- "The list included Carbamazepine, an anti-convulsant,
Methylprednisolone, an anti-inflammatory treatment, Propranolol, a heart
drug, Klonopin and Ativan, both anti-anxiety drugs, Topamax, an anti-seizure
medication, the antibiotic Biaxin, pain reliever Vicoprofen, anti-deressant
Fluoxetine (my note: fluoride-based Prozac) and Hydrocodone, another
pain killer"
-
-
- Interactions between your selected drugs
-
- carbamazepine <--> clarithromycin
-
- Applies to: carbamazepine, Biaxin (clarithromycin)
-
- GENERALLY AVOID: Some macrolide antibiotics can significantly
increase serum carbamazepine levels. The mechanism is probably inhibition
of hepatic CYP450 3A4 isoenzymes. Severe carbamazepine toxicity has been
reported.
-
- MANAGEMENT: Alternative antimicrobial therapy, if available,
is generally recommended for patients on carbamazepine. A macrolide that
does not affect carbamazepine levels, such as azithromycin, may be substituted
if clinically appropriate. If this combination must be used, carbamazepine
levels should be monitored and the patient should be carefully observed
for signs of carbamazepine toxicity. Patients should be advised to report
signs of carbamazepine toxicity (nausea, visual disturbances, dizziness,
or ataxia) to their <http://www.drugs.com/interactions-check.php#>physicians.
The carbamazepine dosage may require reduction.
-
- ibuprofen <--> propranolol
-
- Applies to: Vicoprofen (hydrocodone/ibuprofen), propranolol
-
- MONITOR: Nonsteroidal <http://www.drugs.com/interactions-check.php#>anti-inflammatory drugs
(NSAIDs) may attenuate the antihypertensive effect of beta-blockers. The
proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis,
which results in unopposed pressor activity producing hypertension. In
addition, NSAIDs can cause fluid retention, which also affects blood pressure.
Indomethacin and piroxicam have been reported to have greater attenuating
effects than other NSAIDs, and indomethacin effects may be significant
in patients with eclampsia.
-
- MANAGEMENT: Patients receiving a beta-blocker who require
prolonged (greater than 1 week) concomitant therapy with an NSAID should
have blood pressure monitored more closely following initiation, discontinuation,
or change of dosage of the NSAID.. The interaction is not expected to occur
with low doses (e.g., low-dose aspirin) or intermittent short-term administration
of NSAIDs.
-
- carbamazepine <--> clonazepam
-
- Applies to: carbamazepine, Klonopin (clonazepam)
-
- MONITOR: Carbamazepine may reduce serum clonazepam levels.
The mechanism may be related to induction of metabolism. The risk of CNS-depressant
side effects, such as sedation and apathy, may be increased with this combination.
-
- MANAGEMENT: If these drugs must be used together, observation
for clinical and laboratory evidence of altered clonazepam effect is recommended.
-
- carbamazepine <--> fluoxetine
-
- Applies to: carbamazepine, fluoxetine
-
- MONITOR: Fluoxetine may inhibit the hepatic metabolism
of carbamazepine. Carbamazepine toxicity is possible. Data have been conflicting
and one study has reported no significant pharmacokinetic interaction.
A case of toxic serotonin syndrome has occurred in one patient who was
taking both carbamazepine and fluoxetine.
-
- MANAGEMENT: Until more information is available, close
observation for clinical and laboratory evidence of carbamazepine toxicity
is recommended. Dose adjustments may be required. Patients should be advised
to report possible symptoms of carbamazepine toxicity (nausea, visual disturbances,
dizziness, or ataxia) or serotonin syndrome (uncontrollable shivering,
agitation, incoordination, restlessness, involuntary movements, hyperreflexia,
and hyperarousal).
-
- clarithromycin <--> methylprednisolone
-
- Applies to: Biaxin (clarithromycin), methylprednisolone
-
- MONITOR: Coadministration with inhibitors of CYP450 3A4
may increase the plasma concentrations and pharmacologic effects of corticosteroids,
which are primarily metabolized by the isoenzyme. The interaction has been
reported with potent inhibitors such as clarithromycin, erythromycin, itraconazole,
nefazodone, and ritonavir during concomitant use of various corticosteroids,
including inhaled formulations. Cushing's syndrome and adrenal insufficiency
have been attributed to the interaction.
-
- MANAGEMENT: The possibility of increased corticosteroid
effects should be considered during concomitant therapy with CYP450 3A4
inhibitors, particularly potent ones like itraconazole, ketoconazole, voriconazole,
nefazodone, protease inhibitors, and ketolide and macrolide antibiotics.
