Simplevir

Tablet: Simplevir oral formulations are indicated for the treatment of herpes simplex virus infections of the skin and mucous membranes including initial and recurrent genital herpes.

Simplevir oral formulations are indicated for the suppression (prevention of recurrences) of recurrent herpes simplex infections in immune-competent patients. Simplevir oral formulations are indicated for the prophylaxis of herpes simplex infections in immune-compromised patients.

Simplevir oral formulations are indicated for the treatment of varicella infections (chicken-pox) and herpes zoster (shingles).

Studies have shown that early treatment of shingles with Simplevir has a beneficial effect on pain and can reduce the incidence of post-herpetic neuralgia (zoster-associated pain).

Simplevir oral formulations are indicated for the management of certain severely immunocompromised patients, namely those with advanced HIV disease (CD4+ counts <200/mm³, including patients with AIDS or severe ARC) or following bone marrow transplantation.

Studies have shown that oral Simplevir given in conjunction with antiretroviral therapy (mainly oral RETROVIR) reduced mortality in patients with advanced HIV disease and that oral Simplevir preceded by one month's treatment with intravenous Simplevir reduced mortality in bone marrow transplant recipients. In addition, oral Simplevir provided effective prophylaxis for herpes virus disease.

Injection: Simplevir IV for infusion is indicated for the treatment of herpes simplex infections, prophylaxis of herpes simplex infections in immune-compromised patients, treatment of varicella zoster infections, herpes simplex infections in the neonate.

Simplevir belongs to the family of medicines called antivirals, which are used to treat infections caused by viruses. Usually these medicines work for only one kind or group of virus infections.

Simplevir is used to treat the symptoms of chickenpox, shingles, herpes virus infections of the genitals (sex organs), the skin, the brain, and mucous membranes (lips and mouth), and widespread herpes virus infections in newborns. Simplevir is also used to prevent recurrent genital herpes infections. Although Simplevir will not cure herpes, it does help relieve the pain and discomfort and helps the sores (if any) heal faster.

Simplevir may also be used for other virus infections as determined by your doctor. However, it does not work in treating certain virus infections, such as the common cold.

Simplevir is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although not specifically included in product labeling, Simplevir by injection is used in certain patients with the following medical conditions:

• Herpes simplex (for prevention of repeated infections) in people with a weak immune system
• Herpes zoster infections of the eye
• Shingles (for prevention of repeated infections) in people with a weak immune system

Tablet: Adults: Treatment of Herpes Simplex: For treatment of herpes simplex infections, 200 mg Simplevir should be taken five times daily at approximately four-hourly intervals omitting the night time dose. Treatment should continue for five days but in severe initial infections may have to be extended.

In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.

Dosing should begin as early as possible after the start of an infection; for recurrent episodes this should preferably be during the prodromal period or when lesions first appear.

Suppression of Herpes Simplex: For suppression of herpes simplex infections in immune-competent patients, 200 mg Simplevir should be taken four times daily at approximately six-hourly intervals.

Many patients may be conveniently managed on a regimen of 400 mg Simplevir taken twice daily at approximately twelve-hourly intervals.

Dosage titration down to 200 mg Simplevir taken thrice daily at approximately eight-hourly intervals or even twice daily at approximately twelve-hourly intervals, may prove effective.

Some patients may experience break-through infections on total daily doses of 800 mg Simplevir.

Therapy should be interrupted periodically at intervals of six to twelve months in order to observe possible changes in the natural history of the disease.

Prophylaxis of Herpes Simplex: For prophylaxis of herpes simplex infections in immune-compromised patients, 200 mg Simplevir should be taken four times daily at approximately six-hourly intervals.

In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.

The duration of prophylactic administration is determined by the duration of the period at risk.

Treatment of Varicella and Herpes Zoster: For treatment of varicella and herpes zoster infections, 800 mg Simplevir should be taken five times daily at approximately four-hourly intervals, omitting the night time dose. Treatment should continue for seven days.

In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, consideration should be given to intravenous dosing.

Dosing should begin as early as possible after the start of an infection. Treatment yields better results if initiated as soon as possible after onset of the rash.

