Clarithromycin is an antibiotic (macrolide) used for respiratory and skin infections and in combination to eradicate Helicobacter pylori. It is effective, but blocks the elimination of many other medicines, which can raise their levels and the risk of toxic effects.
Also known as: Klacid
Clarithromycin prolongs QT and inhibits CYP3A4 (involved in Amodiaquine metabolism) — risk of arrhythmias and toxicity.
Amodiaquine is partly metabolised by CYP3A4; clarithromycin inhibits this enzyme and can raise its concentrations, increasing the risk of hepatotoxicity and QT prolongation (both drugs prolong the QT interval). Prefer an alternative antibiotic during artesunate+amodiaquine antimalarial treatment and, if the combination is unavoidable, monitor the ECG, transaminases and electrolytes.
Artesunate+amodiaquine + clarithromycin: clarithromycin raises amodiaquine levels (CYP3A4 inhibition) and both prolong the QT. Avoid if possible.
Additive QT prolongation + enzymatic inhibition that may raise Amodiaquine levels.
ECG (QTc) and signs of toxicity.
Palpitations, jaundice (amodiaquine hepatotoxicity).
Avoid when possible; monitor ECG; consider an alternative antibiotic.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Risk of myopathy and rhabdomyolysis. Clarithromycin raises Atorvastatin levels.
Atorvastatin is metabolised by CYP3A4; clarithromycin, a potent inhibitor, can raise its concentrations several-fold, with risk of myopathy, rhabdomyolysis and renal failure. Hold atorvastatin during the clarithromycin course (and a few days after) or switch to a statin less dependent on CYP3A4 (e.g. pravastatin); monitor myalgia, weakness and CPK in patients who keep the combination.
Atorvastatin + clarithromycin: clarithromycin inhibits CYP3A4 and can markedly raise atorvastatin levels, with risk of myopathy/rhabdomyolysis. Hold the statin during the antibiotic.
Inhibition of CYP3A4, the main Atorvastatin metabolic pathway.
Muscle symptoms (pain, weakness, dark urine) during and after the antibiotic.
Severe muscle pain, proximal weakness, dark-coloured urine (possible rhabdomyolysis).
Hold the statin during a short course of Clarithromycin or prefer Azithromycin.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4
Clarithromycin prolongs the QT interval and inhibits CYP3A4, raising Bedaquiline levels — increased arrhythmia risk.
Bedaquiline is metabolised by CYP3A4 and clarithromycin inhibits this enzyme, potentially raising its concentrations substantially; both drugs prolong the QT interval, with an additive torsades de pointes risk. In multidrug-resistant tuberculosis regimens containing bedaquiline, avoid macrolides; if a macrolide is needed, prefer azithromycin (less interaction) and monitor the ECG and electrolytes.
Bedaquiline + clarithromycin: clarithromycin raises bedaquiline levels (CYP3A4 inhibition) and both prolong the QT. Avoid the combination.
Bedaquiline metabolism inhibition and additive QT prolongation.
ECG (QTc) and electrolytes.
Palpitations, syncope.
Avoid when possible; ECG and surveillance.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Clarithromycin may increase systemic exposure to inhaled budesonide, potentiating corticosteroid effects.
Budesonide (inhaled or oral) is metabolised in the liver by CYP3A4; clarithromycin, a potent inhibitor, can increase its systemic exposure and potentiate corticosteroid effects (Cushing's syndrome, hyperglycaemia, adrenal suppression, osteoporosis), especially with prolonged use and high inhaled doses. Monitor for corticosteroid excess signs, consider reducing the budesonide dose and prefer another antibiotic when possible.
Budesonide + clarithromycin: clarithromycin increases systemic budesonide exposure (CYP3A4 inhibition), with risk of corticosteroid effects. Monitor for corticosteroid excess signs.
Clarithromycin inhibits CYP3A4, which metabolises budesonide.
Monitor bruising, blood glucose and signs of adrenal suppression in at-risk patients.
Cushing's syndrome, adrenal suppression.
Monitor for signs of corticosteroid excess with prolonged use of the combination.
DailyMed (FDA) — approved Budesonide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae1105cd-69fc-4c15-937f-c535304341c2 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Additive QT effect; Clarithromycin may also raise Mefloquine levels.
