BASIC - INFECTIOUS DISEASES Flashcards
Indications of phenomethylpenicillin?
o Oral infections, tonsillitis, otitis media, cellulitis, erysipelas
o Prevention of pneumococcal in asplenia/sickle cell disease
o Prevention of recurrence of rheumatic fever
o Acute sinusitis
Indications of benzylpenicillin?
o Throat infections, otitis media, cellulitis, pneumonia, endocarditis, anthrax
o Intrapartum prophylaxis of Group-B strep
o Meningitis, meningococcal disease
Mechanism of action of penicillin?
- Inhibit enzyme responsible for cross-linking peptidoglycan in bacterial cell walls
- Weakens cell walls, preventing maintenance of osmotic gradient
- Cell swells, lysis and dies
- Penicillins contain B-lactam ring
- Bacteria resist actions of penicillins by making B-lactamase, limiting intracellular concentration of penicillin or change target enzyme to prevent binding
Side effects of penicillins?
- Diarrhoea, nausea, vomiting
- Allergy in 1-10% of people
o Skin rash 7-10 days after first exposure or 1-2 days after repeat exposure (IgG subacute)
o IgE anaphylactic reaction (0.05%) – hypotension, bronchial and laryngeal spasm, angioedema - CNS toxicity in high doses or renal impairment
Contraindications in penicillins?
- History of allergy
- Renal impairment
o Dose reduction in benzylpenicillin
Interactions of penicillins?
- Reduce renal excretion of methotrexate – risk of toxicity
Routes of phenoxymethylpenicillin and benzylpenicillin?
- Benzylpenicillin – only IV/IM as hydrolysis by gastric acid prevents absorption
o Severe infections at high dose only - Pen V – orally taken
- Short half-life so given every 4-6 hours
Indications of amoxicillin & co-amoxiclav?
- CAP, acute bronchiectasis, acute exacerbation of COPD, acute otitis media, sinusitis
- UTI (other alternatives)
- Combination for hospital-acquired infection or intra-abdominal sepsis
- H.pylori eradication
Mechanism of amoxicillin & what addition does co-amoxiclav have?
- Inhibit enzyme responsible for cross-linking peptidoglycan in bacterial cell walls
- Weakens cell walls, preventing maintenance of osmotic gradient
- Cell swells, lysis and dies
- Penicillins contain B-lactam ring
o Addition of amino group – increases activity against aerobic Gram-negative bacteria – broad spectrum
o Addition of B-lactamase inhibitor clavulanic acid increases spectrum of antimicrobial activity further (S.aureus and gram-negative anaerobes) - Bacteria resist actions of penicillins by making B-lactamase, limiting intracellular concentration of penicillin or change target enzyme to prevent binding
Side effects of amoxicillin/co-amoxiclav?
- Diarrhoea, nausea, vomiting
- Antibiotic-associated colitis
o Broad spectrum antibiotics kill normal gut flora and C.diff grows
o Debilitating and can cause colonic perforation - Cholestatic jaundice (co-amoxiclav)
- Allergy in 1-10% of people
o Skin rash 7-10 days after first exposure or 1-2 days after repeat exposure (IgG subacute)
o IgE anaphylactic reaction (0.05%) – hypotension, bronchial and laryngeal spasm, angioedema - CNS toxicity in high doses or renal impairment
Dose changes in renal impairment in amoxcillin/co-amoxiclav?
o Dose reduction (crystalluria)
Interactions of amoxicillin/co-amoxiclav?
- Reduce renal excretion of methotrexate – risk of toxicity
- Enhance anticoagulant effect of warfarin by killing gut flora that synthesise vitamin K
- DO NOT GIVE IN EBV
Dose of amoxicillin?
- IV should be switched to oral after 48h if indicated
- Oral amoxicillin usually 500mg 8-hourly for 7-14 days
Indications of flucloxacillin?
- Otitis externa, impetigo, cellulitis, endocarditis, osteomyelitis, surgical prophylaxis
- Prevention of S.aureus infection in cystic fibrosis
Mechanism of flucloxacillin?
