CIMDUO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CIMDUO (CIMDUO).
CIMDUO is a fixed-dose combination of lamivudine and tenofovir disoproxil fumarate. Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine triphosphate and incorporating into viral DNA, causing chain termination. Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analogue of adenosine monophosphate that, after conversion to tenofovir diphosphate, inhibits HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine triphosphate and causing DNA chain termination.
| Metabolism | Lamivudine is primarily eliminated renally via active secretion; metabolism is minimal (approximately 5-10% is metabolized to the trans-sulfoxide metabolite). Tenofovir disoproxil fumarate is a prodrug that is rapidly converted to tenofovir, which is then phosphorylated to the active tenofovir diphosphate. Tenofovir is eliminated renally by a combination of glomerular filtration and active tubular secretion. No significant metabolism by CYP450 enzymes. |
| Excretion | Renal excretion of unchanged lamivudine and tenofovir via glomerular filtration and active tubular secretion; lamivudine: approximately 70% excreted unchanged in urine; tenofovir: 70-80% excreted unchanged in urine via active tubular secretion and glomerular filtration; fecal elimination is minor (<10% for each component). |
| Half-life | Lamivudine: terminal elimination half-life 5-7 hours in adults; tenofovir: terminal elimination half-life approximately 17 hours in adults (range 12-25 hours), permitting once-daily dosing. |
| Protein binding | Lamivudine: <36% bound to plasma proteins (albumin); tenofovir: <0.7% bound to plasma proteins (albumin). |
| Volume of Distribution | Lamivudine: apparent Vd 1.3 L/kg, indicating distribution into total body water; tenofovir: Vd 0.8-1.2 L/kg, indicating distribution into total body water; both penetrate well into tissues including lymphatic tissue and cerebrospinal fluid. |
| Bioavailability | Lamivudine: oral bioavailability 80-85%; tenofovir disoproxil fumarate: oral bioavailability 25% (fasted), increased to 40% with high-fat meal; Cimduo is a fixed-dose combination tablet administered orally with food. |
| Onset of Action | Lamivudine: intracellular phosphorylation to active triphosphate reaches steady-state within 24 hours; tenofovir: intracellular diphosphate reaches steady-state within 24 hours; clinical antiviral effect detected within 1-2 weeks. |
| Duration of Action | Lamivudine: intracellular triphosphate half-life 16-18 hours, supporting once-daily dosing; tenofovir: intracellular diphosphate half-life >60 hours in activated peripheral blood mononuclear cells, supporting prolonged antiviral activity; clinical effect persists throughout dosing interval. |
| Action Class | Cell wall active agent -Extended spectrum Penicillin |
| Brand Substitutes | Kamox 500mg Tablet, Zamox 500mg Tablet, Nirmox 500mg Tablet, Optimox 500mg Tablet, Emimox 500mg Tablet |
One tablet (300 mg tenofovir disoproxil fumarate and 300 mg lamivudine) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with creatinine clearance (CrCl) less than 50 mL/min. No dose adjustment required for CrCl ≥ 50 mL/min. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Contraindicated in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not recommended for pediatric patients weighing less than 35 kg. For patients weighing ≥ 35 kg, administer one tablet orally once daily. |
| Geriatric use | No specific dose adjustment required; however, monitor renal function due to age-related decreases in creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CIMDUO (CIMDUO).
| Breastfeeding | Lamivudine is excreted in human breast milk with an M/P ratio of approximately 0.6-1.4 (based on limited data). Tenofovir is excreted in breast milk in rats, but human data are scarce. The manufacturer recommends caution due to potential for adverse effects in the nursing infant. The benefits of breastfeeding should be weighed against the risk of HIV transmission if the mother is not on suppressive therapy. |
| Teratogenic Risk | Cimduo (lamivudine and tenofovir disoproxil fumarate) is classified as Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. However, based on animal studies, there is no evidence of teratogenicity. During the first trimester, the risk of major birth defects is not increased compared to the general population. During the second and third trimesters, there is no known fetal risk. However, due to potential for mitochondrial toxicity with nucleoside analogs, close monitoring is recommended. |
■ FDA Black Box Warning
WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine or tenofovir disoproxil fumarate, which are components of CIMDUO. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue CIMDUO and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
| Serious Effects |
["Coadministration with other products containing lamivudine or tenofovir disoproxil fumarate","Coadministration with emtricitabine-containing products","Coadministration with adefovir dipivoxil (for tenofovir component)"]
| Precautions | ["New onset or worsening renal impairment: tenofovir is associated with renal toxicity; monitor creatinine clearance before and during therapy.","Lactic acidosis and severe hepatomegaly with steatosis: reported with NRTIs; risk factors include female sex, obesity, and prolonged exposure.","Bone effects: decreased bone mineral density reported with tenofovir disoproxil fumarate; consider monitoring in patients with fractures or risk factors.","Immune reconstitution syndrome: may occur during initial treatment, including inflammatory responses to indolent infections.","Fat redistribution: accumulation of body fat (e.g., central obesity, buffalo hump) may occur.","Risk of hypersensitivity reactions: although rare, monitor for rash and systemic symptoms.","Hepatotoxicity: monitor liver function tests in patients with HBV co-infection or underlying liver disease."] |
Loading safety data…
| Fetal Monitoring | Monitor HIV viral load and CD4 count regularly during pregnancy. Perform hepatic function tests and renal function tests (serum creatinine, estimated creatinine clearance) at baseline and periodically. Monitor for lactic acidosis and hepatomegaly with steatosis, which can occur with nucleoside analogs. Fetal monitoring should include serial ultrasound for growth and development, particularly if there are maternal co-morbidities. |
| Fertility Effects | Based on animal studies, tenofovir disoproxil fumarate has been shown to have no significant effects on fertility at doses up to 10 times the human dose. Lamivudine did not affect fertility in animal studies. There is no evidence of impaired fertility in humans. However, HIV infection itself may affect fertility, and antiviral therapy may improve fertility outcomes. |