1. LAMISIL HISTORY
(How was Lamisil discovered?)

Lamisil is a product of Novartis Pharmaceuticals.

Novartis Pharmaceuticals Corporation is the U.S. affiliate of Novartis AG, a world leader in healthcare.

Novartis has core businesses in pharmaceuticals, consumer health, generics, eye care, and animal health.

In the U.S. , Novartis has quickly achieved a reputation as an industry leader.

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

2.LAMISIL FACTS

Lamisil inhibits ergosterol biosynthesis via inhibition of squalene epoxidase. This enzyme is part of the fungal sterol synthesis pathway that creates the sterols needed for the fungal cell membrane.

The cell membranes of fungi are vital for their survival. They keep unwanted substances from entering the cells and stop the contents of the cells from leaking out. As Lamisil causes holes to appear in the cell membranes, essential constituents of the fungal cells can leak out. This kills the fungi and hence clears up the infection. 

Uses of Lamisil

Lamisil Tablets are indicated for the treatment of onychomycosis (fungal or parasitic infections) of the toenail or fingernail due to dermatophytes.

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.

3.ABOUT LAMISIL 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.

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.

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. Treatments for thrush include Fluconazole. 

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.

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. 

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.LAMISIL EFFECTIVENESS
(When is Lamisil best taken?)

Following oral administration, Lamisil is well absorbed (>70%) and the bioavailability of Lamisil (terbinafine hydrochloride tablets) Tablets as a result of first-pass metabolism is approximately 40%.

Peak plasma concentrations of 1 µg/mL appear within 2 h after a single Lamisil dose of 250 mg. An increase in the AUC of terbinafine of less than 20% is observed when Lamisil is administered with food. No clinically relevant age-dependent changes in steady-state plasma concentrations of Lamisil have been reported. In patients with renal impairment (creatinine clearance < 50 mL/min) or hepatic cirrhosis, the clearance of Lamisil is decreased by approximately 50% compared to normal volunteers.

No effect of gender on the blood levels of terbinafine was detected in clinical trials. In plasma, Lamisil is >99% bound to plasma proteins and there are no specific binding sites. At steady-state, in comparison to a single Lamisil dose, the peak concentration of Lamisil is 25% higher and plasma AUC increases by a factor of 2.5; the increase in plasma AUC is consistent with an effective half-life of ~36 hours. Lamisil is distributed to the sebum and skin. A terminal half-life of 200-400 h may represent the slow elimination of Lamisil from tissues such as skin and adipose. Prior to excretion, Lamisil is extensively metabolized. No metabolites have been identified that have antifungal activity similar to Lamisil. Approximately 70% of the administered dose is eliminated in the urine. 

5.LAMISIL EFFECTS ON SPECIAL POPULATION
(How do different people react to Lamisil?)

Studies in animals using large dosages of Lamisil have not demonstrated toxic effects on the fetus; however, there have not been conclusive studies in humans. Since fungal infections of the skin and nails usually are not a serious problem, the manufacturer of Lamisil does not recommend therapy during pregnancy.

There is no data on the use of Lamisil during breast-feeding. Nursing mothers should avoid using Lamisil on the breast or taking the drug orally.

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

Lamisil tablets should be used with caution in patients with decreased kidney or liver function and psoriasis.

7.OTHER/ALTERNATE USES OF LAMISIL
(What else does Lamisil treat?)

Lamisil is also used in the treatment of ringworm infections.

8.ADVERSE/SIDE EFFECTS of LAMISIL
(What are the side effects of Lamisil?)

The most frequently reported adverse events observed in the placebo-controlled trials are listed in the table below.

The adverse events reported encompass gastrointestinal symptoms including

• diarrhea,
• dyspepsia,
• abdominal pain,

Other symptoms include

• liver test abnormalities,
• rashes,
• urticaria,
• pruritus, and
• taste disturbances.

In general, the adverse events were mild, transient, and did not lead to discontinuation from study participation. 

Rare adverse events, based on worldwide experience with Lamisil (terbinafine hydrochloride tablets) Tablets use, include: idiosyncratic and symptomatic hepatic injury and more rarely, cases of liver failure, some leading to death or liver transplant, serious skin reactions, severe neutropenia, thrombocytopenia and allergic reactions (including anaphylaxis). Uncommonly, Lamisil may cause taste disturbance (including taste loss), which usually recovers within several weeks after discontinuation of the drug. There have been isolated reports of prolonged (greater than one year) taste disturbance. Rarely, taste disturbances associated with oral Lamisil have been reported to be severe enough to result in decreased food intake leading to significant and unwanted weight loss.

Other adverse reactions, which have been reported, include malaise, fatigue, vomiting, arthralgia, myalgia, and hair loss.

Clinical adverse effects reported spontaneously since the drug was marketed include altered prothrombin time (prolongation and reduction) in patients concomitantly treated with warfarin and Lamisil (terbinafine hydrochloride tablets) Tablets and agranulocytosis (rare).