Mefloquine is partly metabolised by CYP3A4 and prolongs the QT interval; clarithromycin inhibits CYP3A4 (raising mefloquine levels) and also prolongs the QT, so the ventricular arrhythmia risk is additive. In patients receiving mefloquine, prefer another antibiotic and another antimalarial when possible; if the combination is unavoidable, monitor the ECG and electrolytes.
Mefloquine + clarithromycin: additive QT prolongation and raised mefloquine levels (CYP3A4 inhibition). Avoid the combination.
Additive QT prolongation + inhibition of Mefloquine metabolism (CYP3A4).
ECG (QTc) and electrolytes.
Palpitations, dizziness, seizures.
Caution; monitor ECG and signs of toxicity.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Two-way interaction: Clarithromycin raises Rifabutin levels (risk of uveitis and neutropenia) and Rifabutin lowers Clarithromycin levels.
The interaction is bidirectional: rifabutin induces CYP3A4 and lowers clarithromycin concentrations (compromising efficacy), while clarithromycin inhibits CYP3A4 and raises rifabutin levels, increasing the risk of uveitis, neutropenia and arthralgia. In mycobacterial regimens (e.g. Mycobacterium avium complex) with both drugs, reduce the rifabutin dose (often by half), monitor the blood count, ocular symptoms and the clinical response.
Rifabutin + clarithromycin: rifabutin lowers clarithromycin levels and clarithromycin raises rifabutin levels (risk of uveitis, neutropenia). Monitor both.
CYP3A4 inhibition by clarithromycin plus induction by rifabutin.
Ophthalmic review (eye pain and redness) and blood count.
Eye pain, redness, blurred vision (uveitis); fever, neutropenia.
Reduce the rifabutin dose (e.g. 150 mg/day or intermittent) and watch for toxicity.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Clarithromycin prolongs QT and inhibits CYP3A4, raising Lumefantrine exposure — increased risk of arrhythmias.
Clarithromycin inhibits CYP3A4, the pathway that metabolises artemether and lumefantrine, potentially raising antimalarial concentrations; both drugs prolong the QT interval, so the torsades de pointes risk increases additively. In patients treated for malaria with artemether+lumefantrine, prefer an antibiotic without QT effects (e.g. beta-lactams) if a bacterial infection coexists; if the combination is unavoidable, monitor the ECG and electrolytes.
Artemether+lumefantrine + clarithromycin: clarithromycin raises lumefantrine levels (CYP3A4 inhibition) and both prolong the QT. Monitor ECG or prefer another antibiotic.
CYP3A4 inhibition of Artemether/Lumefantrine metabolism (Clarithromycin) + additive QT prolongation.
ECG (QTc), potassium and clinical signs of arrhythmia.
Palpitations, syncope, chest pain.
Avoid when possible; monitor ECG and signs of toxicity; consider an alternative antibiotic if indicated.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Additive QT prolongation with risk of ventricular arrhythmias.
Both chloroquine and clarithromycin prolong the QT interval (hERG blockade); the effect is additive and the torsades de pointes risk increases, especially with hypokalaemia, bradycardia, renal impairment or heart disease. In patients receiving chloroquine (malaria, lupus), prefer an antibiotic without QT effects; if the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Chloroquine + clarithromycin: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG.
Both block cardiac potassium channels; additive effect on repolarisation.
ECG (QTc) and electrolytes.
Palpitations, syncope, dizziness.
Use with caution; monitor the ECG; consider an alternative antibiotic.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Additive QT prolongation — risk of arrhythmias.
Both hydroxychloroquine and clarithromycin prolong the QT interval; the additive effect increases the torsades de pointes risk, especially in patients with a prolonged baseline QT, hypokalaemia, renal impairment or heart disease. In patients with lupus or rheumatoid arthritis on hydroxychloroquine who need an antibiotic, prefer a macrolide with less QT effect or another class; if the combination is unavoidable, monitor the ECG and electrolytes.
Hydroxychloroquine + clarithromycin: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG.
Additive blockade of cardiac potassium channels.
ECG (QTc) and electrolytes.
Palpitations, syncope.
Caution; ECG if risk factors.
DailyMed/FDA (NIH/NLM) — approved Hydroxychloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34496b43-05a2-45fb-a769-52b12e099341 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Clarithromycin inhibits Quinine metabolism and prolongs QT — risk of toxicity and arrhythmias.