- Inhibit enzyme responsible for cross-linking peptidoglycan in bacterial cell walls
- Weakens cell walls, preventing maintenance of osmotic gradient
- Cell swells, lysis and dies
- Penicillins contain B-lactam ring
o Acyl side chain protect B-lactam ring from B-lactamases
Effective against B-lactamase producing staphylococci
MRSA resists flucloxacillin action by reducing penicillin binding affinity - Bacteria resist actions of penicillins by making B-lactamase, limiting intracellular concentration of penicillin or change target enzyme to prevent binding
Side effects of flucloxacillin?
- Liver toxicity – cholestasis and hepatitis
- Allergy in 1-10% of people
o Skin rash 7-10 days after first exposure or 1-2 days after repeat exposure (IgG subacute)
o IgE anaphylactic reaction (0.05%) – hypotension, bronchial and laryngeal spasm, angioedema - CNS toxicity in high doses or renal impairment
Contraindications of flucloxacillin?
- History of allergy
- Prior flucloxacillin-related hepatotoxicity
Dose changes in renal impairment of flucloxacillin?
o Dose reduction if <10eGFR
Interactions of flucloxacillin?
- Reduce renal excretion of methotrexate – risk of toxicity
Dose of flucloxacillin?
- IV high dose 1-2g 4-6 hourly for severe infections
- Osteomyelitis and endocarditis require 6 weeks of high-dose IV
- Oral flucloxacillin 250-500mg 4 times a day
Indications of Tazocin?
- For severe infections
o HAP, sepsis, acute COPD/bronchiectasis
o Complicated UTI, skin, soft-tissue infections - Neutropenic sepsis
Mechanism of Tazocin?
- Inhibit enzyme responsible for cross-linking peptidoglycan in bacterial cell walls
- Weakens cell walls, preventing maintenance of osmotic gradient
- Cell swells, lysis and dies
- Penicillins contain B-lactam ring
o Side chain of broad-spectrum antibiotics converted to form urea
Increases affinity including pseudomonas aeruginosa
o B-lactamase inhibitor tazobactam confers activity against S.aureus and Gram-neg anaerobes - Bacteria resist actions of penicillins by making B-lactamase, limiting intracellular concentration of penicillin or change target enzyme to prevent binding
Side effects of Tazocin?
- Diarrhoea, nausea, vomiting
- Antibiotic-associated colitis
o Broad spectrum antibiotics kill normal gut flora and C.diff grows
o Debilitating and can cause colonic perforation - Allergy in 1-10% of people
o Skin rash 7-10 days after first exposure or 1-2 days after repeat exposure (IgG subacute)
o IgE anaphylactic reaction (0.05%) – hypotension, bronchial and laryngeal spasm, angioedema - CNS toxicity in high doses or renal impairment
Dose changes in renal impairment of Tazocin?
o Max 4.5g every 8 if eGFR 20-40
o Max 4.5g every 12 hours if eGFR <20
Cautions of Tazocin?
o Risk of C.diff infection
Interactions of Tazocin?
- Reduce renal excretion of methotrexate – risk of toxicity
- Enhance anticoagulant effect of warfarin by killing gut flora that synthesise vitamin K
Dose of Tazocin?
- IV infusion only
- Usual dose of 4.5g, given every 6-8 hours
Names of carbapenems?
Meropenem
Ertapenem
Indications of carbapenems?
- IV reserved for severe infections
Mechanism of carbapenems?
- Naturally occurring antimicrobials produced by fungi and bacteria
- B-lactam ring
- Inhibit enymes responsible for cross-linking peptidoglycans in bacterial cell walls
- Weakens walls and causes bacterial cell swelling, lysis and death
- Broad spectrum
- Hydroxyethyl Ring – resistant to B-lactamases
Side Effects of carbapenems?
- Diarrhoea, nausea, vomiting
- Antibiotic-associated colitis
o Broad spectrum antibiotics kill normal gut flora and C.diff grows
o Debilitating and can cause colonic perforation - Allergy in 1-10% of people
o Skin rash 7-10 days after first exposure or 1-2 days after repeat exposure (IgG subacute)
o IgE anaphylactic reaction (0.05%) – hypotension, bronchial and laryngeal spasm, angioedema - CNS toxicity in high doses or renal impairment
Cautions of carbapenems?
o Risk of C.diff infection
o Epilepsy
Dose changes in renal impairment of carbapenems?
o Dose reduction
Interactions of carbapenems?
- Enhance anticoagulant effect of warfarin by killing gut flora that synthesise vitamin K
- Reduce plasma concentrations and efficacy of valproate
Dose of meropenems?