Management of Severely Immunocompromised Patients: For management of severely immunocompromised patients, 800 mg Simplevir should be taken four times daily at approximately six-hourly intervals.

In the management of bone marrow recipients this would normally be preceded by up to one month's therapy with intravenous Simplevir.

The duration of treatment studied in bone marrow transplant patients was 6 months (from 1 to 7 months post-transplant). In patients with advanced HIV disease, study treatment was 12 months, but it is likely that these patients would continue to benefit from a longer duration of treatment.

Infants and Children: For treatment of herpes simplex infections, and for prophylaxis of herpes simplex infections in the immune-compromised, children aged two years and over should be given adult dosages and infants and children below the age of two years should be given half the adult dose.

For treatment of varicella infections in children: 6 years and over: 800 mg Simplevir four times daily; 2-<6 years: 400 mg Simplevir four times daily; Under 2 years: 200 mg Simplevir four times daily. Dosing may be more accurately calculated as 20 mg Simplevir/kg bodyweight (not to exceed 800 mg) four times daily. Treatment should continue for five days.

No specific data are available on the suppression of herpes simplex infections or the treatment of herpes zoster infections in immune-competent children.

Limited data suggest that for management of severely immunocompromised children, over two years of age, the adult dose may be given.

Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly.

Adequate hydration of elderly patients taking high oral doses of Simplevir should be maintained.

Renal Impairment: Caution is advised when administering Simplevir oral formulations to patients with impaired renal function. Adequate hydration should be maintained.

In the treatment and prophylaxis of herpes simplex infections in patients with impaired renal function, the recommended oral doses will not lead to accumulation of Simplevir above levels that have been established safe by intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 ml/minute) an adjustment of dosage to 200 mg twice daily at approximately twelve-hourly intervals is recommended.

In the treatment of varicella and herpes zoster infections, and in the management of severely immunocompromised patients it is recommended to adjust the dosage to 800 mg twice daily, at approximately twelve-hourly intervals, for patients with severe renal impairment (creatinine clearance less than 10 mL/minute) and to 800 mg three times daily, at intervals of approximately eight hours, for patients with moderate renal impairment (creatinine clearance in the range 10 to 25 mL/minute).

Injection: To be gives as intravenous infusion over 1 hour.

A course of treatment with Simplevir IV for infusion usually lasts 5 days, but this may be adjusted according to the patient's condition and response to therapy. Treatment for herpes encephalitis usually lasts 10 days.

Treatment for neonatal herpes usually lasts 14-21 days.

The duration of prophylactic administration of Simplevir IV for infusion is determined by the duration of the period at risk.

Adults: Treatment of Herpes Simplex: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.

Patients with herpes simplex (except herpes encephalitis) should be given Simplevir IV for infusion in doses of 5 mg/kg bodyweight every eight hours if renal function is not impaired.

Patients with herpes encephalitis should be given Simplevir IV for infusion in doses of 10 mg/kg bodyweight every eight hours provided renal function is not impaired.

Prophylaxis of Herpes Simplex in Immune-compromised Patients: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.

Refer to adult dosing recommendations for the treatment of herpes simplex with Simplevir IV for infusion.

Treatment of Varicella and Herpes Zoster: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.

Patients with varicella zoster infections should be given Simplevir IV for infusion in doses of 5 mg/kg bodyweight every eight hours if renal function is not impaired.

Immune-compromised patients with varicella zoster infections should be given Simplevir IV for infusion in doses of 10 mg/kg bodyweight every eight hours provided renal function is not impaired.

Infants and Children: The dose of Simplevir IV for infusion for infants and children aged between 3 months and 12 years is calculated on the basis of body surface area. Infants and children 3 months of age or older with herpes simplex (except herpes encephalitis) or varicella zoster infections should be given Simplevir IV for infusion in doses of 250 mg per square metre body surface area every 8 hours if renal is not impaired.

In immune-compromised infants and children with varicella zoster infections or herpes encephalitis, Simplevir IV for infusion should be given in doses of 500 mg per square metre body surface area every 8 hours if renal function is not impaired.

