of the body, they are named for the part of the body they infect. Scalp ringworm is found on the head, and body ringworm affects the arms, legs, or chest.

Athlete's foot is another type of fungal infection that usually appears between the toes but can also affect toenails and the bottom or sides of the feet.

Histoplasmosis is a fungal infection caused by inhaling dust from spore-infected bird droppings. Histoplasmosis can be a life-threatening fungal infection and commonly occurs in the Southwestern U.S. The acute form is treated with antifungal medication.

Blastomycosis is a fungal infection involving the lungs and occasionally spreading to the skin. The fungus is of unknown natural source. Most reported cases are from the southeastern states and the Mississippi River valley, and occur in men ages 20 to 40. When infection occurs in the lungs, a dry hacking or productive cough, chest pain, fever, chills, drenching sweats, and shortness of breath are initial symptoms. If untreated, the disease slowly causes death. Amphotericin B is highly effective. Improvement begins within a week, with rapid disappearance of organisms.

BLASTOMYCOSIS

Aspergillosis is infection caused by the fungus Aspergillus that usually affects the lungs. Aspergillus is very common and is frequently found in compost heaps, air vents, and airborne dust. Inhalation of Aspergillus spores is the primary cause of aspergillosis.

Aspergillosis usually affects open spaces in the body, such as cavities that have formed in the lungs from preexisting lung diseases. The infection may also occur in the ear canals and sinuses. In the sinuses and lungs, aspergillosis shows up as a ball (aspergilloma) composed of a tangled mass of fungus fibers, blood clots, and white blood cells. The fungus ball gradually enlarges, destroying lung tissue in the process, but usually does not spread to other areas.

Less often, aspergillosis can become very aggressive and rapidly spread throughout the lungs and often through the bloodstream to the brain and kidneys. This rapid spread occurs mainly in people with a weakened immune system.

In addition to causing infection, Aspergillus sometimes produces an allergic reaction when it is present on a person's skin or mucous membranes

ASPERGILLOSIS

Jock itch is a fungal infection of the groin and upper thighs. You might think only men and boys get it, but girls and women can get it, too.

Onychomycosis
A fingernail or toenail infection that is caused by a fungus is called onychomycosis. Toenails are more likely to become infected than fingernails.

This infection can make your nails thick and discolored. Your nails may also be brittle or change their shape. You may even have pain in your toes or fingertips.

Candida is a type of yeast, similar to a fungus. It most often affects the skin around the nails or the soft, moist areas around body openings. Diaper rash in babies is one type of candidal infection, as is thrush (white patches often found in the mouths of babies.) Older girls and women may develop another form of candidal infection in and around the vagina. This is called a yeast infection.

Oral Thrush (in the mouth) looks like white or red patches. It can cause sore throat, pain when swallowing, and nausea. It can also take away your appetite, make eating painful, and make food taste different. Treatments for oral thrush include mouthwash and tablets called troches. Some people try baking soda or hydrogen peroxide mixed with water to rinse the mouth. If the thrush is advanced, this isn't likely to work. 

Vaginal candidiasis is a common yeast infection of the vagina. A yeast infection may be the first sign that a woman is HIV+. Symptoms include severe itching, burning, and a thick discharge, often white in color. It is possible that an infection such as unrecognized TB may be causing a vaginal yeast infection. Nystatin tablets are used for treatment. Clotrimazole ointment is another treatment, which is sold over-the-counter as Gyne-Lotrimin, Lotrimin, or Mycelex. Studies have shown that HIV-negative women may only have to take the drug Fluconazole one time to treat this condition. Always consult with your doctor before beginning treatment.

Cryptococcal meningitis is a very serious fungal infection. It is caused by a fungus found mainly in dirt and bird droppings. Meningitis means swelling of the meninges. The meninges cover the brain and spinal cord. 

What are Antifungals?
Antifungals are drugs that are used to treat fungal infections. Like antibiotics, antifungals stop the fungus from functioning normally. But there are not as many different groups of antifungals as there are antibiotics.