- IV only
- Meropenem 1-2g IV 8-hourly
Names of cephalosporins?
Cephalexin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime and ceftaroline
Indications of cephalosporins?
- 2nd and 3rd line treatment for urinary and respiratory tract infections
- IV reserved for severe infections
Mechanism of cephalosporins?
- Naturally occurring antimicrobials produced by fungi and bacteria
- B-lactam ring
- Inhibit enymes responsible for cross-linking peptidoglycans in bacterial cell walls
- Weakens walls and causes bacterial cell swelling, lysis and death
- Broad spectrum
- Dihydrothiazine Ring – resistant to B-lactamases
Side effects of cephalosporins?
- Diarrhoea, nausea, vomiting
- Antibiotic-associated colitis
o Broad spectrum antibiotics kill normal gut flora and C.diff grows
o Debilitating and can cause colonic perforation - Allergy in 1-10% of people
o Skin rash 7-10 days after first exposure or 1-2 days after repeat exposure (IgG subacute)
o IgE anaphylactic reaction (0.05%) – hypotension, bronchial and laryngeal spasm, angioedema - CNS toxicity in high doses or renal impairment
Contraindications and cautions of cephalosporins?
Contraindication
- History of allergy to penicillins, cephalosporins or carbepenems
Caution
o Risk of C.diff infection
Dose changes in renal impairment of cephalosporins?
o Half dose in eGFR <5
Interactions of cephalosporins?
- Enhance anticoagulant effect of warfarin by killing gut flora that synthesise vitamin K
- Increase nephrotoxicity of aminoglycosides
Dose of cefotaxime?
- Usually over 6-12 hourly
- Cefotaxime 2g IV 6-hourly for bacterial meningitis
Names of aminoglycosides?
Gentamicin, amikacin
Indications of aminoglycosides?
- Severe infections, particularly Gram-negative aerobes
o Severe sepsis
o Pyelonephritis and complicated UTI
o Biliary and other intra-abdominal sepsis
o Endocarditis
o Bacterial eye infections - Lack activity against streptococci and anaerobes
Mechanism of aminoglycosides?
- Bind irreversibility to bacterial ribosomes (30S subunit) and inhibit protein synthesis
- Bactericidal
- Enters bacterial cells via oxygen-dependent transport system
- Spectrum – gram-negative aerobic bacteria, staphylococci and mycobacteria
Side effects of aminoglycosides?
- Nephrotoxicity and ototoxicity
o Accumulate in renal tubular epithelial cells and cochlear hair cells triggering cell death - Tinnitus
Contraindications of aminoglycosides?
- Impair neuromuscular transmission so avoid in Myasthenia gravis
- Caution
o Elderly, neonates, renal impairment
Interactions of aminoglycosides?
- Ototoxicity increases with loop diuretics or vancomycin
- Nephrotoxicity increases with ciclosporin, platinum, cephalosporins or vancomycin
Prescription of gentamicin?
- IV only given over an hour
- Dose calculated using patients’ weight and renal function (IBW = 7mg/kg)
o Use patient’s height to select IBW, if ABW less than IBW – use dose according to ABW - Dose interval determined by drug level monitoring, usually 24 hours but longer in renal impairment
- Often single dose course
Initial monitoring in gentamicin?
o One 10ml blood sample between 6-14 hours after start of first infusion
o Plain tube (clotted blood) – record exact time taken
o Plot of normogram
o Dose interval according to value given off graph – if 24,36 or 48h
o If level is over 48h dosing interval STOP treatment and take daily levels – gentamicin can be restarted once below 2mg/L
Repeat monitoring in gentamicin?
o U&Es and creatinine daily
If creatinine rising >20% and still between 6-14 hours – measure gentamicin levels
If not between 6-14 hours – contact microbiology
o Repeat Gentamicin levels according to dosage interval:
Dosage level - 24 hours = 3 days
Dosage level - 36 hours = 3 days
Dosage level - 48 hours = 2 days
Names of macrolides?
Clarithromycin, Erythromycin, Azithromycin
Indications of macrolides?
- Treatment of respiratory and soft tissue infections as alternative to penicillin
- Severe pneumonia (added to cover atypicals like Legionella, Mycoplasma)
- Eradication of H.pylori
Mechanism of macrolides?
