Valganciclovir
Encyclopedia
Valganciclovir hydrochloride (Valcyte, manufactured by Hoffmann–La Roche (Roche). Also Cymeval, Valcyt,
Valixa, Darilin, Rovalcyte, Valcyte, Patheon, Syntex) is an antiviral medication used to treat cytomegalovirus
infection
s. As the L-valyl
ester
of ganciclovir
, it is actually a prodrug
for ganciclovir
. After oral administration, it is rapidly converted to ganciclovir
by intestinal
and hepatic
esterase
s.
. Following some reported success in 9 out of 12 patients at Stanford University
in California
, a follow-up double-blind, controlled study of 30 patients was completed, and although data has not yet been released, according to the Virus Induced CNS Dysfunction Association, "the data Dr. Montoya presented at the 2008 International Conference on HHV-6&7 indicated that patients on Valcyte experienced significant cognitive improvement.", especially for those with elevated antibody levels to HHV-6 and EBV (VCA and EA)
. However a generic version manufactured by Japanese-owned Indian company Daiichi-Ranbaxy
was found by the District Court of New Jersey
, USA not to infringe Roche's patent.
The price of a four-month course of valganciclovir from Roche is about US$8,500 in high-income countries, $6,000 in India. However, the valganciclovir patent was rejected by the Indian Patent Office
in 2010, although Roche may appeal
the rejection.
Valixa, Darilin, Rovalcyte, Valcyte, Patheon, Syntex) is an antiviral medication used to treat cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s. As the L-valyl
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
of ganciclovir
Ganciclovir
Ganciclovir INN is an antiviral medication used to treat or prevent cytomegalovirus infections.Ganciclovir sodium is marketed under the trade names Cytovene and Cymevene . Ganciclovir for ocular use is marketed under the trade name Vitrasert...
, it is actually a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
for ganciclovir
Ganciclovir
Ganciclovir INN is an antiviral medication used to treat or prevent cytomegalovirus infections.Ganciclovir sodium is marketed under the trade names Cytovene and Cymevene . Ganciclovir for ocular use is marketed under the trade name Vitrasert...
. After oral administration, it is rapidly converted to ganciclovir
Ganciclovir
Ganciclovir INN is an antiviral medication used to treat or prevent cytomegalovirus infections.Ganciclovir sodium is marketed under the trade names Cytovene and Cymevene . Ganciclovir for ocular use is marketed under the trade name Vitrasert...
by intestinal
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
and hepatic
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
esterase
Esterase
An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis.A wide range of different esterases exist that differ in their substrate specificity, their protein structure, and their biological function.- EC classification/list...
s.
Administration
Orally, available in 450 mg pink tablets. For patients who have received a transplant, the recommended dose is 900 mg once daily, starting within 10 days of transplantation and continuing until 100 days post transplantation. HIV patients might initially need to take the dose 900 mg twice daily for the first 3 weeks.Pharmacokinetics
- Oral bioavailabilityBioavailabilityIn pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
is approximately 60%. Fatty foods significantly increase the bioavailability and the peak level in the serumBlood plasmaBlood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
. - It takes about 2 hours to reach maximum concentrationConcentrationIn chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s in the serum. - Valganciclovir is eliminated as ganciclovir in the urine, with a half-lifeHalf-lifeHalf-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of about 4 hours in people with normal kidney function. - The mechanism of this drug is activation via thymidine kinase enzyme. The phosphotransferase enzyme can likewise activate valganciclovir.
Side effects
- BloodBloodBlood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
: neutropeniaNeutropeniaNeutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, low plateletsThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
. Myelosuppression is one of the main side effects that may limit prolonged use of valganciclovir. - Gastrointestinal: diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting, abdominal pain. - Central nervous systemCentral nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
: feverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, headacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, insomniaInsomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, paresthesiaParesthesiaParesthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
, and peripheral neuropathyPeripheral neuropathyPeripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
. - OcularHuman eyeThe human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
: retinal detachmentRetinal detachmentRetinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
Alternative uses
It has been proposed that valganciclovir could be used in the treatment of chronic fatigue syndromeChronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
. Following some reported success in 9 out of 12 patients at Stanford University
Stanford University
The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
in California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
, a follow-up double-blind, controlled study of 30 patients was completed, and although data has not yet been released, according to the Virus Induced CNS Dysfunction Association, "the data Dr. Montoya presented at the 2008 International Conference on HHV-6&7 indicated that patients on Valcyte experienced significant cognitive improvement.", especially for those with elevated antibody levels to HHV-6 and EBV (VCA and EA)
Price and patent status
Roche's Valcyte is protected by patentPatent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
. However a generic version manufactured by Japanese-owned Indian company Daiichi-Ranbaxy
Ranbaxy Laboratories
Ranbaxy Laboratories Limited is a pharmaceutical company that was incorporated in India in 1961. The company went public in 1973 and Japanese pharmaceutical company Daiichi Sankyo gained majority control in 2008...
was found by the District Court of New Jersey
United States District Court for the District of New Jersey
The United States District Court for the District of New Jersey is the federal district court whose jurisdiction is the state of New Jersey....
, USA not to infringe Roche's patent.
The price of a four-month course of valganciclovir from Roche is about US$8,500 in high-income countries, $6,000 in India. However, the valganciclovir patent was rejected by the Indian Patent Office
Indian Patent Office
The Indian Patent Office is administered by the Office of the Controller General of Patents, Designs & Trade Marks . This is a subordinate office of the Indian government and administers the Indian law of Patents, Designs and Trade Marks....
in 2010, although Roche may appeal
Appeal
An appeal is a petition for review of a case that has been decided by a court of law. The petition is made to a higher court for the purpose of overturning the lower court's decision....
the rejection.