Quinine is metabolised by CYP3A4 and prolongs the QT interval; clarithromycin inhibits CYP3A4, potentially raising quinine concentrations (with risk of cinchonism and cardiac toxicity), and also prolongs the QT — the torsades de pointes risk is additive. During quinine malaria treatment, prefer a non-interacting antibiotic; if the combination is unavoidable, monitor the ECG, quinine levels and toxicity signs.
Quinine + clarithromycin: clarithromycin raises quinine levels (CYP3A4 inhibition) and both prolong the QT. Avoid the combination.
CYP3A4 inhibition (raises Quinine) + additive QT prolongation.
ECG, signs of cinchonism and arrhythmia.
Tinnitus, visual changes, palpitations.
Avoid; if needed, reduce Quinine and monitor.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Clarithromycin prolongs QT and inhibits CYP3A4 (which metabolises Piperaquine) — high risk of arrhythmias.
Piperaquine is partly metabolised by CYP3A4; clarithromycin inhibits this enzyme and can raise its concentrations, and both prolong the QT interval — the torsades de pointes risk is additive and potentially severe. During antimalarial treatment with dihydroartemisinin+piperaquine, prefer an antibiotic without QT effects; if the combination is unavoidable, monitor the ECG and electrolytes.
Dihydroartemisinin+piperaquine + clarithromycin: clarithromycin raises piperaquine levels and both prolong the QT. Avoid the combination.
Additive QT prolongation + enzymatic inhibition raising Piperaquine exposure.
ECG (QTc) and electrolytes.
Palpitations, syncope.
Avoid the association; consider an alternative antibiotic.
EMA — EPAR Eurartesim (dihydroartemisinin + piperaquine): https://www.ema.europa.eu/en/medicines/human/EPAR/eurartesim ; DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Combining Efavirenz with Clarithromycin reduces Clarithromycin concentrations, compromising the antimicrobial response; there is also a risk of QT prolongation.
Efavirenz induces CYP3A4 and lowers clarithromycin concentrations by about 40%, while raising its active metabolite (14-hydroxyclarithromycin); the clinical significance is variable, but antibiotic efficacy may be compromised and the QT prolongation risk increases. In HIV patients receiving clarithromycin, consider an alternative (e.g. azithromycin, with less interaction) and monitor the clinical response.
Efavirenz + clarithromycin: efavirenz lowers clarithromycin levels (CYP3A4 induction) and raises the active metabolite; the QT may prolong. Monitor response and ECG.
Efavirenz, a CYP3A4 inducer, accelerates Clarithromycin metabolism (↓ Clarithromycin, ↑ of the metabolite), reducing its efficacy.
Watch for signs of uncontrolled infection and, with risk factors, the QT interval.
Worsening infection during treatment requires review of the antibiotic.
Consider an alternative antibiotic (e.g. azithromycin) to avoid the interaction and reduce the risk of QT prolongation.
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Alprazolam with Clarithromycin increases Alprazolam concentrations, with a risk of excessive sedation.
Alprazolam is metabolised by CYP3A4; clarithromycin, a potent inhibitor of this enzyme, can raise its concentrations and potentiate sedation, ataxia and the risk of respiratory depression, especially in the elderly and in patients with respiratory or liver disease. Reduce the alprazolam dose (up to 50%) during the combination, avoid it in patients with sleep apnoea or severe COPD and monitor sedation; prefer a non-interacting antibiotic (e.g. azithromycin, which has less effect) when possible.
Alprazolam + clarithromycin: clarithromycin inhibits CYP3A4 and may double alprazolam levels, with sedation and respiratory depression. Monitor and reduce the alprazolam dose.
Clarithromycin, a CYP3A4 inhibitor, reduces Alprazolam metabolism, raising its serum levels.
Watch for sedation and central nervous system depression.
Marked sedation or confusion require dose reduction and reassessment.
Consider reducing the Alprazolam dose during Clarithromycin use.
DailyMed/FDA (NIH/NLM) — approved Alprazolam label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0cf8b567-201b-44fa-8fd3-c74023aff44f ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Clarithromycin inhibits theophylline metabolism and may raise its levels, with a risk of toxicity (nausea, tachycardia, seizures).
