Aciclovir 250mg/10ml solution for infusion vials
Requires a prescription from a doctor or prescriber
Antiviral drugs
Official documents, adverse reaction reporting, and safety monitoring
Report a side effect
Submit a Yellow Card report to the MHRA
Official medicine documents
Safety monitoring data
Yellow Card reports
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
View Drug Analysis Profile
Browse all Drug Analysis Profiles A–Z
Browse all iDAP reports
Interactive Drug Analysis Profiles for all medicines
Report a side effect
Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
View EudraVigilance report
Suspected adverse reactions reported for Aciclovir
About EudraVigilance
Learn about EU pharmacovigilance and safety monitoring
EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
4 branded products available
Part of the Cymex brand family (generic: Aciclovir)
MHRA licensed products
View all licensed products for Aciclovir on the MHRA register
Aciclovir 250mg/10ml concentrate for solution for infusion vials
Aciclovir 250mg/10ml concentrate for solution for infusion vials
Aciclovir 250mg/10ml concentrate for solution for infusion vials
Aciclovir 250mg/10ml concentrate for solution for infusion vials
Peckforton Pharmaceuticals Ltd
WHO defined daily dose (DDD)
4 gram
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
Therapeutically similar medicines
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
Clinical guidelines and formulary information
British National Formulary
Aciclovir
Source: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(6)
Atopic eczema in under 12s (QS44)
Atopic eczema in under 12s: diagnosis and management (CG57)
Myeloma: diagnosis and management (NG35)
Letermovir for preventing cytomegalovirus disease after a stem cell transplant (TA591)
Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management (NG240)
Fever in under 5s: assessment and initial management (NG143)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Pharmacy stock checkers
Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
166 found
Half-life
2.5-3 hours
Mechanism
Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase.
Food interactions
2 warnings
Human targets
None mapped
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
10-20%
[L7315]…
Half-life
2.5-3 hours
[A180757]…
Protein binding
9-33%
[A180775][L7315]
Volume of distribution
0.6L/kg
[A180775]
Metabolism
15%
[A180730]
Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase.
[A180757]
Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase.
[A903]
Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase.
[A903][A180781]
Elimination
90-92%
[A180730][L7324]…
Clearance
248mL/min
[A180787]
The total clearance in neonates if 105-122mL/min/1.73m2.
[A180787]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Acyclovir was granted FDA approval on 29 March 1982.[L7318]
[L7303]
Acyclovir oral tablets, capsules, and suspensions are indicated to treat herpes zoster, genital herpes, and chickenpox.
[L7315]
An acyclovir topical ointment is indicated to treat initial genital herpes and limited non-life-threatening mucocutaneous herpes simplex in immunocompromised patients.
[L7318]
An acyclovir cream with hydrocortisone is indicated to treat recurrent herpes labialis, and shortening lesion healing time in patients 6 years and older.
[L7321]
An acyclovir buccal tablet is indicated for the treatment of recurrent herpes labialis.
[L7324]
An acyclovir ophthalmic ointment is indicated to treat acute herpetic keratitis.
[L7327]
Known interactions with other medications. Always consult a healthcare professional.
Showing 50 of 1111 interactions
[L7315]
These symptoms are more common in patients given high doses without monitoring of fluid and electrolyte balance or reduced kidney function.
[L7315][A180730][A180775]
In the case of an overdose, treat with symptomatic and supportive care.
[L7321]
How the body processes this drug — absorption, distribution, metabolism, and elimination
[L7315]
Acyclovir ointment is <0.02-9.4% absorbed.
[L7318]
Acyclovir buccal tablets and ophthalmic ointment are minimally absorbed.
[L7324,L7327]
The bioavailability of acyclovir is not affected by food.
[L7315]
Acyclovir has a mean Tmax of 1.1±0.4 hours, mean Cmax of 593.7-656.5ng/mL, and mean AUC of 2956.6-3102.5h/*ng/mL.
[A180793]
[A180757]
The plasma half life of acyclovir during hemodialysis is approximately 5 hours.
[L7315]
The mean half life in patients from 7 months to 7 years old is 2.6 hours.
[L7315]
[A180775][L7315]
[A180775]
[A180730]
Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase.
[A180757]
Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase.
[A903]
Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase.
[A903][A180781]
[A180730][L7324]
90-92% of the drug can be excreted unchanged through glomerular filtration and tubular secretion.
[A180757]
<2% of the drug is recovered in feces and <0.1% is expired as CO2.
[A180787]
[A180787]
The total clearance in neonates if 105-122mL/min/1.73m2.
[A180787]
Enzymes involved in drug metabolism — important for understanding drug interactions
Proteins that transport this drug across cell membranes
PMID:11388889 PMID:11408531 PMID:12439218 PMID:12719534 PMID:15389554 PMID:16263091 PMID:16272756 PMID:16581093 PMID:19536068 PMID:21128598 PMID:23680637 PMID:24961373 PMID:34040533 PMID:9187257 PMID:9260930 PMID:9655880
Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity).
Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation .
PMID:16263091
Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline .
PMID:12439218 PMID:24961373 PMID:35469921 PMID:9260930
Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover .
PMID:21128598
Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism .
PMID:24961373
Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium .
PMID:15817714
Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency .
PMID:17460754
Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) .
PMID:11907186
May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) PMID:11408531 PMID:15389554 PMID:35469921 PMID:9260930
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
PMID:7592981 PMID:9458785 PMID:9856990
Transports various bile acids, unconjugated or conjugated, such as cholate and taurocholate .
PMID:7592981 PMID:9458785 PMID:9856990
Also responsible for bile acid transport in the renal proximal tubules, a salvage mechanism that helps conserve bile acids (Probable). Works collaboratively with the Na(+)-taurocholate cotransporting polypeptide (NTCP), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation PMID:33222321
PMID:16330770 PMID:17509534
Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Proteins that carry this drug through the body
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
ATC J05AB01
ATC D06BB03
ATC S01AD03
ATC D06BB53
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Additional database identifiers
Drugs Product Database (DPD)
1950
ChemSpider
1945
BindingDB
50021776
PDB
AC2
ZINC
ZINC000001530555
GenBank Gene Database
X14112
GenBank Protein Database
59530
UniProt Accession
DPOL_HHV11
GenBank Gene Database
X04370
GenBank Protein Database
60016
UniProt Accession
DPOL_VZVD
GenBank Gene Database
AF243477
GenBank Protein Database
8100965
UniProt Accession
KITH_HHV1
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4693
GenAtlas
GUK1
GeneCards
GUK1
GenBank Gene Database
L76200
GenBank Protein Database
1196436
UniProt Accession
KGUA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7849
GenAtlas
NME1
GeneCards
NME1
GenBank Gene Database
X75598
UniProt Accession
NDKA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7850
GenAtlas
NME2
GeneCards
NME2
GenBank Gene Database
X58965
UniProt Accession
NDKB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9020
GenAtlas
PKLR
GeneCards
PKLR
GenBank Gene Database
AB015983
GenBank Protein Database
3327365
Guide to Pharmacology
3007
UniProt Accession
KPYR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9021
GenAtlas
PKM2
GeneCards
PKM
GenBank Gene Database
M23725
GenBank Protein Database
189998
Guide to Pharmacology
3006
UniProt Accession
KPYM_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1991
GenAtlas
CKB
GeneCards
CKB
GenBank Gene Database
M16451
GenBank Protein Database
180572
UniProt Accession
KCRB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1994
GenAtlas
CKM
GeneCards
CKM
GenBank Gene Database
M14780
GenBank Protein Database
180576
UniProt Accession
KCRM_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1996
GenAtlas
CKMT2
GeneCards
CKMT2
GenBank Gene Database
J05401
GenBank Protein Database
338237
UniProt Accession
KCRS_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1995
GenAtlas
CKMT1A
GeneCards
CKMT1B
GenBank Gene Database
J04469
GenBank Protein Database
180590
UniProt Accession
KCRU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8896
GeneCards
PGK1
UniProt Accession
PGK1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8898
GeneCards
PGK2
UniProt Accession
PGK2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11448
GenAtlas
SUCLA2
GeneCards
SUCLA2
GenBank Gene Database
AB035863
GenBank Protein Database
7328935
UniProt Accession
SUCB1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11449
GenAtlas
SUCLG1
GeneCards
SUCLG1
GenBank Gene Database
AF104921
GenBank Protein Database
9409794
UniProt Accession
SUCA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11450
GenAtlas
SUCLG2
GeneCards
SUCLG2
GenBank Gene Database
BC007716
GenBank Protein Database
133777003
UniProt Accession
SUCB2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8725
GeneCards
PCK2
UniProt Accession
PCKGM_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8724
GenAtlas
PCK1
GeneCards
PCK1
GenBank Gene Database
L05144
GenBank Protein Database
189945
UniProt Accession
PCKGC_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:20093
GenAtlas
ADSSL1
GeneCards
ADSS1
GenBank Gene Database
AY037159
GenBank Protein Database
21303413
UniProt Accession
PURA1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:292
GenAtlas
ADSS
GeneCards
ADSS2
GenBank Gene Database
X66503
GenBank Protein Database
415849
UniProt Accession
PURA2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10963
GeneCards
SLC22A1
GenBank Gene Database
X98332
GenBank Protein Database
2511670
Guide to Pharmacology
1019
UniProt Accession
S22A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10970
GenAtlas
hROAT1
GeneCards
SLC22A6
GenBank Gene Database
AF057039
GenBank Protein Database
3831566
Guide to Pharmacology
1025
UniProt Accession
S22A6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10972
GeneCards
SLC22A8
GenBank Gene Database
AF097491
GenBank Protein Database
4378059
Guide to Pharmacology
1027
UniProt Accession
S22A8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10906
GeneCards
SLC10A2
GenBank Gene Database
U10417
GenBank Protein Database
595399
Guide to Pharmacology
960
UniProt Accession
NTCP2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:25588
GeneCards
SLC47A1
GenBank Gene Database
AK001709
GenBank Protein Database
7023138
Guide to Pharmacology
1216
UniProt Accession
S47A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:26439
GeneCards
SLC47A2
Guide to Pharmacology
1217
UniProt Accession
S47A2_HUMAN
International reference pricing
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
3 active patents, 4 expired
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications: