VALCIVIR

Prescribing information

For the use of a Registered Medical Practitioner only

Valacyclovir Hydrochloride Tablets

VALCIVIR Tablets

Qualitative and Quantitative Composition

VALCIVIR-500 Tablets

Each film-coated tablet contains:

Valacyclovir Hydrochloride USP equivalent to

Valacyclovir ………….. 500 mg

Colour: Titanium dioxide IP and Lake Indigo carmine

VALCIVIR-1000 Tablets

Each film-coated tablet contains:

Valacyclovir Hydrochloride USP equivalent to

Valacyclovir …………1000 mg

Colour: Titanium dioxide IP and Lake Indigo carmine

Dosage Form(s) and Strength(s)

Tablet, 500mg and 1000mg

Clinical Particulars

Therapeutic Indications

VALCIVIR Tablets are indicated for the treatment of various herpes virus infections, as given below:

Adults

Herpes zoster (shingles)
Initial and recurrent episodes of genital herpes
Suppression of recurrent episodes of genital herpes
Reduction of the transmission of genital herpes

Posology and Method of Administration

VALCIVIR Tablets may be given without regard to food.

Adults

Herpes Zoster

The recommended dosage of valacyclovir for the treatment of herpes zoster is 1 gm orally, three times daily for 7 days. Therapy should be initiated at the earliest sign or symptom of herpes zoster and is most effective when started within 48 hours of the onset of the herpes zoster rash.

Genital Herpes

Initial Episodes

Immunocompetent adults

The recommended dosage of valacyclovir for treatment of initial genital herpes is 1 gm twice daily for 10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms.

Recurrent Episodes

Immunocompetent adults

The recommended dosage of valacyclovir for the treatment of recurrent genital herpes is 500 mg twice daily for 3 days. Initiate treatment at the first sign or symptom of an episode.

Suppressive Therapy

Immunocompetent adults

The recommended dosage of valacyclovir for chronic suppressive therapy of recurrent genital herpes is 1 gm once daily in patients with normal immune function. In patients with a history of nine or fewer recurrences per year, an alternative dose is 500 mg once daily

Immunocompromised adults

The recommended dosage of valacyclovir for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily.

Reduction of Transmission

Immunocompetent adults

The recommended dosage of valacyclovir for reduction of the transmission of genital herpes in patients with a history of nine or fewer recurrences per year is 500 mg once daily for the source partner.

Patients with Renal Impairment

In patients with reduced renal function, a reduction in dosage is recommended (see Table 1).

Table 1: Reduction in dosage for patients with renal impairment

Indications	Normal Dosage	Creatinine Clearance (mL/min)
Indications	Regimen (Creatinine Clearance ≥50 mL/min)	30–49	10–29	<10
Herpes zoster	1 gm every 8 hours	1 gm every 12 hours	1 gm every 24 hours	500 mg every 24 hours
Genital herpes: Initial episode	1 gm every 12 hours	No reduction	1 gm every 24 hours	500 mg every 24 hours
Genital herpes: Recurrent episode	500 mg every 12 hours	No reduction	500 mg every 24 hours	500 mg every 24 hours
Genital herpes: Suppressive therapy
Immunocompetent patients	1 gm every 24 hours	No reduction	500 mg every 24 hours	500 mg every 24 hours
Alternate dose for immunocompetent patients with ≤9 recurrences/year	500 mg every 24 hours	No reduction	500 mg every 48 hours	500 mg every 48 hours
Immunocompromised patients	500 mg every 12 hours	No reduction	500 mg every 24 hours	500 mg every 24 hours

Haemodialysis

During haemodialysis, the half-life of acyclovir after administration of valacyclovir is approximately 4 hours. About one-third of acyclovir in the body is removed by dialysis during a 4-hour haemodialysis session. Patients requiring haemodialysis should receive the recommended dose of valacyclovir after haemodialysis.