Theophylline is metabolised by CYP1A2 and CYP3A4; clarithromycin inhibits CYP3A4 and can raise its concentrations, with risk of toxicity (nausea, vomiting, tachycardia, tremor and, in severe cases, seizures and arrhythmias). Theophylline has a narrow therapeutic window, so monitor its plasma levels and reduce the dose if needed during the combination.
Theophylline + clarithromycin: clarithromycin inhibits theophylline metabolism and may raise its levels, with risk of toxicity. Monitor theophylline levels.
Clarithromycin inhibits CYP1A2/CYP3A4, reducing the clearance of theophylline, which has a narrow therapeutic margin.
Monitor nausea, vomiting, tachycardia, tremor and neurological signs (seizures).
Tachycardia, arrhythmias, repeated vomiting, seizures.
Monitor theophylline levels and reduce the dose if needed; consider an alternative antibiotic.
DailyMed (FDA) — approved Theophylline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e64036a-ee3e-42e7-9e59-881f88a4e298 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin may raise loperamide concentrations, potentiating CNS-depressant and cardiac effects.
Loperamide is a substrate of CYP3A4 and P-glycoprotein; clarithromycin inhibits both pathways and can substantially raise its concentrations, potentiating CNS depression (drowsiness, severe constipation) and QT prolongation (high loperamide doses). Use the lowest effective dose, avoid high doses and monitor drowsiness, constipation and palpitations during the combination.
Loperamide + clarithromycin: clarithromycin raises loperamide levels (CYP3A4/P-gp inhibition), with risk of CNS and QT effects. Use the lowest effective dose.
CYP3A4 inhibition by clarithromycin increases loperamide exposure.
Monitor drowsiness, constipation, palpitations and rhythm changes.
Loperamide toxicity (CNS, QT).
Use the lowest effective dose and monitor adverse effects; avoid high doses.
DailyMed (FDA) — approved Loperamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=568064c9-139d-7233-e063-6294a90a10d4 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Corticosteroid + clarithromycin: CYP3A4 inhibition increases corticosteroid exposure.
Dexamethasone is metabolised by CYP3A4; clarithromycin inhibits this enzyme and can raise its concentrations, potentiating anti-inflammatory effects, hyperglycaemia and the risk of adrenal suppression in prolonged courses. In patients on corticosteroid therapy and a clarithromycin-treated infection, monitor blood glucose and corticosteroid excess signs and consider reducing the dexamethasone dose during the combination.
Dexamethasone + clarithromycin: clarithromycin raises dexamethasone levels (CYP3A4 inhibition), potentiating corticosteroid effects. Monitor corticosteroid effects.
Clarithromycin inhibits CYP3A4, reducing dexamethasone metabolism.
Blood glucose, blood pressure and signs of corticosteroid excess.
Weight gain, oedema, hyperglycaemia.
Watch for corticosteroid effects (hyperglycaemia, fluid retention, Cushing syndrome).
DailyMed (FDA) — approved Dexamethasone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cbd9005-7df2-47ee-adb3-7244c1c69bc3 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin can raise tadalafil blood levels, with a higher risk of side effects. Monitor and consider dose adjustment.
Tadalafil is metabolised by CYP3A4; inhibitors of this enzyme, such as clarithromycin, raise plasma concentrations and the incidence of adverse effects. The label recommends the same dose adjustments as for ketoconazole.
CYP3A4: clarithromycin (inhibitor) increases tadalafil exposure; adjust as with other strong inhibitors (as-needed max. 10 mg/72 h; daily max. 2.5 mg).
CYP3A4 inhibition by clarithromycin.
Tadalafil adverse effects.
Severe headache, symptomatic hypotension, priapism.
Adjust the tadalafil dose per the label during the clarithromycin course.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin can raise vardenafil blood levels, with a higher risk of side effects. Adjust the dose (max. 2.5 mg/24 h during the course).
Clarithromycin inhibits CYP3A4, increasing vardenafil exposure. The vardenafil label sets, for inhibitors such as clarithromycin and ketoconazole, a maximum dose of 2.5 mg in 24 hours during co-administration.
CYP3A4: clarithromycin is a moderate/strong CYP3A4 inhibitor; the label limits vardenafil to 2.5 mg/24 h with clarithromycin.