Adrenal function should be monitored regularly during chronic use of these
agents, and corticosteroid dosage adjusted as necessary. Adverse effects
during prolonged administration of corticosteroids may include symptoms
of hypercorticism (e.g., acne, easy bruising, moon face, edema, hirsutism,
buffalo hump, <http://www.drugs.com/interactions-check.php#>skin striae,
glucose intolerance, irregular menstruations); adrenal suppression (which
reduces patient's ability to respond to stress situations); immunosuppression;
and osteoporosis.
-
- carbamazepine <--> lorazepam
-
- Applies to: carbamazepine, Ativan (lorazepam)
-
- MONITOR: Central nervous system- and/or respiratory-depressant
effects may be additively or synergistically increased in patients taking
multiple drugs that cause these effects, especially in elderly or debilitated
patients.
-
- MANAGEMENT: During concomitant use of these drugs, patients
should be monitored for potentially excessive or prolonged CNS and respiratory
depression. Ambulatory patients should be counseled to avoid hazardous
activities requiring complete mental alertness and motor coordination until
they know how these agents affect them, and to notify their <http://www.drugs.com/interactions-check.php#>physician if
they experience excessive or prolonged CNS effects that interfere with
their normal activities.
-
- clonazepam <--> fluoxetine
-
- Applies to: Klonopin (clonazepam), fluoxetine
-
- MONITOR: Central nervous system- and/or respiratory-depressant
effects may be additively or synergistically increased in patients taking
multiple drugs that cause these effects, especially in elderly or debilitated
patients.
-
- MANAGEMENT: During concomitant use of these drugs, patients
should be monitored for potentially excessive or prolonged CNS and respiratory
depression. Ambulatory patients should be counseled to avoid hazardous
activities requiring complete mental alertness and motor coordination until
they know how these agents affect them, and to notify their physician if
they experience excessive or prolonged CNS effects that interfere with
their normal activities.
-
- carbamazepine <--> hydrocodone
-
- Applies to: carbamazepine, Vicoprofen (hydrocodone/ibuprofen),
hydrocodone
-
- MONITOR: Central nervous system- and/or respiratory-depressant
effects may be additively or synergistically increased in patients taking
multiple drugs that cause these effects, especially in elderly or debilitated
patients.
-
- MANAGEMENT: During concomitant use of these drugs, patients
should be monitored for potentially excessive or prolonged CNS and respiratory
depression. Ambulatory patients should be counseled to avoid hazardous
activities requiring complete mental alertness and motor coordination until
they know how these agents affect them, and to notify their physician if
they experience excessive or prolonged CNS effects that interfere with
their normal activities.
-
- lorazepam <--> hydrocodone
-
- Applies to: Ativan (lorazepam), Vicoprofen (hydrocodone/ibuprofen),
hydrocodone
-
- MONITOR: Central nervous system- and/or respiratory-depressant
effects may be additively or synergistically increased in patients taking
multiple drugs that cause these effects, especially in elderly or debilitated
patients.
-
- MANAGEMENT: During concomitant use of these drugs, patients
should be monitored for potentially excessive or prolonged CNS and respiratory
depression. Ambulatory patients should be counseled to avoid hazardous
activities requiring complete mental alertness and motor coordination until
they know how these agents affect them, and to notify their physician if
they experience excessive or prolonged CNS effects that interfere with
their normal activities.
-
- clonazepam <--> hydrocodone
-
- Applies to: Klonopin (clonazepam), Vicoprofen (hydrocodone/ibuprofen),
hydrocodone
-
- MONITOR: Central nervous system- and/or respiratory-depressant
effects may be additively or synergistically increased in patients taking
multiple drugs that cause these effects, especially in elderly or debilitated
patients.
-
- MANAGEMENT: During concomitant use of these drugs, patients
should be monitored for potentially excessive or prolonged CNS and respiratory
depression. Ambulatory patients should be counseled to avoid hazardous
activities requiring complete mental alertness and motor coordination until
they know how these agents affect them, and to notify their physician if
they experience excessive or prolonged CNS effects that interfere with
their normal activities.
-
- fluoxetine <--> topiramate
-
- Applies to: fluoxetine, Topamax (topiramate)
-
- MONITOR: Central nervous system- and/or respiratory-depressant
effects may be additively or synergistically increased in patients taking
multiple drugs that cause these effects, especially in elderly or debilitated
patients.
-
- MANAGEMENT: During concomitant use of these drugs, patients
should be monitored for potentially excessive or prolonged CNS and respiratory
depression. Ambulatory patients should be counseled to avoid hazardous
activities requiring complete mental alertness and motor coordination until
they know how these agents affect them, and to notify their physician if
they experience excessive or prolonged CNS effects that interfere with
their normal activities.