Infants and children with impaired renal function require an appropriately modified dose, according to the degree of impairment.

Neonates: The dosage of Simplevir IV for infusion in neonates is calculated on the basis of bodyweight.

The recommended regimen for treatment for known or suspected neonatal herpes is Simplevir IV 20 mg/kg body weight IV every 8 hours for 21 days for disseminated and CNS disease, or for 14 days for disease limited to the skin and mucous membranes. Patients with impaired renal function require an appropriately modified dose, according to the degree of impairment.

Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly.

Adequate hydration should be maintained.

Renal Impairment: Caution is advised when administering Simplevir IV for infusion to patients with impaired renal function. Adequate hydration should be maintained.

Dosage adjustment for patients with renal impairment is based on creatinine clearance, in units of mL/min for adults and adolescents and in units of mL/min/1.73 m² for infants and children less than 13 years of age. The following adjustments in dosage are suggested: See Table 1 and Table 2.

See also:
What is the most important information I should know about Simplevir?

Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Simplevir will not treat a viral infection such as the common cold or flu.

Treatment with Simplevir should be started as soon as possible after the first appearance of symptoms (such as tingling, burning, blisters).

Herpes infections are contagious and you can infect other people, even while you are being treated with Simplevir. Avoid letting infected areas come into contact with other people. Avoid touching an infected area and then touching your eyes. Wash your hands frequently to prevent passing the infection to others.

Simplevir will not prevent the spread of genital herpes. Avoid sexual intercourse or use a latex condom to prevent spreading the virus to others.

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

• An extra patient leaflet and detailed instructions for use is available with Simplevir tablets. Talk to your pharmacist if you have questions about this information.
• Use Simplevir tablets within 1 hour after you have the first symptoms of a cold sore (eg, itching, redness, burning, or tingling).
• To use Simplevir tablets, peel back the foil on the blister pack and place the tablet on the upper gum above the incisor tooth. Place Simplevir tablets on the same side of the mouth as the cold sore symptoms. Do not apply to the inside of the lip or cheek. To help the tablet stick to your gum, hold the tablet in place by applying slight pressure with your finger on the outside of your lip for about 30 seconds. Leave the tablet in place until it dissolves.
• Do not crush, suck, chew, or swallow Simplevir tablets.
• You may eat, drink, or rinse your mouth with water while this tablet is in place. After it has been applied, do not touch or press the tablet, wear dentures, chew gum, or brush your teeth until the tablet has dissolved.
• Drink more liquids if your mouth becomes dry while using Simplevir tablets.
• If the tablet does not stick or falls off within the first 6 hours after you apply it, place it back onto your upper gum. If it still does not stick, apply a new tablet.
• If you swallow Simplevir tablets within the first 6 hours of applying it, drink a glass of water and place a new tablet onto your upper gum.
• Do not remove the tablet from the blister pouch until you are ready to take it. Make sure that your hands are dry when you open the blister pack. Do not push the tablet through the foil. Take the tablet immediately after opening the blister pack. Do not store the removed tablet for future use.
• Only 1 dose of Simplevir tablets is required. If you forget to use Simplevir tablets, use it as soon as you remember.

Ask your health care provider any questions you may have about how to use Simplevir tablets.

This medication is used to treat cold sores around the mouth (caused by herpes virus) that keep coming back.

Simplevir is an antiviral drug. However, it is not a cure for the infection. The virus that causes infection continues to live in the body between outbreaks. Simplevir makes outbreaks shorter and less severe. It helps the sores heal faster, keeps new sores from forming, and decreases pain/itching. This medication may also help reduce how long pain lasts after the sores heal.

How to use Simplevir buccal

Read the Patient Information Leaflet and Instructions for Use provided by your pharmacist before you start using Simplevir buccal tablets and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Apply one tablet within one hour after you have the first symptom of a cold sore, and before a cold sore appears. Symptoms may include itching, redness, burning, or tingling. Apply the tablet on the same side of your mouth as the cold sore symptoms.