Peritoneal Dialysis

There is no information specific to administration of valacyclovir in patients receiving peritoneal dialysis. The effect of chronic ambulatory peritoneal dialysis (CAPD) and continuous arteriovenous haemofiltration/dialysis (CAVHD) on acyclovir pharmacokinetics has been studied. The removal of acyclovir after CAPD and CAVHD is less pronounced than with haemodialysis, and the pharmacokinetic parameters closely resemble those observed in patients with end-stage renal disease (ESRD) not receiving haemodialysis. Therefore, supplemental doses of valacyclovir should not be required following CAPD or CAVHD.

Patients with hepatic impairment

Studies with a 1 g unit dose of valacyclovir show that dose modification is not required in patients with mild or moderate cirrhosis (hepatic synthetic function maintained). Pharmacokinetic data in patients with advanced cirrhosis, (impaired hepatic synthetic function and evidence of portal-systemic shunting) do not indicate the need for dosage adjustment; however, clinical experience is limited.

Contraindications

VALCIVIR Tablets are contraindicated in patients with a known hypersensitivity or intolerance to valacyclovir, acyclovir, or any component of the formulation.

Special Warnings and Precautions for Use

Thrombotic Thrombocytopenic Purpura/Haemolytic Uraemic Syndrome (TTP/HUS)

TTP/HUS, in some cases resulting in death, has occurred in patients with advanced HIV-1 disease and also in allogeneic bone marrow transplant and renal transplant recipients participating in clinical trials of valacyclovir at doses of 8 gm per day. Treatment with valacyclovir should be stopped immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS occur.

Acute Renal Failure

Cases of acute renal failure have been reported in the following:

Elderly patients with or without reduced renal function. Caution should be exercised when administering valacyclovir to geriatric patients, and dosage reduction is recommended for those with impaired renal function
Patients with underlying renal disease who received higher than recommended doses of valacyclovir for their level of renal function. Dosage reduction is recommended when administering valacyclovir to patients with renal impairment
Patients receiving other nephrotoxic drugs. Caution should be exercised when administering valacyclovir to patients receiving potentially nephrotoxic drugs.
Patients without adequate hydration. Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Adequate hydration should be maintained for all patients.

In the event of acute renal failure and anuria, the patient may benefit from haemodialysis until renal function is restored.

Central Nervous System Effects

Central nervous system adverse reactions, including agitation, hallucinations, confusion, delirium, seizures, and encephalopathy, have been reported in both adult and paediatric patients with or without reduced renal function and in patients with underlying renal disease who received higher than recommended doses of valacyclovir for their level of renal function. Elderly patients are more likely to have central nervous system adverse reactions. Valacyclovir should be discontinued if central nervous system adverse reactions occur.

Drug reaction with eosinophilia and systemic symptoms (DRESS)

DRESS, which can be life-threatening or fatal, has been reported in associate with valacyclovir treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of DRESS appear, valacyclovir should be withdrawn immediately and an alternative treatment considered (as appropriate). If the patient has developed DRESS with the use of valacyclovir, treatment with valacyclovir must not be restarted in this patient at any time.

Hydration status

Care should be taken to ensure adequate fluid intake in patients who are at risk of dehydration, particularly the elderly.

Transmission of genital herpes

Patients should be advised to avoid intercourse when symptoms are present even if treatment with an antiviral has been initiated. During suppressive treatment with antiviral agents, the frequency of viral shedding is significantly reduced. However, the risk of transmission is still possible. Therefore, in addition to therapy with valacyclovir, it is recommended that patients use safer sex practices.

Drug Interactions

No dosage adjustment is recommended when valacyclovir is co-administered with digoxin, antacids, thiazide diuretics, cimetidine or probenecid in subjects with normal renal function.

The combination of valacyclovir with nephrotoxic medicinal products should be made with caution, especially in subjects with impaired renal function, and warrants regular monitoring of renal function. This applies to concomitant administration with aminoglycosides, organoplatinum compounds, iodinated contrast media, methotrexate, pentamidine, foscarnet, ciclosporin, and tacrolimus.

Use in Special Population

Patients with Renal Impairment

Dosage reduction is recommended when administering VALCIVIR to patients with renal impairment.

Patients with Hepatic Impairment

Dosage modification is not recommended for patients with cirrhosis.

Pregnant Women

Clinical data over several decades with valacyclovir and its metabolite, acyclovir, in pregnant women, based on published literature, have not identified a drug-associated risk of major birth defects. There are insufficient data on the use of valacyclovir regarding miscarriage or adverse maternal or fetal outcomes.