CYP3A4 inhibition by clarithromycin.
Vardenafil adverse effects.
Severe headache, symptomatic hypotension.
Limit vardenafil to 2.5 mg/24 h during the clarithromycin course.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin can increase estradiol levels in the blood, with more side effects. Tell your doctor if you notice anything unusual.
The approved estradiol label (DailyMed) documents that CYP3A4 inhibitors — erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice — can increase plasma oestrogen concentrations and cause side effects. Clarithromycin is a macrolide and potent CYP3A4 inhibitor; during the combination, nausea, breast tenderness, fluid retention and changes in the bleeding pattern may occur.
CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole, itraconazole, grapefruit juice) increase oestrogen concentrations, with a risk of dose-dependent adverse effects. Monitor.
CYP3A4 inhibition by clarithromycin, reducing oestrogen metabolism.
Symptoms of oestrogen excess: nausea, breast pain, oedema, irregular bleeding.
Severe breast pain, oedema, abnormal bleeding — medical evaluation.
Watch for dose-dependent adverse effects during the antibiotic; consider an estradiol dose adjustment if symptoms are relevant.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Carbamazepine toxicity. Clarithromycin inhibits CYP3A4 and greatly raises Carbamazepine levels.
Carbamazepine is extensively metabolised by CYP3A4 and clarithromycin is a potent inhibitor of this isoenzyme and of P-glycoprotein. The combination can double or more than double serum carbamazepine levels, with toxicity symptoms such as diplopia, nystagmus, ataxia, sedation and nausea; severe cases may progress to seizures or coma. Whenever possible, an alternative antibiotic that does not inhibit CYP3A4 should be chosen (e.g. azithromycin); if the combination is necessary, reduce the carbamazepine dose, monitor serum levels and clinical signs of toxicity.
Clarithromycin inhibits CYP3A4 and greatly increases carbamazepine concentrations, with risk of toxicity (diplopia, ataxia, sedation, nausea). Prefer an alternative antibiotic; if unavoidable, reduce the carbamazepine dose and monitor.
Carbamazepine is metabolised by CYP3A4, potently inhibited by Clarithromycin.
Carbamazepine levels and toxicity signs in the first days.
Nystagmus, diplopia, ataxia, sedation, nausea.
Avoid the combination; choose an alternative antibiotic or monitor Carbamazepine levels.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Combining domperidone with clarithromycin is contraindicated: clarithromycin inhibits CYP3A4 and raises domperidone concentrations, with a high risk of QT-interval prolongation and torsade de pointes.
Domperidone prolongs the QT interval and is metabolised by CYP3A4; clarithromycin, a potent inhibitor of this isoenzyme, raises its concentrations and the risk of malignant ventricular arrhythmias (torsades de pointes). For this reason, the combination is formally contraindicated. The risk is higher in patients with heart disease, hypokalaemia, bradycardia or taking other QT-prolonging drugs; an alternative prokinetic or antibiotic should be chosen.
Contraindication: clarithromycin inhibits CYP3A4 and raises domperidone concentrations, increasing the risk of QT prolongation and torsades de pointes. Do not combine; choose an alternative.
Clarithromycin is a potent CYP3A4 inhibitor, the main metabolic pathway of domperidone; both substances prolong the QT interval.
Monitor ECG (QT interval) and arrhythmia symptoms (palpitations, syncope).
Torsade de pointes, sudden death.
Avoid the combination; choose an alternative macrolide or a prokinetic/antiemetic without QT risk.
DailyMed (FDA) — approved Domperidone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cdb0c9b9-388c-4a06-9fe9-bb4e52278a4e ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Colchicine + potent CYP3A4/P-gp inhibitor: risk of severe colchicine toxicity.
Colchicine is a substrate of CYP3A4 and P-glycoprotein; clarithromycin inhibits both pathways and can multiply colchicine exposure, causing severe toxicity: intense gastrointestinal symptoms, pancytopenia, neuropathy and rhabdomyolysis, sometimes fatal. The approved colchicine label contraindicates the combination with potent CYP3A4/P-gp inhibitors in patients with renal or hepatic impairment and, in the others, requires dose reduction — in practice, the combination should be avoided whenever possible, choosing an alternative antibiotic (e.g. azithromycin).