-
- hydrocodone <--> topiramate
-
- Applies to: Vicoprofen (hydrocodone/ibuprofen), hydrocodone,
Topamax (topiramate)
-
- MONITOR: Central nervous system- and/or respiratory-depressant
effects may be additively or synergistically increased in patients taking
multiple drugs that cause these effects, especially in elderly or debilitated
patients.
-
- MANAGEMENT: During concomitant use of these drugs, patients
should be monitored for potentially excessive or prolonged CNS and respiratory
depression. Ambulatory patients should be counseled to avoid hazardous
activities requiring complete mental alertness and motor coordination until
they know how these agents affect them, and to notify their physician if
they experience excessive or prolonged CNS effects that interfere with
their normal activities.
-
- carbamazepine <--> methylprednisolone
-
- Applies to: carbamazepine, methylprednisolone
-
- MONITOR: Carbamazepine may decrease the plasma concentrations
and systemic effects of both endogenous and exogenous corticosteroids.
The mechanism is accelerated corticosteroid metabolism due to induction
of the CYP450 3A4 enzymatic pathway by carbamazepine.
-
- MANAGEMENT: Patients treated concomitantly with carbamazepine
may require higher dosages of corticosteroids or adrenocorticotropic agents.
Pharmacologic response to these agents should be monitored more closely
whenever carbamazepine is added to or withdrawn from therapy in patients
stabilized on their existing corticosteroid or adrenocorticotropic regimen,
and the dosage(s) adjusted as necessary.
-
- propranolol <--> fluoxetine
-
- Applies to: propranolol, fluoxetine
-
- MONITOR: Limited clinical data suggest that selective
serotonin reuptake inhibitors (SSRIs) may potentiate the pharmacologic
effects of some beta-blockers. There have been case reports of patients
stabilized on beta-blocker therapy who developed bradycardia, hypotension,
and complete heart block following the addition of a SSRI, subsequently
requiring discontinuation of one or both agents and/or institution of a
permanent pacemaker. The interaction is also corroborated by data from
in vitro and clinical studies involving paroxetine and metoprolol conducted
by one group of investigators. The proposed mechanism is SSRI inhibition
(competitive and/or noncompetitive) of CYP450 2D6, the isoenzyme responsible
for the metabolic clearance of beta-blockers such as carvedilol, labetalol,
metoprolol, nebivolol, propranolol, and timolol. Paroxetine and norfluoxetine
(the active metabolite of fluoxetine), in particular, are potent inhibitors
of CYP450 2D6 and may be more likely than other SSRIs to cause the interaction.
On the other hand, fluvoxamine is a potent inhibitor of CYP450 1A2 and
may significantly interact with propranolol, which is a substrate of both
CYP450 2D6 and 1A2.
-
- MANAGEMENT: During concomitant therapy with SSRIs, a
lower initial dosage and more cautious titration of the beta-blocker may
be appropriate. Cardiac function should be closely monitored and the beta-blocker
dosage adjusted accordingly, particularly following initiation, discontinuation
or change of dosage of SSRI in patients who are stabilized on their beta-blocker
regimen. Due to the long half-life of fluoxetine and its active metabolite,
norfluoxetine, the risk of an interaction may exist for an extended period
(up to several weeks) after discontinuation of fluoxetine. To avoid the
interaction, use of beta-blockers that are primarily eliminated by the
kidney such as atenolol, acebutolol, betaxolol, carteolol, and nadolol
may be considered.
-
- clarithromycin <--> clonazepam
-
- Applies to: Biaxin (clarithromycin), Klonopin (clonazepam)
-
- MONITOR: Macrolide antibiotics may increase and prolong
the CNS effects of certain benzodiazepines. The mechanism is inhibition
of CYP450 3A4 hepatic oxidation of the benzodiazepines. Midazolam, triazolam,
and alprazolam have been specifically studied in this regard. Lorazepam,
oxazepam, and temazepam are hepatically conjugated and are not expected
to interact. Azithromycin and dirithromycin do not inhibit CYP450 isoenzymes.
-
- MANAGEMENT: Patients receiving this combination should
be monitored for excessive or prolonged sedation. Non-interacting benzodiazepines
or antimicrobials may be considered as alternatives.
-
- carbamazepine <--> topiramate
-
- Applies to: carbamazepine, Topamax (topiramate)
-
- ADJUST DOSE: Carbamazepine, when coadministered with
topiramate may lead to a 40% decrease in the plasma concentration of topiramate.