VALCIVIR Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Lactating Women

Although there is no information on the presence of valacyclovir in human milk, its metabolite, acyclovir, is present in human milk following oral administration of valacyclovir. There is no data on the effects of valacyclovir or acyclovir on the breastfed child or on milk production.

VALCIVIR Tablets should be administered to a nursing mother with caution and only when indicated.

Geriatric Patients

Geriatric patients are more likely to have reduced renal function and require dose reduction. They are also more likely to have renal or central nervous system adverse events.

Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. The clinical status of the patient and the adverse reaction profile of valacyclovir should be borne in mind when considering the patient`s ability to drive or operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance.

Undesirable Effects

The serious adverse reactions reported with valacyclovir are as follows: TTP/HUS, acute renal failure and central nervous system effects.

The most common adverse reactions reported in at least one indication by greater than 10% of adult patients treated with valacyclovir and observed more frequently with valacyclovir compared to placebo are headache, nausea, and abdominal pain. The only adverse reaction reported in greater than 10% of paediatric patients aged less than 18 years was headache.

Clinical Trials Experience in Adults

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

Genital Herpes

Initial Episode

In a clinical study for the treatment of initial episodes of genital herpes, the adverse reactions reported by greater than or equal to 5% of patients receiving valacyclovir 1 gm twice daily for 10 days (n = 318) or oral acyclovir 200 mg 5 times daily for 10 days (n = 318), respectively, included headache (13%, 10%) and nausea (6%, 6%).

Recurrent Episodes

In three clinical studies for the episodic treatment of recurrent genital herpes, the adverse reactions reported by greater than or equal to 5% of patients receiving valacyclovir 500 mg twice daily for 3 days (n = 402), valacyclovir 500 mg twice daily for 5 days (n = 1,136) or placebo (n = 259), respectively, included headache (16%, 11%, 14%) and nausea (5%, 4%, 5%).

Suppressive Therapy

Suppression of Recurrent Genital Herpes in Immunocompetent Adults: In a clinical study for the suppression of recurrent genital herpes infections, the adverse reactions reported by patients receiving valacyclovir 1 gm once daily (n = 269), valacyclovir 500 mg once daily (n = 266) or placebo (n = 134), respectively, included headache (35%, 38%, 34%), nausea (11%, 11%,8%), abdominal pain (11%, 9%, 6%), dysmenorrhoea (8%, 5%, 4%), depression (7%, 5%, 5%), arthralgia (6%, 5%, 4%), vomiting (3%, 3%, 2%), and dizziness (4%, 2%, 1%).

Suppression of Recurrent Genital Herpes in HIV-1 Infected Patients: In HIV-1 infected patients, frequently reported adverse reactions for valacyclovir (500 mg twice daily; n = 194, median days on therapy = 172) and placebo (n = 99, median days on therapy = 59), respectively, included headache (13%, 8%), fatigue (8%, 5%), and rash (8%, 1%). Post-randomization laboratory abnormalities that were reported more frequently in valacyclovir subjects versus placebo included elevated alkaline phosphatase (4%, 2%), elevated ALT (14%, 10%), elevated AST (16%, 11%), decreased neutrophil counts (18%, 10%), and decreased platelet counts (3%, 0%), respectively.

Reduction of Transmission

In a clinical study for the reduction of transmission of genital herpes, the adverse reactions reported by patients receiving valacyclovir 500 mg once daily (n = 743) or placebo once daily (n = 741), respectively, included headache (29%, 26%), nasopharyngitis (16%, 15%), and upper respiratory tract infection (9%, 10%).

Herpes Zoster

In two clinical studies for the treatment of herpes zoster, the adverse reactions reported by patients receiving valacyclovir 1 gm, three times daily for 7 to 14 days (n = 967) or placebo (n = 195), respectively, included nausea (15%, 8%), headache (14%, 12%), vomiting (6%, 3%), dizziness (3%, 2%), and abdominal pain (3%, 2%).