Clarithromycin (CYP3A4 and P-gp inhibitor) greatly increases colchicine levels, with risk of severe and potentially fatal toxicity (diarrhoea, myelosuppression, rhabdomyolysis). Do not combine; use an alternative.
Clarithromycin inhibits CYP3A4 and P-glycoprotein, markedly raising colchicine concentrations.
Watch for colchicine toxicity symptoms (GI, neuromuscular).
Severe diarrhoea, vomiting, rhabdomyolysis, pancytopenia, arrhythmias.
Contraindicated; prefer an alternative antibiotic. If unavoidable, strongly reduce the colchicine dose.
DailyMed (FDA) — approved Colchicine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ae87893-a065-468e-b8da-f1db86afcaef ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin inhibits CYP3A4 and may potentiate the anticoagulant effect of Warfarin, raising the INR and the bleeding risk.
Clarithromycin is a potent CYP3A4 inhibitor, the main enzyme in R-warfarin metabolism, and simultaneously reduces the gut flora producing vitamin K. The result is INR elevation with increased bleeding risk, documented in many reports and mentioned in approved labels. The effect can appear within days of starting and persist after the antibiotic is stopped. Whenever possible, choose an alternative antibiotic (e.g. azithromycin has lower interaction potential); if clarithromycin is needed, monitor the INR frequently and reduce the warfarin dose as needed.
Clarithromycin inhibits CYP3A4 and reduces gut flora, potentially raising the INR and bleeding risk markedly. Monitor the INR during and after the antibiotic; consider an alternative.
Clarithromycin is a potent CYP3A4 inhibitor; it reduces Warfarin metabolism, raising plasma warfarin levels and the INR.
Monitor the INR frequently and watch for bleeding signs during and after the combination.
Active bleeding, a markedly elevated INR or new bruising require urgent intervention.
Adjust the warfarin dose based on the INR; consider an alternative antibiotic when possible.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Alcohol may worsen clarithromycin gastrointestinal effects (nausea, abdominal pain).
Limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5be5f12-6392-4d7d-ab23-ebc205ac1a85
Grapefruit inhibits CYP3A4 and can raise clarithromycin concentrations, increasing the risk of QT prolongation and adverse effects.
Avoid grapefruit juice during treatment.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5be5f12-6392-4d7d-ab23-ebc205ac1a85
Clarithromycin is renally and hepatically excreted; in severe renal impairment it may accumulate and requires dose adjustment.
Reduce the dose in severe renal impairment (CrCl < 30 mL/min).
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5be5f12-6392-4d7d-ab23-ebc205ac1a85
Clarithromycin prolongs the QT interval and may precipitate torsades de pointes in patients with QT prolongation or risk factors.
Avoid in congenital or acquired QT prolongation; monitor ECG and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5be5f12-6392-4d7d-ab23-ebc205ac1a85
Clarithromycin crosses the placenta; human data are limited, but macrolides are generally used in pregnancy when indicated.
Use only if the benefit justifies the risk; not the first-choice macrolide in pregnancy.
Excreted into breast milk; avoid while breastfeeding or use with caution.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5be5f12-6392-4d7d-ab23-ebc205ac1a85
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Macrolide antibacterial agent. It distributes widely into tissues and fluids, reaching tissue concentrations higher than serum (e.g. tonsil 1.6 mcg/g, lung 8.8 mcg/g after 250 mg every 12 h). The active metabolite 14-OH-clarithromycin contributes to antimicrobial activity. Potent inhibitor of CYP3A4 and P-glycoprotein — many clinically relevant interactions.
Exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. The main routes of resistance are modification of the 23S rRNA (insensitivity of the 50S subunit) and efflux pumps.
Well absorbed orally. With the extended-release formulation (1000 mg once daily), steady-state peak plasma concentrations (2–3 mcg/mL) occur 5 to 8 hours after dosing. Take with food: on an empty stomach the clarithromycin AUC is about 30% lower.
Metabolised in the liver, mainly by CYP3A4, with formation of the active metabolite 14-OH-clarithromycin. Elimination is biliary and renal; in hepatic impairment the formation of 14-OH decreases, partially offset by increased renal clearance of clarithromycin.
The elimination half-life of clarithromycin is 3 to 4 hours and that of the active metabolite 14-OH-clarithromycin 5 to 7 hours.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