The mechanism of action appears to be due to increased metabolism of topiramate.
-
- MANAGEMENT: If dosages of topiramate have been adjusted
up, reduction or withdrawal of carbamazepine during adjunctive therapy
may require a downward dose adjustment of topiramate. No adjustment in
carbamazepine dosage is required when topiramate adjunctive therapy is
started. Patients should be monitored for seizure control and should be
advised to notify their physician if seizure control worsens.
-
- ibuprofen <--> methylprednisolone
-
- Applies to: Vicoprofen (hydrocodone/ibuprofen), methylprednisolone
-
- MONITOR: The combined use of oral corticosteroids and
nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential
for serious gastrointestinal (GI) toxicity, including <http://www.drugs..com/interactions-check.php#>inflammation,
bleeding, ulceration, and perforation. In a large, case-control study of
elderly patients, those who used corticosteroids and NSAIDs concurrently
had an estimated relative risk (RR) for peptic ulcer disease and GI hemorrhage
of 14.6 compared to those who used neither. Oral corticosteroid use was
associated with a doubling of the risk (estimated RR = 2.0), but the risk
was confined to those who also used NSAIDs. It is possible that both categories
of agents are ulcerogenic and have additive effects on the GI mucosa during
coadministration. Some investigators have also suggested that the primary
effect of corticosteroids in this interaction is to delay healing of erosions
caused by NSAIDs rather than cause de novo ulcerations.
-
- MANAGEMENT: Caution is advised if oral corticosteroids
and NSAIDs are used together, especially in patients with a prior history
of peptic ulcer disease or GI bleeding and in elderly and debilitated patients.
During concomitant therapy, patients should be advised to take the medications
with food and to immediately report signs and symptoms of GI ulceration
and bleeding such as severe abdominal <http://www.drugs.com/interactions-check.php#>pain,
dizziness, lightheadedness, and the appearance of black, tarry stools.
The selective use of prophylactic anti-ulcer therapy (e.g., antacids, H2-antagonists)
may be considered.
-
- clarithromycin <--> fluoxetine
-
- Applies to: Biaxin (clarithromycin), fluoxetine
-
- GENERALLY AVOID: The use of some macrolide antibiotics
has been associated with increased blood levels of some selective serotonin
reuptake inhibitors (SSRIs), resulting in excessive serotonergic effects
or serotonin syndrome. The mechanism is inhibition of the CYP450 3A4 isoenzyme,
which metabolizes SSRIs.
-
- MANAGEMENT: In cases where both drugs are necessary,
one could consider using a macrolide antibiotic that does not inhibit CYP450
3A4, such as azithromycin or dirithromycin.
-
- ibuprofen <--> fluoxetine
-
- Applies to: Vicoprofen (hydrocodone/ibuprofen), fluoxetine
-
- MONITOR: Serotonin reuptake inhibitors (SRIs) may potentiate
the <http://www.drugs.com/interactions-check.php#>risk of bleeding in
patients treated with agents that affect hemostasis such as anticoagulants,
platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents
that commonly cause thrombocytopenia. The tricyclic antidepressant, clomipramine,
is also a strong SRI and may interact similarly. Serotonin release by platelets
plays an important role in hemostasis, thus SRIs may alter platelet function
and induce bleeding. Published case reports have documented the occurrence
of bleeding episodes in patients treated with psychotropic agents that
interfere with serotonin reuptake. Additional epidemiological studies have
confirmed the association between use of these agents and the occurrence
of upper gastrointestinal bleeding, and concurrent use of NSAIDs or aspirin
was found to potentiate the risk. Preliminary data also suggest that there
may be a pharmacodynamic interaction between SSRIs and oral anticoagulants
that can cause an increased bleeding diathesis. Concomitant administration
of paroxetine and warfarin, specifically, has been associated with an increased
frequency of bleeding without apparent changes in the disposition of either
drug or changes in the prothrombin time. Bleeding has also been reported
with fluoxetine and warfarin, while citalopram and sertraline have been
reported to prolong the prothrombin time of patients taking warfarin by
about 5% to 8%.
-
- MANAGEMENT: Caution is advised if SRIs or clomipramine
are used in combination with other drugs that affect <http://www.drugs.com/interactions-check.php#>hemostasis.
Close clinical and laboratory observation for hematologic complications
is recommended. Patients should be advised to promptly report any signs
of bleeding to their physician, including pain, swelling, headache, dizziness,
weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal
bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding
or bruising, red or brown urine, or red or black stools.
-
- propranolol <--> methylprednisolone
-
- Applies to: propranolol, methylprednisolone
-
- MONITOR: Corticosteroids may antagonize the effects of
antihypertensive medications by causing sodium and fluid retention. These
effects may be more common with the natural corticosteroids (cortisone,
hydrocortisone) because they have greater mineralocorticoid activity. In
addition, some calcium channel blockers such as diltiazem and verapamil
may increase corticosteroid plasma levels and effects by inhibiting their
clearance via CYP450 3A4 metabolism.
-
- MANAGEMENT: Patients on prolonged (i.e., longer than
about a week) or high-dose corticosteroid therapy should have blood pressure,
electrolyte levels, and <http://www.drugs.com/interactions-check.php#>body
weight monitored regularly, and be observed for the development of
edema and congestive heart failure. The dosages of antihypertensive medications
may require adjustment.
-
- propranolol <--> clonazepam
-
- Applies to: propranolol, Klonopin (clonazepam)
-
- MONITOR: Many psychotherapeutic and CNS-active agents
(e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics,
opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially
during initiation of therapy and dose escalation. Coadministration with
antihypertensive agents, in particular vasodilators and alpha-blockers,
may result in additive effects on blood pressure and orthostasis.
-
- MANAGEMENT: Caution is advised during coadministration
of these agents. Close monitoring for development of hypotension is recommended.
Patients should be advised to avoid rising abruptly from a sitting or recumbent
position and to notify their physician if they experience dizziness, lightheadedness,
syncope, orthostasis, or tachycardia.
-
- propranolol <--> lorazepam
-
- Applies to: propranolol, Ativan (lorazepam)
-
- The pharmacologic effects of some benzodiazepines may
be increased by some beta-blockers. Propranolol and metoprolol may inhibit
the hepatic metabolism of diazepam and other mechanisms may also be involved.
Most changes have been clinically insignificant; however, increased reaction
times and/or decreased kinetic visual acuity have been reported with some
combinations. Observation for altered benzodiazepine effects is recommended
if these drugs must be used together. Patients should be warned against
driving or operating hazardous machinery.
-
-
-
- Interactions between your selected drugs and food
-
- propranolol <--> food
-
- Applies to: propranolol
-
- ADJUST DOSING INTERVAL: The bioavailability of propranolol
may be enhanced by food.
-
- MANAGEMENT: Patients may be instructed to take propranolol
at the same time each day, preferably with or immediately following meals.
-
- carbamazepine <--> food
-
- Applies to: carbamazepine
-
- GENERALLY AVOID: In a small, randomized, crossover study,
the administration of carbamazepine with grapefruit juice (compared to
water) increased plasma drug concentrations by approximately 40%. The proposed
mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in
the gut wall by certain compounds present in grapefruits.
-
- MANAGEMENT: Given the drug's narrow therapeutic index,
patients receiving carbamazepine therapy should preferably avoid the regular
consumption of grapefruits and grapefruit juice to prevent any undue fluctuations
in plasma drug levels. Patients should be advised to report signs of carbamazepine
toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.
-
- methylprednisolone <--> food
-
- Applies to: methylprednisolone
-
- MONITOR: Grapefruit juice may increase the plasma concentrations
of some orally administered drugs that are primarily metabolized by the
CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated
first-pass metabolism in the gut wall by certain compounds present in grapefruits.
The extent and clinical significance of many of these interactions are
unknown. Moreover, pharmacokinetic alterations associated with interactions
involving grapefruit juice are often subject to a high degree of interpatient
variability.
-
- MANAGEMENT: Patients who regularly consume grapefruits
and grapefruit juice should be monitored for adverse effects and altered
plasma concentrations of drugs that are metabolized by CYP450 3A4. Grapefruits
and grapefruit juice should be avoided if an interaction is suspected.
Orange juice is not expected to interact with these drugs.
-
- clarithromycin <--> food
-
- Applies to: Biaxin (clarithromycin)
-
- Grapefruit juice may delay the gastrointestinal absorption
of clarithromycin but does not appear to affect the overall extent of absorption
or inhibit the metabolism of clarithromycin. The mechanism of interaction
is unknown but may be related to competition for intestinal CYP450 3A4
and/or absorptive sites. In an open-label, randomized, crossover study
consisting of 12 <http://www.drugs.com/interactions-check.php#>healthy subjects,
coadministration with grapefruit juice increased the time to reach peak
plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin
(the active metabolite) by 80% and 104%, respectively, compared to water.
Other pharmacokinetic parameters were not significantly altered. This interaction
is unlikely to be of clinical significance.
-
-
- Copyright © 2009 Gayle Eversole, DHom, PhD, MH,
NP, ND. All rights reserved.
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