In herpes zoster and genital herpes study populations, laboratory abnormalities were observed in haemoglobin (<0.8 × LLN^*), white blood cells (<0.75 × LLN^*), platelet count (<1,00,000/mm³), AST (SGOT)(>2 × ULN^**) and serum creatinine (>1.5 × ULN^**).

^* LLN = Lower limit of normal.

^**ULN = Upper limit of normal.

Post marketing Experience

In addition to adverse events reported from clinical trials, the following events have been identified during post marketing use of valacyclovir. 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 valacyclovir:

General: Facial oedema, hypertension, tachycardia.

Allergic: Acute hypersensitivity reactions, including anaphylaxis, angio-oedema, dyspnoea.

Central Nervous System Symptoms: Aggressive behaviour; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors, dizziness and delirium. Neurological disorders, sometimes severe, may be linked to encephalopathy and include confusion, agitation, convulsions, hallucinations, coma. These events are generally reversible and usually seen in patients with renal impairment or with other predisposing factors. In organ transplant patients receiving high doses (8,000 mg daily) of valacyclovir for CMV prophylaxis, neurological reactions occurred more frequently compared with lower doses used for other indications.

Eye: Visual abnormalities.

Gastrointestinal: Vomiting, diarrhoea and abdominal discomfort.

Hepatobiliary Tract and Pancreas: Reversible increases in liver function tests (e.g. bilirubin, liver enzymes), hepatitis.

Blood and Lymphatic System Disorders: Leucopenia, thrombocytopenia, aplastic anaemia, leukocytoplastic vasculitis, TTP/HUS. Leucopenia is mainly reported in immunocompromised patients.

Renal and Urinary Disorders: Renal pain, haematuria (often associated with other renal events), renal impairment, acute renal failure (especially in elderly patients or in patients with renal impairment receiving higher than the recommended doses). Renal pain may be associated with renal failure. Intratubular precipitation of aciclovir crystals in the kidneys has also been reported. Adequate fluid intake should be ensured during treatment.

Skin: Erythema multiforme, rashes including photosensitivity, pruritus, urticaria, alopecia and Drug reaction with eosinophilia and systemic symptoms (DRESS).

Additional Information on Special Populations

There have been reports of renal insufficiency, microangiopathic haemolytic anaemia and thrombocytopenia (sometimes in combination) in severely immunocompromised adult patients, particularly those with advanced HIV disease, receiving high doses (8,000 mg daily) of valacyclovir for prolonged periods in clinical trials. These findings have also been observed in patients not treated with valacyclovir who have the same underlying or concurrent conditions.

In case your patient experiences any side-effect/s, write to drugsafety@cipla.com. You can also report side-effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 18002677779. By reporting side-effects, you can help provide more information on the safety of this product.

Overdose

Acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, decreased consciousness and coma, have been reported in patients receiving overdoses of valacyclovir. Nausea and vomiting may also occur. Caution is required to prevent inadvertent overdosing. Many of the reported cases involved renally impaired and elderly patients receiving repeated overdoses, due to lack of appropriate dosage reduction.

Patients should be observed closely for signs of toxicity. Haemodialysis significantly enhances the removal of acyclovir from the blood and may, therefore, be considered a management option in the event of symptomatic overdose.

Pharmacological Properties

Mechanism of Action

Valacyclovir is a deoxynucleoside analogue DNA polymerase inhibitor. Valacyclovir hydrochloride is rapidly converted to acyclovir, which has demonstrated antiviral activity against the herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and the varicella zoster virus (VZV) both in vitro and in vivo.

The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in three ways: 1) Competitive inhibition of viral DNA polymerase; 2) Incorporation and termination of the growing viral DNA chain; and, 3) Inactivation of the viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK.

Pharmacodynamic Properties

Resistance to aciclovir is normally due to a thymidine kinase deficient phenotype which results in a virus which is disadvantaged in the natural host. Reduced sensitivity to aciclovir has been described as a result of subtle alterations in either the virus thymidine kinase or DNA polymerase. The virulence of these variants resembles that of the wild-type virus.