Before applying the tablet, find the area in your mouth in which to place the tablet. It should be placed on the upper gum, just above the left or right incisor tooth. The incisors are the teeth just to the left and right of your two front teeth. With dry hands, remove one tablet from the blister pack and place it in your mouth with the round side facing against your gum and gently push it into place. Remove your hand from inside your mouth and gently press your finger on the outside of your upper lip for 30 seconds. This will make the tablet stick to your gum. The tablet will slowly dissolve over time and should be left in place. You may eat and drink while using this medication. Do not crush, chew, suck, or swallow the tablet.

If the tablet does not stick to your upper gum or falls off within the first 6 hours after you apply it, the same tablet should be placed back onto your upper gum right away. If it still does not stay in place, apply another Simplevir tablet to your upper gum.

If you accidentally swallow the tablet within the first 6 hours after placement, drink a glass of water and apply a new dose to your gum. However, if the tablet has been in place 6 hours or longer and it falls out or you swallow it, do not re-apply the tablet.

Avoid doing things that may keep the buccal tablet from sticking to your gum, including touching or pressing the tablet after placement, wearing an upper denture that interferes with tablet placement, chewing gum, and brushing your teeth while the tablet is in place. You may gently rinse your mouth with water to clean your teeth while the tablet is in place. Drink plenty of liquids if you have dry mouth.

This medication works best when started at the first sign of a cold sore, as directed by your doctor. It may not work as well if you delay treatment.

Tell your doctor if your condition does not improve or if it worsens.

See also:
What other drugs will affect Simplevir?

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Simplevir-Valacyclovir. Avoid combination

Mycophenolate: Simplevir-Valacyclovir may increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Simplevir-Valacyclovir. Monitor therapy

Talimogene Laherparepvec: Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec. Monitor therapy

Tenofovir Products: Simplevir-Valacyclovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Simplevir-Valacyclovir. Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Varicella Virus Vaccine: Simplevir-Valacyclovir may diminish the therapeutic effect of Varicella Virus Vaccine. Management: When possible, avoid use of Simplevir or valacyclovir within the 24 hours prior to administration of the varicella vaccine, and avoid use of these antiviral agents for 14 days after vaccination. Avoid combination

Zidovudine: Simplevir-Valacyclovir may enhance the CNS depressant effect of Zidovudine. Monitor therapy

Zoster Vaccine (Live/Attenuated): Simplevir-Valacyclovir may diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Avoid combination

See also:
What are the possible side effects of Simplevir?

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.

In five double-blind, placebo-controlled trials, 1,124 patients were treated with Simplevir Cream and 1,161 with placebo (vehicle) cream. Local application site reactions were reported by 5% of patients receiving Simplevir Cream and 4% of patients receiving placebo. The most common adverse reactions at the site of topical application were dry lips, desquamation, dryness of skin, cracked lips, burning skin, pruritus, flakiness of skin, and stinging on skin; each adverse reaction occurred in less than 1% of patients receiving Simplevir Cream and placebo. Three patients on Simplevir Cream and one patient on placebo discontinued treatment due to an adverse event.

An additional study, enrolling 22 healthy adults, was conducted to evaluate the dermal tolerance of Simplevir Cream compared with vehicle using single occluded and semi-occluded patch testing methodology. Both Simplevir Cream and placebo showed a high and cumulative irritation potential. Another study, enrolling 251 healthy adults, was conducted to evaluate the contact sensitization potential of Simplevir Cream using repeat insult patch testing methodology. Of 202 evaluable subjects, possible cutaneous sensitization reactions were observed in the same 4 (2%) subjects with both Simplevir Cream and placebo, and these reactions to both Simplevir Cream and placebo were confirmed in 3 subjects upon rechallenge. The sensitizing ingredient(s) has not been identified.

The safety profile in patients 12 to 17 years of age was similar to that observed in adults.

Postmarketing Experience

In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of Simplevir Cream. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Simplevir Cream.

General: Angioedema, anaphylaxis.

Skin: Contact dermatitis, eczema.

Simplevir IV contains Acyclovir as the sodium salt. Each 250-mg vial contains sodium ion approximately 26 mg. When reconstituted as directed, Simplevir IV for infusion has a pH of approximately 11.