Antifungal Agents include
Polyene antibiotics (macrolides)

Amphotericin B - binds to ergosterol moiety in the plasma membrane causing derangement of the membrane integrity and leakage of cytoplasmic contents. Administered systemically.

Nystatin - binds to ergosterol and disrupts plasma membrane. Highly insoluble and toxic and therefore used topically only.

Azoles
Block ergosterol synthesis at one or more sites with the accumulation of 14 -methyl sterol (which replaces ergosterol in the plasma membrane causing selective leakage and increased osmotic sensitivity). They also disrupt chitin synthesis. All effects are due to the binding to cytochrome P-450.

• Butoconazole
• Clotrimazole
• Econazole
• Fluconazole
• Itraconazole
• Ketoconazole
• Miconazole
• Oxiconazole
• Sulconazole
• Terconazole  

Allylamines
Naftifine - Binds to and inhibits squalene epoxidase which blocks ergosterol synthesis.
Terbinafine - Binds to and inhibits squalene epoxidase which blocks ergosterol synthesis.

Pyrimidine analogs
Flucytosine - It is deaminated to fluracil where it is either (1) incorporated into RNA in place of uracil where it inhibits protein synthesis or (2) metabolized to 5-fluorodeoxy-uridylic acid where it inhibits thymidylate synthetase, thus blocking DNA synthesis.

Miscellaneous types
Griseofulvin - causes disruption of the mitotic spindle by interacting with polymerized microtubules through binding to microtubule protein. Administered systemically for dermatophytic infections.

Haloprogin - a halogenated phenolic ether administered topically for dermatophytic infections.

Ciclopirox olamine - a topical for the treatment of dermatophytic infections and Candida albicans.

Tolnaftate - a thiocarbonate used to treat dermatophytic infections.

Potassium iodide - Given orally for sporotrichosis 

4.SPORANOX EFFECTIVENESS
(When is Sporanox best taken?)

In vitro studies have demonstrated that Sporanox inhibits the cytochrome P-450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes

Pharmacokinetics and Metabolism
The plasma concentrations reported below were measured by high performance liquid chromatography (HPLC) specific for Sporanox. When Sporanox in plasma is measured by a bioassay, values reported are approximately 3.3 times higher than those obtained by HPLC due to the presence of the bioactive metabolite, hydroxyitraconazole.

The pharmacokinetics of Sporanox after its absolute oral bioavailability from an oral solution were studied in a randomized cross-over study using six healthy male volunteers. The total plasma clearance averaged 381 ± 95 ml/min and the apparent volume of distribution averaged 796 ± 185 l. The observed absolute oral bioavailability of Sporanox was 55%.

The oral bioavailability of itraconazole is maximal when Sporanox is taken with a full meal. The pharmacokinetics of Sporanox were studied using six healthy male volunteers who received, in a cross-over design, single 100 mg doses of Sporanox as a polyethylene glycol capsule, with or without a full meal. The same six volunteers also received 50 mg or 200 mg with a full meal in a cross-over design. In this study, only Sporanox plasma concentrations were measured.

Results of the pharmacokinetics study suggest that Sporanox may undergo saturation metabolism with multiple dosing.

Sporanox is extensively metabolized by the liver into a large number of metabolites, including hydroxyitraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the Sporanox dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a Sporanox dose. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N- dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission. 

Plasma concentrations of Sporanox in subjects with renal insufficiency were comparable to those obtained in healthy subjects. The effect of hepatic impairment on the plasma concentration of Sporanox is unknown. It is recommended that plasma concentrations of Sporanox in patients with hepatic impairment be carefully monitored. 

The plasma protein binding of itraconazole is 99.8% and that of hydroxyitraconazole is 99.5%. Sporanox is not removed by hemodialysis.