Monitoring of clinical HSV and VZV isolates from patients receiving aciclovir therapy or prophylaxis has revealed that virus with reduced sensitivity to aciclovir is extremely rare in the immunocompetent host and is found infrequently in severely immunocompromised individuals e.g. organ or bone marrow transplant recipients, patients receiving chemotherapy for malignant disease and people infected with the human immunodeficiency virus (HIV).

Pharmacokinetics Properties

Absorption

After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal tract and nearly completely converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism.

The absolute bioavailability of acyclovir after administration of valacyclovir is 54.5% ± 9.1% as determined following a 1 gm oral dose of valacyclovir and a 350 mg intravenous acyclovir dose to 12 healthy volunteers. Acyclovir bioavailability from the administration of valacyclovir is not altered by administration with food.

There is no accumulation of acyclovir after the administration of valacyclovir at the recommended dosage regimens in healthy volunteers with normal renal function.

Distribution

The binding of valacyclovir to human plasma proteins ranged from 13.5% to 17.9%. The binding of acyclovir to human plasma proteins ranges from 9% to 33%.

Metabolism

After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal tract. Valacyclovir is converted to acyclovir and L-valine by firstpass intestinal and/or hepatic metabolism. Acyclovir is converted, to a small extent, to inactive metabolites by aldehyde oxidase and by alcohol and aldehyde dehydrogenase. Neither valacyclovir nor acyclovir is metabolized by cytochrome (CY) P450 enzymes.

Plasma concentrations of unconverted valacyclovir are low and transient, generally becoming non-quantifiable by 3 hours after administration. Peak plasma valacyclovir concentrations are generally less than 0.5 mcg/mL at all doses. After single-dose administration of 1 gm of valacyclovir, average plasma valacyclovir concentrations observed were 0.5, 0.4, and 0.8 mcg/mL in patients with hepatic dysfunction, renal, and in healthy volunteers who received concomitant cimetidine and probenecid, respectively.

Elimination

The pharmacokinetic disposition of acyclovir delivered by valacyclovir is consistent with previous experience from intravenous and oral acyclovir.

Following the oral administration of a single 1 gm dose of radiolabelled valacyclovir to 4 healthy subjects, 46% and 47% of administered radioactivity was recovered in the urine and the faeces over 96 hours, respectively. Acyclovir accounted for 89% of the radioactivity excreted in the urine. The plasma elimination half-life of acyclovir typically averaged 2.5 to 3.3 hours in all studies of valacyclovir in volunteers with normal renal function.

Special Populations

Patients with renal impairment

Reduction in dosage is recommended in patients with renal impairment. Following administration of valacyclovir to volunteers with end-stage renal disease (ESRD), the average acyclovir half-life is approximately 14 hours. During haemodialysis, the acyclovir half-life is approximately 4 hours. Reduction in dosage is recommended in patients with renal impairment.

Patients with hepatic impairment

Administration of valacyclovir to patients with moderate (biopsy-proven cirrhosis) or severe (with and without ascites and biopsy-proven cirrhosis) liver disease indicated that the rate, but not the extent, of conversion of valacyclovir to acyclovir is reduced, and the acyclovir half- life is not affected. Dosage modification is not recommended for patients with cirrhosis.

Geriatric patients

After single-dose administration of 1 gm of valacyclovir in healthy geriatric volunteers, the half-life of acyclovir was 3.11 ± 0.51 hours, compared to 2.91 ± 0.63 hours in healthy younger adult volunteers. The pharmacokinetics of acyclovir following single- and multiple-dose oral administration of valacyclovir in geriatric volunteers varied with renal function. Dose reduction may be required in geriatric patients, depending on the underlying renal status of the patient.

Patients with HIV Disease

In 9 patients with HIV disease and CD4+ cell counts <150 cells/mm³ who received valacyclovir at a dosage of 1 gm, 4 times daily for 30 days, the pharmacokinetics of valacyclovir and acyclovir were not different from that observed in healthy volunteers.

Nonclinical Properties

Animal Toxicity or Pharmacology

Carcinogenesis, Mutagenesis, Impairment of Fertility

The data presented below include references to the steady-state acyclovir AUC observed in humans treated with 1 gram of valacyclovir given orally 3 times a day to treat herpes zoster. Plasma drug concentrations in animal studies are expressed as multiples of human exposure to acyclovir.