- Inhibit bacterial protein synthesis – bind to 50S subunit and block translocation
- Bacteriostatic
Side effects of macrolides?
- Irritant – causing nausea, vomiting, abdominal pain and diarrhoea when taken orally, thrombophlebitis if IV
- Antibiotic-associated colitis (C.diff)
- Cholestatic jaundice
- Prolongation of QT interval
- Ototoxicity at high doses
Contraindications of macrolideS?
- Hepatic elimination mostly – caution in severe hepatic impairment and dose reduction in severe renal impairment
Interactions of macrolides?
- Erythromycin and Clarithromycin inhibit CYP450 enzymes
- Caution with drugs that prolong QT
o Amiodarone, antipsychotics, quinine, quinolone, antibiotics and SSRIs
Common dose of macrolides?
- Oral dosage 250-500mg BDS for 7-14 days
What class of drug is clindamycin?
Semisynthetic Lincosamide
Indications of clindamycin?
- Treatment of staphylococcal bone and joint infections
- Peritonitis
- Intrabdominal sepsis
- Falciparum malaria
- Bacterial vaginosis
- Acne Vulgaris
Mechanisms of clindamycin?
- Inhibit bacterial protein synthesis – bind to 50S subunit and block translocation
- Bacteriostatic
Side effects of clindamycin?
- Skin reactions
- Abdominal pain
- Antibiotic-associated colitis
- Diarrhoea
Contraindications of clindamycin?
- Diarrhoeal states
Interactions of clindamycin?
- Increases effects of actracurium, mivacurium, pancuronium, rocuronium, suxamethonium so caution
Dose of clindamycin?
- Oral dosage 150-300mg QDS up to 450mg
Important patient information given in clindamycin?
o Damages latex condoms with vaginal use
Names of glycopeptides?
Vancomycin, Teicoplanin
Indications of glycopeptides?
- Treatment of Gram-positive infections – bone, joint, CAP, HAP, meningitis, endocarditis if penicillins can’t be used
- Antibiotic associated colitis (C.diff)
Mechanism of glycopeptides?
- Inhibits growth and cross-linking of peptidoglycan chains, inhibiting synthesis of cell wall of Gram-positive bacteria
Side effects of glycopeptides?
- Thrombophlebitis at infusion site
- Anaphylactoid reactions
o Red man syndrome – generalised erythema, hypotension and bronchospasm
o Not true allergy but due to non-specific degranulation of mast cells - Allergy
- IV Vancomycin
o Nephrotoxic (renal failure and interstitial nephritis)
o Ototoxic (tinnitus and hearing loss)
o Neutropenia and thrombocytopenia
Caution of glycopeptides?
- Monitoring of plasma concentrations and dose adjustment
- Caution
o Renal impairment (serial renal function monitoring)
o Elderly
Interactions of glycopeptides?
- Ototoxicity/nephrotoxicity increases with aminoglycosides, loop diuretics or ciclosporin
Dose of glycopeptides?
o Initial loading dose determined by actual body weight (in glucose 5% or NaCl 0.9%)
<60kg = 1g
60-90kg = 1.5g
>90kg = 2g
Monitoring of vancomycin?
How is maintenance level calculated?
o Maintenance dose & dosing interval calculated using patient’s creatinine clearance (keeps trough levels of 10-15mg/L)
o Monitor pre-dose trough levels at 36-48 hours (should be between 10-20mg/L)
How to adjust maintenance dose of vancomycin?
If <5 – move up to two dosing levels from current dosing schedule
If 5-10 – move up 1 or 2 levels depending on target (10-15 or 15-20)
If 10-20 – continue at current dose
If 20-25 – Move down one dosing level
IF >25 – omit next dose & decrease by two dosing levels
If >30 – seek pharmacy advice
Monitoring during vancomycin levels?
o Daily U&Es and creatinine
o Regular FBC during prolonged therapy
Common dose for vancomycin?
- IV only given
- For C.diff – 125mg 6-hourly for 10-14 days
Indications of metronidazole?
- Anaerobic infections in:
o Antibiotic-associated colitis (C.diff)
o Oral infections (dental abscess) or aspiration pneumonia
o Surgical and gynaecological infections
o Protozoal infections (BV, trichomonas, giardiasis)
o H.pylori eradication
Mechanism of metronidazole?