In animal studies, Sporanox is extensively distributed into lipophilic tissues. Concentrations of Sporanox in fatty tissues, omentum, liver, kidney and skin tissues are 2-20 times the corresponding plasma concentrations. Aqueous fluids such as cerebrospinal fluid and saliva contain negligible amounts of the drug.

5.SPORANOX EFFECTS ON SPECIAL POPULATION
(How do different people react to Sporanox?)

Pregnancy Category C:

Sporanox was found to cause a dose-related increase in maternal toxicity, embryotoxicity and teratogenicity in rats at dosage levels at approximately 40-160 mg/kg/day and in mice at dosage levels of approximately 80 mg/kg/day. In rats, the teratogenicity consisted of major skeletal defects; in mice it consisted of encephaloceles and/or macroglossia.

There are no studies in pregnant women. Sporanox should be used for the treatment of systemic fungal infections in pregnancy only if the benefit outweighs the potential risk. Sporanox should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. Sporanox should not be administered to women of child-bearing potential for the treatment of onychomycosis unless they are taking effective measures to prevent pregnancy and the patient begins therapy on the second or third day of the next normal menstrual period. Effective contraception should be continued throughout Sporanox therapy and for 2 months following treatment.

Nursing Mothers
Sporanox is excreted in human milk; therefore, Sporanox should not be administered to nursing women.

Pediatric Use
The efficacy and safety of Sporanox have not been established in pediatric patients. No pharmacokinetic data are available in children. A small number of patients from age 3 to 16 years have been treated with 100 mg/day of Sporanox for systemic fungal infections and no serious unexpected adverse effects have been reported.

6.SPORANOX EFFECTS ON MEDICAL CONDITIONS
(How does Sporanox affect your existing condition/ailment?)

HIV-infected Patients
Because hypochlorhydria has been reported in HIV-infected individuals, the absorption of Sporanox in these patients may be decreased.

The results from a study in which eight HIV-infected individuals were treated with zidovudine, 8 ± 0.4 mg/kg/day, showed that the pharmacokinetics of zidovudine were not affected during concomitant administration of Sporanox, 100 mg b.i.d. 

Sporanox should not be used if you suffer from liver disease, decreased kidney function or numbness and weakness in the extremities, caused by damage to the nerves (peripheral neuropathy). 

7.OTHER/ALTERNATE USES OF SPORANOX
(What else does Sporanox treat?)

Sporanox is also useful in treating systemic (whole body) fungal infections and to prevent them from developing in those with a depleted immune system (for example, AIDS).

8.ADVERSE/SIDE EFFECTS of SPORANOX
(What are the side effects of Sporanox?)

In U.S. clinical trials prior to marketing, there have been three cases of reversible idiosyncratic hepatitis reported among more than 2500 patients. One patient outside the U.S. developed fulminant hepatitis and died during Sporanox administration. Because this patient was on multiple medications, the causal association with Sporanox is uncertain.

Onychomycosis
Adverse events in the following table led to either temporary or permanent discontinuation of treatment:

Systemic Fungal Infections
Adverse experience data in the following table are derived from 602 patients treated for systemic fungal disease in U.S. clinical trials, which were immunocompromised or receiving multiple concomitant medications. Of these patients, treatment was discontinued in 10.5% of patients due to adverse events. The median duration before discontinuation of therapy was 81 days, with a range of 2-776 days. The table lists adverse events reported by at least 1% of patients.

Adverse events infrequently reported in all studies indicated: constipation, gastritis, depression, insomnia, tinnitus, menstrual disorder, adrenal insufficiency, gynecomastia and male breast pain.

In worldwide postmarketing experience with Sporanox, allergic reactions including rash, pruritus, urticaria, angioedema and in rare instances, anaphylaxis and Stevens-Johnson syndrome, have been reported. Marketing experiences have also included reports of elevated liver enzymes and rare hepatitis. Although the causal association with Sporanox is uncertain, rare hypertriglyceridemia and isolated cases of neuropathy have also been reported.