Carcinogenesis

Valacyclovir was noncarcinogenic in lifetime carcinogenicity bioassays at single daily doses (gavage) of valacyclovir giving plasma acyclovir concentrations equivalent to human levels in the mouse bioassay and 1.4 to 2.3 times human levels in the rat bioassay. There was no significant difference in the incidence of tumors between treated and control animals, nor did valacyclovir shorten the latency of tumors.

Mutagenesis

Valacyclovir was tested in 5 genetic toxicity assays. An Ames assay was negative in the absence or presence of metabolic activation. Also negative were an in vitro cytogenetic study with human lymphocytes and a rat cytogenetic study.

In the mouse lymphoma assay, valacyclovir was not mutagenic in the absence of metabolic activation. In the presence of metabolic activation (76% to 88% conversion to acyclovir), valacyclovir was mutagenic.

Valacyclovir was mutagenic in a mouse micronucleus assay.

Impairment of Fertility

Valacyclovir did not impair fertility or reproduction in male or female rats at acyclovir exposures (AUC) 6 times higher than in humans given the MRHD. Testicular atrophy occurred in male rats (orally dosed for 97 days at 18 times the MRHD) and was reversible.

Description

VALCIVIR (valacyclovir hydrochloride) is the hydrochloride salt of the L-valyl ester of the antiviral drug acyclovir.

VALCIVIR tablets are for oral administration.

Pharmaceutical Particulars

Shelf-Life

See on Pack

Packaging Information

VALCIVIR-500 Tablets: Blister pack of 3 tablets

VALCIVIR-1000 Tablets: Blister pack of 3 tablets

Storage and Handling Instructions

Store in a cool, dry place.

Patient Counselling Information

What is VALCIVIR?

VALCIVIR is a prescription medicine used in adults:

to treat or control genital herpes outbreaks in adults.
with safer sex practices to lower the chance of spreading genital herpes to others in adults. Even with safer sex practices, it is still possible to spread genital herpes.
Do not have sexual contact with your partner when you have any symptom or outbreak of genital herpes.
Use a condom whenever you have sexual contact.
Ask your doctor for more information about safer sex practices.
to treat shingles (herpes zoster) in adults.

What you need to know before you take VALCIVIR

Do not take VALCIVIR

if you are allergic to valacyclovir, acyclovir, or any of the ingredients in VALCIVIR.
if you have ever developed an extended rash associated with fever, enlarged lymph nodes, increased levels of liver enzymes and/or eosinophilia (drug reaction with eosinophilia and systemic symptoms) after taking valacyclovir.

Before you take VALCIVIR, tell your doctor about all of your medical conditions, including if you:

have had a bone marrow transplant or kidney transplant, or if you have advanced HIV-1 infection or acquired immune deficiency syndrome (AIDS).
have kidney problems, including if you receive dialysis.
have liver problems
are pregnant or plan to become pregnant. It is not known if valacyclovir will harm your unborn baby. You and your doctor will decide if you will take VALCIVIR if you are pregnant.
are breastfeeding or plan to breastfeed. Valacyclovir may pass into your breastmilk. Talk with your doctor about the best way to feed your child if you take VALCIVIR.

Take special care with VALCIVIR – Important Information:

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with the use of valacyclovir. DRESS appears initially as flu like symptoms and a rash on the face then an extended rash with a high body temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.
If you develop a rash associated with a fever and enlarged lymph nodes, stop taking valacyclovir and contact your doctor or seek medical attention immediately.

Other medicines and VALCIVIR

Tell your doctor about all the medicines you take, including prescription and over-the counter medicines, vitamins, and herbal supplements.

Tell your doctor or pharmacist if you are taking any other medicines that affect the kidneys. These include aminoglycosides, organoplatinum compounds, iodinated contrast media, methotrexate, pentamidine, foscarnet, ciclosporin, tacrolimus, cimetidine and probenecid.

Pregnancy and lactation

Valacyclovir is not usually recommended for use during pregnancy. If you are pregnant, or think you could be, or if you are planning to become pregnant, don’t take VALCIVIR without checking with your doctor. Your doctor will weigh up the benefit to you against the risk to your baby of taking VALCIVIR while you are pregnant or breastfeeding.