- Enter bacterial cells via passive diffusion
- In anaerobic bacteria, reduction of metronidazole generates nitroso free radicals that bind to DNA and cause DNA degradation and cell death
Side effects of metronidazole?
- Dry mouth, metallic taste
- Nausea and vomiting
- Diarrhoea
- Immediate or delayed hypersensitivity reactions
- High doses/prolonged course
o Peripheral or optic neuropathy
o Seizures
o Encephalopathy
Cautions of metronidazole?
o Renal impairment (serial renal function monitoring)
o Elderly
Interactions of metronidazole?
- Metabolised by CYP450 enzymes – dose reduction in severe liver impairment
- Some inhibitory effect on CYP450 enzymes
- Inhibits acetaldehyde dehydrogenase – responsible for clearing alcohol so no alcohol when on metronidazole
o Gives disulfiram reaction (flushing, nausea, headache, vomiting) - Increased risk of lithium toxicity
Typical dose of metronidazole?
- Oral typical and starting dose is 400mg 8-hourly
- Can be prescribed IV, rectally, topical, vaginal
Monitoring of metronidazole?
o If treatment >10 days measure:
FBC and LFTs
Important communication to patients of metronidazole?
o No alcohol during or 48 hours after metronidazole treatment
Indications of nitrofurantoin?
- Uncomplicated UTI
- Prophylaxis in recurrent, catheter-associated or surgical prophylaxis of UTI
Mechanism of nitrofurantoin?
- Metabolised (reduced) in bacterial cells by nitrofuran reductase
- Active metabolite damages bacterial DNA and causes cell death
Side effects of nitrofurantoin?
- N & V, diarrhoea
- Immediate or delayed hypersensitivity reactions
- Turn urine dark yellow/brown
- Pneumonitis, hepatitis, peripheral neuropathy
- Neonates – haemolytic anaemia
Contraindications of nitrofurantoin?
o Porphyria, G6PD deficiency
o Infants <3m
o Pregnancy 3rd trimester
o Renal Impairment
Dose change in renal impairment of nitrofurantoin?
o Avoid if <45 eGFR
Typical dose in UTI of nitrofurantoin? And dose of prophylactic?
- Acute UTI – 50-100mg QDS either 3 day (uncomplicated women) or 7 days (men or more complicated women)
- Prevention of recurrent UTI – single nightly dose of 50-100mg
Monitoring of nitrofurantoin?
o Long term therapy: LFT, pulmonary symptoms
Names of quinolones?
Ciprofloxacin, Moxifloxacin, Levofloxacin
Indications of quinolones?
- 2nd or 3rd generation due to resistance and C.diff
o UTI
o Severe GI infection – Shigella, campylobacter
o LRTI
Mechanism of quinolones?
- Inhibit DNA synthesis
- Rapid resistance can develop though
Side effects of quinolones?
- N&V, diarrhoea
- Oesophageal irritation
- Lower seizure threshold
- Hallucinations
- Rupture of muscle tendons
- Prolong QT interval
- C.diff Colitis
Contraindications of quinolones?
o Hx of tendon disorders
o Pregnancy
Cautions of quinolones?
o Risk of seizures
o Risk factors for QT prolongation
Dose changes in renal impairment of quinolones?
o Reduce dose if eGFR <60
Interactions of quinolones?
- Drugs containing divalent cations reduce absorption of quinolones
- Inhibits CYP450 enzymes
- Avoid in drugs that prolong QT:
o Amiodarone, antipsychotics, quinine, macrolides, SSRIs
Typical dose of ciprofloxacin?
- Ciprofloxacin typically 250-750mg orally 12-hourly or 400mg IV 12-hourly
Names of tetracyclines?
Doxycycline, lymecycline, Tigecycline
Indications of tetracyclines?
- Acne vulgaris and rosacea
- LRTIs including exacerbation of COPD, pneumonia and atypical pneumonia
- Chlamydia, Syphilis, and PID
- Typhoid anthrax, malaria and Lyme Disease
Mechanism of tetracyclines?
- Inhibits bacterial protein synthesis by binding to ribosomal 30S subunit
- Prevents transfer of tRNA to mRNA – bacteriostatic
Sides effects of tetracyclines?