Driving and using machines

Valacyclovir can cause side effects that affect your ability to drive.

Do not drive or use machines unless you are sure you are not affected.

How should I take VALCIVIR?

Take VALCIVIR exactly as your doctor tells you to take it.
Your dose of VALCIVIR and length of treatment will depend on the type of infection that you have and any other medical problems that you have.
Do not stop VALCIVIR or change your treatment without talking to your doctor.
Take VALCIVIR with or without food.
If you are taking VALCIVIR to treat outbreaks of shingles, or genital herpes, take VALCIVIR as soon as you have the first symptoms of infection such as tingling, itching, or burning, or when the sore appears.
It is important for you to stay well hydrated during treatment with VALCIVIR. Be sure to drink plenty of fluids during this time.
If you miss a dose of VALCIVIR, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time or take more VALCIVIR than prescribed.
If you take too much VALCIVIR, call your doctor or go to the nearest hospital emergency room right away.

What are the possible side effects of VALCIVIR?

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Conditions you need to look out for:

Stop using VALCIVIR and seek medical attention immediately if you notice any of the following symptoms:

Severe allergic reactions (anaphylaxis). These are rare in people taking valacyclovir. Rapid development of symptoms including:

flushing, itchy skin rash
swelling of the lips, face, neck and throat, causing difficulty in breathing (angiodema)
fall in blood pressure leading to collapse.

Skin rashes or redness. The adverse reaction of the skin may appear as rashes with or without blisters. Skin irritation, oedema (DRESS syndrome) and fever and flu like symptoms may occur

The following side effects may also happen with this medicine:

Very Common (may affect more than 1 in 10 people):

headache

Common (may affect up to 1 in 10 people)

feeling sick
dizziness
vomiting
diarrhoea
skin reaction after exposure to sunlight (photosensitivity).
rash
itching (pruritus)

Uncommon (may affect up to 1 in 100 people)

feeling confused
seeing or hearing things that aren’t there (hallucinations)
feeling very drowsy
tremors
feeling agitated

These nervous system side effects usually occur in people with kidney problems, the elderly or in organ transplant patients taking high doses of 8 grams or more of valacyclovir a day. They usually get better when valacyclovir is stopped or the dose reduced.

Other uncommon side effects:

shortness of breath (dyspnoea)
stomach discomfort
rash, sometimes itchy, hive-like rash (urticaria)
low back pain (kidney pain)
blood in urine (haematuria)

Uncommon side effects that may show up in blood tests:

reduction in the number of white blood cells (leucopenia)
reduction in the number of blood platelets which are cells that help blood to clot (thrombocytopenia)
increase in substances produced by the liver.

Rare (may affect up to 1 in 1,000 people)

unsteadiness when walking and lack of coordination (ataxia)
slow, slurred speech (dysarthria)
fits (convulsions)
altered brain function (encephalopathy)
unconsciousness (coma)
confused or disturbed thoughts (delirium)

Other rare side effects:

kidney problems where you pass little or no urine.

Frequency Not Known (cannot be estimated from the available data)

Drug Reaction with Eosinophilia and Systemic Symptoms also known as DRESS or drug reaction hypersensitivity syndrome, which is characterised by widespread rash, high body temperature, liver enzyme elevations, blood abnormalities (eosinophilia), enlarged lymph nodes and possibly other body organs.

These are not all the possible side effects of valacyclovir. For more information, ask your doctor.

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side-effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 18002677779. By reporting side-effects, you can help provide more information on the safety of this product.

How should I store VALCIVIR?

Store in a cool dry place
Keep VALCIVIR out of the reach of children.

General information about the safe and effective use of VALCIVIR. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VALCIVIR for a condition for which it was not prescribed. Do not give VALCIVIR to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about VALCIVIR.

Details of Manufacturer

Mfd. by Cipla Ltd.

Registered Office: Cipla House, Peninsula Business Park,

Ganpatrao Kadam Marg, Lower Parel, Mumbai-400 013, India

Details of Permission or Licence Number with Date

M/447/2007 dated 29/11/2022

Date of Revision

01/12/2022