- N, V and diarrhoea
- Oesophageal irritation
- Photosensitivity
- Discolouration and/or hypoplasia of tooth enamel in children
- Intracranial hypertension
Contraindications of tetracyclines?
o Pregnancy
o Breastfeeding
o Children <12 years old
Dose changes in renal impairment of tetracyclines?
o Avoid – raise plasma urea
Interactions of tetracyclines?
- Bind to divalent cations
o Do not give within 2 hours of Ca, antacids, iron - Enhance anticoagulant effect of warfarin
Dose of doxycycline?
- Oral typically 100-200mg daily
Indications of trimethoprim?
- Uncomplicated UTI
- Co-trimoxazole (trimethoprim and sulfamethoxazole) - PCP in HIV
Mechanism of trimethoprim?
- Inhibits bacterial folate synthesis, bacteriostatic
- However, widespread resistance in areas of UK
Side effects of trimethoprim?
- Nausea and vomiting
- Diarrhoea
- Hypersensitivity reactions – anaphylaxis, drug fever, erythema multiforme
- Megaloblastic anaemia, leukopenia and thrombocytopenia
- Hyperkalaemia and elevate creatinine concentrations
Contraindications of trimethoprim?
o Blood dyscrasias
o 1st trimester of pregnancy (folate antagonist associated with foetal abnormalities (CV defects, oral cleft))
Dose change in renal impairment of trimethoprim?
o Dose reduction – half dose after 3 days if eGFR 15-30, half dose if <15 eGFR
Interactions of trimethoprim?
- Elevates potassium in conjunction with:
o Aldosterone antagonists, ACE inhibitors, ARBs - Risk of haematological effects increased with:
o Methotrexate, phenytoin - Enhance anticoagulant effect of warfarin
Usual dose of trimethoprim? And prophylactic dose?
- Acute UTI – 200mg BDS either 3 day (uncomplicated women) or 7 days (men or more complicated women)
- Prevention of recurrent UTI – single nightly dose of 100mg
Monitoring of trimethoprim?
o Long term therapy: FBC
Names of common antifungals?
Clotrimazole (Nystatin), Fluconazole
Indications of azoles?
- Local fungal infections of oropharynx, vagina or skin (topical or oral)
- Systemic treatment of invasive fungal infections
Mechanism of azoles?
- Antifungals bind to ergosterol in fungal cell membranes, creating polar pore which allows intracellular ions to leak out
- Imidazole (clotrimazole) and triazole (fluconazole) inhibit ergosterol synthesis, impairing cell membrane synthesis and replication
Side effects of topical azoles and fluconazole?
- Topical – local irritation where applied
- Fluconazole
o GI upset (nausea, vomiting, diarrhoea, abdominal pain)
o Headache
o Hepatitis
o Hypersensitivity causing skin rash - Rarely:
o Severe hepatic toxicity
o Prolonged QT interval
Contraindications of fluconazole?
o Pregnancy
Cautions in fluconazole?
o Risk factors for QT prolongation
o Hepatic Impairment
Dose changes in renal impairment in fluconazole?
o Reduce dose if eGFR <50
Interactions with fluconazole?
o Inhibits CYP450 enzymes
o Reduce antiplatelet actions of clopidogrel
o Risk of arrhythmias in drugs that prolong QT
Amiodarone, antipsychotics, quinine, quinolone, macrolides and SSRIs
Prescriptions of nystatin, clotrimazole & fluconazole?
o Nystatin – topical or oral – thrush - 100,000 units QDS for 7 days or 48h after lesions resolve
o Clotrimazole – 1% cream applied BDS/TDS
o Fluconazole – Oral 150mg single dose
Indications of aciclovir?
- Herpes Simplex Infection
- VZV
- Herpes Zoster Virus
Mechanism of aciclovir?
- Converted by thymidine kinase to acyclovir monophosphate which inhibits HSV-specific DNA polymerases and prevents synthesis
Side effects of aciclovir?
- Oral – abdominal pain, diarrhoea, headache, nausea and vomiting
o Rarely encephalopathy, neutropenia, leukopenia, thrombocytopenia - Topical – dry skin, stinging sensation
Dose changes in renal impairment of aciclovir?
o Maintain adequate hydration
o Dose reduction if eGFR <10
Interactions of aciclovir?
- Increases exposure to aminophylline and theophylline so adjust dose
